BioFactorsPub Date : 2024-07-29DOI: 10.1002/biof.2107
Walaa Bayoumie El Gazzar, Amina A. Farag, Mohamed Samir, Heba Bayoumi, Heba S. Youssef, Yasmin Mohammed Marei, Shimaa K. Mohamed, Azza M. Marei, Reham M. Abdelfatah, Manal Moustafa Mahmoud, Elshaimaa Ahmed Fahmy Aboelkomsan, Eman Kamel M. Khalfallah, Hala Magdy Anwer
{"title":"Berberine chloride loaded nano-PEGylated liposomes attenuates imidacloprid-induced neurotoxicity by inhibiting NLRP3/Caspase-1/GSDMD-mediated pyroptosis","authors":"Walaa Bayoumie El Gazzar, Amina A. Farag, Mohamed Samir, Heba Bayoumi, Heba S. Youssef, Yasmin Mohammed Marei, Shimaa K. Mohamed, Azza M. Marei, Reham M. Abdelfatah, Manal Moustafa Mahmoud, Elshaimaa Ahmed Fahmy Aboelkomsan, Eman Kamel M. Khalfallah, Hala Magdy Anwer","doi":"10.1002/biof.2107","DOIUrl":"10.1002/biof.2107","url":null,"abstract":"<p>Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides, and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism by which IMI would trigger neuroinflammation is particularly important. This study examined the neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential neuroprotective effect of berberine (Ber) chloride loaded nano-PEGylated liposomes (Ber-Lip) (10 mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological changes, anti-oxidant and oxidative stress markers (GSH, SOD, and MDA), proinflammatory cytokines (IL1β and TNF-α), microglia phenotype markers (CD86 and iNOS for M1; CD163 for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD, and IL-18) and Alzheimer's disease markers (Neprilysin and beta amyloid [Aβ] deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress, predominance of M1 microglia phenotype, significantly upregulated NLRP3, <i>caspase-1</i>, <i>GSDMD</i>, <i>IL-18</i> and Aβ deposits and significantly decreased Neprilysin expression. Berberine reduced the IMI-induced aberrations in the measured parameters and improved the IMI-induced histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI neurotoxic effect and its potential contribution to the development of Alzheimer's disease and displayed the neuroprotective effect of Ber-Lip.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-07-25DOI: 10.1002/biof.2092
Gourabamani Swalsingh, Punyadhara Pani, Unmod Senapati, Bijayashree Sahu, Sunil Pani, Benudhara Pati, Subhasmita Rout, Naresh C. Bal
{"title":"Intramuscular administration of fractalkine modulates mitochondrial properties and promotes fast glycolytic phenotype","authors":"Gourabamani Swalsingh, Punyadhara Pani, Unmod Senapati, Bijayashree Sahu, Sunil Pani, Benudhara Pati, Subhasmita Rout, Naresh C. Bal","doi":"10.1002/biof.2092","DOIUrl":"10.1002/biof.2092","url":null,"abstract":"<p>A newly categorized myokine called fractalkine (CX3CL1) has been associated with divergent conditions such as obesity, tissue inflammation, and exercise. CX3CL1 works through specific membrane-bound receptors (CX3CR1) found in various tissues including skeletal muscles. Studies indicate CX3CL1 induces muscles to uptake energy substrates thereby improving glucose utilization and countering diabetes. Here, we tested if the administration of purified CX3CL1 directly into mice skeletal muscles affects its histoarchitecture, mitochondrial activity, and expression of metabolic proteins. We analyzed four muscles: two upper-limb (quadriceps, hamstrings) and two lower-limb (tibialis anterior, gastrocnemius), contralateral leg muscles were taken as controls. The effects of CX3CL1 treatment on histoarchitecture, mitochondrial activity, and expression of metabolic proteins in muscles were characterized. We used histochemical staining succinate dehydrogenase (SDH)/cytochrome c oxidase (COX), myosin ATPase, alkaline phosphatase (ALP) to evaluate the mitochondrial activity, fiber types, and vascularization in the muscles, respectively. Western blotting was used to evaluate the expression of proteins associated with mitochondrial metabolism (OXPHOS), glycolysis, and vascularization. Overall, this study indicates CX3CL1 primarily modulates mitochondrial metabolism and shifts substrate preference toward glucose in the skeletal muscle. Evidence also supports that CX3CL1 stimulates the relative composition of fast fiber types, influencing selection of energy substrates in the skeletal muscle.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-07-18DOI: 10.1002/biof.2093
