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2.
Health Econ Rev ; 14(1): 71, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235715

ABSTRACT

INTRODUCTION: This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic. METHODS: Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period. RESULTS: The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%. CONCLUSIONS: The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals.

3.
Animals (Basel) ; 14(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39272377

ABSTRACT

The Formosan pangolin (Manis pentadactyla pentadactyla) is an endemic animal of Taiwan. Due to their reduced population and behavior, very little is known about this enigmatic species. To unravel male pangolin reproduction, in the present study, we built a complete genomic database of the male Formosan pangolin reproductive tract and revealed highly expressing genes as well as critical signaling pathways and their associated biological processes in both the testis and the epididymis. Moreover, we evaluated the domestic cat (Felis catus) as a potential model species for male pangolin reproduction by comparing their testicular transcriptomes. We demonstrated a clear tissue-specific gene expression supporting the unique biological signature of each reproductive tissue and identified critical genes of the different reproductive organs. Pathway enrichment analysis revealed unique pathways in the testis as well as a clear epididymal transition. Furthermore, domestic cats, despite being the closest domestic species to pangolin, demonstrated their unfitness as a male reproduction model species as clear differences in spermatid differentiation and metabolism were observed. These results enable a better understanding of male pangolin reproduction characteristics and may inspire improvements in in Formosan pangolin conservation strategies.

4.
Front Microbiol ; 15: 1418817, 2024.
Article in English | MEDLINE | ID: mdl-39228379

ABSTRACT

Introduction: Antimicrobial therapy plays a crucial role in the management of CDI patients. However, the standard agent for treating CDIs is limited to oral fidaxomicin or vancomycin. For patients made nil by mouth, there is a clinically urgent and essential need to develop an intravenous antibiotic. Methods: For C. difficile with the lowest MIC of nemonoxacin and vancomycin, the inhibitory effects were tested using the kinetic time-kill assay and ex vivo co-culture model. The effectiveness of nemonoxacin and vancomycin in inhibiting spore germination, the sporicidal activity, and the treatment of mice with CDIs were compared. Results: For clinical isolates and laboratory strains, lower MICs of nemonoxacin against C. difficile than levofloxacin and ciprofloxacin were observed, even in those harboring point mutations in the quinolone-resistance determining region. Although nemonoxacin failed to suppress spore outgrowth and germination in C. difficile, it exhibited an effective inhibitory effect against C. difficile in the kinetic time-kill assay and the ex vivo co-culture model. Mice receiving intraperitoneal nemonoxacin had less weight loss, higher cecum weight, a longer colon length, and lower expression of the tcdB gene, compared with untreated mice. Notably, there were no significant differences observed in weight loss, cecum weight, colon length, or tcdB gene expression between mice treated with vancomycin and those treated with any dose of nemonoxacin. Similarly, no significant differences were found between mice receiving combination therapy of intraperitoneal nemonoxacin plus oral vancomycin and those treated with intraperitoneal nemonoxacin or oral vancomycin alone. Discussion: The potential role of nemonoxacin, which can be administered parenterally, for treating CDIs was evidenced through the in vitro, ex vivo, and mouse models.

5.
Article in English | MEDLINE | ID: mdl-39300270

ABSTRACT

High relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABAa and GABAb receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p < 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p < 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p < 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p < 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention.

6.
Article in English | MEDLINE | ID: mdl-39287631

ABSTRACT

The seminal vesicle contributes to a large extent of the semen volume and composition. Removal of seminal vesicle or lack of seminal vesicle proteins leads to decreased fertility. Seminal plasma proteome revealed that seminal fluid contained a wide diversity of proteins. Many of them are known to modulate sperm capacitation and serve as capacitation inhibitors or decapacitation factors. Despite identifying secretory vesicles from the male reproductive tract, such as epididymosomes or prostasomes, isolation, identification, and characterization of seminal vesicle-derived exosomes are still unknown. This chapter aims to review the current understanding of the function of seminal vesicles on sperm physiology and male reproduction and provide ultracentrifugation-based isolation protocols for the isolation of seminal vesicle exosomes. Moreover, via proteomic analysis and functional categorization, a total of 726 proteins IDs were identified in the purified seminal vesicle exosomes fraction. Preliminary data showed seminal vesicle-derived exosomes inhibited sperm capacitation; however, more studies will be needed to reveal other functional involvements of seminal vesicle-derived exosomes on the sperm physiology and, more importantly, how these exosomes interact with sperm membrane to achieve their biological effects.

