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1.
J Cancer ; 15(16): 5415-5424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247610

RESUMEN

Lung squamous cell carcinoma (LUSC), a subset of non-small cell lung cancer (NSCLC), accounts for about 30% of all lung cancers (LC) and exhibits a dismal response to current therapeutic protocols. Existed studies have indicated that aberrations in fibroblast growth factor receptors (FGFRs) play a pivotal role in the progression of LUSC, rendering them as attractive targets for therapeutic intervention in this cancer type. This study found that Erdafitinib (Erda), a novel pan-FGF receptor tyrosine kinase inhibitor (TKI), exerted a cytotoxic effect on LUSC cells. However, STAT3, the downstream target of FGFRs, remained still activated despite Erdafitinib treatment. Then, a STAT3 inhibitor, Stattic (Sta), was concurrently used with Erdafitinib, and the combined treatment demonstrated a synergistic efficacy in both in vitro and in vivo models of LUSC when compared to that of the treatment of the Erdafitinib or Stattic alone. Further molecular studies showed that such an effect of Erdafitinib and Stattic was associated with their concurrently inhibitory effect on FGFR1 and STAT3 signaling in LUSC cells. Therefore, the findings of this study indicated that the concurrent use of Erdafitinib and Stattic is a promising therapeutic approach for the treatment of FGFR1-positive LUSC.

2.
Front Endocrinol (Lausanne) ; 15: 1429514, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247918

RESUMEN

Background: Evidence suggests a connection between DNA methylation (DNAm) aging and reproductive aging. However, the causal relationship between DNAm and age at menopause remains uncertain. Methods: Employing established DNAm epigenetic clocks, such as DNAm Hannum age acceleration (Hannum), Intrinsic epigenetic age acceleration (IEAA), DNAm-estimated granulocyte proportions (Gran), DNAm GrimAge acceleration (GrimAgeAccel), DNAm PhenoAge acceleration (PhenoAgeAccel), and DNAm-estimated plasminogen activator inhibitor-1 levels (DNAmPAIadjAge), a bidirectional Mendelian randomization (MR) study was carried out to explore the potential causality between DNAm and menopausal age. The primary analytical method used was the inverse variance weighted (IVW) estimation model, supplemented by various other estimation techniques. Results: DNAm aging acceleration or deceleration, as indicated by Hannum, IEAA, Gran, GrimAgeAccel, PhenoAgeAccel, and DNAmPAIadjAge, did not exhibit a statistically significant causal effect on menopausal age according to forward MR analysis. However, there was a suggestive positive causal association between age at menopause and Gran (Beta = 0.0010; 95% confidence interval (CI): 0.0004, 0.0020) in reverse MR analysis. Conclusion: The observed increase in granulocyte DNAm levels in relation to menopausal age could potentially serve as a valuable indicator for evaluating the physiological status at the onset of menopause.


Asunto(s)
Metilación de ADN , Epigénesis Genética , Análisis de la Aleatorización Mendeliana , Menopausia , Humanos , Femenino , Menopausia/genética , Persona de Mediana Edad , Envejecimiento/genética , Adulto , Factores de Edad
3.
Langmuir ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250229

RESUMEN

Aggregation-induced electrochemiluminescence (AIECL) combines the merits of aggregation-induced emission (AIE) and electrochemiluminescence (ECL), which has become a research hot spot in recent years. Therefore, we synthesized a novel AIE compound (Z)-3-(4-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)phenyl)-2-(4-(1,2,2-triphenylvinyl)phenyl)acrylonitrile (TPENI) with a donor-acceptor (D-A) structure, that is, a simple peripheral modification of 4-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl) benzaldehyde (NI-CHO) with AIE-active tetraphenylethylene (TPE) to achieve the transition of NI-CHO from aggregation-caused quenching (ACQ) to an AIE molecule. When TPENI was in the aggregated state, the luminescence intensity was significantly enhanced due to the TPE structural unit restricting the free rotation of the intramolecular benzene ring, as well as the π-π stacking interactions of the molecules, which was conducive to the preparation of TPENI NPs as ECL materials. Satisfactorily, we found that the ECL intensity of TPENI NPs was increased by about 4.8-fold compared with that of the molecules dispersed in organic solution, and the stability reached about 1000 s. Based on the excellent ECL properties of TPENI NPs, an "on-off-on" ECL biosensor with a wider detection range (1 fg/mL to 100 ng/mL) and a lower detection limit of 0.20 fg/mL (S/N = 3) was proposed for sensitive analysis of a carcinoembryonic antigen (CEA). Overall, this work provided a new approach to the realization of AIECL and laid the foundation for the application of naphthalimide derivatives in ECL.

