Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
ACS Omega ; 9(35): 37386-37395, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39246456

RESUMEN

Lanthanides (Ln) from the f-blocks of the periodic table have gained significant interest due to their unique characteristics, including magnetism, photoluminescence, and catalysis. In this study, a series of lanthanide metal-organic frameworks [Ln-MOFs, Ln = Eu(III), Tb(III), Nd(III), Er(III), Ho(III), Gd(III), Pr(III), and Dy(III)] were constructed based on oxalic acid and lanthanide metals as the building blocks. These MOFs were comprehensively characterized using various analytical and spectroscopic techniques, including powder X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy-dispersive X-ray spectroscopy, nitrogen adsorption-desorption, and Raman spectroscopy. The magnetic properties of the investigated materials were examined, revealing both antiferromagnetic and ferromagnetic interactions within the Ln-Ox MOFs. The catalytic activities of Ln-Ox MOFs were evaluated through the heterogeneous acetalization of benzaldehyde with methanol. Reaction yields by the reported catalysts varied up to 90% depending on the MOF's metal center, and the product was confirmed by gas chromatography-mass spectrometry. Recycling experiments have confirmed the stable regeneration of Ln-Ox MOFs in which the product yields remained the same over four consecutive cycles. The hydrothermal synthesis of these MOFs paves the way for a diverse array of materials showcasing unique lanthanide properties, making them suitable for various applications.

2.
Sci Rep ; 14(1): 19059, 2024 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154086

RESUMEN

A modified carbon paste sensor based on N,N'-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))bis(pyridine-2-amine; BPA Schiff base as Cr(III) selective carrier was fabricated and studied in this work. The proposed sensor homogenization and mechanism of action was studied by infra-red (IR) and scanning electron microscope (SEM) with energy dispersive X-ray (EDX) tools. The sensor covered 1.0 × 10-7-1.0 × 10-1 mol L-1 linear range and a detection limit of 7.22 × 10-8 mol L-1 for Cr(III) with 20.17 ± 0.13 mV decade-1 Nernstian slope. 5 s was the response time of the prepared sensor and it was reproducible and stable for 3 months. The working pH range was 3.3-6.0 and it also works well to determine Cr(III) ion in presence of water miscible solvents up to 12.5% content of the methanol and 17.5% of ethanol. The electrode's selectivity was studied using separate and mixed solution methods for selectivity coefficients determination and the sensor showed good selectivity relative to a variety of metal ions (selectivity coefficients = 1.01 × 10-5-8.57 × 10-3). In addition, the practical analysis value of the sensor was demonstrated by measurement of Cr(III) quantitatively in mineral water, supplement and also as an indicator electrode in Cr(III) against EDTA potentiometric titration with good reproducibility (RSDs of 0.91-2.15%).


Asunto(s)
Carbono , Cromo , Cromo/análisis , Cromo/química , Carbono/química , Agua/química , Suplementos Dietéticos/análisis , Bases de Schiff/química , Límite de Detección , Concentración de Iones de Hidrógeno , Contaminantes Químicos del Agua/análisis , Electrodos , Reproducibilidad de los Resultados , Iones/análisis , Técnicas Electroquímicas/métodos
3.
J Funct Biomater ; 15(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38921536

RESUMEN

Titanium has a long history of clinical use, but the naturally forming oxide is not ideal for bacterial resistance. Anodization processes can modify the crystallinity, surface topography, and surface chemistry of titanium oxides. Anatase, rutile, and mixed phase oxides are known to exhibit photocatalytic activity (PCA)-driven bacterial resistance under UVA irradiation. Silver additions are reported to enhance PCA and reduce bacterial attachment. This study investigated the effects of silver-doping additions to three established anodization processes. Silver doping showed no significant influence on oxide crystallinity, surface topography, or surface wettability. Oxides from a sulfuric acid anodization process exhibited significantly enhanced PCA after silver doping, but silver-doped oxides produced from phosphoric-acid-containing electrolytes did not. Staphylococcus aureus attachment was also assessed under dark and UVA-irradiated conditions on each oxide. Each oxide exhibited a photocatalytic antimicrobial effect as indicated by significantly decreased bacterial attachment under UVA irradiation compared to dark conditions. However, only the phosphorus-doped mixed anatase and rutile phase oxide exhibited an additional significant reduction in bacteria attachment under UVA irradiation as a result of silver doping. The antimicrobial success of this oxide was attributed to the combination of the mixed phase oxide and higher silver-doping uptake levels.

