The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Introduction: Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. Methods: This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. Results: A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Discussion: Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.

Prevalence, cognitive characteristics, and influencing factors of amnestic mild cognitive impairment among older adults residing in an urban community in Chengdu, China.

Objective: Dementia is a significant public health concern, and mild cognitive impairment (MCI) serves as a transitional stage between normal aging and dementia. Among the various types of MCI, amnestic MCI (aMCI) has been identified as having a higher likelihood of progressing to Alzheimer's dimension. However, limited research has been conducted on the prevalence of aMCI in China. Therefore, the objective of this study is to investigate the prevalence of aMCI, examine its cognitive characteristics, and identify associated risk factors. Methods: In this cross-sectional study, we investigated a sample of 368 older adults aged 60 years and above in the urban communities of Chengdu, China. The participants underwent a battery of neuropsychological assessments, including the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), Auditory Verbal Learning Test (AVLT), Wechsler's Logical Memory Task (LMT), Boston Naming Test (BNT) and Trail Making Test Part A (TMT-A). Social information was collected by standard questionnaire. Multiple logistic regression analysis was utilized to screen for the risk and protective factors of aMCI. Results: The data analysis included 309 subjects with normal cognitive function and 59 with aMCI, resulting in a prevalence of 16.0% for aMCI. The average age of participants was 69.06 ± 7.30 years, with 56.0% being females. After controlling for age, gender and education, the Spearman partial correlation coefficient between various cognitive assessments and aMCI ranged from -0.52 for the long-term delayed recall scores in AVLT to 0.19 for the time-usage scores in TMT-A. The results indicated that all cognitive domains, except for naming scores (after semantic cue of BNT) and error quantity (in TMT-A), showed statistically significant associations with aMCI. Furthermore, the multiple logistic regression analysis revealed that older age (OR = 1.044, 95%CI: 1.002~1.087), lower educational level, and diabetes (OR = 2.450, 95%CI: 1.246~4.818) were risk factors of aMCI. Conclusion: This study found a high prevalence of aMCI among older adults in Chengdu, China. Individuals with aMCI exhibited lower cognitive function in memory, language, and executive domains, with long-term delayed recall showing the strongest association. Clinicians should prioritize individuals with verbal learning and memory difficulties, especially long-term delayed recall, in clinical practice.

A Novel HPLC Method for Quality Inspection of NRK Biosynthesized ß-Nicotinamide Mononucleotide.

ß-nicotinamide mononucleotide (NMN) has a good effect on delaying aging, repairing DNA and ameliorating metabolic disease. Biosynthesis with nicotinamide riboside kinase (NRK) takes a large part in NMN manufacture, but there is no available NMN quality standard and analytical method at present. In this study, we developed a specific high-performance liquid chromatography method for the assessment of NMN-related substances, including NMN and its potential impurities from NRK biological production and storage. Forced degradation study was performed under acid, base, oxidative, photolytic and thermal conditions. The separation of related substances was achieved on an Elite Hypersil ODS column using phosphate buffer-methanol gradient at a flow rate of 1.0 mL/min. The detection wavelength was maintained at 260 nm. The resolutions among all related substances were better than 1.5. Significant degradation was observed in basic and thermal conditions. All related substances showed good linearity with a coefficient of determination (R2) higher than 0.999. The accuracy values of all related substances were between 91.2% and 108.6%. Therefore, the validated analytical method is appropriate for inspecting the quality of NMN in its NRK biosynthetic manufacture and storage, thus further helping to unify NMN quality standards and facilitate related studies on NMN.

Hippocampal circAnk3 Deficiency Causes Anxiety-like Behaviors and Social Deficits by Regulating the miR-7080-3p/IQGAP1 Pathway in Mice.