4.
Medicine (Baltimore) ; 103(36): e39433, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252323

RESUMEN

The causal effects of mental health problems on the risk of infectious diseases remain vague. Investigating them via observational study is challenging as it presents possible confounding factors. Therefore, the objective of this study was to utilize Mendelian randomization (MR) techniques to evaluate the causal relationship between mental health problems and the risk of infectious diseases. Multivariable MR analyses were performed using genome-wide association data for sleep disorders (N = 216,700), depression (N = 500,199), anxiety (N = 290,361), nervous feelings (N = 450,700), unspecified mental disorder (N = 218,792), pneumonia (N = 486,484), skin and subcutaneous tissue infection (SSTI; N = 218,792), intestinal infectious diseases (IIDs; N = 218,792), urinary tract infection (N = 463,010), and central nervous system (CNS) infections (N = 218,792) among individuals of European ancestry. Independent genetic variants significantly (P < 10-8) associated with each exposure were considered instruments. The primary analysis used an inverse variance-weighted method, followed by a series of sensitivity analyses. Genetically predicted sleep disorders were associated with an increased risk of SSTI (odds ratio [OR], 1.29 [95% confidence interval (CI), 1.05-1.59]; P = .017). Genetically predicted depression was linked with an increased risk of CNS infections (OR, 1.59 [95% CI, 1.00-2.53]; P = .049) and SSTI (1.24 [95% CI, 1.03-1.49]; P = .024). Genetically predicted anxiety was associated with IIDs (OR, 1.19 [95% CI, 1.03-1.37]; P = .017) and SSTI (OR, 1.21 [95% CI, 1.02-1.43]; P = .029). There was no significant causal evidence for genetic prediction of nervous feelings and unspecified mental disorders in IIDs, CNS infections, SSTI, pneumonia, or urinary tract infection. Sensitivity analyses showed that the above causal association estimates were robust. In this MR study, we demonstrated a causal relationship between sleep disorders, depression, anxiety, and the risk of infectious diseases. However, no evidence was found to support causality between nervous feelings, unspecified mental disorders, and the risk of infectious diseases.


Asunto(s)
Enfermedades Transmisibles , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Humanos , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/genética , Trastornos Mentales/epidemiología , Trastornos Mentales/genética , Factores de Riesgo , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/genética , Polimorfismo de Nucleótido Simple , Masculino
5.
Mycoses ; 67(9): e13785, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39245647

RESUMEN

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.


Asunto(s)
Antifúngicos , Consenso , Farmacorresistencia Fúngica , Tiña , Humanos , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , China , Tiña/tratamiento farmacológico , Tiña/microbiología , Tiña/diagnóstico , Trichophyton/efectos de los fármacos , Trichophyton/aislamiento & purificación
6.
Thorac Cancer ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233498

RESUMEN

INTRODUCTION: Lung and bronchus cancer is a leading cause of death in the United States. Compared with the national average, Michigan has an increased mortality rate and low early screening and treatment rates. This study aimed to explore the epidemiological trends and assess overall survival (OS) of patients diagnosed with lung cancer in Michigan from 1996 to 2017. METHODS: Data was acquired from the Michigan Cancer Surveillance Program (MCSP). Log-rank test was used to test OS among the time periods, univariate and multivariate cox regression models were employed to determine factors that significantly affected OS. We hypothesized that the introduction of more inclusive lung cancer screening guidelines in 2013 would improve OS for patients diagnosed after its implementation and that individual characteristics and tumor characteristics would both affect OS. RESULTS: Notably, 153 742 individuals met inclusion criteria: 54.22% male and 45.78% female. Mean age at diagnosis was 69 years. No significant difference in OS was found among the three time periods (p = 0.99). Univariate analyses identified four individual characteristics associated with reduced OS: age at diagnosis, male sex, American Indian race, and living in rural or urban area. Reduced OS was associated with primary sites tumors at main bronchus, lung base, or within overlapping lobes, and SEER stage 7. CONCLUSIONS: This study highlights several factors that influence OS. Consideration of these factors may be helpful as a community outreach tool to help increase early detection and reduce overall mortality.

