Peroxiredoxin 1 modulates oxidative stress resistance and cell apoptosis through stemness in liver cancer under non-thermal plasma treatment.

The role of peroxiredoxin 1 (PRDX1), a crucial enzyme that reduces reactive oxygen and nitrogen species levels in HepG2 human hepatocellular carcinoma (HCC) cells, in the regulation of HCC cell stemness under oxidative stress and the underlying mechanisms remain largely unexplored. Here, we investigated the therapeutic potential of non-thermal plasma in targeting cancer stem cells (CSCs) in HCC, focusing on the mechanisms of resistance to oxidative stress and the role of PRDX1. By simulating oxidative stress conditions using the plasma-activated medium, we found that a reduction in PRDX1 levels resulted in a considerable increase in HepG2 cell apoptosis, suggesting that PRDX1 plays a key role in oxidative stress defense mechanisms in CSCs. Furthermore, we found that HepG2 cells had higher spheroid formation capability and increased levels of stem cell markers (CD133, c-Myc, and OCT-4), indicating strong stemness. Interestingly, PRDX1 expression was notably higher in HepG2 cells than in other HCC cell types such as Hep3B and Huh7 cells, whereas the expression levels of other PRDX family proteins (PRDX 2-6) were relatively consistent. The inhibition of PRDX1 expression and peroxidase activity by conoidin A resulted in markedly reduced stemness traits and increased cell death rate. Furthermore, in a xenograft mouse model, PRDX1 downregulation considerably inhibited the formation of solid tumors after plasma-activated medium (PAM) treatment. These findings underscore the critical role of PRDX 1 in regulating stemness and apoptosis in HCC cells under oxidative stress, highlighting PRDX1 as a promising therapeutic target for NTP-based treatment in HCC.

Peroxiredoxin I and II as novel therapeutic molecular targets in cervical cancer treatment through regulation of endoplasmic reticulum stress induced by bleomycin.

Cervical cancer, significantly affecting women worldwide, often involves treatment with bleomycin, an anticancer agent targeting breast, ovarian, and cervical cancers by generating reactive oxygen species (ROS) to induce cancer cell death. The Peroxiredoxin (PRDX) family, particularly PRDX1 and 2, plays a vital role in maintaining cellular balance by scavenging ROS, thus mitigating the damaging effects of bleomycin-induced mitochondrial and cellular oxidative stress. This process reduces endoplasmic reticulum (ER) stress and prevents cell apoptosis. However, reducing PRDX1 and 2 levels reverses their protective effect, increasing apoptosis. This research highlights the importance of PRDX1 and 2 in cervical cancer treatments with bleomycin, showing their potential to enhance treatment efficacy by managing ROS and ER stress and suggesting a therapeutic strategy for improving outcomes in cervical cancer treatment.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

Hispidin Increases Cell Apoptosis and Ferroptosis in Prostate Cancer Cells Through Phosphatidylinositol-3-Kinase and Mitogen-activated Protein Kinase Signaling Pathway.

BACKGROUND/AIM: Chemotherapy is mainly used in the clinical treatment of prostate cancer. Different anticancer mechanisms can induce cell death in various cancers. Reactive oxygen species (ROS) play crucial roles in cell proliferation, differentiation, apoptosis, and signal transduction. It is widely accepted that ROS accumulation is closely related to chemical drug-induced cancer cell death. MATERIALS AND METHODS: We utilized the MTT assay to detect changes in cell proliferation. Additionally, colony formation and wound healing assay were conducted to investigate the effect of hispidin on cell colony formation and migration ability. Fluorescence microscopy was used to detect intracellular and mitochondrial ROS levels, while western blot was used for detection of cell apoptosis. RESULTS: Hispidin treatment significantly decreased viability of PC3 and DU145 cancer cells but exhibited no cytotoxicity in WPMY-1 cells. Furthermore, hispidin treatment inhibited cell migration and colony formation and triggered cellular and mitochondrial ROS accumulation, leading to mitochondrial dysfunction and mitochondrion-dependent apoptosis. Moreover, hispidin treatment induced ferroptosis in PC3 cells. Scavenging of ROS with N-acetyl cysteine significantly inhibited hispidin-induced apoptosis by altering the expression of apoptosis-related proteins, such as cleaved caspase-3, 9, Bax, and Bcl2. Furthermore, hispidin treatment dramatically up-regulated MAPK (involving p38, ERK, and JNK proteins) and NF-kB signaling pathways while down-regulating AKT phosphorylation. Hispidin treatment also inhibited ferroptosis signaling pathways (involving P53, Nrf-2, and HO-1 proteins) in PC3 cells. In addition, inhibiting these signaling pathways via treatment with specific inhibitors significantly reversed hispidin-induced apoptosis, cellular ROS levels, mitochondrial dysfunction, and ferroptosis. CONCLUSION: Hispidin may represent a potential candidate for treating prostate cancer.

