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1.
Gut Microbes ; 16(1): 2409924, 2024.
Article in English | MEDLINE | ID: mdl-39369445

ABSTRACT

Helicobacter pylori, a dominant member of the gastric microbiota was associated with various gastrointestinal diseases and presents a significant challenge due to increasing antibiotic resistance. This study identifies H. pylori's phospholipase A (PldA) as a critical factor in modulating host macrophage responses, facilitating H. pylori 's evasion of the immune system and persistence. PldA alters membrane lipids through reversible acylation and deacylation, affecting their structure and function. We found that PldA incorporates lysophosphatidylethanolamine into macrophage membranes, disrupting their bilayer structure and impairing TNFR1-mediated p38-MK2 signaling. This disruption results in reduced macrophage autophagy and elevated RIP1-dependent apoptosis, thereby enhancing H. pylori survival, a mechanism also observed in multidrug-resistant strains. Pharmacological inhibition of PldA significantly decreases H. pylori viability and increases macrophage survival. In vivo studies corroborate PldA's essential role in H. pylori persistence and immune cell recruitment. Our findings position PldA as a pivotal element in H. pylori pathogenesis through TNFR1-mediated membrane modulation, offering a promising therapeutic target to counteract bacterial resistance.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Macrophages , Receptors, Tumor Necrosis Factor, Type I , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor, Type I/genetics , Macrophages/immunology , Macrophages/microbiology , Macrophages/metabolism , Animals , Mice , Helicobacter Infections/microbiology , Helicobacter Infections/immunology , Helicobacter Infections/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Signal Transduction , Mice, Inbred C57BL , Humans , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , MAP Kinase Signaling System , Apoptosis
2.
J Neurosci Res ; 102(10): e25388, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39367566

ABSTRACT

Thalamocortical connectivity is associated with cognitive and affective processing. The role of thalamocortical connectivity in the pathomechanism of treatment-resistant depression (TRD) remains unclear. This study included 48 patients with TRD and 48 healthy individuals. We investigated thalamocortical connectivity by performing resting-state functional MRI with the bilateral thalamus as the seed. In addition, patients with TRD were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Compared with the healthy individuals, the patients with TRD exhibited increased functional connectivity (FC) of the thalamus with the insula and superior temporal cortex and reduced the FC of the thalamus with the anterior paracingulate cortex and cerebellum crus II. Our study may support the crucial role of thalamocortical dysconnectivity in the TRD pathomechanism. However, the small sample size may limit the statistical power. A future study with a large sample size of patients with TRD would be required to validate our findings.


Subject(s)
Cerebral Cortex , Depressive Disorder, Treatment-Resistant , Magnetic Resonance Imaging , Thalamus , Humans , Female , Male , Thalamus/diagnostic imaging , Thalamus/physiopathology , Depressive Disorder, Treatment-Resistant/diagnostic imaging , Depressive Disorder, Treatment-Resistant/physiopathology , Adult , Middle Aged , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Brain Mapping
3.
medRxiv ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39371130

ABSTRACT

The CandyCollect device is a lollipop-inspired open fluidic oral sampling device designed to provide a comfortable user sampling experience. We demonstrate that the CandyCollect device can be coupled with a rapid antigen detection test (RADT) kit designed for Group A Streptococcus (GAS). Through in vitro experiments with pooled saliva spiked with Streptococcus pyogenes we tested various reagents and elution volumes to optimize the RADT readout from CandyCollect device samples. The resulting optimized protocol uses the kit-provided reagents and lateral flow assay (LFA) while replacing the kit's pharyngeal swab with the CandyCollect device, reducing the elution solution volume, and substituting the tube used for elution to accommodate the CandyCollect device. Positive test results were detected by eye with bacterial concentrations as low as the manufacturer's "minimal detection limit" - 1.5×10 5 CFU/mL. LFA strips were also scanned and quantified with image analysis software to determine the signal-to-baseline ratio (SBR) and categorize positive test results without human bias. We tested our optimized protocol for integrating CandyCollect and RADT using CandyCollect clinical samples from pediatric patients (n=6) who were previously diagnosed with GAS pharyngitis via pharyngeal swabs tested with RADT as part of their clinical care. The LFA results of these CandyCollect devices and interspersed negative controls were determined by independent observers, with positive results obtained in four of the six participants on at least one LFA replicate. Taken together, our results show that CandyCollect devices from children with GAS pharyngitis can be tested using LFA rapid tests.