7.
Front Pharmacol ; 15: 1393861, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239648

RESUMEN

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

10.
Glob Health Med ; 6(4): 236-243, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39219582

RESUMEN

The aim of this study was to explore the effects of low-frequency ultrasound (US) combined with microbubbles (MBs) on breast cancer xenografts and explain its underlying mechanisms. A total of 20 xenografted nude mice were randomly divided into four groups: a group treated with US plus MBs (the US + MBs group), a group treated with US alone (the US group), a group treated with MBs alone (the MBs group), and a control group. In different groups, mice were treated with different US and injection regimens on an alternate day, three times in total. Histological changes, apoptosis of cells, microvascular changes, and the apoptosis index (AI) and microvascular density (MVD) of the breast cancer xenograft were analyzed after the mice were sacrificed. Results indicated that the tumor volume in the US + MBs group was smaller than that in the other three groups (p < 0.001 for all). The rate of tumor growth inhibition in the US + MBs group was significantly higher than that in the US and MBs groups (p < 0.001 for both). There were no significant differences in histological changes among the four groups. However, the AI was higher in the US + MBs group than that in the other three groups while the MVD was lower (p < 0.001 for all). All in all, low-frequency US combined with MBs can effectively slow down the growth of breast cancer in nude mice. In summary, low-frequency US combined with MBs has a significant effect on breast cancer treatment. Cavitation, thermal effects, and mechanical effects all play a vital role in the inhibition of tumor growth.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39230735

RESUMEN

BACKGROUND: Despite evidence suggesting that insecure attachment is a significant risk factor for Problematic Social Media Use (PSMU), there remains a lack of comprehensive studies exploring this relationship, and a unified understanding of its role has yet to be established. METHODS: We employed network analysis to construct an integrated model for examining the complex interrelations between negative emotions, trait and state attachment, motives, and PSMU across three platforms (i.e., WeChat, Sina Weibo, and TikTok), as well as for identifying potential mediating variables between attachment and PSMU. Data were collected from 685 young adults via online self-reported questionnaires. RESULTS: We found that negative emotions are positively correlated with insecure trait and state attachment but have a negligible direct relationship with PSMU. The conformity motive and state attachment security emerged as important central nodes when measured by strength, closeness, and betweenness. Moreover, attachment states and motives were found to be clustered. Such strong interrelationships were also evident between insecure attachment and PSMU, while trait attachment anxiety and avoidance were observed to be related to PSMU across various platforms. CONCLUSIONS: Our findings promote a deeper understanding of the relationship between insecure attachment and PSMU from a cross-platform perspective and offer novel insights into the mechanisms underlying their co-occurrence, which may guide the development of effective interventions for healthier social media engagement.

12.
Front Oncol ; 14: 1393833, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281383

RESUMEN

Background: Some studies have reported that sunburns and cutaneous melanoma (CM) risk is increasing, but a clear causal link has yet to be established. Methods: This current study conducted a two-sample Mendelian randomization (MR) approach to clarify the association and causality between sunburn history and CM using large-scale genome-wide association study data. Results: The inverse-variance weighted method result showed that sunburn might be associated with the risk of CM increasing (p = 2.21 × 10-23, OR = 1.034, 95% CI= 1.027-1.041), causally. The MR-Egger regression, weighted median method, simple mode method, and weighted mode method results showed similar results. Conclusion: This study offers evidence of sunburn history and increased risk of CM, and it shows that there might be common genetic basics regarding sunburns and CM susceptibility in Caucasian, European, or British ethnic groups.

13.
Heliyon ; 10(17): e36826, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281431

RESUMEN

Background and purpose: The composite score for insulin resistance (IR), known as the Metabolic Score of Insulin Resistance (METS-IR), serves as an assessment tool for IR and has been previously linked to symptomatic intracranial hemorrhage and poor functional outcomes in patients with acute ischemic stroke (AIS). Despite these associations, the impact of METS-IR on early neurological deterioration (END) in patients with minor AIS who underwent intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) remains inadequately established. This investigation explored the link between METS-IR and END in patients with minor AIS receiving IV-rtPA treatment. Methods: In this study, a cohort comprising 425 consecutive patients with National Institutes of Health Stroke Scale Score (NIHSS)≤5 who underwent IV-rtPA treatment was included. The METS-IR was computed using the formula ln METS-IR=ln (2 × FBG + TG) × BMI/ln (HDL). END was defined as a NIHSS ≥2 within 24 h post IV-rtPA administration, while poor functional outcome was defined as a modified Rankin Scale (mRS) of 2-6. Multivariate logistical regression was performed to investigate the association between METS-IR and both poor functional outcomes and END. Results: Among the 425 enrolled patients, 64 (15.1 %) patients experienced END, while 80 (18.8 %) had poor functional outcomes three months post-discharge. Upon adjusting for confounding factors, a higher METS-IR emerged as an independent predictor for both END and poor functional outcomes. Similarly, noteworthy findings were observed when METS-IR was defined as a categorical group. The restricted cubic spline (RCS) analysis indicated a linear relationship between METS-IR and END (P = 0.593 for non-linearity, P = 0.034 for overall). The incorporation of METS-IR into the conventional model resulted in a significant enhancement of predictive accuracy for both END and poor functional outcomes. Conclusion: METS-IR emerges as an independent predictor for END and poor functional outcome at three months post-discharge in patients with minor AIS subjected to IV-rtPA. Considering its simplicity and clinical accessibility as an indicator of IR, METS-IR may hold guiding significance in clinical practice.

