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Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis
No full text[[abstract]]Connection and crosstalk among the organelles critically contribute to cellular functions. Destruction of any kind of organelle is likely to induce a series of intracellular disorders and finally lead to cell death. Because of its subcellular locations, CDGSH iron-sulfur domain-containing protein 1 (Cisd1) and Cisd2 have functions that are related to maintaining mitochondria and ER homeostasis. As previous reports have shown, Cisd2 knockout mice have a decreased body weight and poor survival rate, and the primary defects were conducted in skeletal muscle. Our previous findings indicated that Cisd1 deletion causes a range of skeletal muscle defects in mice with Cisd2 deficiency, including mitochondrial degeneration, endoplasmic reticulum (ER) stress, and alteration of protein process, as well as programmed cell death. In Cisd1 and Cisd2 deficient condition, the whole of the protein biosynthesis was damaged, including translation, modification, transport, and degradation. Changes in the immune response, redox regulation, and metabolism were also present in Cisd1 and Cisd2 double knockout mice. Overall, we have demonstrated that Cisd1 and Cisd2 knockout have a synergistic effect on skeletal muscles, and that Cisd2 plays a more critical role than Cisd1. These synergistic effects impact signaling regulation and interrupt the crosstalk and homeostasis of organelles. This creates severe disorders in various tissues and organs
Sublobar resection versus lobectomy for small (≤3 cm) NSCLC with visceral pleural invasion: A propensity-score-matched survival analysis from a nationwide cohort
No full text[[abstract]]Background/Objectives: While sublobar resection (SLR) is accepted for selected small, early non-small-cell lung cancers (NSCLCs), its efficacy for tumors with visceral pleural invasion (VPI) remains debated. This study aimed to compare lung-cancer-specific survival (LCSS) between SLR and lobectomy in pT2a (tumor 75 years), PL2 VPI, and lymphovascular invasion were independent predictors of worse LCSS (all p < 0.001). Conclusions: This large population-based study, after rigorous adjustment for confounders, found that SLR and lobectomy provided comparable LCSS. SLR may be an alternative for selected patients, but prospective validation is recommended
High-growth enterovirus 71 strains and vaccines
No full text[[abstract]]The present invention relates to adapted Enterovirus 71 (EV71) vaccine strains suitable for increased vaccine production for mammals. The EV71 vaccine strains contain at least one modified enterovirus protein that results in increased production of the EV71 virus from a mammalian host cell, such as a Vero cell. The present invention also relates to the vaccines produced from the adapted EV71 virus vaccine strains, and the producing method of the vaccines
阳离子型生物可降解性陶瓷聚合物微粒子用以递送疫苗的用途
No full text[[abstract]]本发明涉及一种以阳离子型生物可降解性陶瓷聚合物微粒子作为递送疫苗载体的用途，该阳离子型生物可降解性陶瓷聚合物微粒子是以磷酸氢钙(calcium hydrogenphosphate；CHP)修饰表面，在本发明中，以此磷酸氢钙修饰的陶瓷聚合物微粒子所制备的蛋白质疫苗，显现出较低的毒性，并可延长抗原的停留时间和增强免疫反应
Methods to enhance nerve regeneration utilizing neural stem cells and IL12p40
No full text[[abstract]]The present application provides a composition and methods to enhance nerve regeneration utilizing at least one component of neural stem cells or IL12p40. The composition comprises neural stem cells and a neurotrophic factor, which is constructed by IL12p40 as at least one subunit. The methods to enhance nerve regeneration comprise providing a nerve regeneration composition comprising a neurotrophic factor containing IL12p40 as at least one subunit to a subject. The composition of the methods can further comprise neural stem cells
Investigating the impact of azithromycin on the lung microbiome and immune response in patients with bronchiectasis
No full text[[abstract]]RATIONALE: While azithromycin (AZM) has demonstrated a reduction in exacerbations in patients with bronchiectasis, its impact on the lung microbiome and host immunity remains unclear. This study seeks to investigate the alterations in lung microbiota and airway inflammation before and after AZM treatment in individuals with bronchiectasis.METHODS: We conducted a prospective cohort study involving patients with non-cystic fibrosis bronchiectasis. Participants who were prescribed 250mg of oral AZM daily for 12 weeks were enrolled. We collected bronchoalveolar lavage fluid (BAL) and blood samples on both Day 0 (before treatment) and Day 84 (after treatment). The lung microbiome was assessed using 16S ribosomal RNA (V1-V9) sequencing, both before and after the AZM treatment. Additionally, we evaluated BAL cytokines and serum biomarkers. To assess the radiological severity of bronchiectasis, we employed quantitative high- resolution computed tomography (HRCT). The primary outcome of our study focused on changes in microbial diversity and composition. Throughout the study duration, participants were closely monitored for any potential side effects from AZM. Any variations in clinical symptoms, pulmonary function, and exacerbation rates were duly documented.RESULTS: A total of 71 patients were enrolled, with 57 completing the AZM treatment. The median age of participants was 65.5 years; 54% were female, and 75.4% were nonsmokers. Our data indicated that AZM did not significantly affect alpha