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1.
Asia Pac Psychiatry ; 16(2): e12556, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38727090

ABSTRACT

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.


Subject(s)
Hand Strength , Resistance Training , Schizophrenia , Humans , Schizophrenia/rehabilitation , Male , Female , Aged , Resistance Training/methods , Hand Strength/physiology , Middle Aged , Frailty/rehabilitation , Cognitive Dysfunction/rehabilitation , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Cognition/physiology , Outcome Assessment, Health Care
2.
CNS Spectr ; : 1-7, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38708739

ABSTRACT

BACKGROUND: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD. METHODS: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections. RESULTS: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5). CONCLUSION: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

3.
Materials (Basel) ; 17(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38793339

ABSTRACT

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

4.
Redox Rep ; 29(1): 2354625, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38794801

ABSTRACT

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.


Subject(s)
Alveolar Epithelial Cells , Membrane Potential, Mitochondrial , Animals , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Mice , Humans , Membrane Potential, Mitochondrial/physiology , Mitochondrial Precursor Protein Import Complex Proteins , Male , Apoptosis , Female , Cell Proliferation , Mice, Inbred C57BL , Disease Models, Animal , Cryptogenic Organizing Pneumonia/pathology , Cryptogenic Organizing Pneumonia/metabolism , Organizing Pneumonia
5.
Front Endocrinol (Lausanne) ; 15: 1354614, 2024.
Article in English | MEDLINE | ID: mdl-38800470

ABSTRACT

Background: The coexistence of heart failure and diabetes is prevalent, particularly in Intensive Care Units (ICU). However, the relationship between the triglyceride-glucose (TyG) index, heart failure, diabetes, and the length of hospital stay (LHS) in patients with cerebrovascular disease in the ICU remains uncertain. This study aims to investigate the association between the TyG index and LHS in patients with heart failure and diabetes. Methods: This retrospective study utilized the Medical Information Mart for Intensive Care (MIMIC)-IV database to analyze patients with diabetes and heart failure. Participants were categorized into quartiles based on the TyG index, and the primary outcome was LHS. The association between the TyG index at ICU admission and LHS was examined through multivariable logistic regression models, restricted cubic spline regression, and subgroup analysis. Results: The study included 635 patients with concurrent diabetes and heart failure. The fully adjusted model demonstrated a positive association between the TyG index and LHS. As a tertile variable (Q2 and Q3 vs Q1), the beta (ß) values were 0.88 and 2.04, with a 95% confidence interval (95%CI) of -0.68 to 2.44 and 0.33 to 3.74, respectively. As a continuous variable, per 1 unit increment, the ß (95% CI) was 1.13 (0.18 to 2.08). The TyG index's relationship with LHS showed linearity (non-linear p = 0.751). Stratified analyses further confirmed the robustness of this correlation. Conclusion: The TyG index exhibited a linearly positive association with the LHS in patients with both heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are imperative to substantiate and validate the findings presented in this investigation.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Heart Failure , Intensive Care Units , Length of Stay , Triglycerides , Humans , Heart Failure/blood , Heart Failure/epidemiology , Female , Male , Retrospective Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Intensive Care Units/statistics & numerical data , Triglycerides/blood , Aged , Length of Stay/statistics & numerical data , Blood Glucose/analysis , Blood Glucose/metabolism , Middle Aged , Aged, 80 and over
6.
Sci Rep ; 14(1): 9493, 2024 04 25.
Article in English | MEDLINE | ID: mdl-38664527

ABSTRACT

The symptoms of tracheobronchial foreign body in the elderly are not typical, so they are often missed or misdiagnosed. This study aims to depict the clinical characteristics of tracheobronchial foreign body inhalation in the elderly. We retrospectively analysed the clinical data of elder patients (age ≥ 65 years) diagnosed with tracheal and bronchial foreign bodies. The data included age, sex, clinical symptoms, type and location of foreign bodies, prehospital duration, Chest CT, bronchoscopic findings, and frequencies and tools for removing these elderly patients' tracheal and bronchial foreign bodies. All patients were followed up for a half year. Fifty-nine cases were included, of which only 32.2% had a definite aspiration history. Disease duration > 30 days accounted for 27.1% of the patients. 27.1% of the patients had a history of stroke, and 23.8% had Alzheimer's Disease. Regarding clinical symptoms, patients mainly experience cough and expectoration. The most common CT findings were abnormal density shadow (37.3%) and pulmonary infiltration (22.0%). Under bronchoscopy, purulent secretions were observed in 52.5% of patients, and granulation tissue hyperplasia was observed in 45.8%. Food (55.9%) was the most common foreign object, including seafood shells (5.1%), bones (20.3%), dentures (18.6%), and tablets (20.3%). The success rate of foreign body removal under a bronchoscope was 96.7%, 28.8% of the foreign bodies were on the left and 69.5% on the right. 5.1% of the elderly patients required rigid bronchoscopy, and 6.8% required two bronchoscopies. In elderly cohorts, tracheal foreign bodies are obscured by nonspecific clinical presentations and a paucity of aspiration history, challenging timely diagnosis. Predominantly constituted by food particles, with a notable predilection for the left bronchial tree, these cases demand skilled bronchoscopic management, occasionally requiring sophisticated approaches for successful extraction.