4.
J Psychiatry Neurosci ; 49(5): E289-E300, 2024.
Article in English | MEDLINE | ID: mdl-39299780

ABSTRACT

BACKGROUND: Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). METHODS: We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. RESULTS: We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC. LIMITATIONS: The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. CONCLUSION: We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.


Subject(s)
Gastrointestinal Microbiome , Magnetic Resonance Imaging , Humans , Gastrointestinal Microbiome/physiology , Male , Female , Aged , Case-Control Studies , Brain-Gut Axis/physiology , Brain/diagnostic imaging , Brain/physiopathology , Brain/microbiology , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Depressive Disorder, Major/microbiology , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/diagnostic imaging , Middle Aged
5.
Res Sq ; 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39257993

ABSTRACT

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by complex sensory processing deficits. A key unresolved question is how alterations in neural connectivity and communication translate into the behavioral manifestations seen in ASD. Here, we investigate how oligodendrocyte dysfunction alters myelin plasticity and neuronal activity, leading to auditory processing disorder associated with ASD. We focus on the SCN2A gene, an ASD-risk factor, to understand its role in myelination and neural processing within the auditory nervous system. Through transcriptional profiling, we identified alterations in the expression of myelin-associated genes in Scn2a conditional knockout mice, highlighting the cellular consequences engendered by Scn2a deletion in oligodendrocytes. The results reveal a nuanced interplay between oligodendrocytes and axons, where Scn2a deletion causes alterations in the intricate process of myelination. This disruption instigates changes in axonal properties, presynaptic excitability, and synaptic plasticity at the single cell level. Furthermore, oligodendrocyte-specific Scn2a deletion compromises the integrity of neural circuitry within auditory pathways, leading to auditory hypersensitivity. Our findings reveal a novel pathway linking myelin deficits to synaptic activity and sensory abnormalities in ASD.

6.
Nat Sci Sleep ; 16: 1451-1467, 2024.
Article in English | MEDLINE | ID: mdl-39318396

ABSTRACT

Patients with allergic rhinitis (AR) have a high incidence of sleep disorders, such as insomnia, which can easily exacerbate nasal symptoms. The aggravation of nasal symptoms further promotes the deterioration of sleep disorders, forming a vicious cycle. Severe cases may even trigger psychological and neurological issues, such as anxiety, depression, and cognitive impairment, causing significant distress to patients, making clinical diagnosis and treatment difficult, and increasing costs. Furthermore, satisfactory therapeutics remain lacking. As the pathogenesis of AR-associated sleep disorders is not clear and research is still insufficient, paying attention to and understanding AR-related sleep disorders is crucial in clinical practice. Multiple studies have shown that the most crucial issues in current research on AR and sleep are analyzing the relationship between AR and sleep disorders, searching for the influencing factors, and investigating potential targets for diagnosis and treatment. This review aimed to identify and summarize the results of relevant studies using "AR" and "sleep disorders" as search terms. In addition, we evaluated the correlation between AR and sleep disorders and examined their interaction and potential mechanisms, offering a foundation for additional screening of potential diagnostic biomarkers and therapeutic targets.

7.
Sci Rep ; 14(1): 19538, 2024 08 22.
Article in English | MEDLINE | ID: mdl-39174693

ABSTRACT

Macrophages played an important role in the progression and treatment of head and neck squamous cell carcinoma (HNSCC). We employed weighted gene co-expression network analysis (WGCNA) to identify macrophage-related genes (MRGs) and classify patients with HNSCC into two distinct subtypes. A macrophage-related risk signature (MRS) model, comprising nine genes: IGF2BP2, PPP1R14C, SLC7A5, KRT9, RAC2, NTN4, CTLA4, APOC1, and CYP27A1, was formulated by integrating 101 machine learning algorithm combinations. We observed lower overall survival (OS) in the high-risk group and the high-risk group showed elevated expression levels in most of the immune checkpoint and human leukocyte antigen (HLA) genes, suggesting a strong immune evasion capacity. Correspondingly, TIDE score positively correlated with risk score, implying that high-risk tumors may resist immunotherapy more effectively. At the single-cell level, we noted macrophages in the tumor microenvironment (TME) predominantly stalled in the G2/M phase, potentially hindering epithelial-mesenchymal transition and playing a crucial role in the inhibition of tumor progression. Finally, the proliferation and migration abilities of HNSCC cells significantly decreased after the expression of IGF2BP2 and SLC7A5 reduced. It also decreased migration ability of macrophages and facilitated their polarization towards the M1 direction. Our study constructed a novel MRS for HNSCC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy for HNSCC patients.