Exploring the role of Prx II in mitigating endoplasmic reticulum stress and mitochondrial dysfunction in neurodegeneration.

BACKGROUND: Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration. METHODS: We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs. RESULTS: Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca2+ homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases. CONCLUSIONS: This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.

Argon non-thermal plasma treatment promotes the development of rice (Oryza sativa L.) in saline alkali environments.

Soil salinization leads to a reduction in arable land area, which seriously endangers food security. Developing saline-alkali land has become a key measure to address the contradiction between population growth and limited arable land. Rice is the most important global food crop, feeding half of the world's population and making it a suitable choice for planting on saline-alkali lands. The traditional salt-alkali improvement method has several drawbacks. Currently, non-thermal plasma (NTP) technology is being increasingly applied in agriculture. However, there are few reports on the cultivation of salt/alkali-tolerant rice. Under alkaline stress, argon NTP treatment significantly increased the germination rate of Longdao 5 (LD5) rice seeds. In addition, at 15 kV and 120 s, NTP treatment significantly increased the activity of antioxidant enzymes such as catalase and SOD. NTP treatment induced changes in genes related to salt-alkali stress in rice seedlings, such as chitinase and xylanase inhibitor proteins, which increased the tolerance of the seeds to salt-alkali stress. This experiment has expanded the application scope of NTP in agriculture, providing a more cost-effective, less harmful, and faster method for developing salt-alkali-tolerant rice and laying a theoretical foundation for cultivating NTP-enhanced salt-alkali-tolerant rice.

Cisplatin Induces Kidney Cell Death via ROS-dependent MAPK Signaling Pathways by Targeting Peroxiredoxin I and II in African Green Monkey (Chlorocebus aethiops sabaeus) Kidney Cells.

BACKGROUND/AIM: Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDP-induced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS). MATERIALS AND METHODS: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed. RESULTS: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis. CONCLUSION: The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.

Identification and diagnostic potential of serum microRNAs as biomarkers for early detection of Alzheimer's disease.

This study aimed to investigate the differential expression of serum microRNAs in cognitive normal subjects (NC), patients with mild cognitive impairment (MCI), and patients with Alzheimer's disease (AD), with the objective of identifying potential diagnostic biomarkers. A total of 320 clinical samples, including 32 MCI patients, 288 AD patients, and 288 healthy controls, were collected following international standards. The expression of microRNAs in serum was analyzed using the Agilent human microRNA oligonucleotide microarray, and bioinformatics methods were employed to predict target genes and their involvement in AD-related pathways. Among the 122 microRNAs screened, five microRNAs (hsa-miR-208a-5p, hsa-miR-125b-1-3p, hsa-miR-3194-3p, hsa-miR-4652-5p, and hsa-miR-4419a) exhibited differential expression and met quality control standards. Bioinformatics analysis revealed that the target genes of these microRNAs were involved in multiple AD-related pathways, which changed with disease progression. These findings demonstrate significant differences in serum microRNA expression between NC, MCI, and AD patients. Three microRNAs were identified as potential candidates for the development of diagnostic models for MCI and AD. The results highlight the crucial role of microRNAs in the pathogenesis of AD and provide a foundation for the development of novel therapeutic strategies and personalized treatment approaches for AD. This study contributes to the understanding of AD at the molecular level and offers potential avenues for early diagnosis and intervention in AD patients.