Subject(s)
Bronchi , Bronchoscopy , Foreign Bodies , Trachea , Humans , Foreign Bodies/surgery , Foreign Bodies/diagnosis , Foreign Bodies/diagnostic imaging , Aged , Male , Female , Bronchi/diagnostic imaging , Bronchi/pathology , Trachea/diagnostic imaging , Bronchoscopy/methods , Aged, 80 and over , Retrospective Studies , Tomography, X-Ray Computed
7.
Nutrients ; 16(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38612975

ABSTRACT

Aging-related sarcopenia exerts harmful impacts on muscle mass, strength, and physical mobility. Protein supplementation has been demonstrated to augment efficacy of resistance training (RT) in elderly. This study compared the relative effects of different protein supplements on muscle mass, strength, and mobility outcomes in middle-aged and older individuals undergoing RT. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) examining the efficacy of protein supplement plus RT in untrained community-dwelling adults, hospitalized, or institutionalized residents who suffered acute or chronic health conditions. Network meta-analysis (NMA) was performed using a frequentist method for all analyses. Treatment effects for main outcomes were expressed as standard mean difference (SMD) with 95% confidence interval (CI). We used the surface-under-the cumulative-ranking (SUCRA) scores to rank probabilities of effect estimation among all identified treatments. Meta-regression analyses were performed to identify any relevant moderator of the treatment efficacy and results were expressed as ß with 95% credible interval (CrI). We finally included 78 RCTs (5272 participants) for analyses. Among the six protein sources identified in this NMA, namely whey, milk, casein, meat, soy, and peanut, whey supplement yielded the most effective treatments augmenting efficacy of RT on muscle mass (SMD = 1.29, 95% CI: 0.96, 1.62; SUCRA = 0.86), handgrip strength (SMD = 1.46, 95% CI: 0.92, 2.00; SUCRA = 0.85), and walking speed (SMD = 0.73, 95% CI: 0.39, 1.07; SUCRA = 0.84). Participant's health condition, sex, and supplementation dose were significant factors moderating the treatment efficacy on muscle mass (ß = 0.74; 95% CrI: 0.22, 1.25), handgrip strength (ß = -1.72; 95% CrI: -2.68, -0.77), and leg strength (ß = 0.76; 95% CrI: 0.06, 1.47), respectively. Our findings suggest whey protein yields the optimal supplements to counter sarcopenia in older individuals undergoing RT.


Subject(s)
Resistance Training , Sarcopenia , Aged , Middle Aged , Humans , Network Meta-Analysis , Independent Living , Sarcopenia/therapy , Randomized Controlled Trials as Topic , Dietary Supplements , Muscles
8.
Clin Transl Sci ; 17(3): e13754, 2024 03.
Article in English | MEDLINE | ID: mdl-38476031

ABSTRACT

This study examined the levels of soluble CD146 (sCD146) in plasma samples from patients with chronic obstructive pulmonary disease (COPD) and assessed the relationship between sCD146 and the severity of COPD. A total of 97 COPD patients were recruited from 20 medical centers in Jiangsu, China, including 13 stable subjects and 84 exacerbated subjects. The plasma sCD146 level in exacerbated subjects (28.77 ± 10.80 ng/mL) was significantly lower than that in stable subjects (38.84 ± 15.00 ng/mL). In the high sCD146 group, the proportion of subjects with modified Medical Research Council (mMRC) scores of 0-1 was higher, the proportion of subjects with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 was lower, and the proportion of subjects with ≥1 hospitalizations in the past year was lower. The plasma sCD146 level was negatively correlated with the COPD Assessment Test (CAT) score (r = -0.2664, p = 0.0087). Logistic regression analysis showed that sCD146 was an independent risk factor for acute exacerbation of COPD (AECOPD). Receiver operating characteristic (ROC) analysis suggested that sCD146 combined with sex, age, pulmonary function, and acute exacerbations in the past year had clinical value for the accurate identification of AECOPD, with an area under the ROC curve (AUC) of 0.908 (95% CI: 0.810-1.000, p < 0.001). In addition, there was a significant negative correlation between plasma sCD146 and S100A9 (r = -0.3939, p < 0.001).


Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Lung , Biomarkers , Risk Factors , Hospitalization , Disease Progression
9.
J Org Chem ; 89(7): 4438-4443, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38471105

ABSTRACT

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.

10.
Sci Rep ; 14(1): 5038, 2024 02 29.
Article in English | MEDLINE | ID: mdl-38424104

ABSTRACT

Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3ß may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3ß in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3ß. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3ß increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3ß signaling pathway.


Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , Aged , Humans , COVID-19/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Interferon-gamma/metabolism , Post-Acute COVID-19 Syndrome , Programmed Cell Death 1 Receptor/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
11.
J Chin Med Assoc ; 87(2): 219-225, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38305484

ABSTRACT

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.


Subject(s)
Dementia , Lewy Body Disease , Transients and Migrants , Humans , Caregivers/psychology , Lewy Body Disease/psychology , Taiwan , Employment
12.
Aging (Albany NY) ; 16(4): 3231-3240, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38334965

ABSTRACT

PURPOSE: We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. METHODS: RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RESULTS: RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. CONCLUSIONS: OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.


Subject(s)
MicroRNAs , Neoplasms , Phenanthrenes , Sleep Apnea, Obstructive , Humans , Mice , Animals , Up-Regulation , Heterografts , Vascular Endothelial Growth Factor A/metabolism , Hypoxia/metabolism , MicroRNAs/genetics
13.
Sensors (Basel) ; 24(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38339679

ABSTRACT

Electrodeposited amorphous hydrated iridium oxide (IrOx) is a promising material for pH sensing due to its high sensitivity and the ease of fabrication. However, durability and variability continue to restrict the sensor's effectiveness. Variation in probe films can be seen in both performance and fabrication, but it has been found that performance variation can be controlled with potentiostatic conditioning (PC). To make proper use of this technique, the morphological and chemical changes affecting the conditioning process must be understood. Here, a thorough study of this material, after undergoing PC in a pH-sensing-relevant potential regime, was conducted by voltammetry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Fitting of XPS data was performed, guided by raw trends in survey scans, core orbitals, and valence spectra, both XPS and UPS. The findings indicate that the PC process can repeatably control and conform performance and surface bonding to desired calibrations and distributions, respectively; PC was able to reduce sensitivity and offset ranges to as low as ±0.7 mV/pH and ±0.008 V, respectively, and repeat bonding distributions over ~2 months of sample preparation. Both Ir/O atomic ratios (shifting from 4:1 to over 4.5:1) and fitted components assigned hydroxide or oxide states based on the literature (low-voltage spectra being almost entirely with suggested hydroxide components, and high-voltage spectra almost entirely with suggested oxide components) trend across the polarization range. Self-consistent valence, core orbital, and survey quantitative trends point to a likely mechanism of ligand conversion from hydroxide to oxide, suggesting that the conditioning process enforces specific state mixtures that include both theoretical Ir(III) and Ir(IV) species, and raising the conditioning potential alters the surface species from an assumed mixture of Ir species to more oxidized Ir species.

14.
Cell Oncol (Dordr) ; 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38170381

ABSTRACT

BACKGROUND: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results. CONCLUSION: This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.

15.
Allergy Asthma Immunol Res ; 16(1): 71-90, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38262392

ABSTRACT

PURPOSE: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. METHODS: LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. RESULTS: LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. CONCLUSIONS: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

16.
Int Immunopharmacol ; 127: 111410, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38109838

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a leading cause of global death. As a molecule beyond adhesion, CD146 is involved in COPD pathogenesis. However, the mechanisms of CD146 in COPD remain largely elusive. We hypothesized that CD146 regulates the production of matrix metalloproteinase-9 (MMP-9) in macrophages and thereby contributes to COPD. Here, we constructed a murine model of COPD using lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). In COPD-like mice, LPS and PPE decreased the pulmonary expression of CD146. MMP-9 expression and bioactivity were increased in CD146 knockout COPD-like mice. In vitro, LPS decreased CD146 expression in macrophages. With or without LPS challenge, CD146-defective macrophages produced more MMP-9. Transcriptome analysis based on next-generation sequencing (NGS) revealed that S100A9 regulated MMP-9 production in CD146-defective macrophages. Targeting S100A9 with paquinimod decreased lung inflammation and alleviated alveolar destruction in COPD-like mice. Collectively, our study suggests that CD146 negatively regulates MMP-9 production in macrophages via the S100A9 pathway in COPD.


