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1.
Heliyon ; 10(16): e35728, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220918

RESUMEN

Renal fibrosis represents a pivotal characteristic of chronic kidney disease (CKD), for which effective interventions are currently lacking. The Src kinase activates the phosphatidylinositol-3 kinases (PI3K)/Akt1 pathway to promote renal fibrosis, casting a promising target for anti-fibrosis treatment. Chaihuang-Yishen formula (CHYS), a traditional Chinese medicinal prescription, has a validated efficacy in the treatment of CKD, however, with the underlying mechanism unresolved. This study aimed to uncover the pharmacological mechanisms mediating the effect of CHYS in treating renal fibrosis using network pharmacology followed by experimental validation. The chemical compounds of CHYS were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database or published literature, followed by the prediction of their targets using SwissTargetPrediction software. Disease (CKD/renal fibrosis)-related targets were retrieved from the Genecards database. Protein-protein interaction (PPI) network was generated using the drug-disease common targets and visualized in Cytoscape software. The drug-disease targets were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by Metascape software. Additionally, the compound-target-pathway network was established in Cytosape to identify key compounds, targets, and pathways. Network pharmacology analysis screened out 96 active compounds and 837 potential targets within the 7 herbal/animal medicines of CHYS, among which 237 drug-disease common targets were identified. GO and KEGG analysis revealed the enrichment of fibrosis-related biological processes and pathways among the 237 common targets. Compound-target-pathway network analysis highlighted protein kinases Src and Akt1 as the top two targets associated with the anti-renal fibrosis effects of CHYS. In UUO mice, treatment with CHYS attenuates renal fibrosis, accompanied by suppressed expression and phosphorylation activation of Src. Unlike Src, CHYS reduced Akt1 phosphorylation without affecting its expression. In summary, network pharmacology and in vivo evidence suggest that CHYS exerts its anti-renal fibrosis effects, at least in part, by inhibiting the Src/Akt1 signaling axis.

2.
Heliyon ; 10(16): e35747, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253205

RESUMEN

Objective: The objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. Methods: We conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. Results: After treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). Conclusion: We found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

3.
Am J Clin Nutr ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218305

RESUMEN

Recent litigation has led to a situation where preterm cow milk-based infant nutritional products (PCMBPs) may soon have limited or no availability in the United States. Given their limited availability, similar products based only on human milk are unlikely to meet the needs of most preterm infants requiring such products, especially those born >1500 g or very preterm infants born at <1500 g after they reach 34-35 wk postmenstrual age. Alternative nutritional strategies, used before the introduction of specialized preterm products, would require modular nutrient additions to a formula designed for full-term infants and donor or maternal milk. The addition of modular products would require careful calibration to provide needed macro and micronutrients which would expose infants to risks of contamination, poor growth, and limited bioavailability of some of these modulars. Substantial risks of metabolic derangements, and ultimately, poor outcomes would occur. In the long-term greater availability and support for the use of human milk-based products is needed. However, policymakers cannot assume that PCMBPs will not be critically needed and should identify strategies for their continued marketplace availability.

4.
Heliyon ; 10(16): e35889, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39229535

RESUMEN

The GM(1,1) model's prediction accuracy is significantly influenced by the accuracy of background value estimation. The traditional trapezoidal background value can only be applied to a specific data sequence. Therefore, this study proposes a GM(1,1) model background value reconstruction approach based on the combination of intelligent trapezoidal and variable weights in order to increase the model's application as well as its prediction accuracy. The trapezoidal background value function with slope and point position parameters is called model I. Then, a set of point position parameter sequences, with a new background value function is constructed, called model II. A genetic algorithm is utilized to seek for the values of the parameters to be determined in both models I and II. The results showed that for the exponential growth data series, model I and II have higher prediction accuracy compared to traditional models. For data sequences, taking the traffic volume series of a road from 2014 to 2023, the prediction accuracy of this paper's model I method can be improved by 0.3643 % and 0.2725 % compared with Deng's and Wang's models. The prediction accuracy of this paper's model II method has been further improved by 0.1075 % compared with that of model I.