14.
PLoS Genet ; 20(9): e1011391, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39241053

RESUMEN

Mendelian Randomization (MR) is a widely embraced approach to assess causality in epidemiological studies. Two-stage least squares (2SLS) method is a predominant technique in MR analysis. However, it can lead to biased estimates when instrumental variables (IVs) are weak. Moreover, the issue of the winner's curse could emerge when utilizing the same dataset for both IV selection and causal effect estimation, leading to biased estimates of causal effects and high false positives. Focusing on one-sample MR analysis, this paper introduces a novel method termed Mendelian Randomization with adaptive Sample-sPLitting with cross-fitting InstrumenTs (MR-SPLIT), designed to address bias issues due to IV selection and weak IVs, under the 2SLS IV regression framework. We show that the MR-SPLIT estimator is more efficient than its counterpart cross-fitting MR (CFMR) estimator. Additionally, we introduce a multiple sample-splitting technique to enhance the robustness of the method. We conduct extensive simulation studies to compare the performance of our method with its counterparts. The results underscored its superiority in bias reduction, effective type I error control, and increased power. We further demonstrate its utility through the application of a real-world dataset. Our study underscores the importance of addressing bias issues due to IV selection and weak IVs in one-sample MR analyses and provides a robust solution to the challenge.

15.
Mar Pollut Bull ; 207: 116906, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217871

RESUMEN

Marine thermal fluctuation profoundly influences energy metabolism, physiology, and survival of marine life. In the present study, short-term and long-term high-temperature stresses were found to affect gluconeogenesis by inhibiting PEPCK activity in the Pacific oyster (Crassostrea gigas), which is a globally distributed species that encounters significant marine thermal fluctuations in intertidal zones worldwide. CgCREBL2, a key molecule in the regulation of gluconeogenesis, plays a critical role in the transcriptional regulation of PEPCK in gluconeogenesis against high-temperature stress. CgCREBL2 was able to increase the transcription of CgPEPCK by either binding the promoter of CgPEPCK gene or activating CgPGC-1α and CgHNF-4α after short-term (6 h) high-temperature stress, while only by binding CgPEPCK after long-term (60 h) high-temperature stress. These findings will further our understanding of the effect of marine thermal fluctuation on energy metabolism on marine organisms.


Asunto(s)
Crassostrea , Regulación de la Expresión Génica , Gluconeogénesis , Animales , Crassostrea/genética , Crassostrea/fisiología , Gluconeogénesis/genética , Calor
16.
Neuropharmacology ; : 110158, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276863

RESUMEN

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p-NF-κB/NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

17.
Ann Hepatol ; : 101564, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276983

RESUMEN

INTRODUCTION AND OBJECTIVES: To study the effect of eukaryotic initiation factor 3B (EIF3B) on the invasion and migration of hepatocellular carcinoma (HCC) and its potential mechanism. MATERIALS AND METHODS: The clinical significance of EIF3B expression was studied with The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interaction Analysis datasets. Immunohistochemical staining and western blotting were used to examine EIF3B expression in cell lines and tissues from HCC patients. The scratch assay and transwell assay were used to measure the invasion and metastasis of different HCC cell lines in vitro. The molecular mechanism of EIF3B was determined using RNA-seq and identification of dysregulated signaling pathways. Western blotting was used to verify the alterations of EIF3B signaling functioned in the promotion of HCC progression. RESULTS: Elevated expression of EIF3B in HCC correlated significantly with aggressive clinicopathologic characteristics, including advanced tumor grade and poor prognosis. Studies with cultured cells indicated that EIF3B knockdown inhibited HCC cell invasion and metastasis by depressing the epithelial-mesenchymal transition (EMT). EIF3B also activated the TGFBI/MAPK/ERK signaling pathway by increasing the levels of pMEK and pERK. CONCLUSIONS: Our results indicate that EIF3B functions as an oncogene in HCC that accelerates cell invasion, metastasis, and the EMT by stimulation of the TGFBI/MAPK/ERK signaling pathway. EIF3B is a potential target for the treatment of HCC.