4.
Sci Rep ; 14(1): 2602, 2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297106

RESUMEN

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14 post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE + BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p < 0.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p < 0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.


Asunto(s)
Hesperidina , Ratas , Animales , Ratas Sprague-Dawley , Hesperidina/farmacología , Microtomografía por Rayos X , Regeneración Ósea , Osteogénesis , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/genética , Colágeno/farmacología , Inflamación
5.
Cureus ; 15(8): e44433, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37791224

RESUMEN

Patients with "penta-refractory" multiple myeloma (MM) are challenging to treat given the limited treatment options available to them. Belantamab mafodotin is the first B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory MM (RRMM). In this case report, we reviewed in detail three female patients who were diagnosed with MM international scoring system (ISS)-3 and were heavily pretreated, and refractory to CD38 monoclonal antibodies, two proteasome inhibitors, and two immunomodulatory agents. These patients were started on belantamab mafodotin and experienced rapid and explosive clinical, biochemical, and extramedullary disease progression within a short period of time. All three patients experienced worsening cytopenia, increased transfusion requirement, severe uncontrolled bony pain, recurrent infections, and frequent hospital admissions. Two of them passed away due to disease progression complications within a few months of starting belantamab mafodotin. Although belantamab mafodotin as a single agent was withdrawn from the market after the DREAMM-3 trial failed to achieve its primary endpoint in late RRMM, BCMA-targeted therapy may still be a promising treatment approach, and the role of belantamab mafodotin is yet to be revealed in combination therapy in early RRMM.

6.
Sudan J Paediatr ; 23(1): 4-12, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37663104

RESUMEN

Diagnosis of pharyngotonsillitis is challenging due to the wide range of symptoms and signs. Sudan Federal Ministry of Health and Sudanese Association of Paediatricians, along with Sudan Heart Society reached a consensus about the clinical prediction rule which aids in diagnosing and managing bacterial pharyngotonsillitis. This audit aimed to assess doctors' knowledge and practice regarding diagnosis and management of bacterial pharyngotonsillitis at Ribat Teaching Hospital, Khartoum, Sudan. This audit was done at Pediatric Department, Ribat Teaching Hospital, and data collection was done over 2 weeks either in the first or the second cycle. Inclusion criteria were children who presented at the emergency room and were diagnosed with acute pharyngotonsillitis. The criteria used in this audit were from Sudan guidelines for prevention, diagnosis and management of rheumatic heart disease. Regular training sessions were done between the first and second cycles. There were 19 patients in the first cycle, 17 of them (89.4%) were diagnosed clinically with bacterial pharyngotonsillitis, and 8 of these 17 (47%) were fitting the criteria. Regarding the management of bacterial pharyngotonsillitis, no patient was given the recommended antibiotics in the guidelines (0.00%). In the second cycle, there were 21 patients, of whom 11 patients were diagnosed clinically with bacterial pharyngotonsillitis (52%). Of those 11, 8 patients were fitting the criteria (72.7%), and the recommended antibiotics were given in 9 of them (82%). The current practice toward acute pharyngotonsillitis management revealed a lack of doctors' knowledge about local guidelines which can be improved by simple ways such as posters, lectures, and focused group discussions.