5.
J Dairy Sci ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218066

RESUMEN

Oligosaccharides (OS) in milk have been suggested to influence the health and development of the newborn by promoting growth of beneficial gut bacteria, stimulating brain development, and enhancing immune functions. Goat milk is a natural source of specific OS, which could be a potential beneficial ingredient for infant formula. In this study, goat milk oligosaccharide (gMOS) content from approximately 1,000 dairy goats across 18 commercial farms was studied. A genomic relationship matrix was used to unravel genetic and environmental factors shaping gMOS content. The most abundant gMOS identified was 3'-NGL, with a concentration of 32.05 mg/kg, while 3-FL exhibited the lowest concentration at 1.85 mg/kg. Acidic OS had a notably higher content (81.67 mg/kg) than neutral OS (24.88 mg/kg). High variability in gMOS content was observed among individual goats, which could for a large extent be attributed to genetic differences. Heritability estimates ranged from 31% for 3'-GL to 85% for 3-FL. High positive genetic correlations (>0.57) were estimated between 3'-SL and 6'-SL, and between 6'-GL and 3'-GL. The contribution of differences between farms to variation in milk OS content varied from 3% for 3'-NGL to 45% for 6'-SL. While gMOS like 3'-GL, 6'-GL, and 6'-NGL, were significantly influenced by systematic environmental factors such as the lactation stage, the impact of these factors was relatively minor compared with the importance of genetic and farm effects. This research, which stands out due to its relatively large sample size, underscores the pivotal role of genetics, and to a smaller extent farm practices like feed ration, in determining gMOS composition.

6.
Technol Health Care ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39240601

RESUMEN

BACKGROUND: This study aimed to investigate the effects of the Kidney-Tonifying and Blood-Activating Formula on combating the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies. OBJECTIVE: This study aimed to investigate the effects of kidney-tonifying and blood-activating formulations on combating the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies. METHODS: Mice in the phospholipid antibody group and phospholipid antibody + kidney-tonifying and blood-activating formula group underwent repeated implantation experiments, and the expression of integrin ß3 and integrin ß5 in placental tissue was observed. The effects of the kidney-tonifying and blood-activating formula on mouse placental tissue were evaluated through biochemical index tests, histopathological observations, and immunohistochemical staining. RESULTS: After intervention with the kidney-tonifying and blood-activating formula, the expression of integrin ß3 and integrin ß5 in placental tissue was notably upregulated, and placental structure was restored. Kidney-Tonifying and Blood-Activating Formula significantly improved abnormal biochemical indices and exerted a remarkable protective effect on placental tissue pathology. CONCLUSION: The kidney-tonifying and blood-activating formula effectively counteracted the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies and alleviated placental tissue pathology through structural improvement and protection. Therefore, kidney-tonifying and blood-activating formulas may serve as potential therapeutic agents for recurrent implantation failure, offering new insights and approaches for clinical treatment.

7.
J Dairy Sci ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245164

RESUMEN

This study investigated the potential of 2'-Fucosyllactose (2'-FL) and galactooligosaccharides (GOS) combinations as a novel and cost-effective substitute for human milk oligosaccharides (HMOs) in promoting gut health and reducing inflammation. In vitro studies using Caco-2 cells showed that 2'-FL and GOS combinations (H1: GOS:2'-FL ratio of 1.8:1; H2: ratio of 3.6:1) reduced lipopolysaccharide-induced inflammation by decreasing pro-inflammatory markers, while individual treatments had no significant effects. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, combined 2'-FL and GOS supplementation alleviated symptoms, improved gut permeability, and enhanced intestinal structure, with the GH1 group (H1 combo with DSS) being the most effective. 2'-FL and GOS combinations also enhanced short-chain fatty acid production in infant fecal batch fermentation and mouse fecal analysis, with GH1 showing the most promising results. GH1 supplementation altered gut microbiota in mice with DSS-induced colitis, promoting microbial diversity and a more balanced Firmicutes to Bacteroidota ratio. Infant formula products (IFPs) containing 2'-FL and GOS combinations (IFP2: 174 mg GOS and 95 mg 2'-FL per 14 g serving, 1.8:1 ratio; IFP3: 174 mg GOS and 48 mg 2'-FL per 14 g serving, 3.6:1 ratio) demonstrated gastrointestinal protective and anti-inflammatory properties in a coculture model of Caco-2 and THP-1 cells. These findings suggest that 2'-FL and GOS combinations have potential applications in advanced infant formulas and supplements to promote gut health and reduce inflammation.

