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1.
PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.
Hu, X, Zhang, Z, Liu, C, Li, M, Liu, Y, Cheng, A, Yu, Q, Guo, H, Zou, Y, Zhou, L, et al
International journal of stroke : official journal of the International Stroke Society. 2024;:17474930241270447
Abstract
RATIONALE Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. AIM AND HYPOTHESIS To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. SAMPLE SIZE ESTIMATES With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. METHODS AND DESIGN This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. STUDY OUTCOMES The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. DISCUSSION This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. TRIAL REGISTRATION NUMBER ChiCTR2300068868; https://www.chictr.org.cn/.
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2.
Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.
Cornelissen, MEB, Bloemsma, LD, Vaes, AW, Baalbaki, N, Deng, Q, Beijers, RJHCG, Noij, LCE, Houweling, L, Bazdar, S, Spruit, MA, et al
Journal of translational medicine. 2024;(1):191
Abstract
BACKGROUND In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort. METHODS In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found. RESULTS According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients. CONCLUSIONS This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort.
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3.
Modulation of growth, microcystin production, and algal-bacterial interactions of the bloom-forming algae Microcystis aeruginosa by a novel bacterium recovered from its phycosphere.
Xiao, Y, Du, M, Deng, Y, Deng, Q, Wang, X, Yang, Y, Zhang, B, Zhang, YQ
Frontiers in microbiology. 2024;:1295696
Abstract
Harmful algal blooms (HABs) in natural waters are of escalating global concern due to their detrimental impact on environmental health. Emerging evidence indicates that algae-bacteria symbionts can affect HAB features, though much about this interplay remains largely unexplored. The current study isolated a new species of Mucilaginibacter (type strain JXJ CY 39T) from culture biomass of the bloom-causing Microcystis aeruginosa FACHB-905 (Maf) from Lake Dianchi, China. Strain JXJ CY 39T was an aerobic, Gram-stain-negative rod bacterium that grew at 5-38°C, pH 4.0-11.0, and 0-3.0% NaCl. Taxonomic evaluation proposed a new species, with Mucilaginibacter lacusdianchii sp. nov., as the species epithet. Experimental results revealed that strain JXJ CY 39T spurred the growth of Maf by supplying soluble phosphorus and nitrogen during cultivation, despite the unavailability of soluble phosphorus and nitrogen. Additionally, by producing the plant hormone indole-3-acetate, strain JXJ CY 39T possibly impacted Maf's functionality. Results from co-culture experiments with other strains from Maf biomass showed possible effects of strain JXJ CY 39T on the relationship between Maf and other cohabiting bacteria, as well as microcystin toxin production characteristics. Although Maf could foster the growth of strain JXJ CY 39T by supplying organic carbon, the strain's growth could be regulated via specific chemical compounds based on antibiotic assays. Community composition analysis disclosed that this Mucilaginibacter strain positively affected Maf's growth and modified densities and types of bacteria linked to Maf. Overall, these results suggest that the interactions between important HAB-causing organisms and their attached bacteria are complex, dynamic, and may influence the growth characteristics of algae.
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4.
Aβ-binding with alcohol dehydrogenase drives Alzheimer's disease pathogenesis: A review.
Ye, Z, Liu, Y, Jin, X, Wu, Y, Zhao, H, Gao, T, Deng, Q, Cheng, J, Lin, J, Tong, Z
International journal of biological macromolecules. 2024;(Pt 2):130580
Abstract
Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aβ) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aβ-derived formaldehyde (FA) and FA-induced Aβ aggregation in the onset course of AD. Document evidence has shown that Aβ can bind with alcohol dehydrogenase (ADH) to form the complex of Aβ/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H2O2 and FA promotes Aβ self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.
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5.
BVES-AS1 suppresses the colorectal cancer progression via the miR-1269a/b-SVEP1-PI3K/AKT axis.
Yang, J, Deng, Q, Chen, Z, Chen, Y, Fu, Z
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024
Abstract
BACKGROUND Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive. OBJECTIVES The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC. MATERIAL AND METHODS The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1. RESULTS The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway. CONCLUSIONS These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.
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6.
Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial.
Xie, P, Shao, T, Long, Y, Xie, W, Liu, Y, Yang, Y, Huang, Y, Wu, R, Deng, Q, Tang, H
Lipids in health and disease. 2024;(1):225
Abstract
BACKGROUND Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. METHODS Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. RESULTS Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. CONCLUSIONS These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. TRIAL REGISTRATION ClinicalTrials.gov NCT03451734.
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7.
Identification of Auxiliary Organellar Targeting Signals for Plant Peroxisomes Using Bioinformatic Analysis of Large Protein Sequence Datasets Followed by Experimental Validation.
Deng, Q, Jiang, H, Hu, J, Pan, R
Methods in molecular biology (Clifton, N.J.). 2024;:265-275
Abstract
Eukaryotic cells are compartmentalized by membrane-bounded organelles to ensure that specific biochemical reactions and cellular functions occur in a spatially restricted manner. The subcellular localization of proteins is largely determined by their intrinsic targeting signals, which are mainly constituted by short peptides. A complete organelle targeting signal may contain a core signal (CoreS) as well as auxiliary signals (AuxiS). However, the AuxiS is often not as well characterized as the CoreS. Peroxisomes house many key steps in photorespiration, besides other crucial functions in plants. Peroxisome targeting signal type 1 (PTS1), which is carried by most peroxisome matrix proteins, was initially recognized as a C-terminal tripeptide with a "canonical" consensus of [S/A]-[K/R]-[L/M]. Many studies have shown the existence of auxiliary targeting signals upstream of PTS1, but systematic characterizations are lacking. Here, we designed an analytical strategy to characterize the auxiliary targeting signals for plant peroxisomes using large datasets and statistics followed by experimental validations. This method may also be applied to deciphering the auxiliary targeting signals for other organelles, whose organellar targeting depends on a core peptide with assistance from a nearby auxiliary signal.