BACKGROUND: Circular RNAs are highly enriched in the synapses of the mammalian brain and play important roles in neurological function by acting as molecular sponges of microRNAs. circAnk3 is derived from the 11th intron of the ankyrin-3 gene, Ank3, a strong genetic risk factor for neuropsychiatric disorders; however, the function of circAnk3 remains elusive. In this study, we investigated the function of circAnk3 and its downstream regulatory network for target genes in the hippocampus of mice. METHODS: The DNA sequence from which circAnk3 is generated was modified using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) technology, and neurobehavioral tests (anxiety and depression-like behaviors, social behaviors) were performed in circAnk3+/- mice. A series of molecular and biochemical assays were used to investigate the function of circAnk3 as a microRNA sponge and its downstream regulatory network for target genes. RESULTS: circAnk3+/- mice exhibited both anxiety-like behaviors and social deficits. circAnk3 was predominantly located in the cytoplasm of neuronal cells and functioned as a miR-7080-3p sponge to regulate the expression of Iqgap1. Inhibition of miR-7080-3p or restoration of Iqgap1 in the hippocampus ameliorated the behavioral deficits of circAnk3+/- mice. Furthermore, circAnk3 deficiency decreased the expression of the NMDA receptor subunit GluN2a and impaired the structural plasticity of dendritic synapses in the hippocampus. CONCLUSIONS: Our results reveal an important role of the circAnk3/miR-7080-3p/IQGAP1 axis in maintaining the structural plasticity of hippocampal synapses. circAnk3 might offer new insights into the involvement of circular RNAs in neuropsychiatric disorders.

Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Differentiating Alzheimer's disease from mild cognitive impairment: a quick screening tool based on machine learning.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterised by cognitive decline, behavioural and psychological symptoms of dementia (BPSD) and impairment of activities of daily living (ADL). Early differentiation of AD from mild cognitive impairment (MCI) is necessary. METHODS: A total of 458 patients newly diagnosed with AD and MCI were included. Eleven batteries were used to evaluate ADL, BPSD and cognitive function (ABC). Machine learning approaches including XGboost, classification and regression tree, Bayes, support vector machines and logical regression were used to build and verify the new tool. RESULTS: The Alzheimer's Disease Assessment Scale (ADAS-cog) word recognition task showed the best importance in judging AD and MCI, followed by correct numbers of auditory verbal learning test delay recall and ADAS-cog orientation. We also provided a selected ABC-Scale that covered ADL, BPSD and cognitive function with an estimated completion time of 18 min. The sensitivity was improved in the four models. CONCLUSION: The quick screen ABC-Scale covers three dimensions of ADL, BPSD and cognitive function with good efficiency in differentiating AD from MCI.

Neurodevelopmental defects in human cortical organoids with N-acetylneuraminic acid synthase mutation.

Biallelic genetic variants in N-acetylneuraminic acid synthase (NANS), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that NANS mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical organoids and notably reduced the proliferation and expansion of neural progenitors. NANS mutation dysregulated neural migration and differentiation, disturbed synapse formation, and weakened neuronal activity. Single-cell RNA sequencing revealed that NANS loss of function markedly altered transcriptional programs involved in neuronal differentiation and ribosomal biogenesis in various neuronal cell types. Similarly, Nans heterozygous mice exhibited impaired cortical neurogenesis and neurobehavioral deficits. Collectively, our findings reveal a crucial role of NANS-mediated endogenous sialic acid biosynthesis in regulating multiple features of human cortical development, thus linking NANS mutation with its clinically relevant neurodevelopmental disorders.

Single cell and bulk transcriptome analysis identified oxidative stress response-related features of Hepatocellular Carcinoma.

Background: Hepatocellular Carcinoma (HCC) is a common lethal digestive system tumor. The oxidative stress mechanism is crucial in the HCC genesis and progression. Methods: Our study analyzed single-cell and bulk sequencing data to compare the microenvironment of non-tumor liver tissues and HCC tissues. Through these analyses, we aimed to investigate the effect of oxidative stress on cells in the HCC microenvironment and identify critical oxidative stress response-related genes that impact the survival of HCC patients. Results: Our results showed increased oxidative stress in HCC tissue compared to non-tumor tissue. Immune cells in the HCC microenvironment exhibited higher oxidative detoxification capacity, and oxidative stress-induced cell death of dendritic cells was attenuated. HCC cells demonstrated enhanced communication with immune cells through the MIF pathway in a highly oxidative hepatoma microenvironment. Meanwhile, using machine learning and Cox regression screening, we identified PRDX1 as a predictor of early occurrence and prognosis in patients with HCC. The expression level of PRDX1 in HCC was related to dysregulated ribosome biogenesis and positively correlated with the expression of immunological checkpoints (PDCD1LG2, CTLA4, TIGIT, LAIR1). High PRDX1 expression in HCC patients correlated with better sensitivity to immunotherapy agents such as sorafenib, IGF-1R inhibitor, and JAK inhibitor. Conclusion: In conclusion, our study unveiled variations in oxidative stress levels between non-tumor liver and HCC tissues. And we identified oxidative stress gene markers associated with hepatocarcinogenesis development, offering novel insights into the oxidative stress response mechanism in HCC.