7.
Front Pharmacol ; 14: 1108992, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36874031

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common cancers reported worldwide with poor morbidity and high mortality rates. HCC is a very vascular solid tumour as angiogenesis is not only a key driver for tumour progression but also an exciting therapeutic target. Our research investigated the use of fucoidan, a sulfated polysaccharide readily abundant in edible seaweeds commonly consumed in Asian diet due to their extensive health benefits. Fucoidan was reported to possess a strong anti-cancer activity, but its anti-angiogenic potential is still to be fully unraveled. Our research investigated fucoidan in combination with sorafenib (an anti-VEGFR tyrosine kinase inhibitor) and Avastin® (bevacizumab, an anti-VEGF monoclonal antibody) in HCC both in vitro and in vivo. In vitro on HUH-7 cells, fucoidan had a potent synergistic effect when combined with the anti-angiogenic drugs and significantly reduced HUH-7 cell viability in a dose dependent manner. Using the scratch wound assay to test cancer cell motility, sorafenib, A + F (Avastin and fucoidan) or S + F (sorafenib and fucoidan) treated cells consistently showed an unhealed wound and a significantly smaller %wound closure (50%-70%) versus untreated control (91%-100%) (p < 0.05, one-way ANOVA). Using RT-qPCR; fucoidan, sorafenib, A + F and S + F significantly reduced the expression of the pro-angiogenic PI3K/AKT/mTOR and KRAS/BRAF/MAPK pathways by up to 3 folds (p < 0.05, one-way ANOVA versus untreated control). While ELISA results revealed that in fucoidan, sorafenib, A + F and S + F treated cells, the protein levels of caspases 3, 8, and 9 was significantly increased especially in the S + F group showing 40- and 16-times higher caspase 3 and 8 protein levels, respectively (p < 0.05, one-way-ANOVA versus untreated control). Finally, in a DEN-HCC rat model, H&E staining revealed larger sections of apoptosis and necrosis in the tumour nodules of rats treated with the combination therapies and immunohistochemical analysis of the apoptotic marker caspase 3, the proliferation marker Ki67 and the marker for angiogenesis CD34 showed significant improvements when the combination therapies were used. Despite the promising findings reported herein that highlighted a promising chemomodulatory effect of fucoidan when combined with sorafenib and Avastin, further investigations are required to elucidate potential beneficial or adversary interactions between the tested agents.

9.
J Biomed Mater Res B Appl Biomater ; 111(5): 1100-1111, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36585829

RESUMEN

Titanium anodization has been shown to produce crystalline oxides exhibiting photocatalytic reactions that form reactive oxygen species (ROS) when exposed to UV light. The ROS subsequently attack bacteria cells, and thus reduce bacteria attachment on titanium implant surfaces. Polyaniline (PANI) is a conductive polymer that has shown antibacterial properties when electropolymerized onto titanium. Our research group hypothesized the addition of PANI to crystalline titanium oxide surfaces would increase the available free electrons and thus increase photocatalytic activity (PCA). This research led to the development of a novel single-step anodization approach for PANI doping crystalline titanium oxide layers. The objective of the present study was to determine the proper aniline electrolyte concentration needed to maximize the PCA and reduce bacterial attachment on the formed oxides. Aniline concentrations up to 1 M were added into a 1 M sulfuric acid electrolyte. The formed oxides exhibited increased PANI surface coverage but decreased anatase and rutile crystalline titanium oxide phase formation with increasing aniline electrolyte concentrations. Despite exhibiting the lowest levels of anatase and rutile formation, the 0.75 M and 1 M aniline oxides with the greatest PANI surface coverage also exhibited the highest PCA levels. 1 M aniline oxides showed significantly higher PCA under UVA irradiation compared to oxides formed from aniline concentrations up to 0.5 M (p < 0.001). 0.75 M aniline oxides exhibited significant reductions in Staphylococcus aureus attachment with or without UVA irradiation compared to control oxides without PANI. MTT and live/dead assays confirmed cytocompatibility and nearly 100% cell viability for the PANI doped oxides.


Asunto(s)
Óxidos , Titanio , Titanio/farmacología , Titanio/química , Especies Reactivas de Oxígeno , Óxidos/química , Compuestos de Anilina/farmacología , Compuestos de Anilina/química , Antibacterianos/farmacología
10.
Heliyon ; 8(11): e11680, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36439744

