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1.
APL Bioeng ; 8(3): 036103, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38983108

RESUMEN

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

2.
Mol Cancer ; 23(1): 136, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965534

RESUMEN

BACKGROUND: BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance compromises their therapeutic efficacy. Diverse genomic and transcriptomic alterations are found in BRAF inhibitor resistant melanoma, posing a pressing need for convergent, druggable target that reverse therapy resistant tumor with different resistance mechanisms. METHODS: CRISPR-Cas9 screens were performed to identify novel target gene whose inhibition selectively targets A375VR, a BRAF V600E mutant cell line with acquired resistance to vemurafenib. Various in vitro and in vivo assays, including cell competition assay, water soluble tetrazolium (WST) assay, live-dead assay and xenograft assay were performed to confirm synergistic cell death. Liquid Chromatography-Mass Spectrometry analyses quantified polyamine biosynthesis and changes in proteome in vemurafenib resistant melanoma. EIF5A hypusination dependent protein translation and subsequent changes in mitochondrial biogenesis and activity were assayed by O-propargyl-puromycin labeling assay, mitotracker, mitoSOX labeling and seahorse assay. Bioinformatics analyses were used to identify the association of polyamine biosynthesis with BRAF inhibitor resistance and poor prognosis in melanoma patient cohorts. RESULTS: We elucidate the role of polyamine biosynthesis and its regulatory mechanisms in promoting BRAF inhibitor resistance. Leveraging CRISPR-Cas9 screens, we identify AMD1 (S-adenosylmethionine decarboxylase 1), a critical enzyme for polyamine biosynthesis, as a druggable target whose inhibition reduces vemurafenib resistance. Metabolomic and proteomic analyses reveal that polyamine biosynthesis is upregulated in vemurafenib-resistant cancer, resulting in enhanced EIF5A hypusination, translation of mitochondrial proteins and oxidative phosphorylation. We also identify that sustained c-Myc levels in vemurafenib-resistant cancer are responsible for elevated polyamine biosynthesis. Inhibition of polyamine biosynthesis or c-Myc reversed vemurafenib resistance both in vitro cell line models and in vivo in a xenograft model. Polyamine biosynthesis signature is associated with poor prognosis and shorter progression free survival after BRAF/MAPK inhibitor treatment in melanoma cohorts, highlighting the clinical relevance of our findings. CONCLUSIONS: Our findings delineate the molecular mechanisms involving polyamine-EIF5A hypusination-mitochondrial respiration pathway conferring BRAF inhibitor resistance in melanoma. These targets will serve as effective therapeutic targets that can maximize the therapeutic efficacy of existing BRAF inhibitors.


Asunto(s)
Resistencia a Antineoplásicos , Factor 5A Eucariótico de Iniciación de Traducción , Melanoma , Mutación , Factores de Iniciación de Péptidos , Poliaminas , Proteínas Proto-Oncogénicas B-raf , Proteínas de Unión al ARN , Vemurafenib , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Resistencia a Antineoplásicos/genética , Animales , Poliaminas/metabolismo , Ratones , Factores de Iniciación de Péptidos/metabolismo , Factores de Iniciación de Péptidos/genética , Línea Celular Tumoral , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Vemurafenib/farmacología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Sistemas CRISPR-Cas , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Lisina/análogos & derivados
3.
BJOG ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992913

RESUMEN

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

4.
Aging Cell ; : e14231, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38952076

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.

5.
J Mater Chem B ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953113

RESUMEN

In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by Staphylococcus aureus (S. aureus), a common opportunistic pathogen. Infections caused by S. aureus during surgical procedures highlight the need for effective strategies to inhibit its adhesion, growth, and colonization, particularly on the surfaces of invasive medical devices. Until now, most existing research has focused on nanopillar structures (positive topographies). Uniform nanopillar arrays have been shown to control bacterial behavior based on the spacing between nanopillars. However, nanopillar structures are susceptible to external friction, impact, and force, making it challenging to maintain their antibacterial properties. Therefore, in this study, we investigate the antibacterial behavior of nanohole structures, which offer relatively superior mechanical robustness compared to nanopillars. Moreover, for applications in medical devices such as laparoscopes, there is a pressing need for surfaces that are not only transparent and flexible (or curved) but are also equipped with antibacterial properties. Our study introduces a scalable multi-functional surface that synergistically combines antibacterial and anti-fog properties. This is achieved by fabricating thin films with variously sized holes (ranging from 0.3 µm to 4 µm) using polyurethane acrylate (PUA). We assessed the activity of S. aureus on these surfaces and found that a 1 µm-diameter-hole pattern significantly reduced the presence of live S. aureus, without any detection of dead S. aureus. This bacteriostatic effect is attributed to the restricted proliferation due to the confined area provided by the hole pattern. However, the persistence of some live S. aureus on the surface necessitates further measures to minimize bacterial adhesion and enhance antibacterial effectiveness. To address this challenge, we coated the zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the nanohole pattern surface to reduce S. aureus adhesion. Moreover, in long-term experiments on surfaces, the MPC-coated effectively inhibited the colonization of S. aureus (18 h; 82%, 7 days; 83%, and 14 days; 68% antibacterial rate). By integrating PUA, MPC, and nanohole architectures into a single, flexible platform, we achieved a multi-functional surface catering to transparency, anti-fogging, and anti-biofouling requirements. This innovative approach marks a significant advancement in surface engineering, offering a versatile solution applicable in various fields, particularly in preventing S. aureus contamination in invasive medical devices like laparoscopes. The resultant surface, characterized by its transparency, flexibility, and antibacterial functionality, stands out as a promising candidate for mitigating S. aureus-related risks in medical applications.

