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1.
Toxicol In Vitro ; 101: 105934, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39237058

RESUMEN

Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [FOLR1], solute carrier [SLC]-19A1, and SLC46A1) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of SLC46A1. These inhibitors downregulated SLC19A1 expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. HDAC1/2 knockdown upregulated FOLR1 and SLC46A1 levels, whereas HDAC1/3 knockdown downregulated FOLR1 levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.

2.
Gastro Hep Adv ; 3(6): 773-782, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280907

RESUMEN

Background and Aims: Anxiety over food choices and symptoms related to food consumption diminish quality of life (QoL) in inflammatory bowel disease (IBD) patients. However, the specific factors that impact QoL among IBD patients remain unclear. In this study, we analyzed the relationships of demographic and disease factors with food-related QoL (FRQoL) in a large, diverse US cohort of IBD patients. Methods: In this cross-sectional analysis of 1108 IBD patients aged ≥18 years, we measured FRQoL with the 29-item Food-Related Quality of Life Questionnaire (FR-QoL-29) and disease activity with the Harvey-Bradshaw index in Crohn's disease (CD) patients or the Simple Clinical Colitis Activity Index in ulcerative colitis (UC) patients. Latinx immigrants completed a Spanish translation of the FR-QoL-29. A subset of patients had colonoscopy and inflammatory marker data available. We used univariate, multivariate, and subgroup analyses to examine the factors that influence FRQoL. Results: In our cohort, 55% of IBD patients self-identified as Latinx. Latinx and non-Latinx patients had similar FR-QoL-29 scores. Female patients had significantly lower FRQoL than male patients (P = .001). Increasing age and IBD duration correlated with higher FRQoL (P < .0001). In UC patients, higher Simple Clinical Colitis Activity Index scores (P < .0001), higher Mayo scores (P = .0009), and longer disease duration (P = .03) predicted significantly lower FRQoL. Disease activity and FRQoL were not significantly related in CD patients. Conclusion: This is the largest study to date to examine FRQoL in American IBD patients, and the first to include Latinx patients. Disease-related factors had a greater impact on FRQoL than ethnicity. Clinical and endoscopic disease activity had a more detrimental impact on FRQoL in UC than in CD. Diet intervention studies are needed to alleviate symptoms and improve FRQoL in the IBD population.

3.
Mol Med Rep ; 30(4)2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39129298

RESUMEN

Subsequently to the publication of the above paper, the authors drew to the attention of the Editorial Office that they had assembled the data shown for the cell migration assay experiments in Fig. 4F (on p. 8), incorrectly; essentially, the 'Control' data panel had inadvertently been copied across for the '10 µg/ml' data panel. The revised version of Fig. 4, showing the correct data panel for the '10 µg/ml' experiment in Fig. 4F,  is shown on the next page. Note that the replacement of the erroneous data does not affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for granting them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 27: 88, 2023; DOI: 10.3892/mmr.2023.12975].

4.
EJHaem ; 5(4): 698-708, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157631

RESUMEN

Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B-cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED-2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1-JH, VHFR2-JH, and VHFR3-JH) in the BIOMED-2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline-based immunochemotherapy. Complete detection of the FR1 to FR3 primer-based IgH VH PCR patterns in the BIOMED-2 protocol was associated with low frequency of VH SHMs (p < 0.001). Patients who were positive for all these three PCRs (n = 79) were significantly associated with shorter 5-year overall survival (OS; 54.2% vs. 73.2%; p = 0.002) and progression-free survival (PFS; 34.3% vs. 59.3%; p < 0.001) compared to patients with other PCR patterns (n = 202). Specifically, the successful FR3-JH detection was associated with significantly worse OS (p < 0.001) and PFS (p < 0.001). PCR patterns of complete IgH rearrangement using the BIOMED-2 protocol are clinically meaningful indicators for prognostic stratification of DLBCL patients.