7.
Article in English | MEDLINE | ID: mdl-39312087

ABSTRACT

This article provides an overview of literature pertaining to epididymosome origin, composition and their functional significance. Broadly, epididymosomes are defined as extracellular vesicles that are secreted by the epididymal epithelium and thereafter facilitate intercellular communication within the male reproductive tract. Epididymosomes fulfil this communication role via their encapsulation and delivery of a diverse macromolecular payload to recipient cells. This complex cargo includes proteins, lipids, and nucleic acids, which are delivered to maturing spermatozoa, thereby influencing their viability and function. Additionally, epididymosomes have been implicated in the post-translational modification of intrinsic sperm proteins, protection of sperm from oxidative stress and immune surveillance, and in the transmission of epigenetic information capable of mediating intergenerational effects. Hence, continued research into the biogenesis, cargo composition, and functional significance of epididymosomes holds promise for advancing male reproductive health and fertility treatments.

8.
Environ Geochem Health ; 46(11): 424, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316302

ABSTRACT

Per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants that severely threaten the environment and human health due to their distinct chemical composition, extensive production, widespread distribution, bioaccumulation in nature, and long-term persistence. This review focuses on the occurrence and sources of PFAS in seafood, with a particular emphasis on advanced detection methods viz. nanoparticle-based, biosensor-based, and metal-organic frameworks-based, and mass spectrometric techniques. The challenges associated with these advanced detection technologies are also discussed. Recent research and regulatory updates about PFAS, including hazardous and potential health effects, epidemiological studies, and various risk assessment models, have been reviewed. In addition, the need for global monitoring programs and regulations on PFAS are critically reviewed by underscoring their crucial role in protecting human health and the environment. Further, approaches for reducing PFAS in seafood are highlighted with future innovative remediation directions. Although advanced PFAS analytical methods are available, selectivity, sample preparation, and sensitivity are still significant challenges associated with detection of PFAS in seafood matrices.  Moreover, crucial research gaps and solutions to essential concerns are critically explored in this review.


Subject(s)
Environmental Monitoring , Fluorocarbons , Seafood , Water Pollutants, Chemical , Seafood/analysis , Fluorocarbons/analysis , Water Pollutants, Chemical/analysis , Humans , Environmental Monitoring/methods , Food Contamination/analysis , Animals , Risk Assessment , Mass Spectrometry/methods
10.
Article in English | MEDLINE | ID: mdl-39178609

ABSTRACT

Dolutegravir (DLG) has become a distinctive first-line antiretroviral therapy for the treatment of HIV in most countries due to its affordability, high efficacy, and low drug-drug interactions. However, the evaluation of genotoxic impurities (GTIs) in DLG and their toxicity assessment has not been explored thoroughly. Thus, in this study, a simple, fast, and selective analytical methodology was developed for the identification and determination of 7 GTIs in the comprehensive, explicit route of synthesis for the dolutegravir sodium (DLG-Na) drug. A facile, fast ultrasonication-assisted liquid-liquid extraction procedure was adapted to isolate the GTIs in DLG-Na and then analyzed using the gas chromatography (GC)-electron impact (EI)/mass spectrometer (MS) quantification (using selective ion monitoring mode) technique. This EI-GC/MS method was validated as per the current requirements of ICH Q2 (R1) guidelines. Under optimal method conditions, excellent linearities were achieved with R between 0.9959 and 0.9995, and high sensitivity was obtained in terms of detection limits (LOD) between 0.15 to 0.63 µg/g, and quantification limits (LOQ) between 0.45 to 1.66 µg/g for the seven GTIs in DLG. The obtained recoveries ranged from 98.2 to 104.3 % at LOQ, 15 µg/g, and 18 µg/g concentration levels (maximum daily dose of 100 mg). This developed and validated method is rapid, easy to adopt, specific, sensitive, and accurate in estimating the seven GTIs in a relatively complex sodium matrix of the DLG-Na drug moiety. As a method application, two different manufactured samples of DLG-Na drug substances were analyzed for the fate of the GTIs and drug safety for the intended dosage applications. Moreover, an in-silico QSAR toxicity prediction assessment was carried out to prove scientifically the potential GTI nature of each impurity from the alerting functional groups.