RESUMEN

Introduction: Systemic lupus erythematosus (SLE) is a chronic, inflammatory, multiorgan, systemic autoimmune disease. It is characterized by the high production of autoantibodies against nuclear compounds. TLRs (toll-like receptors 7/9) are pattern-recognition receptors that recognize nucleic acids and induce proinflammatory responses by activating NF-kB and producing type I interferon, which play a role in eliciting innate/adaptive immune responses and developing chronic inflammation. TLR7 and TLR9 single nucleotide polymorphisms (SNPs) have been linked to systemic lupus erythematosus in numerous studies (SLE). In this work, we wanted to evaluate and analyze single nucleotide polymorphisms (SNPs) in the TLR7 (rs3853839) and TLR9 (rs187084) genes among Egyptian SLE patients and healthy controls. Method: Whole blood samples were taken from 100 SLE patients and 100 controls; DNA was extracted and then processed for TLR7 rs3853839 and TLR9 rs187084 single nucleotide polymorphisms analysis by real-time polymerase chain reaction technology and restriction fragment-length polymorphism. We also assessed the association between TLR 7 and TLR 9 genes polymorphism with SLE clinical parameters. Results: Our results showed that TLR7 rs3853839 CG genotypes and G allele were significantly associated with SLE. Also, TLR7 rs3853839 genotypes and alleles were significantly associated with nephritis, arthritis, oral ulcers, and thrombocytopenia.Whereas genotypes and alleles of TLR9 were not significantly associated with the risk nor the clinical characteristics of SLE except for malar rash. Conclusion: In the investigated Egyptian cohort, our findings suggest that TLR7 rs3853839 gene polymorphisms increase the risk for SLE development and play a role in developing clinical characteristics, especially nephritis.

11.
Biomed Mater ; 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36384042

RESUMEN

Crystalline titanium oxides have shown photocatalytic activity (PCA) and the formation of antibacterial reactive oxygen species (ROS) when stimulated with UV light. Polyaniline (PANI) is a conductive polymer that has shown antibacterial effects. Previously, titanium oxides have been PANI-doped using a multi-step approach. In the present study, we compared PANI-doped specimens produced with a two-step method (ACV), to PANI-doped specimens produced by a novel single-step direct anodization (AAn) method, and a control group of anodized un-doped specimens. The surface morphology, oxide crystallinity, surface elemental composition, surface roughness, surface wettability, oxide adhesion, corrosion resistance, PCA, and ROS generation of each oxide group were evaluated. All groups exhibited mixed anatase and rutile phase oxides. The AAn group revealed less anatase and rutile, but more PANI-surface coverage. The AAn group exhibited significantly increased PCA after 60 minutes of direct UVA illumination compared to the ACV group, despite containing lower amounts of anatase and rutile. The ACV and AAn groups showed significant increases in ROS production after 4 hours UVA illumination while the control group showed similar ROS production. These findings suggested that PANI doping using the novel direct anodization technique significantly improved PCA even for oxides containing less crystallinity. The S. aureus attachment response to each oxide group was also compared under UVA pre-illumination, UVA direct illumination, and no illumination (dark) lighting conditions. Although no significant differences were shown in the bacterial response, both PANI-doped groups exhibited less average bacterial attachment compared to the control group. The response of MC3T3-E1 pre-osteoblast cells to each oxide group was evaluated using MTT and live/dead assays, and no evidence of cytotoxicity was found. Since many, if not most, titanium implant devices are routinely anodized as a part of the manufacturing processes, these study findings are applicable to a wide variety of implant applications.

12.
Microb Pathog ; 171: 105747, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36064102

RESUMEN

Human papillomavirus (HPV) is the most prevalent sexually transmitted disease in the world. Even though preventive vaccines against HPV are effective, the effective treatment of HPV infections is much less satisfactory due to multi-drug resistance and secondary adverse effects. Nanotechnology was employed for the delivery of anti-cancer drugs to increase the effectiveness of the treatment and minimize the side effects. Nanodelivery of both preventive and therapeutic HPV vaccines has also been studied to boost vaccine efficacy. Overall, such developments suggest that the nanoparticle-based vaccine might emerge as the most cost-effective way to prevent and treat HPV cancer, assisted or combined with another nanotechnology-based therapy. This review focuses on the current knowledge on pathogenesis and vaccines against HPV, highlighting the current value and perspective regarding the widespread diffusion of HPV vaccines-based nanomaterials. The ongoing advancements in the design of vaccines-based nanomaterials are expanding their therapeutic roles against HPV.


Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Nanotecnología , Papillomaviridae
13.
Diabetes Res Clin Pract ; 192: 110041, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35985426

RESUMEN

AIMS: To assess the clinical characteristics and outcomes of patients hospitalized with DKA. METHODS: We examined the hospital database for patients admitted with DKA to all government hospitals in Qatar over 6 years. RESULTS: We evaluated a total of 1330 patients [(37.3 % with type 1 diabetes (T1DM) and 62.7 % with type 2 diabetes (T2DM)] with 1613 episodes of DKA. Patients with T2DM were older than those with T1DM [48.0 (38.0-60.0), 26.0 (21.0-31.0) years] while there was no difference in DKA severity and laboratory values on admission or time to resolution of DKA. Admission to the intensive care unit was higher (38.9 % vs. 26.6 %; P < 0.001) with a longer hospital stay [5 (2.0-9.0) vs. 2 (2.0-4.0) days, P < 0.001] and markedly higher mortality (7.4 % vs. 1 %; P < 0.001) in patients with T2DM compared to T1DM. On multivariable logistic regression analysis, significant predictors of mortality were older age (odds ratio, 1.11; 95 % CI, 1.07-1.15; P = 0.0001), and admission to the intensive care unit (odds ratio, 3.61; 95 % CI, 1.69-7.72;P = 0.001). CONCLUSION: In this national cohort of patients hospitalized with DKA, those with T2DM had a 7-fold increase in inpatient mortality associated with older age and admission to the intensive care unit.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Humanos , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/terapia , Cetoacidosis Diabética/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicaciones , Estudios Retrospectivos , Hospitalización
14.
J Dent Sci ; 16(2): 691-699, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33854720

RESUMEN

BACKGROUND/PURPOSE: The prescription of antibiotics as an adjunct to mechanical periodontal therapy in patients with severe periodontitis is recommended; however, the side effects of antibiotics are a major concern. The aim of this study was to evaluate the efficacy of lycopene (Lyc) antioxidant gel versus minocycline hydrochloride microspheres (ARISTIN) as an adjunct to the nonsurgical treatment of periodontitis. MATERIALS AND METHODS: Three identical periodontal pockets/patient received root surface debridement followed by the random application of either ARISTIN, Lyc, or placebo gel (control, Ctrl). Clinical parameters, plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss, were recorded at the baseline and after 30 days. Additionally, the levels of interleukin-8 (IL-8), matrix metallopeptidase 9, and tissue inhibitor of metalloproteinases 1 (TIMP1) in gingival crevicular fluid samples were assessed at the same time points. RESULTS: Twenty-three patients with periodontitis completed the study. Both ARISTIN and Lyc treatments showed significantly greater gains in attachment (1.94 ±â€¯1.33 and 1.72 ±â€¯0.88, respectively) than the Ctrl treatment (1.04 ±â€¯0.96). Compared with those in the Ctrl, only ARISTIN showed a significant reduction in IL-8 level, whereas TIMP1 levels were significantly upregulated in the Lyc gel and ARISTIN sites. The effect size estimation indicated that Lyc gel exhibited considerably greater efficacy than the Ctrl gel. CONCLUSION: Lyc gel and ARISTIN offer almost equal improvement in both clinical and biochemical parameters of periodontitis.

15.
J Biomed Mater Res B Appl Biomater ; 109(11): 1866-1875, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33872457

RESUMEN

The mechanical stability and long-term success of an implant depends on the early healing phase and osseointegration of the bone around it. In addition, a healthy gingival tissue around the implant acts as a barrier that prevents bacteria and pathological byproducts from reaching the implant site. This study investigated the in-vitro attachment and spreading of human gingival fibroblasts (HGF) on bacterial grade polystyrene (PS) at different distances from radio-frequency glow-discharge (RFGD)-treated commercially pure titanium (cpTi) specimens. Controls included sterile cpTi specimens without RFGD treatment. A second set of experiments utilized media transferred to new bacterial grade polystyrene dishes (no cpTi) after the medium was conditioned by exposure to cpTi, either with or without RFGD treatment, for 24 hr. Surface characterization of the dishes was conducted through contact angle measurements and infrared spectroscopy. Cell numbers and surface areas were determined from Image J analysis of multiple microscopic images of fixed, stained cells. The results showed significantly greater numbers and surface areas on bacterial grade PS dishes at distances up to 15 mm from the RFGD-treated cpTi groups than for the controls. Moreover, a significant effect of the conditioned medium from RFGD-treated cpTi versus control cultures was shown on the numbers of fibroblasts attached to bacterial grade polystyrene dishes after 24 hr (p < 0.005) and 48 hr (p = 0.002) incubation. Surface areas of cells exposed to conditioned medium were not significantly different (p ≥ 0.05). Surface characterization of the PS dishes showed a higher value of the critical surface tensions of the treated group when compared to the control group.