Peroxiredoxin II regulates exosome secretion from dermal mesenchymal stem cells through the ISGylation signaling pathway.

BACKGROUND: Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. RESULTS: In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. CONCLUSIONS: Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. Video Abstract.

RNA-Seq-Based Transcriptome Analysis of Nitric Oxide Scavenging Response in Neurospora crassa.

While the biological role of naturally occurring nitric oxide (NO) in filamentous fungi has been uncovered, the underlying molecular regulatory networks remain unclear. In this study, we conducted an analysis of transcriptome profiles to investigate the initial stages of understanding these NO regulatory networks in Neurospora crassa, a well-established model filamentous fungus. Utilizing RNA sequencing, differential gene expression screening, and various functional analyses, our findings revealed that the removal of intracellular NO resulted in the differential transcription of 424 genes. Notably, the majority of these differentially expressed genes were functionally linked to processes associated with carbohydrate and amino acid metabolism. Furthermore, our analysis highlighted the prevalence of four specific protein domains (zinc finger C2H2, PLCYc, PLCXc, and SH3) in the encoded proteins of these differentially expressed genes. Through protein-protein interaction network analysis, we identified eight hub genes with substantial interaction connectivity, with mss-4 and gel-3 emerging as possibly major responsive genes during NO scavenging, particularly influencing vegetative growth. Additionally, our study unveiled that NO scavenging led to the inhibition of gene transcription related to a protein complex associated with ribosome biogenesis. Overall, our investigation suggests that endogenously produced NO in N. crassa likely governs the transcription of genes responsible for protein complexes involved in carbohydrate and amino acid metabolism, as well as ribosomal biogenesis, ultimately impacting the growth and development of hyphae.

Regulation of anoikis by extrinsic death receptor pathways.

Metastatic cancer cells can develop anoikis resistance in the absence of substrate attachment and survive to fight tumors. Anoikis is mediated by endogenous mitochondria-dependent and exogenous death receptor pathways, and studies have shown that caspase-8-dependent external pathways appear to be more important than the activity of the intrinsic pathways. This paper reviews the regulation of anoikis by external pathways mediated by death receptors. Different death receptors bind to different ligands to activate downstream caspases. The possible mechanisms of Fas-associated death domain (FADD) recruitment by Fas and TNF receptor 1 associated-death domain (TRADD) recruitment by tumor necrosis factor receptor 1 (TNFR1), and DR4- and DR5-associated FADD to induce downstream caspase activation and regulate anoikis were reviewed. This review highlights the possible mechanism of the death receptor pathway mediation of anoikis and provides new insights and research directions for studying tumor metastasis mechanisms. Video Abstract.

Role of NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases.

BACKGROUND: Neurodegenerative diseases are a common group of neurological disorders characterized by progressive loss of neuronal structure and function leading to cognitive impairment. Recent studies have shown that neuronal pyroptosis mediated by the NLRP3 inflammasome plays a crucial role in the pathogenesis of neurodegenerative diseases. OBJECTIVE AND METHOD: The NLRP3 inflammasome is a multiprotein complex that, when activated within cells, triggers an inflammatory response, ultimately leading to pyroptotic cell death of neurons. Pyroptosis is a typical pro-inflammatory programmed cell death process occurring downstream of NLRP3 inflammasome activation, characterized by the formation of pores on the cell membrane by the GSDMD protein, leading to cell lysis and the release of inflammatory factors. It has been found that NLRP3 inflammasome-mediated neuronal pyroptosis is closely associated with the development of various neurodegenerative diseases, such as Alzheimer's disease, traumatic brain injury, and Parkinson's disease. Therefore, inhibiting NLRP3 inflammasome activation and attenuating neuronal pyroptosis could potentially serve as novel strategies for the treatment of neurodegenerative diseases. RESULTS: The aim of this review is to explore the role of NLRP3 activation-mediated neuronal pyroptosis and neuroinflammation in neurodegenerative diseases. Firstly, we extensively discuss the relationship between NLRP3 inflammasome-mediated neuronal pyroptosis and neuroinflammation in various neurodegenerative diseases. Subsequently, we further explore the mechanisms driving NLRP3 activation and assembly, as well as the post-translational modifications regulating NLRP3 inflammasome activation. CONCLUSION: Understanding these mechanisms will contribute to a deeper understanding of the link between neuronal pyroptosis and neurodegenerative diseases, and hold significant implications for the treatment and prevention of neurodegenerative diseases.