Subject(s)
Drug Contamination , Gas Chromatography-Mass Spectrometry , Heterocyclic Compounds, 3-Ring , Limit of Detection , Oxazines , Piperazines , Pyridones , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/analysis , Piperazines/chemistry , Piperazines/analysis , Pyridones/chemistry , Pyridones/analysis , Gas Chromatography-Mass Spectrometry/methods , Oxazines/chemistry , Reproducibility of Results , Linear Models , Mutagens/analysis , Anti-HIV Agents/analysis , Anti-HIV Agents/chemistry , Liquid-Liquid Extraction/methods , Sonication/methods , Computer Simulation , Humans
11.
Environ Res ; 261: 119759, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39122163

ABSTRACT

Fabrication of ternary composited photocatalytic nanomaterials with strong interaction is vital to deriving the fast charge separation for efficient photodegradation of organic contaminants in wastewater under visible light. In this work, novel ternary 2D/3D/2D MoS2-In2O3-WS2 multi-nanostructures were synthesized using facile hydrothermal processes. XRD, FTIR, and XPS results confirmed the phase, functional groups, and element composition of pure MoS2, MoS2-In2O3, and MoS2-In2O3-WS2 hybrids. UV-DRS spectra of the MoS2-In2O3-WS2 ternary hybrid indicate maximum absorption in the visible light range with a band-gap energy value of 2.4 eV. The surface of the 2D WS2 nanosheet structure tightly blends and densely disperses 2D MoS2 nanosheets and 3D In2O3 nanocubes. This confirmed the formation of the MoS2-In2O3-WS2 ternary hybrid in the form of 2D/3D/2D multi-nanostructures, which is also indicated from SEM and HR-TEM images. The synthesized MoS2-In2O3-WS2 ternary hybrid showed maximum photocatalytic activity under visible-light for antimicrobial agents such as triclosan (TCS) and trichlorocarban (TCC). The photocatalytic activity of TCS was revealed to be 95% at 90 min, while that of TCC was 93% at 100 min. The reusability and stability tests of the prepared MoS2-In2O3-WS2 ternary hybrid after four consecutive photocatalytic cycles were analyzed by FTIR and SEM, which indicated that the prepared ternary hybrid was very stable. Overall results suggested that the developed MoS2-In2O3-WS2 (2D/3D/2D) multi-nanostructures are environmentally friendly and low-cost nanocomposites as a potential photocatalyst for the removal of antimicrobial agents from wastewater.


Subject(s)
Disulfides , Light , Molybdenum , Nanocomposites , Photolysis , Molybdenum/chemistry , Nanocomposites/chemistry , Disulfides/chemistry , Catalysis , Anti-Infective Agents/chemistry , Sulfides/chemistry , Water Pollutants, Chemical/chemistry , Wastewater/chemistry
12.
iScience ; 27(7): 110388, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39092178

ABSTRACT

Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23-cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF-κB1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF-κB1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency.

13.
J Chin Med Assoc ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39118204

ABSTRACT

BACKGROUND: TBK1 variants have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia spectrum disorder. The current study elucidated the clinical and molecular genetic features of a novel TBK1 variant identified in a patient with young-onset, rapidly progressive ALS. METHODS: The coding regions of TBK1, SOD1, TARDBP, and FUS were genetically analyzed using Sanger sequencing. Repeat-primed PCR was used to survey the GGGGCC repeat in C9ORF72. The study participant underwent a comprehensive clinical evaluation. The functional effects of the TBK1 variant were analyzed through in vitro transfection studies. RESULTS: We identified a novel frameshift truncating TBK1 variant, c.456_457delGT (p.Y153Qfs*9), in a man with ALS. The disease initially manifested as right hand weakness at the age of 39 years but progressed rapidly, with the revised ALS Functional Rating Scale score declining at an average monthly rate of 1.92 points in the first year after diagnosis. The patient had no cognitive dysfunction. However, Technetium-99m single photon emission tomography indicated hypoperfusion in his bilateral superior and middle frontal cortices. In vitro studies revealed that the p.Y153Qfs*9 variant resulted in a truncated TBK1 protein product, reduced TBK1 protein expression, loss of kinase function, reduced interaction with optineurin, and impaired dimerization. CONCLUSION: The heterozygous TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive ALS through a haploinsufficiency mechanism.