Subject(s)
Matrix Metalloproteinase 9 , Pulmonary Disease, Chronic Obstructive , Animals , Mice , Calgranulin B/genetics , Calgranulin B/metabolism , CD146 Antigen/genetics , CD146 Antigen/metabolism , Lipopolysaccharides/metabolism , Macrophages/metabolism , Macrophages, Alveolar/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Swine
17.
Parasitol Res ; 123(1): 18, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38063934

ABSTRACT

Toxoplasma gondii is a pathogen that poses a serious threat to human health and causes significant economic losses to the global livestock industry. The prevalence of toxoplasmosis infection has been reported to be high in humans and animals around the world, but the occurrence of the disease has not yet been reported in water buffaloes in Guangxi Zhuang Autonomous Region, southern China. To understand the overall seroprevalence of T. gondii infection in Guangxi, a total of 1041 water buffalo and 114 cat serum samples were examined using an indirect enzyme-linked immunosorbent assay (I-ELISA). Of the 1041 water buffaloes analyzed, an overall seroprevalence of 52.9% (551/1041) was obtained, with year, season, and city location being significant factors affecting the rate of T. gondii infection in water buffaloes (P < 0.001). The results also revealed a high seroprevalence of 57% (65/114) in cats. Given that buffalo milk and meat products are vital food sources, these findings suggest that toxoplasmosis in water buffaloes may be a public health threat. This study provides the first T. gondii seroprevalence data in Guangxi, which could contribute to the prevention and control of toxoplasmosis in the region.


Subject(s)
Bison , Toxoplasma , Toxoplasmosis, Animal , Cats , Humans , Animals , Buffaloes , Toxoplasmosis, Animal/epidemiology , Seroepidemiologic Studies , China/epidemiology , Antibodies, Protozoan , Risk Factors
18.
J Formos Med Assoc ; 2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38072742

ABSTRACT

BACKGROUND: Health-related quality of life (HRQoL) is an essential outcome parameter in geriatric research; however, the available evidence is mixed regarding the factors associated with HRQoL among people with dementia. We aimed to identify factors that contribute to HRQoL among people with dementia in residential long-term care (LTC) institutions. METHODS: We randomly selected 299 of 1607 registered residential LTC institutions in Taiwan. A cross-sectional survey was conducted between 2019 and 2020, including items on demographic characteristics, comorbidities, the EuroQol-5 dimensions-5 levels (EQ-5D-5L; utility and visual analog scale [VAS] scores), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), behavioral and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL (IADL). RESULTS: In total, 1313 people with dementia from 267 institutions were enrolled (mean age, 76.4 ± 12.7 years). The mean EQ-5D-5L utility and VAS scores were 0.10 (standard deviation [SD] = 0.48) and 66.57 (SD = 20.67), respectively. In multivariate linear regression analysis, higher scores for ADL, IADL, and CDR sum of boxes were associated with higher utility scores. Higher VAS scores were associated with higher ADL and MMSE scores. Lower utility scores and VAS scores were associated with more frequent depressive symptoms. CONCLUSION: ADL, dementia severity, cognitive function, and depressive symptoms influenced the HRQoL of people with dementia in residential LTC institutions. Longitudinal studies should be conducted to better understand how HRQoL changes over time among people with disabilities.

19.
Int J Mol Sci ; 24(24)2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38139175

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/genetics , Mouth Neoplasms/radiotherapy , Mouth Neoplasms/metabolism , Cell Line, Tumor , Head and Neck Neoplasms/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Protein-Tyrosine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism
20.
Sci Rep ; 13(1): 19914, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37964096

ABSTRACT

Declines in oral consumption and swallowing function are common reasons which may elevate the risk of malnutrition in the older adults. This study aimed to provide valuable information and contribute to the existing body of knowledge in this field as well as highlight the importance of a comprehensive assessment of oral health, swallowing function, and nutritional status in long-term care residents. This was a cross-sectional study. Thirty-nine participants were recruited from a nursing home. The comprehensive assessment was evaluated in participants, including oral health (Oral Health Assessment Tool (OHAT)), swallowing function (Functional Oral Intake Scale (FOIS) and Eating Assessment Tool (EAT)-10), and nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF). The average age of participants was 80.4 ± 11.7 years, and 46% of these older adults were found to be at the risk of malnutrition. There was a negative correlation between the OHAT and MNA-SF scores. In addition, subjects with poor oral health (OHAT score = 5~8), oral consumption of a modified diet (FOIS score = 4~6), and reduced swallowing function (EAT-10 score ≥ 3) were more likely to be at risk of malnutrition. A comprehensive evaluation of oral health and swallowing function was closely connected with the nutritional status of older nursing home dwellers.


Subject(s)
Malnutrition , Nutritional Status , Humans , Aged , Aged, 80 and over , Cross-Sectional Studies , Deglutition , Oral Health , Malnutrition/epidemiology , Nursing Homes , Geriatric Assessment
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