diversity (p=0.49) but did alter the lung microbiota communities (β diversity, p=0.001). Differential Abundance Analysis (DAA) using DESeq2 identified a decrease in six species post- AZM treatment, including Haemophilus parainfluenzae and Neisseria subflava. Notably, 64.9% (n=37) of patients showed symptomatic improvement (CAT> 2) after AZM treatment, 43% (n=23) exhibited improved lung function (FEV1> 100ml), and 21% (n=12) demonstrated radiological improvement (resolution of Tree-in-bud patterns). We categorized patients who showed symptomatic improvement as the “responder group.” In comparison to non-responders, this group exhibited distinct microbiome profiles (β diversity, p=0.025) associated with higher levels of Proteobacteria, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. This group also had elevated neutrophilic markers (like IL-1β) before treatment, but displayed reduced neutrophilic inflammation (levels of IL-1β, IL-18, IL-6, and TNF-alpha) post-treatment.CONCLUSION: Our study revealed that AZM treatment led to a therapeutic response in some but not all patients with bronchiectasis. There were noticeable post-AZM treatment changes in the lung microbiome. The association between specific microbial taxa and airway neutrophilic inflammation underscores the potential for personalized therapeutic approaches in bronchiectasis patients
Associations between polygenic risk score for schizophrenia and schizotypal traits in the multiplex families of patients with schizophrenia
No full text[[abstract]]Background: A possible connection between schizotypy and schizophrenia (SZ) might be attributable to their overlapping genetic determinants in terms of the polygenic risk score (PRS). Using multiplex SZ families, this study aims to (1) investigate the relationship of the PRS for SZ (SZ-PRS) and dimensional schizotypal traits, including schizophrenic symptom in the patients with SZ and schizotypy in their unaffected relatives; (2) evaluate the changes of the association patterns of SZ-PRS and dimensional schizotypal traits after combining patients with their unaffected relatives; and (3) examine whether the dimensional schizotypal traits were also associated with PRS for general personality, bipolar disorder (BIP), and major depression disorder (MDD). Methods: Among 557 multiplex families recruited in Taiwan Schizophrenia Linkage Study, 1275 individuals were genotyped using Illumina PsychChip array. A total of 538 patients and their 543 unaffected relatives from 315 families, who had passed the quality control and completed the measurements of schizotypal traits, were included for subsequent analyses. A modified Structured Interview for Schizotypy were used for assessing schizotypy factors among unaffected relatives and the Scales for Positive and Negative Symptoms for assessing schizophrenic symptom factors among patients. A PRS was derived first using the summary statistics of the GWAS from the Psychiatric Genomic Consortium-2 SZ cohort as the discovery dataset, and then a weighted sum of SNPs was calculated using the logarithm of each SNP's odds ratio for the effect allele from the discovery dataset. Results: Among the three groups of participants (538 patients, 53 unaffected siblings, and 490 unaffected parents), both patients and unaffected siblings had similar age and educational levels, whereas parents had lower educational levels compared to their offspring. An alignment approach was used to derive the 2-factor schizotypal trait (i.e., the Aligned Positive Schizophrenic-Schizotypy and the Aligned Negative Schizophrenic-Schizotypy factor). We found that the SZ-PRS was correlated only with Disorganization factor from three Schizophrenic symptom factors in the patients as well as with Social isolation/Introversion factor from four Schizotypy factors in their unaffected relatives. Second, after pooling patients and their unaffected relatives, SZ-PRS explained more variance of Aligned Negative Schizophrenic-Schizotypy factor than that of Aligned Positive Schizophrenic-Schizotypy factor. Also, the association effects were slightly increased in the pooled sample compared to that of analyzing patients and unaffected relatives separately. Finally, Aligned Schizophrenic-Schizotypy factors were only associated with SZ-PRS but not with PRS for BIP, MDD, or general personality traits. Discussion: To our knowledge, this is the first study using multiplex SZ families to exam the association of schizotypal traits (including four Schizotypy factors, three Schizophrenic symptom factors, and two Aligned Schizophrenic-Schizotypy factors) and polygenic risk of SZ. Our findings indicated that SZ-PRS only correlated with specific individual dimension (i.e., Social isolation/Introversion factor) of schizotypy in unaffected relatives of patients with SZ. These results offer support to the hypotheses that the negative dimension of schizotypy reflects more the genetic vulnerability to SZ than the positive dimension of schizotypy
Genetic variants in mitochondria contribute the risk of familial lung cancer