5.
J Ovarian Res ; 17(1): 161, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118097

RESUMEN

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages. While chemotherapy is a common treatment, it often leads to tumor recurrence, necessitating further interventions. In recent years, antibody-drug conjugates (ADCs) have emerged as a valuable tool in targeted cancer therapy. These complex biotherapeutics combine an antibody that specifically targets tumor specific/associated antigen(s) with a high potency anti-cancer drug through a linker, offering a promising approach for ovarian cancer treatment. The identification of molecular targets in various human tumors has paved the way for the development of targeted therapies, with ADCs being at the forefront of this innovation. By delivering cytotoxic agents directly to tumors and metastatic lesions, ADCs show potential in managing chemo-resistant ovarian cancers. Mucins such as MUC16, MUC13, and MUC1 have shown significantly higher expression in ovarian tumors as compared to normal and/or benign samples, thus have become promising targets for ADC generation. While traditional markers are limited by their elevated levels in non-cancerous conditions, mucins offer a new possibility for targeted treatment in ovarian cancer. This review comprehensively described the potential of mucins for the generation of ADC therapy, highlighting their importance in the quest to improve the outcome of ovarian cancer patients.


Asunto(s)
Inmunoconjugados , Mucinas , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Mucinas/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Animales
6.
Chem Biodivers ; : e202401029, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135377

RESUMEN

This comprehensive analysis of the fruits of Rosa spp. (FR) evaluates their chemical components and antioxidant activity. The study quantified total flavonoids and polyphenols using aluminum trichloride colorimetric assay and Folin-Ciocalteu methods, with the fruit of Rosa. laxa Rtez. var. mollis Yü et Ku. sample exhibiting the highest concentrations of 59.21 mg/g and 81.13 mg/g, respectively. Ultra-High-Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry (UPLC-TQ-MS) assessed seven primary components, with notable levels of euscaphic acid, ursolic acid, and gallic acid. Antioxidant activities were tested using DPPH and ABTS methods, showing strong activities in samples the fruits of Rosa. persica Mickx ex Juss. and Rosa. laxa Rtez. var. kaschgarica (Rupr.) Y. L. Han.. Chemometric analyses, including similarity, cluster, principal component, and grey relational analyses, were used to explore relationships between FR varieties and their antioxidant properties. The study provides a vital basis for future FR quality assessments.

7.
MedComm (2020) ; 5(8): e641, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39021516

RESUMEN

Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.

9.
Front Immunol ; 15: 1395854, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39076979

RESUMEN

Introduction: Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans. Methods: Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies. Results: While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background. Discussion: The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.


Asunto(s)
Regiones Determinantes de Complementariedad , Receptor de Muerte Celular Programada 1 , Animales , Humanos , Ratones , Receptor de Muerte Celular Programada 1/inmunología , Regiones Determinantes de Complementariedad/inmunología , Regiones Determinantes de Complementariedad/genética , Anticuerpos Monoclonales Humanizados/inmunología , Epítopos de Linfocito T/inmunología
10.
Reprod Biol Endocrinol ; 22(1): 92, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085882

RESUMEN

BACKGROUND: Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging. METHODS: Gene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment. RESULTS: Gene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm. CONCLUSION: Overall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.


Asunto(s)
Endometriosis , Molécula de Adhesión Celular Epitelial , Receptor 1 de Folato , Poli(ADP-Ribosa) Polimerasa-1 , Endometriosis/metabolismo , Endometriosis/cirugía , Endometriosis/genética , Endometriosis/diagnóstico , Endometriosis/patología , Femenino , Humanos , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Molécula de Adhesión Celular Epitelial/genética , Molécula de Adhesión Celular Epitelial/metabolismo , Adulto , Biomarcadores/metabolismo , Inmunohistoquímica , Endometrio/metabolismo , Endometrio/patología , Endometrio/cirugía
11.
J Agric Food Chem ; 72(29): 16334-16346, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38994810

RESUMEN

Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ connected in a proportion of 5:1 and a ß-Glcp-(1→ side residue attached at C6 of the →4,6)-α-Glcp-(1→ residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.