Subject(s)
Head and Neck Neoplasms , Immunotherapy , Machine Learning , Macrophages , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Immunotherapy/methods , Prognosis , Macrophages/immunology , Macrophages/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Male , Cell Line, Tumor
8.
Eye (Lond) ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39090253

ABSTRACT

BACKGROUND: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients. SUBJECTS: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population. RESULTS: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations. CONCLUSIONS: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.

9.
BMC Cardiovasc Disord ; 24(1): 430, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39148039

ABSTRACT

BACKGROUND: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. METHODS: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA2DS2-VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF. RESULTS: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA2DS2-VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05). CONCLUSIONS: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group.


Subject(s)
Atrial Fibrillation , Atrial Function, Left , Heart Failure , Left Atrial Appendage Closure , Stroke , Ventricular Function, Left , Aged , Female , Humans , Male , Middle Aged , Atrial Appendage/diagnostic imaging , Atrial Appendage/physiopathology , Atrial Appendage/surgery , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Failure/surgery , Left Atrial Appendage Closure/adverse effects , Recovery of Function , Retrospective Studies , Risk Assessment , Risk Factors , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Stroke Volume , Time Factors , Treatment Outcome
10.
Cureus ; 16(7): e64494, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39139321

ABSTRACT

A 62-year-old male undergoing peritoneal dialysis (PD) for over two years presented with sudden bloody peritoneal dialysate, but no other symptoms. Laboratory tests indicated anemia, and a computed tomographic scan revealed a 4.4 cm tumor in the liver with hemoperitoneum, leading to a diagnosis of ruptured hepatocellular carcinoma (HCC), stage IIIB T4N0M0. The patient underwent a successful laparoscopic segmentectomy, and PD was resumed after a month of hemodialysis without complications. This case underscores the importance of considering malignancy in PD patients presenting with hemoperitoneum, as timely detection of HCC can significantly improve prognosis.

11.
Nucleic Acids Res ; 52(16): 9551-9573, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39021337

ABSTRACT

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.


Subject(s)
DNA Breaks, Double-Stranded , Hypocreales , Meiosis , Meiosis/genetics , Hypocreales/genetics , DNA Methylation , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA (Cytosine-5-)-Methyltransferases/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Genome, Fungal , Homologous Recombination , Endodeoxyribonucleases/metabolism , Endodeoxyribonucleases/genetics
12.
Mol Psychiatry ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971895

ABSTRACT

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

13.
BMC Public Health ; 24(1): 1939, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030506

ABSTRACT

BACKGROUND: Human flourishing is an emerging concept, extending beyond the conventional boundaries of subjective well-being and evolving into a comprehensive capture of the diverse dimensions of human life within complex societal structures. Therefore, moving away from traditional approaches centered on the single latent construct, this study aims to explore the multiple aspects of human flourishing and the intricate interplay of their contributing factors. METHODS: Data were collected from the Health and Living Environments Survey of Taiwanese Retirees during 2023 (valid sample n = 1,111). Human flourishing was measured using the Secure Flourish Index developed by Harvard University, which includes 12 indicators: (1) life satisfaction, (2) happiness, (3) mental health, (4) physical health, (5) meaning in life, (6) sense of purpose, (7) promoting good, (8) delaying gratification, (9) content relationships, (10) satisfying relationships, (11) financial stability, and (12) material stability. A mixed graphical network analysis was employed to analyze the related determinants, divided into four groups: (a) sociodemographic factors, (b) physical functions and health status, (c) social and family engagement, and (d) community environmental characteristics as nodes. RESULTS: We analyzed 31 variables and identified 133 nonzero edges out of 465 potential connections in the comprehensive network. Results showed that happiness and promoting good were the two most critical indicators influencing retirees' overall flourishing. Different flourishing indicators were also associated with various influential factors. For instance, personal characteristics, especially gender and education, emerged as central factors. Family caregiving negatively affected happiness and financial stability, whereas social engagement was positively associated with life satisfaction and meaning in life. Employment status had mixed effects, negatively associated with life satisfaction but positively associated with mental health. Community environments, such as a sense of community and neighborhood safety, generally enhanced flourishing. However, the accessibility of neighborhood resources was paradoxically associated with material stability, pointing to the complexity of environmental factors in human flourishing. CONCLUSION: This study provides a comprehensive network analysis that reveals intricate connections between personal, behavioral, and environmental factors, offering profound insights for targeted interventions to foster human flourishing.