No full text[[abstract]]Background: Family history, especially among non-smoking females, is a significant risk factor for lung cancer. Our previous research indicated that individuals with a maternal family history of lung cancer face a notably higher lung cancer risk than those without such a family history. Mitochondrial DNA is typically inherited from the mother. Therefore, we aimed to explore whether mitochondria variants might contribute to the susceptibily of lung cancer. Methods: In this study, 741 non-smoking individuals with a family history of lung cancer participated, and 4.7% were diagnosed with lung cancer. We extracted and sequenced mitochondrial DNA from peripheral blood samples. We identified germline variants associated with maternal inheritance by comparing mitochondrial variant frequencies in individuals with or without a family history of maternal lung cancer and with or without a lung cancer diagnosis. Candidate varaints were furthur vailidated in 57 subjects from 10 families and in an independent cohort consisting of 962 cases and 952 controls. Results: In the exploratory cohort, 8 mitochondria variants assocaited with materal interiance were identified, and subjects with family history of lung cancer in their mothers and a diagnosis of lung cancer had higher carrier frequencies of these variants compared to others(p<0.05). Among 57 subjects from 10 families, the results also demostrated that 6 out of 8 variants were transmitted from mothers to their children. In the independent case-control study, 3 variants were remains significantly associated with lung cancer, with odds ratio were ranging from 1.47 to 1.69. Conclusions: Mitochondria variants contribute to the susceptibility of lung cancer, and help explain why family history is an implortant risk factor, especially for invididual with a family history of materanl relatives with lung cancer. These variants can potentially serve as biomarkers for identifying high-risk individuals, facilitating early detection
Profiling social detachment in older people in Taiwan: A cluster analysis
No full text[[abstract]]ObjectivesThe Social Detachment Questionnaire for the Older Population (SDQO) is a validated tool that assesses various dimensions of social relationships. This study aimed to profile social detachment among older people in Taiwan using the SDQO and explore its use in distinguishing groups with varying levels of social engagement.MethodsA telephone-based survey was conducted, collecting demographic data and responses to the SDQO and Brief Symptom Rating Scale-5 (BSRS-5). Cluster analysis based on SDQO dimension scores was performed to identify groupings. Regression analyses examined the association between social engagement clusters, demographic variables, and BSRS-5 scores. A receiver operating characteristic curve was established and the area under the curve was calculated to identify the cutoff for distinguishing individuals with high and low social engagement.ResultsIn a representative sample of 2549 individuals aged 55 and above in Taiwan, cluster analysis identified two groups based on social engagement levels as measured by the SDQO. The low social engagement cluster, indicating higher social detachment, was more likely to consist of older individuals (>= 75 years), those without children, and those with lower education levels (<= 9 years). After adjusting for demographics, the low social engagement cluster was associated with higher BSRS-5 scores. The optimal SDQO cutoff for identifying low social engagement was 27/28.ConclusionsThe SDQO can identify socially detached older people, who are more likely to experience increased psychological distress. Screening older individuals with demographic risk factors using the SDQO could help identify those most vulnerable to adverse health outcomes related to social detachment
Association between infant feeding and ADHD development in childhood: A birth cohort study in Taiwan
No full text[[abstract]]BackgroundInfant feeding plays a vital role in neurodevelopment, and a lack of breastfeeding and complementary feeding may increase the risk of developing attention-deficit/hyperactivity disorder (ADHD). However, empirical evidence on this relationship remains uncertain, as most studies are based on cross-sectional designs. Therefore, this study aimed to examine this temporal relationship using longitudinal data from a birth cohort.MethodsA retrospective cohort study was conducted using data from Wave I (starting at 6 months old, 2005-2006) to Wave IV (up to 5 years old, 2010-2011) of the Taiwan Birth Cohort Study. A total of 19,721 pairs completed the four-wave interviews and provided information on infant feeding, medical history, ADHD occurrence, and sociodemographic characteristics. An extended Cox model with time-dependent covariates was used to examine this association.ResultsIn total, 207 infants developed ADHD during the 54-month observational period, with an estimated cumulative incidence of 5.56 per 1,000 person-years. The average breastfeeding duration was approximately 2 months. With complementary feeding, rice solid food (HR = 0.73) was found to be a protective factor against developing ADHD. Significantly associated factors for increasing ADHD risk included males, lower family income, low birth weight, maternal weight, advanced maternal age, child gastrointestinal disease, child seizures, maternal heart disease, and paternal diabetes mellitus.ConclusionsComplementary feeding within 6 months is important to protect infants from developing ADHD. The beneficial effect of breastfeeding within 6 months was not observed while controlling for other risk factors. However, owing to the limitation of a smaller number of ADHD cases, further studies should rely on larger observational periods