Asunto(s)
Antineoplásicos , Apoptosis , Proliferación Celular , Linfoma no Hodgkin , Polisacáridos , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Linfoma no Hodgkin/tratamiento farmacológico , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Peso Molecular , Basidiomycota/química
12.
Chembiochem ; : e202400491, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39076125

RESUMEN

The natural product FR900359 (FR) has generated significant attention lately, due to its characteristics as potent and selective inhibitor of Gq/11 mediated signal transduction of associated G protein-coupled receptors (GPCRs). This makes FR both a widely used pharmacological tool compound and a lead molecule for targeted cancer therapy. The exploration of structure-activity-relationship (SAR) of the scaffold by total synthesis has been complicated by its structural complexity and its incompatibility with standard approaches of solid-phase peptide synthesis. Options for late-stage functionalization of FR are limited due to a lack of tractable functional groups. Here we present a mixed approach combining i) genetic engineering of the FR-assembly line in Chromobacterium vaccinii, to obtain a novel FR analog featuring a primary amine, with ii) its subsequent synthetic modification and biological profiling for further SAR exploration of the FR scaffold.

13.
Carbohydr Res ; 543: 109207, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39018698

RESUMEN

Folic acid receptor-targeted drug delivery system is a promising candidate for tumor-targeted delivery because its elevated expression specifically on tumor cells enables the selective delivery of cytotoxic cargo to cancerous tissue, thereby minimizing toxic side effects and increasing the therapeutic index. Pyridine bisfolate-chitosan (PyBFA@CS NPs) and folate-chitosan nanocomposite (FA@CS NPs) were synthesized with suitable particle size (256.0 ± 15.0 and 161.0 ± 5.0 nm), high stability (ζ = -27.0 ± 0.1 and -30.0 ± 0.2 mV), respectively, and satisfactory biocompatibility to target cells expressing folate receptors and try to answer the question: Is the metal center always important for activity? Since almost all pharmaceuticals work by binding to specific proteins or DNA, the in vitro binding of human serum albumin (HSA) to PyBFA@CS NPs and FA@CS NPs has been investigated and compared with PyBFA. Strong affinity to HSA is shown by quenching and binding constants in the range of 105 and 104 M-1, respectively with PyBFA@CS NPs showing the strongest. The compounds-HSA kinetic stability, affinity, and association constants were investigated using a stopped-flow method. The findings showed that all formulations bind by a static quenching mechanism that consists of two reversible steps: rapid second-order binding and a more slowly first-order isomerization reaction. The overall coordination affinity of HSA to PyBFA@CS NPs (6.6 × 106 M-1), PyBFA (4.4 × 106 M-1), and FA@CS NPs (1.3 × 106 M-1) was measured and The relative reactivity is roughly (PyBFA@CS NPs)/(PyBFA)/(FA@CS NPs) = 5/3/1. Additionally, in vitro cytotoxicity revealed that, consistent with the binding constants and coordination affinity, active-targeting formulations greatly inhibited FR-positive MCF-7 cells in compared to FRs-negative A549 cells in the following trend: PyBFA@CS NPs > PyBFA > FA@CS NPs. Furthermore, in vitro drug release of PyBFA@CS NPs was found to be stable in PBS at pH 7.4, however, the in pH 5.4 and in pH 5.4 containing 10 mM glutathione (GSH) (mimicking the tumor microenvironment) reached 43 % and 73 %, respectively indicating that the PyBFA@CS NPs system is sensitive to GSH. Folate-modified nanoparticles, PyBFA@CS NPs, are a promising therapeutic for MCF-7 therapy because they not only showed a greater affinity for HSA, but also showed higher cleavage efficiency toward the minor groove of pBR322 DNA via the hydrolytic way, as well as effective antibacterial activity that avoids the usage of extra antibiotics.‬‬‬‬‬‬‬‬‬‬‬‬ ‬‬‬‬‬‬‬‬‬‬‬‬‬‬.


Asunto(s)
Quitosano , Ácido Fólico , Glutatión , Nanopartículas , Piridinas , Humanos , Quitosano/química , Quitosano/farmacología , Células MCF-7 , Ácido Fólico/química , Nanopartículas/química , Piridinas/química , Piridinas/farmacología , Glutatión/química , Glutatión/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Receptores de Folato Anclados a GPI/metabolismo , Sistemas de Liberación de Medicamentos , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Liberación de Fármacos , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula
14.
Front Plant Sci ; 15: 1409116, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38916036