18.
J Clin Med ; 13(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39274343

RESUMEN

Background: In advanced head and neck cancer (HNC) patients, 50-60% experience loco-regional relapse and distant metastasis. Boron neutron capture therapy (BNCT) has shown remarkable therapeutic response in recurrent HNC, but there is still a 70% chance of local recurrence. This study aimed to identify a suitable liquid biomarker to assess patient response following BNCT. Myeloid-derived suppressor cells (MDSCs) are immune-suppressive cells that inhibit cytotoxic T cells. Circulating MDSC levels have been linked to the clinical stage and prognosis in HNSCC. Methods: Five patients with recurrent head and neck cancer underwent a treatment regimen that commenced with BNCT, followed by fractionated image-guided intensity-modulated radiotherapy (IG-IMRT). Liquid biopsy analysis via flow cytometry and tumor volume analysis by clinical imaging were conducted at three stages: before BNCT, before the first fraction of IG-IMRT, and one month after the last fraction of IG-IMRT. Results: Compared to other MDSC subtypes, monocytic MDSCs (M-MDSCs) exhibited a notable correlation with tumor volume. This strong correlation was observed at all testing time points except one month after BNCT treatment. Conclusions: This case series highlights a strong link between tumor size and circulating M-MDSC levels before BNCT and one month after the last IG-IMRT treatment in recurrent head and neck cancer patients. These results suggest that the level of circulating M-MDSCs could be a marker for monitoring tumor progression in recurrent HNC patients following radiation therapy, including BNCT.

19.
Technol Health Care ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39269865

RESUMEN

BACKGROUND: Folic acid supplementation has been shown to provide benefits in preventing neural tube defects and other birth defects, as well as reducing adverse pregnancy outcomes. OBJECTIVE: This study aimed to examine the impact of various folic acid supplementation methods on pregnancy. METHODS: TaqMan-MGB technology was used to detect polymorphisms in the folate metabolism-related genes, MTHFR C677T and A1298C. Blood-related biochemical indicators, including HCY levels and history of adverse pregnancy, were examined in relation to different exposure factors (MTHFR gene polymorphism, HCY levels, and adverse pregnancy history) and their impact on pregnancy outcomes. Various forms of folic acid intervention were implemented in a population with an adverse pregnancy history and high HCY levels to analyze the effects of reducing HCY levels and improving pregnancy outcomes. RESULTS: Exposure factors, such as adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were closely associated with pregnancy outcomes. Interestingly, methylfolate efficiently reduced the serum HCY levels. More importantly, the methylfolate group exhibited a significantly lower incidence of adverse pregnancies than the synthetic folic acid group. CONCLUSION: In this study, the risk factors, including adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were confirmed to lead to the poorer pregnancy outcomes in our cohort. 5-methyltetrahydrofolate may be an effective approach for decreasing the incidence of adverse pregnancy outcomes.

20.
Int J Biol Macromol ; 279(Pt 4): 135359, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39244121

RESUMEN

Soybean meal (SM) serves as a primary alternative to fish meal in aquafeeds. However, a high-SM diet may result in intestinal injury. Our previous study demonstrated the probiotic effects of heat-inactivated Bacillus subtilis (LCBS1) on bullfrogs (Aquarana catesbeianus) fed a high-SM diet, probably attributed to the bioactive constituent of cell wall. Therefore, in this study, the main constituents of cell wall from LCBS1, including peptidoglycan (PGN), lipoteichoic acid (LTA), cell wall protein (CWP), and whole cell wall (WCW), were extracted and added to a high-SM (~55 %) diet to investigate their probiotic effects on bullfrogs and reveal the possible mechanisms. The results indicated that bullfrogs fed the LTA of LCBS1 showed the highest weight gain, feed efficiency, and protein efficiency ratio. Additionally, the LTA of LCBS1 could activate the humoral immunity and modulate intestinal microbiota. It might activate JAK2-STAT3 and MAPK-ERK pathways, as well as up-regulate tlr5 gene to promote intestinal cell proliferation, thereby alleviating jejunal injury. The WCW of LCBS1 effectively increased the growth performance of bullfrogs by improving the humoral immunity, enhancing intestinal barrier function, and alleviating intestinal inflammatory response. The PGN and CWP of LCBS1 could stimulate the humoral immunity and enhance intestinal barrier function, but had no significant effect on the growth performance of bullfrogs. In conclusion, the LTA might be the primary bioactive constituent of heat-inactivated LCBS1, with the beneficial effects of promoting intestinal cell proliferation and enhancing intestinal barrier function, therefore alleviating the intestinal injury induced by SM on bullfrogs. This study establishes a theoretical basis for the efficient utilization of plant proteins by the application of postbiotics additive in aquafeed, which further saves the feed costs and promotes development of economically sustainable aquaculture.

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