6.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000159

RESUMEN

The fungicide tebuconazole (TEB) poses risks to human and animal health via various exposure routes. It induces toxicity in multiple organs and disrupts reproductive health by affecting steroid hormone synthesis and fetal development. In this study, we investigated the impact of TEB on fetal testes using in vitro models, focusing on germ, Sertoli, and Leydig cells, and explored the mechanisms underlying cellular damage. The results revealed significant damage to germ cells and disruption of Leydig cell development. TEB exposure led to a decrease in germ cell numbers, as indicated by histological and immunostaining analyses. TEB induced the up- and down-regulation of the expression of fetal and adult Leydig cell markers, respectively. Additionally, TEB-treated fetal testes exhibited increased expression of oxidative-stress-related genes and proteins. However, co-treatment with the antioxidant N-acetylcysteine mitigated TEB-induced germ cell damage and prevented abnormal Leydig cell development. These findings suggest that administration of antioxidants can prevent the intratesticular damage typically caused by TEB exposure.


Asunto(s)
Células Intersticiales del Testículo , Técnicas de Cultivo de Órganos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Testículo , Triazoles , Masculino , Animales , Testículo/efectos de los fármacos , Testículo/metabolismo , Triazoles/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Técnicas de Cultivo de Órganos/métodos , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Antioxidantes/farmacología , Feto/efectos de los fármacos , Fungicidas Industriales/toxicidad , Células Germinativas/efectos de los fármacos , Células Germinativas/metabolismo
7.
Diagnostics (Basel) ; 14(13)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39001342

RESUMEN

The study "Spaces of the Face for Filler Procedures: Identification of subSMAS Spaces Based on Anatomical Study" explores the anatomy of facial spaces crucial for safe and effective filler injections. By delineating the subSMAS (sub-superficial musculoaponeurotic system) spaces, this research highlights how these virtual compartments, bordered by fat, muscles, fascia, and ligaments, facilitate independent muscle movement and reduce the risk of damaging critical structures. The thicker and more robust skin of East Asians necessitates deeper filler injections, emphasizing the significance of accurately identifying these spaces. A cadaver study with dyed gelatin validated the existence and characteristics of these subSMAS spaces, confirming their safety for filler procedures. Key spaces, such as the subgalea-frontalis, interfascial and temporalis, and prezygomatic spaces, were examined, illustrating safe zones for injections. The findings underscore the importance of anatomical knowledge for enhancing facial aesthetics while minimizing complications. This study serves as a guide for clinicians to perform precise and safe filler injections, providing a foundation for further research on the dynamic interactions of these spaces and long-term outcomes.

8.
J Anim Sci Technol ; 66(3): 543-554, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38975586

RESUMEN

This study investigated the correlation between piglet performance and sow body weight change (BWC) during two gestational periods: 35-70, 70-105, and 35-105 days. A cohort of 70 sows was evaluated for BWC, backfat thickness change (BFC), caliper score change (CALC), feed intake, and weaning-to-estrus interval (WEI). The collected data were then analyzed according to the two specified periods. Our findings highlighted that piglet birth weight, weaning weight, and average daily weight gain (ADG) correlated with sow body characteristics, including BFC and CALC. The strongest correlation was observed with BWC. Piglet mortality was intimately associated with BFC. Piglet birth weight, weaning weight, and ADG showed a positive correlation with sow BWC, particularly during the 35-70 day period. Furthermore, sows displaying a higher BWC during the 70-105 day period, and also exhibiting a higher BW gain from 35-70 days, registered greater piglet weight gains and higher weaning weights. These trends became more apparent as the sow's BWC increased during the 70-105 day period. Piglet mortality increased when the sow exhibited a lower BWC during both the 35-70 and 70-105 day periods. No significant observations were found concerning the number of stillborn piglets, live-born piglets, or weaned piglets, and no interaction effects were detected between these periods. In conclusion, our findings underscore the significance of sow BWC during the early stages of gestation (d 35-70) for enhancing piglet performance from birth to weaning.