Methamphetamine exposure drives cell cycle exit and aberrant differentiation in rat hippocampal-derived neurospheres.

Introduction: Methamphetamine (METH) abuse by pregnant drug addicts causes toxic effects on fetal neurodevelopment; however, the mechanism underlying such effect of METH is poorly understood. Methods: In the present study, we applied three-dimensional (3D) neurospheres derived from the embryonic rat hippocampal tissue to investigate the effect of METH on neurodevelopment. Through the combination of whole genome transcriptional analyses, the involved cell signalings were identified and investigated. Results: We found that METH treatment for 24 h significantly and concentration-dependently reduced the size of neurospheres. Analyses of genome-wide transcriptomic profiles found that those down-regulated differentially expressed genes (DEGs) upon METH exposure were remarkably enriched in the cell cycle progression. By measuring the cell cycle and the expression of cell cycle-related checkpoint proteins, we found that METH exposure significantly elevated the percentage of G0/G1 phase and decreased the levels of the proteins involved in the G1/S transition, indicating G0/G1 cell cycle arrest. Furthermore, during the early neurodevelopment stage of neurospheres, METH caused aberrant cell differentiation both in the neurons and astrocytes, and attenuated migration ability of neurospheres accompanied by increased oxidative stress and apoptosis. Conclusion: Our findings reveal that METH induces an aberrant cell cycle arrest and neuronal differentiation, impairing the coordination of migration and differentiation of neurospheres.

Strain-level structure of gut microbiome showed potential association with cognitive function in major depressive disorder: A pilot study.

BACKGROUND: Although the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether gut microbiota affects cognitive function in patients with MDD. In this study, we explored the association between gut microbiota and cognitive function in MDD and its possible mechanisms. METHODS: We enrolled 57 patients with MDD and 30 healthy controls (HCs) and used 16S rRNA gene sequencing analysis and shotgun metagenomic sequencing analysis to determine gut microbial composition. RESULTS: The richness and diversity of gut microbiota in patients with MDD were the same as those in HCs, but there were differences in the abundance of Bifidobacterium and Blautia. Compared with HCs, two strains (bin_32 and bin_55) were significantly increased, and one strain (bin_31) was significantly decreased in patients with MDD based on the strain-level meta-analysis. Time to complete the Stroop-C had significant negative correlations with bin_31 and bin_32. Bin_55 had significant negative correlations with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 s but significant positive correlations with correct answers in 120 s on the Stroop-CW. LIMITATIONS: This study only tested the cognitive function of MDD in a small sample, which may have caused some bias. CONCLUSIONS: Based on our strain-level analysis, we found that gut microbiota may be associated with the pathogenesis of MDD and may have potential effects on cognitive function.

Prognostic Role of Unfolded Protein Response-Related Genes in Hepatocellular Carcinoma.

AIMS: To reveal the prognostic role of unfolded protein response (UPR) -related genes in hepatocellular carcinoma (HCC). BACKGROUND: Hepatocellular carcinoma is a genetically heterogeneous tumor, and the prediction of its prognosis remains a challenge. Studies elucidating the molecular mechanisms of UPR have rapidly increased. However, the UPR molecular subtype characteristics of the related genes in HCC progression have yet to be thoroughly studied. OBJECTIVE: Conducting a comprehensive assessment of the prognostic signature of genes related to the UPR in patients with HCC can advance our understanding of the cellular processes contributing to the progression of HCC and offer innovative strategies in precise therapy. METHODS: Based on the gene expression profiles associated with UPR in HCC, we explored the molecular subtypes mediated by UPR-related genes and constructed a UPR-related genes signature that could precisely predict the prognosis for HCC. RESULTS: Using microarray data of HCC patients, differentially expressed UPR-related genes (DEGs) were discovered in malignancies and normal tissues. The HCC was classified into two molecular subtypes by the NMF algorithm based on DEGs modification of the UPR. Moreover, we developed a UPR-related model for predicting HCC patients' prognosis. The robustness of the UPR- related model was confirmed in external validation. Moreover, we analyzed immune responses in different risk groups. Analysis of immune functions revealed that Treg, Macrophages, aDCs, and MHC class-I were significantly up-regulated in high-risk HCC. At the same time, cytolytic activity and type I and II INF response were higher in a low-risk subgroup. CONCLUSION: This study identified two UPR molecular subtypes of HCC and developed a ten-gene HCC prognostic signature model (EXTL3, PPP2R5B, ZBTB17, CCT3, CCT4, CCT5, GRPEL2, HSP90AA1, PDRG1, and STC2), which can robustly forecast the progression of HCC.