8.
Int Breastfeed J ; 19(1): 62, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39238032

RESUMEN

BACKGROUND: On 6 February 2023, an Mw 7.8 earthquake struck southern and central Türkiye and north-western Syria, affecting the lives of 4.6 and 2.5 million children, respectively. In such crises, infants who are dependent on commercial milk formula (CMF) face increased vulnerability to diseases and malnutrition as safe preparation of CMF becomes difficult and sometimes impossible. The Operational Guidance on Infant and Young Child Feeding in Emergencies (OG-IFE) provides guidance on protecting and supporting recommended infant and young child feeding and minimizing the risks that come with CMF feeding. In addition, the International Code of Marketing of Breastmilk Substitutes (the Code) ensures adequate nutrition for infants by protecting and promoting breastfeeding and ensuring the proper usage of CMF. This study aims to document violations of the Code and the OG-IFE during the earthquake relief efforts to help strengthen infant and young child feeding emergency responses and inform future disaster relief policies. METHODS: Data was collected from 6 February to 10 March 2023 through Internet sources. Social media, news websites, and the Emergency Nutrition Network forum were used for data collection. Turkish content was translated into English for analysis, with a focus on donation-related information and Code violations related to baby food and infant feeding. RESULTS: A total of 40 reports on CMF, complementary food, and feeding equipment donations were collected. Three main types of violations of the OG-IFE and the Code were identified, with the majority of them being incidences of individuals, humanitarian organizations, and government agencies seeking or accepting donations. Infant formula companies continued to violate the Code by donating large quantities of CMF and feeding equipment to the Turkish Red Crescent, government agencies, and disaster relief infant and young child feeding (IYCF) coordination authorities. CONCLUSIONS: These incidents reflected a systematic violation of the Code and non-compliance with the OG-IFE. Globally accepted IYCF standards and recommendations were not consistently followed due to fragmented early responses. There is a critical need to step up efforts to ensure appropriate and safe IYCF practice protecting and supporting breastfed and non-breastfed infants in emergencies.


Asunto(s)
Terremotos , Fórmulas Infantiles , Sistemas de Socorro , Humanos , Lactante , Femenino , Turquía , Recién Nacido , Lactancia Materna , Siria , Masculino
9.
Bioresour Technol ; 413: 131435, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39244104

RESUMEN

This study assessed the methane production from food waste (FW) with dominant components of Meat (MFW), Fruit &Veg (VFW), Grain (GFW), Dairy (DFW), and the mixed feed of these components (MixFW). The high protein and lipid content FW (HPLFW) of MFW, DFW, and MixFW showed the methane yields of 337.0 ± 3.0, 307.4 ± 0.8, and 297.1 ± 1.2 ml-CH4/gCOD, respectively, while those for the high carbohydrate content FW (HCFW) of VFW and GFW were 238.3 ± 1.2 and 171.2 ± 0.3 ml-CH4/gCOD, respectively. A modified two-component kinetic (MTK) model was demonstrated to be the best to describe the methane production kinetics of both HPLFW and HCFW types of feeds. The element balance analysis revealed the element formula of the FW feeds and the methane-conversion organic content. The results obtained from this study showed that the high lipid and animal protein content increased the methane yield and biogas methane composition.