10.
Dev Neurorehabil ; : 1-7, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965666

RESUMEN

The study examined how neck muscle imbalance and plagiocephaly affect the lying and rolling activities in 118 infants aged 4 to 6 months with postural torticollis. Outcome measures included age, sex, cervical movement, and plagiocephaly severity. Neck muscle function was assessed with the Muscle Function Scale (MFS), and infant motor abilities in lying and rolling were evaluated through the corresponding dimensions of the Gross Motor Function Measure (GMFM). Multiple regression analysis showed that a better MFS score of the affected neck was significantly associated with improved lying and rolling activities in the GMFM (p < .01), and importantly, the interaction between the plagiocephaly and the MFS scores of the affected neck muscle in these activities was found to be significant (p < .05). These results highlight the need for early intervention in infants with torticollis to address muscle imbalance and plagiocephaly, crucial for early motor development (KCT0008367).

11.
Eur J Med Chem ; 276: 116620, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38971048

RESUMEN

A series of indazole analogs, derived from the B,C-ring-truncated scaffold of deguelin, were designed to function as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antitumor agents against HER2-positive breast cancer. Among the synthesized compounds, compound 12d exhibited substantial inhibitory effects in trastuzumab-sensitive (BT474) and trastuzumab-resistant (JIMT-1) breast cancer cells, with IC50 values of 6.86 and 4.42 µM, respectively. Notably, compound 12d exhibited no cytotoxicity in normal cells. Compound 12d markedly downregulated the expression of the major HSP90 client proteins in both cell types, attributing its cytotoxicity to the destabilization and inactivation of HSP90 client proteins. Molecular docking studies using the homology model of an HSP90 homodimer demonstrated that inhibitor 12d fit nicely into the C-terminal domain, boasting a higher electrostatic complementary score than ATP. In vivo pharmacokinetic study indicated the high oral bioavailability of compound 12 d at F = 66.9 %, while toxicological studies indicated its negligible impact on hERG channels and CYP isozymes. Genotoxicity tests further confirmed its safety profile. The findings collectively position compound 12d as a promising candidate for further development as an antitumor agent against HER2-positive breast cancer.

12.
Biomed Pharmacother ; 177: 117090, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38968796

RESUMEN

Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by irreversible cognitive impairment. A deleterious feedback loop between oxidative stress and neuroinflammation in early AD exacerbates AD-related pathology. Platycodon grandiflorum root extract (PGE) has antioxidant and anti-inflammatory effects in several organs. However, the mechanisms underlying the effects of PGE in the brain remain unclear, particularly regarding its impact on oxidative/inflammatory damage and Aß deposition. Thus, we aim to identify the mechanism through which PGE inhibits Aß deposition and oxidative stress in the brain by conducting biochemical and histological analyses. First, to explore the antioxidant mechanism of PGE in the brain, we induced oxidative stress in mice injected with scopolamine and investigated the effect of PGE on cognitive decline and oxidative damage. We also assessed the effect of PGE on reactive oxygen species (ROS) generation and the expressions of antioxidant enzymes and neurotrophic factor in H2O2- and Aß-treated HT22 hippocampal cells. Next, we investigated whether PGE, which showed antioxidant effects, could reduce Aß deposition by mitigating neuroinflammation, especially microglial phagocytosis. We directly verified the effect of PGE on microglial phagocytosis, microglial activation markers, and pro-inflammatory cytokines in Aß-treated BV2 microglial cells. Moreover, we examined the effect of PGE on neuroinflammation, inducing microglial responses in Aß-overexpressing 5XFAD transgenic mice. PGE exerts antioxidant effects in the brain, enhances microglial phagocytosis of Aß, and inhibits neuroinflammation and Aß deposition, ultimately preventing neuronal cell death in AD. Taken together, our findings indicate that the therapeutic potential of PGE in AD is mediated by its targeting of multiple pathological processes.