Asunto(s)
Fibroblastos/metabolismo , Encía/metabolismo , Ondas de Radio , Titanio/química , Humanos
16.
Biochem Pharmacol ; 186: 114497, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33675775

RESUMEN

Despite the recent substantial progress in the treatment of hepatocellular carcinoma (HCC) from viral etiology, non-alcoholic steatohepatitis (NASH) is on a trajectory to become the fastest growing indication for HCC-related liver transplantation. The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily with multifaceted roles in several metabolic disorders, particularly NASH. Its role as a tumor suppressor was also highlighted. Herein, we investigated the effect of obeticholic acid (OCA), as an FXR agonist, on NASH-associated HCC (NASH-HCC) animal model induced by diethylnitrosamine and high fat choline-deficient diet, exploring the potential impact on the suppressor of cytokine signaling 3 (SOCS3)/Janus kinase 2 (Jak2)/signal transducer and activator of transcription 3 (STAT3) pathway. Results indicated that OCA treatment upregulated FXR and its key mediator, small heterodimer partner (SHP), with remarkable amelioration in the dysplastic foci observed in the NASH-HCC group. This was paralleled with noticeable downregulation of alpha fetoprotein along with reduction in interferon gamma and transforming growth factor beta-1 hepatic levels besides caspase-3 and p53 upregulation. Moreover, sirtuin-1 (SIRT-1), a key regulator of FXR that controls the regenerative response of the liver, was elevated following OCA treatment. Modulation in the SOCS3/Jak2/STAT3 signaling axis was also reported. In conclusion, OCA attenuated the development and progression of NASH-dependent HCC possibly by interfering with SOCS3/Jak2/STAT3 pathway suggesting the potential use of FXR activators in NASH-related disorders, even at later stages of the disease, to impede its progression to the more deteriorating condition of HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Janus Quinasa 2/metabolismo , Neoplasias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factor de Transcripción STAT3/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/farmacología , Ácido Quenodesoxicólico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Receptores Citoplasmáticos y Nucleares/agonistas , Transducción de Señal/fisiología
17.
Sci Rep ; 11(1): 5179, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33664352

RESUMEN

Radiotherapy-induced dermatitis (RID) is an inflammatory cutaneous disorder that is acquired as an adverse effect of undergoing radiotherapy. Skin microbiome dysbiosis has been linked to the outcomes of several dermatological diseases. To explore the skin microbiota of RID and deduce their underlying impact on the outcome of RID, cutaneous microbiomes of 78 RID patients and 20 healthy subjects were characterized by sequencing V1-V3 regions of 16S rRNA gene. In total, a significantly apparent reduction in bacterial diversity was detected in microbiomes of RID in comparison to controls. Overall, the raised Proteobacteria/ Firmicutes ratio was significantly linked to delayed recovery or tendency toward the permanence of RID (Kruskal Wallis: P = 2.66 × 10-4). Moreover, applying enterotyping on our samples stratified microbiomes into A, B, and C dermotypes. Dermotype C included overrepresentation of Pseudomonas, Staphylococcus and Stenotrophomonas and was markedly associated with delayed healing of RID. Strikingly, coexistence of diabetes mellitus and RID was remarkably correlated with a significant overrepresentation of Klebsiella or Pseudomonas and Staphylococcus. Metabolic abilities of skin microbiome could support their potential roles in the pathogenesis of RID. Cutaneous microbiome profiling at the early stages of RID could be indicative of prospective clinical outcomes and maybe a helpful guide for personalized therapy.