14.
J Nurs Res ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39158856

ABSTRACT

BACKGROUND: A mismatch between biological and social time, often referred to as social jetlag (SJL), can lead to inadequate sleep and activities or taking meals at times that do not align with our biological rhythms, increasing the risk of metabolic abnormalities. Although the association between sleep and metabolic syndrome (MetS) is well established, the effects of SJL on MetS and the components of MetS in adults remain unclear. PURPOSE: This study was designed to explore the relationship between SJL and MetS components in adults. METHODS: A systematic review and meta-analysis was conducted on studies registered in PubMed, Cochrane, Web of Science, and Embase between the inception of each database until November 15, 2023. We focused on studies designed to evaluate the relationship between SJL and either MetS or its components. Only studies using cross-sectional, prospective, or retrospective designs were considered for inclusion. The relationship between SJL and MetS was depicted as an odds ratio with a corresponding 95% confidence interval (CI). We determined the mean differences and 95% CIs to estimate the associations between SJL and MetS components. The Joanna Briggs Institute Critical Appraisal Checklist was used to evaluate the methodological rigor of the selected studies. Data were analyzed using RevMan software Version 5.4. RESULTS: The systematic review included 16 studies, with five analyzed via a meta-analysis covering four outcomes, each based on two to three studies. When comparing SJL of less than 1 hour with SJL of 2 hours or more, the latter showed a higher likelihood of MetS (pooled odds ratio: 1.52). Although a significant decrease in systolic blood pressure (pooled mean differences = -3.52 mmHg, 95% CI [-6.41, -0.64]) and a significant increase in waist circumference (pooled mean differences = 2.17 cm, 95% CI [0.61, 3.73]) were observed, the correlation between SJL and diastolic blood pressure failed to reach statistical significance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The meta-analysis conducted in this study found an association between SJL and MetS. Healthcare practitioners should prioritize the management of sleep quality and duration, especially for individuals exhibiting substantial SJL. Improving sleep can aid in controlling blood pressure and managing weight and should form part of MetS management strategies.

15.
J Formos Med Assoc ; 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39168745

ABSTRACT

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

16.
Cell Rep Med ; 5(9): 101699, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39208801

ABSTRACT

Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. Here, we perform the most comprehensive integrative proteo-metabolomic analysis of FLC. We also conduct nutrient manipulation, respirometry analyses, as well as key loss-of-function assays in FLC tumor tissue slices from patients. We propose a model of cellular energetics in FLC pointing to proline anabolism being mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism fueling the process. We highlight FLC's potential dependency on voltage-dependent anion channel (VDAC), a mitochondrial gatekeeper for anions including pyruvate. The metabolic rewiring in FLC that we propose in our model, with an emphasis on mitochondria, can be exploited for therapeutic vulnerabilities.


Subject(s)
Amino Acids , Carcinoma, Hepatocellular , Metabolomics , Mitochondria , Humans , Mitochondria/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Metabolomics/methods , Amino Acids/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Voltage-Dependent Anion Channels/metabolism , Voltage-Dependent Anion Channels/genetics , Proteomics/methods , Female
17.
Viruses ; 16(7)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39066315

ABSTRACT

To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTENC124A. p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex.