13.
Biochem Biophys Res Commun ; 729: 150368, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38986258

RESUMEN

Penicillin-binding protein 2 (PBP2), a vital protein involved in bacterial cell-wall synthesis, serves a target for ß-lactam antibiotics. Acinetobacter baumannii is a pathogen notorious for multidrug resistance; therefore, exploration of PBPs is pivotal in the development of new antimicrobial strategies. In this study, the tertiary structure of PBP2 from A. baumannii (abPBP2) was elucidated using X-ray crystallography. The structural analysis demonstrated notable movement in the head domain, potentially critical for its glycosyltransferase function, suggesting that abPBP2 assumes a fully closed conformation. Our findings offer valuable information for developing novel antimicrobial agents targeting abPBP2 that are applicable in combating multidrug-resistant infections.

14.
Ann Occup Environ Med ; 36: e12, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38872633

RESUMEN

Background: Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental toxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, immunotoxicity, and hormone toxicity. PFASs are used in the production of disposable food packages, aircraft and automobile devices, cooking utensils, outdoor gear, furniture and carpets, aqueous film forming foam (AFFF), cables and wires, electronics, and semiconductors. This study aimed to determine the association between crustacean consumption and serum PFASs. Methods: Adult participants (2,993) aged ≥ 19 years were extracted from the 4th cycle data of the Korean National Environmental Health Survey (KoNEHS). Based on the 50th percentile concentrations of serum PFASs, participants were divided into the low-concentration group (LC) and the high-concentration group (HC). General characteristics, dietary factors, coated product usage, and personal care product usage, an independent t-test and χ2 test were analyzed. The odds ratio (OR) of serum PFAS concentration against crustacean consumption was estimated via logistic regression analysis adjusting for general characteristics, dietary factors, coated product usage, and personal care product usage. Results: The OR for the HC of serum PFASs was higher in individuals with ≥once a week crustacean consumption than in those with < once a week crustacean consumption. Estimated ORs were perfluorohexanesulfonic acid 2.15 (95% confidence interval [CI]: 1.53-3.02), perfluorononanoic acid (PFNA) 1.23 (95% CI: 1.07-1.41), and perfluorodecanoic acid (PFDeA) 1.42 (95% CI: 1.17-1.74) in males, and perfluorooctanoic acid 1.48 (95% CI: 1.19-1.84), perfluorooctanesulfonic acid 1.39 (95% CI: 1.27-1.52), PFNA 1.70 (95% CI: 1.29-2.26) and PFDeA 1.43 (95% CI: 1.32-1.54) in females. Conclusions: This study revealed the association between the crustacean consumption and concentrations of serum PFASs in general Korean population.

15.
Front Public Health ; 12: 1401254, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903578

RESUMEN

Introduction: Hypertension is a primary risk factor for cardiovascular disease and all-cause mortality. This study investigated sex-based differences in the association between the risk of hypertension and resistance training (RT) levels, including training frequency and period. Methods: We enrolled 162,102 participants from nationwide Korean cohorts. The training period (months) and frequency (per week) of RT were used to investigate the presence of an inverse dose-response relationship between RT levels and the risk of hypertension. Multiple logistic regression models were used to evaluate the risk of hypertension in relation to RT levels. Results: The prevalence of hypertension in the study population was 36.28% in men and 26.94% in women. Performing RT was associated with an 8% reduction in the risk of hypertension in women but not in men. In women, performing RT for 3-4 days/week, compared with not performing RT, reduced the risk of hypertension by 11%, even after adjusting for covariates, including RT time per week and period. However, in men, no significant association was observed between training frequency and the risk of hypertension. We also evaluated the risk of hypertension by simultaneously considering both the RT frequency and period. Performing RT for 3-4 days/week and ≥5 days/week were markedly related to 14 and 11% hypertension risk reduction, respectively, in women who had been performing RT for at least 6 months. Conclusion: Given that no inverse dose-response association was observed between RT frequency and hypertension risk, engaging in RT for 3-4 days/week for at least 6 months is recommended for women. Further longitudinal studies are needed to verify sex-based differences in the antihypertensive effects of regular RT.


Asunto(s)
Hipertensión , Entrenamiento de Fuerza , Humanos , Hipertensión/epidemiología , Masculino , Femenino , República de Corea/epidemiología , Factores Sexuales , Persona de Mediana Edad , Entrenamiento de Fuerza/estadística & datos numéricos , Adulto , Factores de Riesgo , Prevalencia
16.
Front Pharmacol ; 15: 1381406, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38904000

RESUMEN

Introduction: Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Results: Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. Conclusion: These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.