10.
Cureus ; 16(7): e64194, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130997

RESUMEN

Background Breastfeeding is recognized as a crucial determinant of child health and development, yet its multifaceted effects remain underexplored in many contexts. This cross-sectional study investigates the association between breastfeeding practices and various health and developmental outcomes in infants and young children, focusing on exclusive breastfeeding, partial breastfeeding, and formula feeding. Done at Khyber Teaching Hospital, Pakistan, the research aims to provide comprehensive insights into the nuanced impacts of breastfeeding on child well-being. Objectives This study aims to assess the association between breastfeeding duration and practices with the incidence of infectious diseases in infants and young children. It investigates the relationship between different breastfeeding practices: exclusive breastfeeding, partial breastfeeding, and formula feeding and cognitive development outcomes in early childhood. Additionally, the study evaluates the role of breastfeeding in the development of motor skills in infants and young children. Methodology A cohort of 390 participants, aged one month to three years, participated in the study. Data collection encompassed parental interviews, clinical assessments using standardized tools such as the Bayley Scales of Infant Development, and reviews of medical records. Statistical analyses, including frequency analysis and chi-square tests, were conducted to elucidate the relationships between breastfeeding practices and health outcomes. Results Exclusive breastfeeding exhibited a significantly lower incidence of infectious diseases compared to partial breastfeeding and formula feeding. Specifically, among exclusively breastfed children, incidences of colds, pneumonia, and diarrhea were 32%, 39.7%, and 40%, respectively. These rates were notably higher in partially breastfed and formula-fed children. Cognitive development outcomes also varied significantly across feeding groups. Exclusively breastfed children demonstrated superior cognitive performance, with 34.2% rated above average, compared to only 6.5% in the formula-fed group. Additionally, the prevalence of developmental delays was lowest among exclusively breastfed children (14.1%), contrasting with 62.8% in the partial breastfeeding group and 77.0% in the formula-feeding group. Conclusions The study underscores the pivotal role of exclusive breastfeeding in promoting optimal child health and development. Exclusive breastfeeding is associated with significantly reduced incidences of infectious diseases, superior cognitive development outcomes, and a lower prevalence of developmental delays. These findings highlight the importance of supportive interventions and policies aimed at encouraging exclusive breastfeeding practices, ultimately enhancing child well-being and developmental trajectories.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39136510

RESUMEN

OBJECTIVE: Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. In recent decades, its incidence and prevalence have sharply increased. Yiqi Huatan Huoxue recipe is a traditional Chinese medicine formula we use to treat AIT. Its clinical efficacy is clear, but the specific mechanism remains unclear. This study aims to explore whether pyroptosis mediated by the SIRT1/NF-κB/NLRP3 signaling pathway is one of the therapeutic mechanisms of Yiqi Huatan Huoxue recipe. METHODS: Forty 8-week-old female NOD.H-2h4 mice were randomly divided into four groups: the normal group (NG), model group (MG), Yiqi Huatan Huoxue recipe group (YG), and western medicine group (selenium yeast tablet, SeG). The normal group was gavaged with distilled water, while the remaining groups were gavaged with 0.05% sodium iodide (NaI) solution for 8 weeks. After the AIT animal model formed naturally, the mice were euthanized by gavage after 8 weeks. Hematoxylin-eosin staining was used to observe thyroid tissue changes, and enzymelinked immunosorbent assay (ELISA) was used to detect serum anti-thyroglobulin antibodies (TGAb) and mouse anti-thyroid peroxidase antibodies (TPOAb). Real-time quantitative PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect the expression of sirtuin 1 (SIRT1), nuclear factor κB p65 (NF-κB p65), nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase- 1, gasdermin D (GSDMD), and interleukin (IL)-1ß in thyroid tissue. RESULTS: Compared with the NG group, the thyroid structure of rats in the MG group was severely damaged, with significant lymphocyte infiltration, significantly increased serum TGAb and TPOAb levels, and significantly increased expression levels of SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1ß mRNA, and protein. Compared with the MG group, the thyroid structure damage and lymphocyte infiltration in rats of each treatment group were improved, and the serum TGAb, TPOAb, SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1ß mRNA, and protein expression levels were significantly reduced. CONCLUSION: Yiqi Huatan Huoxue recipe can alleviate thyroid structural damage in AIT mice, and its mechanism may be related to the upregulation of SIRT1, NF-κB deacetylation, and inhibition of NLRP3-mediated pyroptosis.

12.
J Appl Crystallogr ; 57(Pt 4): 1154-1157, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39108826

RESUMEN

Unlike most of the periodic table, many rare-earth elements display considerable resonant scattering for thermal neutrons. Although this property is accompanied by strong neutron absorption, modern high-intensity neutron sources make diffraction experiments possible with these elements. Computation of scattering intensities is accomplished by fitting the variation in resonant scattering lengths (b 0, b' and b'') to a semi-empirical Breit-Wigner formalism, which can be evaluated over the range of neutron energies useful for diffraction, typically E = 10-600 meV; λ = 0.4-2.8 Š(with good extrapolation to longer wavelengths).