Subject(s)
Personal Satisfaction , Retirement , Humans , Taiwan , Retirement/psychology , Retirement/statistics & numerical data , Female , Male , Middle Aged , Aged , Health Status , Happiness , Mental Health , Quality of Life/psychology
14.
Trends Chem ; 6(2): 95-96, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38827493
15.
Article in English | MEDLINE | ID: mdl-38867482

ABSTRACT

CONTEXT: Patients with Cushing's syndrome (CS) have higher risk of obesity and diabetes, which are important risk factors of cancers. However, if patients with CS have a higher incidence of cancer remains unknown. OBJECTIVE: To investigate if endogenous CS is associated with increased cancer incidence. DESIGN: A nationwide cohort study. SETTING: Analysis of the data retrieved from Taiwan's National Health Insurance program in 2006-2017. PARTICIPANTS: Between 2006-2017, 1278 patients with newly diagnosed endogenous CS were identified. Among them, 1246 patients without a history of malignancy were enrolled in this study. EXPOSURES: Endogenous CS. MAIN OUTCOMES MEASURES: The age- and sex-standardized incidence rate of all-cause cancer and age-sex-calendar year standardized incidence ratio (SIR) of cancer in association with endogenous CS. RESULTS: The age- and sex-standardized incidences of CS decreased from 4.84 to 3.77 per million person-years between 2006-2017. The age at diagnosis of CS was 45.3 ± 14.8 years, and 80.0% of the patients were female. Cushing's disease and adrenal CS accounted for 35.4% and 64.6% of patients with CS, respectively. The incidence rate of cancer in patients with CS was 7.77 (95% Confidence Interval [CI] = 5.84-10.14) per 1000 person-years, with an SIR of 2.08 (95% CI = 1.54-2.75). The three most common cancer types were liver (27.7%), kidney (16.7%), and lung (13.0%). CONCLUSIONS: Patients with endogenous CS have a higher incidence of cancer.

16.
J Affect Disord ; 361: 556-563, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38925314

ABSTRACT

OBJECTIVE: To investigate the effect of 20/4Hz transcutaneous auricular vagus nerve stimulation (taVNS) on anxiety symptoms in Parkinson's disease (PD) and the potential neural mechanism. METHODS: In the current randomized, double-blind, sham-controlled trial, 30 PD patients with anxiety (PD-A), 30 PD patients without anxiety (PD-nA), and 30 healthy controls (HCs) were enrolled. PD-A patients were randomly (1:1) allotted to real taVNS stimulation group (RS) or sham stimulation group (SS) to explore the efficacy of a two-week treatment of taVNS to promote anxiety recovery. Simultaneously, all participants were measured activation in the bilateral prefrontal cortex during verbal fluency task (VFT) using functional near-infrared spectroscopy. RESULTS: PD-A patients showed significantly decreased oxyhemoglobin in the left triangle part of the inferior frontal gyrus (IFG) during VFT, which was negatively related to the severity of anxiety symptoms. After two-week treatment of taVNS, the interaction of group and time had significant effect on HAMA scores (F = 18.476, p < 0.001, η2 = 0.398). In RS group, compared with baseline, HAMA scores decreased significantly in the post-treatment and follow-up condition (both p < 0.001). Meanwhile, in RS group, HAMA scores were lower than those in SS group in the post-treatment and follow-up condition (p = 0.006, <0.001, respectively). Furthermore, the 20/4Hz taVNS remarkably ameliorated anxiety symptoms in PD patients, directly correlated with the increased activation of the left triangle part of the IFG during VFT in RS group. CONCLUSION: Our results depicted that taVNS could ameliorate the anxiety symptoms of PD-A patients and regulated the function of the left triangle part of the IFG.