17.
Front Microbiol ; 15: 1385582, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38894968

RESUMEN

Toxoplasmosis, while often asymptomatic and prevalent as a foodborne disease, poses a considerable mortality risk for immunocompromised individuals during pregnancy. Point-of-care serological tests that detect specific IgG and IgM in patient sera are critical for disease management under limited resources. Despite many efforts to replace the T. gondii total lysate antigens (TLAs) by recombinant antigens (rAgs) in commercial kits, while IgG detection provides significant specificity and sensitivity, IgM detection remains comparatively low in sensitivity. In this study, we attempted to identify novel antigens targeting IgM in early infection, thereby establishing an IgM on-site detection kit. Using two-dimensional gel electrophoresis (2DE) and mouse serum immunoblotting, three novel antigens, including EF1γ, PGKI, and GAP50, were indicated to target T. gondii IgM. However, rAg EF1γ was undetectable by IgM of mice sera in Western blotting verification experiments, and ELISA coated with PGKI did not eliminate cross-reactivity, in contrast to GAP50. Subsequently, the lateral flow reaction employing a strip coated with 0.3 mg/mL purified rAg GAP50 and exhibited remarkable sensitivity compared with the conventional ELISA based on tachyzoite TLA, which successfully identified IgM in mouse sera infected with tachyzoites, ranging from 103 to 104 at 5 dpi and 104 at 7 dpi, respectively. Furthermore, by using standard T. gondii-infected human sera from WHO, the limit of detection (LOD) for the rapid fluorescence immunochromatographic test (FICT) using GAP50 was observed at 0.65 IU (international unit). These findings underline the particular immunoreactivity of GAP50, suggesting its potential as a specific biomarker for increasing the sensitivity of the FICT in IgM detection.

18.
J Clin Nurs ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38894583

RESUMEN

AIM: The systematic review aims to synthesize the literature examining the effectiveness of nurse-led remote digital support on health outcomes in adults with chronic conditions. BACKGROUND: Adults with chronic diseases have increased rates of mortality and morbidity and use health care resources at a higher intensity than those without chronic conditions-placing strain on the patient, their caregivers and health systems. Nurse-led digital health disease self-management interventions have potential to improve outcomes for patients with chronic conditions by facilitating care in environments other that the hospital setting. DESIGN AND METHODS: We searched PubMed/MEDLINE, Embase, PsycINFO and Cochrane Central databases from inception to 7 December 2022. We included randomized controlled trials assessing the impact of nurse-led remote digital support interventions compared to usual care on health-related outcomes in adults with chronic illness. The Cochrane risk-of-bias tool was used to assess bias in studies. Outcomes were organized into four categories: self-management, clinical outcomes, health care resource use and satisfaction with care. Results are presented narratively based on statistical significance. RESULTS: Forty-four papers pertaining to 40 unique studies were included. Interventions most targeted diabetes (n = 11) and cardiovascular disease (n = 8). Websites (n = 10) and mobile applications (n = 10) were the most used digital modalities. Nurses supported patients either in response to incoming patient health data (n = 14), virtual appointment (n = 8), virtual health education (n = 5) or through a combination of these approaches (n = 13). Positive impacts of nurse-led digital chronic disease support were identified in each outcome category. Mobile applications were the most effective digital modality. CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Results show that nurse-led remote digital support interventions significantly improve self-management capacity, clinical health outcomes, health care resource use and satisfaction with care. Such interventions have potential to support overall health for adults with chronic conditions in their home environments.

19.
Polymers (Basel) ; 16(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38891511

RESUMEN

As the use of stretchable electronic devices increases, the importance of flexible electromagnetic interference (EMI) shielding films is emerging. In this study, a highly flexible shielding film was fabricated using poly(styrene-co-butyl acrylate) (p(St-co-BA)) latex as a matrix and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as a conductive filler, and then the mechanical properties and EMI shielding performance of the film were examined. Styrene and butyl acrylate were copolymerized to lower the high glass transition temperature and increase the ductility of brittle polystyrene. The latex blending technique was used to produce a shielding film in which the aqueous filler dispersion was uniformly dispersed in the emulsion polymerized resin. To determine the phase change in the copolymer matrix with temperature, the storage modulus was measured, and a time-temperature superposition master curve was constructed. The drying temperature of water-based copolymer resin suitable for film fabrication was set based on this curve. The glass transition temperature and flexibility of the blends were determined by evaluating the thermomechanical analysis and tensile tests. The EMI shielding effectiveness (SE) of the films was analyzed at frequencies from 50 MHz to 1.5 GHz, covering the VHF and UHF ranges. As the filler content increased, the SE of the blend film increased, but the elongation increased until a certain content and then decreased. The optimal content of PEDOT:PSS that satisfied both the ductility and shielding performance of the film was found to be 10 wt%. In this case, the elongation at break reached 300%, and the SE of a 1.6 mm thick film was about 35 dB. The film developed in this study can be used as an EMI shielding material that requires high flexibility.

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