A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis.

Purpose: This study intends to uncover a more thorough knowledge structure, research hotspots, and future trends in the field by presenting an overview of the relationship between stroke and gut microbiota in the past two decades. Method: Studies on stroke and gut microbiota correlations published between 1st January 2002 and 31st December 2021 were retrieved from the Web of Science Core Collection and then visualized and scientometrically analyzed using CiteSpace V. Results: A total of 660 papers were included in the study, among which the United States, the United Kingdom, and Germany were the leading research centers. Cleveland Clinic, Southern Medical University, and Chinese Academy of Science were the top three institutions. The NATURE was the most frequently co-cited journal. STANLEY L HAZEN was the most published author, and Tang WHW was the most cited one. The co-occurrence analysis revealed eight clusters (i.e., brain-gut microbiota axis, fecal microbiome transplantation, gut microbiota, hypertension, TMAO, ischemic stroke, neuroinflammation, atopobiosis). "gut microbiota," "Escherichia coli," "cardiovascular disease," "risk," "disease," "ischemic stroke," "stroke," "metabolism," "inflammation," and "phosphatidylcholine" were the most recent keyword explosions. Conclusion: Findings suggest that in the next 10 years, the number of publications produced annually may increase significantly. Future research trends tend to concentrate on the mechanisms of stroke and gut microbiota, with the inflammation and immunological mechanisms, TMAO, and fecal transplantation as hotspots. And the relationship between these mechanisms and a particular cardiovascular illness may also be a future research trend.

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder.

Background: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD. Methods: A total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein-protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway. Results: Our analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress. Conclusion: These results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD.

Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons.

The expression of linear DNA sequence is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neurons is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops, and were further validated for changed expression. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

Cellular senescence-related gene signature as a valuable predictor of prognosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a lethal tumor. Its prognosis prediction remains a challenge. Meanwhile, cellular senescence, one of the hallmarks of cancer, and its related prognostic genes signature can provide critical information for clinical decision-making. METHOD: Using bulk RNA sequencing and microarray data of HCC samples, we established a senescence score model via multi-machine learning algorithms to predict the prognosis of HCC. Single-cell and pseudo-time trajectory analyses were used to explore the hub genes of the senescence score model in HCC sample differentiation. RESULT: A machine learning model based on cellular senescence gene expression profiles was identified in predicting HCC prognosis. The feasibility and accuracy of the senescence score model were confirmed in external validation and comparison with other models. Moreover, we analyzed the immune response, immune checkpoints, and sensitivity to immunotherapy drugs of HCC patients in different prognostic risk groups. Pseudo-time analyses identified four hub genes in HCC progression, including CDCA8, CENPA, SPC25, and TTK, and indicated related cellular senescence. CONCLUSIONS: This study identified a prognostic model of HCC by cellular senescence-related gene expression and insight into novel potential targeted therapies.

Interactions Between Antidepressants and Intestinal Microbiota.

The microbiota-gut-brain axis has been shown to influence human health and diseases, including depression. The interactions between drugs and intestinal microbiota are complex and highly relevant to treat diseases. Studies have shown an interaction between antidepressants and intestinal microbiota. Antidepressants may alter the abundance and composition of intestinal microbiota, which are closely related to the treatment outcomes of depression. Intestinal microbiota can influence the metabolism of antidepressants to change their availability (e.g., tryptophan can be metabolized to kynurenine by intestinal microbiota) and regulate their absorption by affecting intestinal permeability. In addition, the permeability of the blood-brain barrier can be altered by intestinal microbiota, influencing antidepressants to reach the central nervous system. Bioaccumulation is also a type of drug-microbiota interaction, which means bacteria accumulate drugs without biotransformation. These findings imply that it is important to consider intestinal microbiota when evaluating antidepressant therapy regimens and that intestinal microbiota can be a potential target for depression treatment.

Adverse events of tumor necrosis factor alpha inhibitors for the treatment of ankylosing spondylitis: A meta-analysis of randomized, placebo-controlled trials.