13.
Breastfeed Med ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109418

RESUMEN

Background: Women with gestational diabetes mellitus (GDM) have lower rates of exclusive breastfeeding compared with women without diabetes. Objectives: To assess associations between GDM and breastfeeding intentions and attitudes, formula supplementation, reasons for formula supplementation, and knowledge of type 2 diabetes mellitus (T2DM) risk reduction associated with breastfeeding among U.S. mothers. Design/Methods: Participants completed an online survey assessing infant feeding knowledge, attitudes, and practices; demographics; and pregnancy-related medical history. Multivariable logistic regression was used to estimate adjusted odds ratios for formula supplementation in the hospital and at home. Results: Of 871 respondents, a smaller proportion of women with GDM compared with women without diabetes intended to exclusively breastfeed. There were no differences between groups in attitudes toward public breastfeeding, attitudes toward breastfeeding beyond infancy, or actual duration of any breastfeeding. Approximately one in four participants believed that breastfeeding mothers may be less likely to develop T2DM, regardless of GDM status. Among those who intended to exclusively breastfeed, GDM was associated with higher odds of formula supplementation in the hospital (adjusted odds ratio [OR] 1.75, 95% confidence interval [CI] 0.97-3.18) and at home (adjusted OR 2.02, 95% CI 1.05-3.89). "Medical reasons," which was reported as an important reason for formula supplementation, was reported more frequently by women with GDM. Conclusions: Women with GDM who intended to exclusively breastfeed had higher odds of in-hospital and at-home formula supplementation, cited medical reasons as a main reason for formula supplementation more often, and were largely unaware of T2DM risk reduction associated with breastfeeding.

14.
BMC Ophthalmol ; 24(1): 326, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103785

RESUMEN

PURPOSE: To research the accuracy of intraocular lens (IOL) calculation formulas and investigate the effect of anterior chamber depth (ACD) and lens thickness (LT) measured by swept-source optical coherence tomography biometer (IOLMaster 700) in patients with posterior chamber phakic IOL (PC-pIOL). METHODS: Retrospective case series. The IOLMaster 700 biometer was used to measure axial length (AL) and anterior segment parameters. The traditional formulas (SRK/T, Holladay 1 and Haigis) with or without Wang-Koch (WK) AL adjustment, and new-generation formulas (Barret Universal II [BUII], Emmetropia Verifying Optical [EVO] v2.0, Kane, Pearl-DGS) were utilized in IOL power calculation. RESULTS: This study enrolled 24 eyes of 24 patients undergoing combined PC-pIOL removal and cataract surgery at Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China. The median absolute prediction error in ascending order was EVO 2.0 (0.33), Kane (0.35), SRK/T-WKmodified (0.42), Holladay 1-WKmodified (0.44), Haigis-WKC1 (0.46), Pearl-DGS (0.47), BUII (0.58), Haigis (0.75), SRK/T (0.79), and Holladay 1 (1.32). The root-mean-square absolute error in ascending order was Haigis-WKC1 (0.591), Holladay 1-WKmodified (0.622), SRK/T-WKmodified (0.623), EVO (0.673), Kane (0.678), Pearl-DGS (0.753), BUII (0.863), Haigis (1.061), SRK/T (1.188), and Holladay 1 (1.513). A detailed analysis of ACD and LT measurement error revealed negligible impact on refractive outcomes in BUII and EVO 2.0 when these parameters were incorporated or omitted in the formula calculation. CONCLUSION: The Kane, EVO 2.0, and traditional formulas with WK AL adjustment displayed high prediction accuracy. Furthermore, the ACD and LT measurement error does not exert a significant influence on the accuracy of IOL power calculation formulas in highly myopic eyes implanted with PC-pIOL.