Bioinformatics Analysis of Novel Targets for Treating Cervical Cancer by Immunotherapy Based on Immune Escape.

BACKGROUND/AIM: Cervical cancer (CC) is a high-risk disease in women, and advanced CC can be difficult to treat even with surgery, radiotherapy, and chemotherapy. Hence, developing more effective treatment methods is imperative. Cancer cells undergo a renewal process to escape immune surveillance and then attack the immune system. However, the underlying mechanisms remain unclear. Currently, only one immunotherapy drug has been approved by the Food and Drug Administration for CC, thus indicating the need for and importance of identifying key targets related to immunotherapy. MATERIALS AND METHODS: Data on CC and normal cervical tissue samples were downloaded from the National Center for Biotechnology Information database. Transcriptome Analysis Console software was used to analyze differentially expressed genes (DEGs) in two sample groups. These DEGs were uploaded to the DAVID online analysis platform to analyze biological processes for which they were enriched. Finally, Cytoscape was used to map protein interaction and hub gene analyses. RESULTS: A total of 165 up-regulated and 362 down-regulated genes were identified. Among them, 13 hub genes were analyzed in a protein-protein interaction network using the Cytoscape software. The genes were screened out based on the betweenness centrality value and average degree of all nodes. The hub genes were as follows: ANXA1, APOE, AR, C1QC, CALML5, CD47, CTSZ, HSP90AA1, HSP90B1, NOD2, THY1, TLR4, and VIM. We identified the following 12 microRNAs (miRNAs) that target the hub genes: hsa-miR-2110, hsa-miR-92a-2-5p, hsa-miR-520d-5p, hsa-miR-4514, hsa-miR-4692, hsa-miR-499b-5p, hsa-miR-5011-5p, hsa-miR-6847-5p, hsa-miR-8054, hsa-miR-642a-5p, hsa-miR-940, and hsa-miR-6893-5p. CONCLUSION: Using bioinformatics, we identified potential miRNAs that regulated the cancer-related genes and long noncoding RNAs (lncRNAs) that regulated these miRNAs. We further elucidated the mutual regulation of mRNAs, miRNAs, and lncRNAs involved in CC occurrence and development. These findings may have major applications in the treatment of CC by immunotherapy and the development of drugs against CC.

Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3ß signaling axis.

Psoriasis is a chronic, systemic immune-mediated disease caused by abnormal proliferation, decreased apoptosis, and over-differentiation of keratinocytes. The psoriatic skin lesions due to abnormal keratinocytes are closely associated with ROS produced by inflammatory cells. Peroxiredoxin II (Prx II) is an efficient antioxidant enzyme, which were highly expressed in skin tissues of psoriasis patient. However, the detailed mechanical functions of Prx II on psoriatic skin remain to be elucidated. Present study showed that depletion of Prx II results in alleviation of symptoms of IMQ-induced psoriasis in mice, but no significant differences in the amounts of serum inflammatory factors. Prx II-knockdown HaCaT cells were susceptible to H2O2-induced apoptosis mediated by Ca2+ release from the endoplasmic reticulum through 1,4,5-triphosphate receptors (IP3Rs), the PI3K/AKT pathway and phosphorylated GSK3ß (Ser9) were significant downregulated. Additionally, significantly reduced sensitivity of Prx II-knockdown HaCaT cells to apoptosis was evident post NAC, 2-APB, BAPTA-AM, SC79 and LiCl treated. These results suggest that Prx II regulated apoptosis of keratinocytes via the PI3K/AKT/GSK3ß signaling axis. Furthermore, treatment with the Prx II inhibitor Conoidin A significantly alleviated psoriatic symptoms in IMQ model mice. These findings have important implications for developing therapeutic strategies through regulate apoptosis of keratinocytes in psoriasis, and Prx II inhibitors may be exploited as a therapeutic drug to alleviate psoriatic symptoms.