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8.
Association Between Vitamin D Level and Clinical Outcomes of Assisted Reproductive Treatment: A Systematic Review and Dose-Response Meta-Analysis.
Xu, C, An, X, Tang, X, Yang, Y, Deng, Q, Kong, Q, Hu, Y, Yuan, D
Reproductive sciences (Thousand Oaks, Calif.). 2024
Abstract
The investigation about association between vitamin D level and clinical outcomes of assisted reproductive treatment showed various outcomes. This study aimed to review the correlation between vitamin D and outcomes of assisted reproductive treatment. The search was registered on the PROSPERO database (CRD42023458040). PubMed, Embase, Medline, ClinicalTrials.gov, and Cochrane databases were searched up to July 2023. Twenty-three observational studies were selected for meta-analysis. Comparing groups with deficient and 'insufficient + sufficient' vitamin D level, meta-analysis showed positive correlation between clinical pregnancy rate and vitamin D (OR 0.81, 95%CI: 0.70, 0.95, P = 0.0001). Comparing groups with 'deficient + insufficient' and sufficient vitamin D level, meta-analysis showed positive correlation between vitamin D and clinical pregnancy rate (OR 0.71, 95%CI: 0.55, 0.91, P = 0.006), vitamin D and live birth rate (OR 0.69, 95%CI: 0.54, 0.89, P = 0.003). Subgroup analysis did not show the source of high heterogeneity. No correlation was found in biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. In dose-response meta-analysis, a nonlinear association was found between vitamin D levels and outcomes when levels are below approximately 24 ng/L. The study shows that vitamin D level is associated with clinical pregnancy rate and live birth rate. Low vitamin D level does not influence biochemical pregnancy rate, ongoing pregnancy rate, miscarriage rate and implantation rate. Furthermore, 24 ng/L may be a possible threshold of vitamin D concentration in assisted reproduction therapy.
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9.
One case of congenital myopathy caused by new mutation of RYR1 gene and literature review.
Deng, Q, Ding, Z, Fu, Q, Lin, M
Gene. 2023;:147493
Abstract
To report a case of congenital myopathy caused by RYR1 gene complex heterozygous mutation and analyze the pathogenicity of the mutation. Method The clinical manifestation, laboratory examination, imaging findings, muscle pathology and gene test results of a child with congenital myopathy were analyzed retrospectively. Combined with literature review, it is analyzed and discussed. Result The child, female, was admitted to hospital because of "dyspnea for 22 min after asphyxia resuscitation". The main manifestations are low muscle tension, the original reflex cannot be drawn out, the trunk and proximal muscles are weak, and the tendon reflex is not drawn out. The pathological signs were negative. The electrolyte of blood liver and kidney function, blood thyroid and blood ammonia were not abnormal, and creatine kinase increased temporarily. Electromyography suggests myogenic damage. Whole exome sequencing showed that there was a new compound heterozygous variation in RYR1 gene c.14427_ 14429del/c.14138C＞T.Western blot showed that the expression of RYR1 protein in patients was significantly lower than that in normal controls. Conclusion The compound heterozygous variation of RYR1 gene c.14427 was reported for the first time in China_ 14429del/c.14138c > t is the pathogenic gene of the child. The new discovery of RYR1 gene spectrum was revealed, which expanded the RYR1 gene spectrum.
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10.
Mitochondrial phosphoenolpyruvate carboxykinase inhibits kidney renal clear cell carcinoma malignant progression, leading to cell energy metabolism imbalance.
Chen, Y, Wang, Z, Deng, Q, Chen, Y, Liang, H
American journal of cancer research. 2023;(3):886-899
Abstract
Mitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a key gluconeogenesis enzyme. Its differential expression is related to kidney renal clear cell carcinoma (KIRC) malignancy, possibly by influencing energy metabolism. Therefore, it is possible that PKC2 plays a significant part in the emergence and progression of KIRC. To systematically and comprehensively identify the significance of PCK2 in KIRC, we further studied PCK2 in terms of its relationship to clinical features and various clinical subgroups' prognoses. Moreover, we verified the effect of PCK2 and KIRC cells using experimental methods. PCR and western blotting analyses confirmed PCK2 expression in KIRC cell lines and tissues. As a cell model, we constructed cells that overexpress PCK2. Proliferation was detected by EdU experiments. Scratch tests and transwell assays were used, respectively, to analyze cell migration and invasion. Mass spectrometry detected energy metabolite expression in KIRC cells. The findings revealed that KIRC patients with lower levels of PCK2 expression exhibited shorter progression-free intervals, shorter disease-specific survival, and shorter overall survival. The experimental results showed that compared with 293t, PCK2 was downregulated in three KIRC lines (OSRC-2, 786-O, and A498). Relative to surrounding tissues, PCK2 was downregulated in KIRC. PCK2 overexpression inhibited KIRC cell proliferation, migration, and invasion and upregulated energy metabolite expression. Mass spectrometry revealed that thiamine pyrophosphate, cyclic AMP, beta-D-fructose 6-phosphate, lactate, flavin mononucleotide, NAD, NADP, and D-glucose 6-phosphate were upregulated. PCK2 has the potential to serve as both a diagnostic and prognostic molecular biomarker for KIRC, as well as an independent prognostic risk factor for KIRC. It is hoped that PCK2 will emerge as a therapeutic target for KIRC.