Asunto(s)
Biometría , Catarata , Lentes Intraoculares Fáquicas , Refracción Ocular , Tomografía de Coherencia Óptica , Humanos , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Femenino , Masculino , Persona de Mediana Edad , Biometría/métodos , Refracción Ocular/fisiología , Catarata/complicaciones , Adulto , Óptica y Fotónica , Reproducibilidad de los Resultados , Anciano , Longitud Axial del Ojo/diagnóstico por imagen , Longitud Axial del Ojo/patología , Cámara Anterior/diagnóstico por imagen , Agudeza Visual/fisiología , Implantación de Lentes Intraoculares/métodos
15.
Int J Nanomedicine ; 19: 7871-7893, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114180

RESUMEN

Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer. Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system. Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (**p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo. Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer.


Asunto(s)
Micelas , Neoplasias Ováricas , Ftalazinas , Piperazinas , Polietilenglicoles , Polivinilos , Sirolimus , Vitamina E , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Piperazinas/química , Piperazinas/farmacología , Polietilenglicoles/química , Humanos , Animales , Línea Celular Tumoral , Vitamina E/química , Vitamina E/farmacología , Sirolimus/química , Sirolimus/farmacología , Sirolimus/administración & dosificación , Sirolimus/farmacocinética , Ftalazinas/química , Ftalazinas/farmacología , Ftalazinas/administración & dosificación , Ftalazinas/farmacocinética , Polivinilos/química , Polivinilos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Ratones , Portadores de Fármacos/química , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Ratones Endogámicos BALB C , Supervivencia Celular/efectos de los fármacos
16.
Front Pharmacol ; 15: 1428817, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114366

RESUMEN

Background: The effect of combining prone ventilation with traditional Chinese medicine on severe pneumonia remains unclear. Objective: To evaluate the effect of Fu Zheng Jie Du Formula (FZJDF) combined with prone ventilation on clinical outcomes in patients with severe pneumonia. Methods: This single-center retrospective cohort study included 188 severe pneumonia patients admitted to the ICU from January 2022 to December 2023. Patients were divided into an FZJD group (receiving FZJDF for 7 days plus prone ventilation) and a non-FZJD group (prone ventilation only). Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was the change in PaO2/FiO2 ratio after treatment. Secondary outcomes included 28-day mortality, duration of mechanical ventilation, length of ICU stay, PaCO2, lactic acid levels, APACHE II score, SOFA score, Chinese Medicine Score, inflammatory markers, and time to symptom resolution. Results: After PSM, 32 patients were included in each group. Compared to the non-FZJD group, the FZJD group showed significantly higher PaO2/FiO2 ratios, lower PaCO2, and lower lactic acid levels after treatment (p < 0.05 for all). The FZJD group also had significantly lower APACHE II scores, SOFA scores, Chinese Medicine Scores, and levels of WBC, PCT, hs-CRP, and IL-6 (p < 0.05 for all). Time to symptom resolution, including duration of mechanical ventilation, length of ICU stay, time to fever resolution, time to cough resolution, and time to resolution of pulmonary rales, was significantly shorter in the FZJD group (p < 0.05 for all). There was no significant difference in 28-day mortality between the two groups. Conclusion: FZJDF as an adjuvant therapy to prone ventilation can improve oxygenation and other clinical outcomes in severe pneumonia patients. Prospective studies are warranted to validate these findings.

17.
BMC Oral Health ; 24(1): 917, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118109

RESUMEN

BACKGROUND: This study aimed to develop a new formula to easily estimate the vertical dimension of occlusion (VDO) by using the distance between the mental foramen on a panoramic radiograph. SUBJECTS AND METHODS: A total of 508 dentulous subjects were selected from outpatient dental clinics at the College of Dental Medicine, Al-Azhar University. The vertical dimension of the occlusion was measured using a single calibrated calliper. For each subject, a digital panoramic radiograph was taken with fixed exposure parameters. The intermental foramina distance (IMFD) was measured. The data were collected and then analysed using the IBM SPSS version 20.0 software package. (Armonk, NY: IBM Corp.). Linear regression was used to determine the relationship between the intermental foramina distance (IMFD) and the vertical dimension at occlusion (VDO). RESULTS: Pearson's correlation analysis revealed that there was a strong correlation between the intermental foramina distance (IMFD) and the VDO. Thus, a novel formula was developed for determining the VDO using panoramic radiography. CONCLUSION: The novel formula developed herein facilitated the determination of the VDO among prosthetic rehabilitation for subjects who lost vertical dimension due to loss of posterior teeth or severe wear of natural posterior teeth. Further studies are needed to determine the clinical applicability of the derived formulae for edentulous subjects.