Induction of Targeted Differentiation of Dermal Mesenchymal Stem Cells Into Neural Lineage According to Peroxiredoxin II Expression.

BACKGROUND/AIM: To optimize the therapeutic potential of stem cells in stem cell therapy for neurological diseases, it is crucial to enhance the differentiation, migration, and neural network formation of stem cells, and to eliminate uncertain cell differentiation and proliferation factors. Several studies have shown that reactive oxygen species (ROS) are important factors in the regulation of neurogenesis, and Prx II (Peroxiredoxin II) is a gene that regulates ROS. MATERIALS AND METHODS: As the entry point in this study to conduct a bioinformatics analysis of the sequencing results of Prx II+/+ dermal mesenchymal stem cells (DMSCs) and Prx II-/- DMSCs. lncRNA/miRNA/mRNA networks were then constructed and preliminarily verified in RT-qPCR experiments. RESULTS: In this study, a total of 11 hub genes (Gria1, Nrcam, Sox10, Snap25, Cntn2, Dlg2, Ngf, Ntrk3, Amph, Syt1, and Cd24a), eight miRNAs (miRNA-4661, miRNA-34a, miRNA-185, miRNA-34b-5p, miRNA-34c, miRNA-449a, miRNA-449b, miRNA-449c) and 12 lncRNAs (Dubr, Gas5, Gm20427, Gm26917, Gm42547, Gm8066, Kcnq1ot1, Malat1, Mir17hg, Neat1, Rian, and Tug1) were predicted in lncRNA/miRNA/mRNA network. CONCLUSION: The regulatory mechanism of Prx II in the differentiation of DMSCs into neurons through ROS was explored, and a theoretical basis was determined that can be applied in future research on nervous system diseases and the clinical applications of stem cells.

Identification of Hub Genes and Upstream Regulatory Factors Based on Cell Adhesion in Triple-negative Breast Cancer by Integrated Bioinformatical Analysis.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by metastasis and invasion, as well as poor prognosis, with chemotherapy being the main treatment option. Cell adhesion regulates tumorigenesis and new blood vessel formation. Thus, accurately identifying effective targets for TNBC and cell adhesion is challenging. Herein, we screened for differentially expressed genes between TNBC and normal cancer-free tissues to identify genes contributing to TNBC. MATERIALS AND METHODS: Microarray data were obtained using a comprehensive gene-expression database. We used Database for Annotation, Visualization and Integrated Discovery, Kyoto Encyclopedia of Genes and Genomes and Functional Enrichment (FunRich) to perform Gene Ontology functional enrichment and predict signal pathways. The protein interaction network was predicted using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape v. 3.8.2. for visualization of results. TargetScan, miRanda, miRDB, miRWalk and RNA22 were used to predict miRNAs regulating key genes, and long non-coding RNAs (lncRNAs) regulating miRNAs were predicted using StarBase V2.0 from a comprehensive gene-expression database. RESULTS: Differentially expressed genes were mainly concentrated in the biological process of cell-cell adhesion. The protein-protein interaction network identified eight hub genes: Fibronectin 1 (FN1), Rac family small GTPase 1 (RAC1), heat-shock protein 90 alpha family class B member 1 (HSP90AB1), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), heat-shock protein family A member 8 (HSPA8), IQ motif containing GTPase-activating protein 1 (IQGAP1), CD44 molecule (CD44), and catenin beta 1 (CTNNB1). miRNAs related to TNBC occurrence and development were hsa-miR-142-5p, hsa-miR-144, hsa-miR-28-5p, hsa-miR-548d-3p, hsa-miR-587, hsa-miR-641, and hsa-miR-708. StarBase v2.0 predicted 12 lncRNAs, namely NEAT1, XIST, OIP5-AS1, MALAT1, AL035425.3, NORAD, AL391069.4, AC118758.3, AC026362.1, AC009065.4, AC016876.2, and AC093010.3, as upstream molecules that regulate miRNAs and which may regulate TNBC. CONCLUSION: Overall, mRNA-miRNA-lncRNA interactions appear to play a role in TNBC development.

PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin. METHODS: Experimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study. RESULTS: PRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-ß secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways. CONCLUSIONS: Our findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis.

Lipophagy: A potential therapeutic target for nonalcoholic and alcoholic fatty liver disease.

Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a crucial role in the prevention of metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), and is a potential therapeutic target for treating these dysfunctions. In this review, we highlighted recent research and discussed advances in key proteins and molecular mechanisms related to lipophagy in liver disease. Reactive oxygen species (ROS) is an inevitable product of metabolism in alcohol-treated or high-fat-treated cells. Under this light, the potential role of ROS in autophagy in lipid droplet removal was initially explored to provide insights into the link between oxidative stress and metabolic liver disease. Subsequently, the current measures and drugs that treat NAFLD and AFLD through lipophagy regulation were summarized. The complexity of molecular mechanisms underlying lipophagy in hepatocytes and the need for further studies for their elucidation, as well as the status and limitations of current therapeutic measures and drugs, were also discussed.

Regulatory pathway underpinning the development of encephalitis after simian immunodeficiency virus infection in rhesus macaques (Macaca mulatta).

BACKGROUND: Simian immunodeficiency virus (SIV) infection in rhesus macaques (Macaca mulatta) can lead to the development of SIV encephalitis (SIVE), which is closely related to human immunodeficiency virus (HIV)-induced dementia. METHODS: This was done by analyzing SIV and SIVE encephalitis in infected M. mulatta hippocampus samples from two microarray data sets, identifying two groups of common differentially expressed genes and predicting associated protein interactions. RESULTS: We found that eight genes-MX1, B2M, IFIT1, TYMP, STAT1, IFI44, ISG15, and IFI27-affected the negative regulation of biological processes, hepatitis C and Epstein-Barr viral infection, and the toll-like receptor signaling pathway, which mediate the development of encephalitis after SIV infection. In particular, STAT1 played a central role in the process by regulating biopathological changes during the development of SIVE. CONCLUSION: These findings provide a new theoretical basis for the treatment of encephalopathy after HIV infection by targeting STAT1.

Immunogenicity of the Non-toxic Form of Staphylococcus Aureus α-Hemolysin Using a Chimeric Fusion in Mice.

Background: Staphylococcus aureus is an opportunistic pathogen responsible for various infections with diverse clinical presentation and severity. The α-hemolysin is a major virulence factor in the pathogenesis of S. aureus infections. Objective: To produce a chimeric fusion protein for hemolytic detection of the S. aureus isolates and as a component of a multi-antigen vaccine. Methods: The fused strategy employed a flexible linker to incorporate the possible B cell and T cell determinants into one chimera (HlaD). The humoral and cellular response to the HlaD in mice was assessed to reveal a non-significant difference compared with the full-length α-hemolysin mutant (Hla H35L). Results: The results of the protective effect, the mimetic lung cell injury, and bacterial clearness demonstrated that the mice vaccinated with the HlaD alleviated the severity of the infection of the S. aureus, and the HlaD could similarly function with Hla H35L. Conclusion: The chimeric fusion (HlaD) provided a diagnostic antigen for hemolysis of the S. aureus strains and a potential vaccine component.