Subject(s)
Anxiety , Parkinson Disease , Prefrontal Cortex , Transcutaneous Electric Nerve Stimulation , Vagus Nerve Stimulation , Humans , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Parkinson Disease/psychology , Parkinson Disease/complications , Male , Female , Vagus Nerve Stimulation/methods , Middle Aged , Double-Blind Method , Anxiety/therapy , Anxiety/physiopathology , Transcutaneous Electric Nerve Stimulation/methods , Prefrontal Cortex/physiopathology , Aged , Spectroscopy, Near-Infrared , Treatment Outcome
17.
Bioorg Med Chem ; 109: 117792, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38897139

ABSTRACT

Cancer has been a leading cause of death over the last few decades in western countries as well as in Taiwan. However, traditional therapies are limited by the adverse effects of chemotherapy and radiotherapy, and tumor recurrence may occur. Therefore, it is critical to develop novel therapeutic drugs. In the field of HDAC inhibitor development, apart from the hydroxamic acid moiety, 2-aminobenzamide also functions as a zinc-binding domain, which is shown in well-known HDAC inhibitors such as Entinostat and Chidamide. With recent successful experiences in synthesizing 1-(phenylsulfonyl)indole-based compounds, in this study, we further combined two features of the above chemical compounds and generated indolyl benzamides. Compounds were screened in different cancer cell lines, and enzyme activity was examined to demonstrate their potential for anti-HDAC activity. Various biological functional assays evidenced that two of these compounds could suppress cancer growth and migration capacity, through regulating epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis mechanisms. Data from 3D cancer cells and the in vivo zebrafish model suggested the potential of these compounds in cancer therapy in the future.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Cycle , Cell Proliferation , Drug Screening Assays, Antitumor , Epithelial-Mesenchymal Transition , Histone Deacetylase Inhibitors , Zebrafish , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/chemical synthesis , Humans , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Epithelial-Mesenchymal Transition/drug effects , Animals , Cell Cycle/drug effects , Structure-Activity Relationship , Cell Proliferation/drug effects , Molecular Structure , Dose-Response Relationship, Drug , Cell Line, Tumor , Histone Deacetylases/metabolism
18.
Int J Soc Welf ; 33(2): 355-369, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38800468

ABSTRACT

This study investigated the associations between early parental warmth, harsh discipline, and adolescent depressive symptoms from early to late adolescence, with attention to gender differences in these associations. The sample was drawn from a longitudinal study, the Taiwan Youth Project, including 2,690 Taiwanese adolescents from wave 1 in 2000 (first year in junior high school) to wave 6 (third year in high school) in 2005. The results showed a nonlinear developmental trajectory of adolescent depressive symptoms during the middle- to high-school period. Harsh discipline was associated with the significantly higher initial presence and faster growth rate of depressive symptoms, while parental warmth and monitoring were associated with the significantly lower initial presence of depressive symptoms. In addition, female adolescents displayed a higher initial level of depressive symptoms than males when parents exercised higher levels of monitoring and harsh discipline. Finally, we provided suggestions for practice and research.

19.
bioRxiv ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38798664

ABSTRACT

Sperm cryopreservation is important for individuals undergoing infertility treatment, and for those who wish to preserve fertility potential, prior to treatments like chemotherapy, radiation therapy, gender-affirming medical interventions, elective fertility delay, or individuals in high-risk professions such as the military. Current methods for sperm cryopreservation result in approximately 30-50% decrease in sperm motility. However, recent studies have shown that ultra-rapid freezing (vitrification) is a valuable approach for maintaining sperm quality after freeze-thawing processes in the clinical laboratory setting and requires submicroliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present a method that leverages open-channel droplet microfluidics to autonomously generate sub-microliter to microliter volumes of purified human sperm samples. Using a novel, open-channel droplet generator, we found no change in sperm movement and kinematic data after exposure to device and reagents in our platform. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.

20.
Clin Immunol ; 263: 110220, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38642783

ABSTRACT

As the number of vaccinated individuals has increased, there have been increasing reports of cutaneous hypersensitivity reactions. The main COVID-19 vaccines administered include messenger ribonucleic acid vaccines, non-replicating viral vector vaccines, inactivated whole-virus vaccines, and protein-based vaccines. These vaccines contain active components such as polyethylene glycol, polysorbate 80, aluminum, tromethamine, and disodium edetate dihydrate. Recent advances in understanding the coordination of inflammatory responses by specific subsets of lymphocytes have led to a new classification based on immune response patterns. We categorize these responses into four patterns: T helper (Th)1-, Th2-, Th17/22-, and Treg-polarized cutaneous inflammation after stimulation of COVID-19 vaccines. Although the association between COVID-19 vaccination and these cutaneous adverse reactions remains controversial, the occurrence of rare dermatoses and their short intervals suggest a possible relationship. Despite the potential adverse reactions, the administration of COVID-19 vaccines is crucial in the ongoing battle against severe acute respiratory syndrome coronavirus 2.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , COVID-19/prevention & control , COVID-19/immunology , Drug Eruptions/etiology , Drug Eruptions/immunology
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