Subject(s)
Cell Movement , Focal Adhesion Kinase 1 , Orthoreovirus, Avian , Podosomes , Signal Transduction , Animals , Mice , Orthoreovirus, Avian/physiology , Orthoreovirus, Avian/genetics , Cell Line, Tumor , Podosomes/metabolism , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Oncolytic Viruses/physiology , Oncolytic Viruses/genetics , src-Family Kinases/metabolism , src-Family Kinases/genetics , Viral Proteins/metabolism , Viral Proteins/genetics , Melanoma, Experimental/therapy , Melanoma, Experimental/pathology , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics
18.
Healthcare (Basel) ; 12(14)2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39057563

ABSTRACT

BACKGROUND: Lymphedema is a debilitating condition that significantly affects quality of life due to its chronic nature and visible symptoms. Lymphaticovenous anastomosis (LVA) has emerged as a promising surgical intervention, yet its effects on body image and spiritual health alongside physical symptoms have not been thoroughly examined. This study evaluates the efficacy of LVA in improving symptoms, quality of life (QOL), body image, and spiritual well-being in lymphedema patients. METHODS: A prospective cohort study was conducted at Kaohsiung Chang Gung Memorial Hospital, Taiwan, involving 44 patients with lymphedema undergoing LVA surgery. Evaluations were made pre-surgery, one month post-surgery, and six months post-surgery using the 36-Item Short Form Health Survey (SF-36), Multidimensional Body-Self Relations Questionnaire-Appearance Scales (MBSRQ-AS), and a spiritual health scale. Statistical analysis was performed using one-way repeated measures ANOVA. RESULTS: Significant improvements were observed in lymphedema symptoms and QOL measures at six months post-operation. SF-36 results showed enhanced scores in nearly all domains, particularly in physical functioning and role-physical. The appearance orientation scores from the MBSRQ-AS significantly increased, indicating improved perceptions in some dimensions of body image. CONCLUSIONS: LVA surgery significantly enhances physical and psychological outcomes in patients with lymphedema, with marked improvements in symptoms, QOL, and body image perceptions. The findings suggest that while LVA is effective in addressing the physical and psychological aspects of lymphedema, it does not impact spiritual dimensions. This underscores the need for holistic approaches in the management of lymphedema to address all facets of patient well-being.

19.
Environ Res ; 260: 119653, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39038773

ABSTRACT

Methoxy-DDT is an organochlorine pesticide extensively used in agricultural practices as a DDT substitute. Methoxy-DDT has been found and quantified in several investigations in groundwater, drinking water, sediment, and various biota. Therefore, designing efficient and cost-effective adsorbents for removing methoxy-DDT is vital. In this work, we embedded Ficus benghalensis L. derived carbon dots (CDs) in mesoporous silica (MS) to fabricate MS-CDs nanohybrid material. MS-CDs nanohybrid exhibited remarkable selectivity and removal efficiency towards methoxy-DDT, outperforming other endocrine disruptors. Parameters for industrial-scale fixed-bed adsorption columns, such as bed capacity, length, and breakthrough times, were analyzed. The kinetic study revealed that pseudo-second-order (PSO) adsorption and isotherm analysis confirmed the Langmuir model as the best fit. Small bed adsorption (SBA) column analysis was carried out using spiked Yamuna river water, and the breakthrough curves were demonstrated by varying MS-CDs bed height. The maximum adsorption capacity obtained for methoxy-DDT was 17.16 mg/g at breakthrough and 49.98 mg/g at exhaustion. The adsorbent showed 86.53% removal efficiency in the 5th cycle, demonstrating good reusability. These results indicate that the developed material MS-CDs-based organic sphere is an effective adsorbent for aqueous methoxy-DDT adsorption and can be applied to wastewater treatment.


Subject(s)
Carbon , DDT , Silicon Dioxide , Water Pollutants, Chemical , Water Purification , Adsorption , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Silicon Dioxide/chemistry , Carbon/chemistry , DDT/chemistry , DDT/analysis , Water Purification/methods , Nanospheres/chemistry , Ficus/chemistry , Kinetics , Porosity
20.
Clin Mol Hepatol ; 2024 07 29.
Article in English | MEDLINE | ID: mdl-39069721

ABSTRACT

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1C (6.0% vs. 5.9%, P<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, P<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, P<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, P<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (P=0.17). Body mass index (BMI) (odds ratio [OR]/95% confidence intervals [CI]: 0.89/0.85-0.92, P<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR/CI: 1.10/1.06-1.14, P<0.001) and HbA1c (OR/CI: 1.19/1.04-1.35, P=0.01), were independently associated with MASLD development after HCV cure. Conclusions: HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

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