Asunto(s)
Bacterias/genética , Disbiosis/microbiología , Radiodermatitis/microbiología , Piel/microbiología , Adulto , Bacterias/clasificación , Bacterias/efectos de la radiación , Disbiosis/etiología , Disbiosis/genética , Disbiosis/patología , Femenino , Humanos , Inflamación/etiología , Inflamación/microbiología , Inflamación/patología , Masculino , Microbiota/efectos de la radiación , Persona de Mediana Edad , Pronóstico , ARN Ribosómico 16S/genética , Radiodermatitis/genética , Radiodermatitis/patología
18.
Arch Pharm (Weinheim) ; 353(5): e2000011, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32128876

RESUMEN

Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphate-containing physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in the last 5 years (between 2015 and 2019).


Asunto(s)
Fosfatasa Alcalina/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Fosfatasa Alcalina/metabolismo , Inhibidores Enzimáticos/química , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Estructura Molecular , Relación Estructura-Actividad
19.
RSC Adv ; 10(30): 17552-17560, 2020 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35515636

RESUMEN

Due to the toxicity of lead(ii) to all living organisms as it destroys the central nervous system leading to circulatory system and brain disorders, the development of effective and selective lead(ii) ionophores for its detection is very important. In this work, 1,3-bis[2-(N-morpholino)acetamidophenoxy]propane (BMAPP), belonging to acyclic diamides, was applied as a highly selective lead(ii) ionophore in a carbon paste ion selective electrode for the accurate and precise determination of Pb(ii) ions even in the presence of other interfering ions. Factors affecting the electrode's response behavior were studied and optimized. Scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and FT-IR spectroscopy were used for studying the morphology and response mechanism of the prepared sensor. The lipophilicity of the used ionophore, which contributes to the mechanical stability of the sensor, was studied using the contact angle measurement technique. The selectivity coefficients obtained by the separate solution method (SSM) and fixed interference method (FIM) confirmed the selectivity of the proposed sensor for Pb(ii) ions. The proposed sensor exhibited a Nernstian slope of 29.96 ± 0.34 mV per decade over a wide linear range of 5 × 10-8 to 1 × 10-1 mol L-1 and detection limit of 3 × 10-8 mol L-1 for 2 months with a fast response time (<10 s) and working pH range (2.5-5.5). To further ensure the practical applicability of the sensor, it was successfully applied for the lead(ii) ion determination in different water samples and the obtained data showed an agreement with those obtained by atomic absorption spectroscopy. In addition, it was successfully applied for the potentiometric titration of Pb(ii) against K2CrO4 and Na2SO4.

20.
Int J Gynaecol Obstet ; 145(2): 139-148, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30784056

RESUMEN

BACKGROUND: Two tocolytic drugs-atosiban and nifedipine-are currently used for first-line treatment of preterm labor (PTL). OBJECTIVE: To compare the efficacy and safety of atosiban with nifedipine for PTL treatment. SEARCH STRATEGY: In May 2017, we searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Clinical Trials with search terms including "nifedipine", "atosiban", and "preterm labor". SELECTION CRITERIA: Randomized controlled trials of women with PTL. DATA COLLECTION AND ANALYSIS: Data were extracted for study design, patient characteristics, risk of bias domains, and study outcomes. A random-effects model was used to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included seven studies that enrolled 992 patients. There was no significant difference between atosiban and nifedipine for pregnancy prolongation of 48 hours or more regarding efficacy (RR 1.06, 95% CI 0.92-1.22; P=0.440) or effectiveness (0.93, 0.84-1.03; P=0.177). Pregnancy prolongation for 7 days or more also did not differ between groups for efficacy (RR 1.04, 95% CI 0.89-1.21; P=0.656) or effectiveness (0.91, 0.79-1.05; P=0.177). Atosiban-however-was associated with fewer maternal side-effects than nifedipine. CONCLUSION: Atosiban resulted in fewer maternal side-effects than nifedipine, with no difference in pregnancy prolongation. PROSPERO registration: CRD42018090223.


Asunto(s)
Nifedipino/administración & dosificación , Trabajo de Parto Prematuro/tratamiento farmacológico , Tocolíticos/administración & dosificación , Vasotocina/análogos & derivados , Adulto , Femenino , Humanos , Nifedipino/efectos adversos , Oportunidad Relativa , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Tocolíticos/efectos adversos , Vasotocina/administración & dosificación , Vasotocina/efectos adversos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...