RESUMEN

Prasiola crispa, an aerial green alga, exhibits remarkable adaptability to the extreme conditions of Antarctica by forming layered colonies capable of utilizing far-red light for photosynthesis. Despite a recent report on the structure of P. crispa's unique light-harvesting chlorophyll (Chl)-binding protein complex (Pc-frLHC), which facilitates far-red light absorption and uphill excitation energy transfer to photosystem II, the specific genes encoding the subunits of Pc-frLHC have not yet been identified. Here, we report a draft genome sequence of P. crispa strain 4113, originally isolated from soil samples on Ongul Island, Antarctica. We obtained a 92 Mbp sequence distributed in 1,045 scaffolds comprising 10,244 genes, reflecting 87.1% of the core eukaryotic gene set. Notably, 26 genes associated with the light-harvesting Chl a/b binding complex (LHC) were identified, including four Pc-frLHC genes, with similarity to a noncanonical Lhca gene with four transmembrane helices, such as Ot_Lhca6 in Ostreococcus tauri and Cr_LHCA2 in Chlamydomonas reinhardtii. A comparative analysis revealed that Pc-frLHC shares homology with certain Lhca genes found in Coccomyxa and Trebouxia species. This similarity indicates that Pc-frLHC has evolved from an ancestral Lhca gene with four transmembrane helices and branched out within the Trebouxiaceae family. Furthermore, RNA-seq analysis conducted during the initiation of Pc-frLHC gene induction under red light illumination indicated that Pc-frLHC genes were induced independently from other genes associated with photosystems or LHCs. Instead, the genes of transcription factors, helicases, chaperones, heat shock proteins, and components of blue light receptors were identified to coexpress with Pc-frLHC. Those kinds of information could provide insights into the expression mechanisms of Pc-frLHC and its evolutional development.

15.
Phytochemistry ; 224: 114148, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38763311

RESUMEN

Seven previously undescribed triterpenes (1-7), as well as one triterpene (8) previously described as a synthetic product, were isolated from the antler-shaped fruiting body of Ganoderma lucidum. Their structures were established based on comprehensive spectroscopy analysis. At a concentration of 10 µM, (24E)-3-oxo-15α-acetoxy-lanosta-7,9(11),24-trien-26-al (3) and (24R,25S)-3-oxo-lanosta-7,9(11)-dien-25-ethoxyl-24,26-diol (5) provided significant protection against acetaminophen-induced necrosis in human HepG2 liver cancer cells, and the cell survival rates were 69.7 and 76.1% respectively, similar to that of the positive control (glutathione, 72.1%). Based on the present results, these compounds could be potential hepatoprotective agents.


Asunto(s)
Cuerpos Fructíferos de los Hongos , Sustancias Protectoras , Reishi , Triterpenos , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Humanos , Células Hep G2 , Cuerpos Fructíferos de los Hongos/química , Reishi/química , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/aislamiento & purificación , Estructura Molecular , Supervivencia Celular/efectos de los fármacos , Acetaminofén/farmacología , Relación Estructura-Actividad , Hígado/efectos de los fármacos , Relación Dosis-Respuesta a Droga
16.
Nutrients ; 16(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38732639

RESUMEN

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.


Asunto(s)
Neoplasias de los Genitales Femeninos , Vitaminas , Humanos , Femenino , Vitaminas/farmacología , Vitaminas/administración & dosificación , Neoplasias Ováricas , Vitamina D/administración & dosificación , Suplementos Dietéticos , Protocolos de Quimioterapia Combinada Antineoplásica , Vitamina A , Antineoplásicos/farmacología , Vitamina E/farmacología
17.
Vaccines (Basel) ; 12(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38793705

RESUMEN

Altruism plays an essential role in promoting vaccine uptake, an issue that came to the fore during the COVID-19 pandemic through discussions of herd immunity and altruistic motivations. In response, the primary objective of this cross-sectional survey was to explore how altruistic attitudes have evolved in the post-pandemic era and to assess their effectiveness in motivating vaccination behavior in different age groups. The study aimed to elucidate changes in altruistic motivations for vaccination and their implications for public health strategies. Using a representative sample of the adult population of South Tyrol, Italy, including 1388 participants, altruism was assessed in 2023 with the scales of the Elderly Care Research Center (ECRC) and the International Personality Item Pool (IPIP) subscale of the version 5F30F-R1. Its association with demographic variables, vaccination attitudes and personal beliefs in two age groups (18-69 years, 70+ years) was analyzed. The results reveal distinct predictors of altruism across these scales and age groups, suggesting a shift in altruistic attitudes towards vaccination when comparing data from a similar survey conducted in 2021 with the 2023 results. Consequently, the use of altruism scales for different age groups is warranted. This study highlights the need for further research in this field. It concludes that while promoting altruistic behavior to increase vaccine uptake appears to be effective primarily among the younger population, emphasizing personal safety is more appropriate for encouraging vaccination among older individuals.