Objective: Tumor necrosis factor alpha inhibitors (TNFi) have shown substantial efficacy in alleviating and treating ankylosing spondylitis (AS). However, the heightened interest is accompanied by concerns over adverse events. In this meta-analysis, we analyzed both serious and common adverse events in patients treated with tumor necrosis factor alpha inhibitors compared with those in the placebo group. Methods: We searched for clinical trials in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP Data. Studies were selected based on strict inclusion and exclusion criteria. Only randomized, placebo-controlled trials were included in the final analysis. RevMan 5.4 software was used for performing meta-analyses. Results: A total of 18 randomized controlled trials recruiting 3,564 patients with ankylosing spondylitis were included, with overall moderate to high methodological quality. Compared with the placebo group, the incidences showed no difference and were only slightly increased numerically for serious adverse events, serious infections, upper respiratory tract infection, and malignancies in patients treated with tumor necrosis factor alpha inhibitors. However, tumor necrosis factor alpha inhibitor treatment significantly increased the incidence of overall adverse events, nasopharyngitis, headache, and injection-site reactions in ankylosing spondylitis patients when compared with placebo. Conclusion: The available data indicated that ankylosing spondylitis patients who received tumor necrosis factor alpha inhibitors had no significantly increased risks of serious adverse events when compared with the placebo group. However, tumor necrosis factor alpha inhibitors significantly increased the incidence rate of common adverse events, including nasopharyngitis, headache, and injection-site reactions. Large-scale and long-term follow-up clinical trials are still necessary to further investigate the safety of tumor necrosis factor alpha inhibitors in ankylosing spondylitis treatment.

Liver Protection of a Low-Polarity Fraction from Ficus pandurata Hance, Prepared by Supercritical CO2 Fluid Extraction, on CCl4-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Ferroptosis Mediated by Strengthened Antioxidation.

Ficus pandurata Hance (FPH) is a Chinese herbal medicine widely used for health care. This study was designed to investigate the alleviation efficacy of the low-polarity ingredients of FPH (FPHLP), prepared by supercritical CO2 fluid extraction technology, against CCl4-induced acute liver injury (ALI) in mice and uncover its underlying mechanism. The results showed that FPHLP had a good antioxidative effect determined by the DPPH free radical scavenging activity test and T-AOC assay. The in vivo study showed that FPHLP dose-dependently protected against liver damage via detection of ALT, AST, and LDH levels and changes in liver histopathology. The antioxidative stress properties of FPHLP suppressed ALI by increasing levels of GSH, Nrf2, HO-1, and Trx-1 and reducing levels of ROS and MDA and the expression of Keap1. FPHLP significantly reduced the level of Fe2+ and expression of TfR1, xCT/SLC7A11, and Bcl2, while increasing the expression of GPX4, FTH1, cleaved PARP, Bax, and cleaved caspase 3. The results demonstrated that FPHLP protected mouse liver from injury induced by CCl4 via suppression of apoptosis and ferroptosis. This study suggests that FPHLP can be used for liver damage protection in humans, which strongly supports its traditional use as a herbal medicine.

Identification of potential ferroptosis hub genes in acute-on-chronic liver failure based on bioinformatics analysis and experimental verification.

BACKGROUND: Ferroptosis plays an important role in the development of acute-on-chronic liver failure (ACLF). The present project aimed to identify and validate the potential ferroptosis-related genes in ACLF by bioinformatics analysis and experimental verification. MATERIALS AND METHODS: The GSE139602 dataset was obtained from the Gene Expression Omnibus database and intersected with ferroptosis genes. Ferroptosis-related differentially expressed genes (DEGs) between the ACLF tissue and healthy group were analyzed using bioinformatics methods. Analysis of enrichment, protein‒protein interactions, and hub genes was conducted. Potential drugs targeting these hub genes were retrieved from the DrugBank database. Finally, we performed real-time quantitative PCR (RT-qPCR) to validate the expression of the hub genes. RESULTS: A total of 35 ferroptosis-related DEGs were screened, which were enriched in the biosynthesis of amino acids, peroxisomes, fluid shear stress and atherosclerosis. PPI network analysis indicated five ferroptosis-related hub genes, namely, HRAS, TXNRD1, NQO1, PSAT1, and SQSTM1. The experimental validation indicated that the expression levels of HRAS, TXNRD1, NQO1, and SQSTM1 were lower, while the expression level of PSAT1 was higher in ACLF model rats than in healthy rats. CONCLUSIONS: Our findings reveal that PSAT1, TXNRD1, HRAS, SQSTM1 and NQO1 may affect the development of ACLF by regulating ferroptotic events. These results provide a valid reference for potential mechanisms and identification in ACLF.