Asunto(s)
Mandíbula , Radiografía Panorámica , Dimensión Vertical , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Mandíbula/diagnóstico por imagen , Mandíbula/anatomía & histología , Anciano
18.
Foods ; 13(15)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39123568

RESUMEN

In the melamine scandals of the early 2000s, different companies of the dairy industry cheated their products by applying chemical substances to feign a higher content of nitrogen. However, this had a severe toxic impact on the kidney health of consumers. As a result, tremendous effort was put into the prevention of further harm to the public. In the present study, a fast-screening method for the determination of melamine and cyanuric acid in infant formula was developed. While a 1D-LC approach is faster and easier to set up, a 2D-LC approach allows for a more accurate result with better selectivity and sensitivity. For both instrumental approaches, the signal ratio of the isotopologues was crucial and had a dominant effect on the results and the measurement uncertainty. For this reason, the different contributions to the measurement uncertainty were determined experimentally using Matched Standard Addition-IDMS and compared to the Exact Matching Double IDMS.

19.
Materials (Basel) ; 17(15)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39124493

RESUMEN

In this paper, we propose a new approach for numerically simulating the growth of cracks in unidirectional composite materials, termed extended isogeometric analysis, evaluating the maximum stress intensity factor and T-stress. To validate our approach, we used a small anisotropic plate with two edge cracks, beginning with formulating the governing equations based on the energy integral method, Stroh's Formula, and the Elastic Law describing the behaviour of anisotropic materials, while considering boundary conditions and initial states. A MATLAB code was developed to solve these equations numerically and to post-process the tensile stress and the stress intensity factor (SIF) in the first mode. The results for the SIF closely match those obtained using the extended finite element method (X-FEM), with a discrepancy of only 0.0021 Pa·m0.5. This finding underscores the credibility of our approach. The extended finite element method has demonstrated robustness in predicting crack propagation in composite materials in recent years, leading to its adoption by several widely used software packages in various industries.

20.
Molecules ; 29(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125005

RESUMEN

Polarization and charge-transfer interactions play an important role in ligand-receptor complexes containing metals, and only quantum mechanics methods can adequately describe their contribution to the binding energy. In this work, we selected a set of benzenesulfonamide ligands of human Carbonic Anhydrase II (hCA II)-an important druggable target containing a Zn2+ ion in the active site-as a case study to predict the binding free energy in metalloprotein-ligand complexes and designed specialized computational methods that combine the ab initio fragment molecular orbital (FMO) method and GRID approach. To reproduce the experimental binding free energy in these systems, we adopted a machine-learning approach, here named formula generator (FG), considering different FMO energy terms, the hydrophobic interaction energy (computed by GRID) and logP. The main advantage of the FG approach is that it can find nonlinear relations between the energy terms used to predict the binding free energy, explicitly showing their mathematical relation. This work showed the effectiveness of the FG approach, and therefore, it might represent an important tool for the development of new scoring functions. Indeed, our scoring function showed a high correlation with the experimental binding free energy (R2 = 0.76-0.95, RMSE = 0.34-0.18), revealing a nonlinear relation between energy terms and highlighting the relevant role played by hydrophobic contacts. These results, along with the FMO characterization of ligand-receptor interactions, represent important information to support the design of new and potent hCA II inhibitors.


Asunto(s)
Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica , Unión Proteica , Ligandos , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/química , Anhidrasa Carbónica II/metabolismo , Humanos , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Termodinámica , Interacciones Hidrofóbicas e Hidrofílicas , Sulfonamidas/química , Sulfonamidas/farmacología , Metaloproteínas/química , Metaloproteínas/antagonistas & inhibidores , Metaloproteínas/metabolismo , Modelos Moleculares , Aprendizaje Automático , Bencenosulfonamidas , Sitios de Unión
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