18.
Heliyon ; 10(7): e28981, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596079

RESUMEN

A tightly packed irregular polygon with a distinctive protruding strip, specifically tailored for the N78/48 application, enhances a highly compact and effectively designed two-port MIMO (multiple-input, multiple-output) antenna. Its dimensions measure 20x31.5 × 1.6 mm3, with εr being 4.4 of FR-4 substrate, and it impressively delivers an extensive impedance bandwidth (Sxx < -10 dB) spanning the 3.25-3.85 GHz range. The design incorporates a MIMO antenna with closely spaced elements, merely 1.5 mm (0.012 λ0) apart. The microstrip inserts a feeding line with a partially truncated ground, a grounded stub, and a side stubs embedded in the ground plane, which improve isolation. Positioning T shaped decoupling elements between radiators helps the antenna's bandwidth enhance and improves isolation (S21) across the band. Extensive validation of the antenna's performance has been carried out through comprehensive s-parameter analysis, closely mirroring the results obtained through measurements. Despite its compact form, this antenna efficiently minimizes coupling, achieving S21 levels exceeding -19.25 dB throughout the band. Notably, the antenna attains an impressive peak gain of 3.3 dBi and exhibits a radiation efficiency of 92%. A total affective reflection coefficient (TARC) that starts at-10 dB, a MEG of 0.481 dB, and a channel capacity loss (CCL) of 0.3016 bits/s/Hz are some of the things that make up its MIMO diversity performance. The envelope correlation coefficient (ECC) is 0.0089. It's particularly suitable for 5G-NR sub-6GHz requirements, offering an efficient and compact solution.

19.
Surg Neurol Int ; 15: 93, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628508

RESUMEN

Background: The persistent primitive trigeminal artery (PPTA) is a persistent embryological carotid-basilar connection. Endovascular thrombectomy (EVT) for hypoplastic PPTA occlusion is a challenge. This case report aims to describe the successful recanalization of simultaneous occlusions in both the PPTA and basilar artery (BA) using the Solitaire FR (RECO SR)/Stent and Intermediate Catheter Assisting (SWIM) technique in a patient with acute cardiogenic cerebral embolism. To the best of our knowledge, this is the first report of such a case. Case Description: We present a case of a 70-year-old female patient who presented with acute right-sided hemiparesis and altered consciousness. Digital subtraction angiography confirmed the occlusion of both the distal portion of the PPTA and the BA. The patient underwent EVT using the SWIM technique, resulting in successful recanalization and significant improvement in the patient's condition. Conclusion: This case report demonstrates the successful application of the SWIM technique in achieving recanalization and improving outcomes in a patient with simultaneous occlusion of the acute PPTA and BA. These findings support the potential use of EVT in similar cases.

20.
Materials (Basel) ; 17(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38673074

RESUMEN

The foundation ring (FR) is a steel component embedded within the concrete of a wind turbine foundation, playing a pivotal role in connecting the wind turbine tower to the foundation structure. In this paper, the FR-foundation connection is equivalent to the exposed foundation and the shallow foundation by analyzing the anchorage characteristics of the foundation ring. Based on the ABAQUS concrete damaged plasticity model, full-scale modeling of the wind turbine foundation is carried out. The influence of embedment depth, ring radius and base flange width of the foundation ring on moment capacity is simulated. Based on the observed stress distributions under ultimate loads, analytical expressions were proposed to estimate the variation law of anchorage load-bearing capacity in the ultimate load state. Compared with the numerical simulation, the average errors under different influencing factors are 8.2%, 9.6% and 10.8%, respectively. The results indicate that the base flange provided the majority of the moment capacity, though the contribution of the sidewall increased to 25-50% that of the base flange in later stages.

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