{"title":"RETRACTION: Systemic inflammation and oxidative stress induced by inhaled Paraquat in rat improved by Carvacrol, possible role of PPARγ receptors","authors":"","doi":"10.1002/biof.2093","DOIUrl":"10.1002/biof.2093","url":null,"abstract":"<p><b>RETRACTION</b>: F. Amin, A. Memarzia, H. K. Rad, F. Shakeri and M. H. Boskabady, “Systemic Inflammation and Oxidative Stress Induced by Inhaled Paraquat in Rat Improved by Carvacrol, Possible Role of PPARγ Receptors,” <i>Biofactors</i> 47, no. 5 (2021): 778–787, https://doi.org/10.1002/biof.1761.</p><p>The above article, published online on 05 June 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Irene Diaz-Moreno; the International Union of Biochemistry and Molecular Biology; and Wiley Periodicals LLC. The retraction has been agreed due to considerable overlap with previously published articles from a similar group of authors. As a result, the editors consider a significant portion of the results reported in this study redundant. The authors disagree with the retraction.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 4","pages":"863"},"PeriodicalIF":5.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-07-12DOI: 10.1002/biof.2091
Francesca Fortini, Francesco Vieceli Dalla Sega, Edoardo Lazzarini, Giorgio Aquila, Polina Sysa-Shah, Edoardo Bertero, Alessia Ascierto, Paolo Severi, Achille Wilfred Ouambo Talla, Alessio Schirone, Kathleen Gabrielson, Giampaolo Morciano, Simone Patergnani, Gaia Pedriali, Paolo Pinton, Roberto Ferrari, Elena Tremoli, Pietro Ameri, Paola Rizzo
{"title":"ErbB2-NOTCH1 axis controls autophagy in cardiac cells","authors":"Francesca Fortini, Francesco Vieceli Dalla Sega, Edoardo Lazzarini, Giorgio Aquila, Polina Sysa-Shah, Edoardo Bertero, Alessia Ascierto, Paolo Severi, Achille Wilfred Ouambo Talla, Alessio Schirone, Kathleen Gabrielson, Giampaolo Morciano, Simone Patergnani, Gaia Pedriali, Paolo Pinton, Roberto Ferrari, Elena Tremoli, Pietro Ameri, Paola Rizzo","doi":"10.1002/biof.2091","DOIUrl":"10.1002/biof.2091","url":null,"abstract":"<p>Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post-transcriptional, p38-dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation. Moreover, incubation of H9c2 cells with lapatinib resulted in stalled autophagic flux and decreased proliferation, consistent with the established cardiotoxicity of this and other ErbB2-targeting drugs. Confirming the findings in H9c2 cells, exposure of primary neonatal mouse cardiomyocytes to exogenous neuregulin-1, which engages ErbB2, stimulated proliferation, and this effect was abrogated by concomitant inhibition of the enzyme responsible for Notch1 activation. Furthermore, the hearts of transgenic mice specifically overexpressing ErbB2 in cardiomyocytes had increased levels of active Notch1 and of Notch-related genes. These data expand the knowledge of ErbB2 and Notch1 functions in the heart and may allow better understanding the mechanisms of the cardiotoxicity of ErbB2-targeting cancer treatments.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-07-11DOI: 10.1002/biof.2090
Oğuz Kaan Kırbaş, Derya Sağraç, Özgün Cem Çiftçi, Gökçeçiçek Özdemir, Dilek Öztürkoğlu, Batuhan Turhan Bozkurt, Ümit Cem Derman, Ezgi Taşkan, Pakize Neslihan Taşlı, Bahar Soğutmaz Özdemir, Fikrettin Şahin
{"title":"Unveiling the potential: Extracellular vesicles from plant cell suspension cultures as a promising source","authors":"Oğuz Kaan Kırbaş, Derya Sağraç, Özgün Cem Çiftçi, Gökçeçiçek Özdemir, Dilek Öztürkoğlu, Batuhan Turhan Bozkurt, Ümit Cem Derman, Ezgi Taşkan, Pakize Neslihan Taşlı, Bahar Soğutmaz Özdemir, Fikrettin Şahin","doi":"10.1002/biof.2090","DOIUrl":"10.1002/biof.2090","url":null,"abstract":"<p>Extracellular vesicles are secreted by all eukaryotic cells and they have an important role in intercellular signaling. Plant extracellular vesicles (PEVs) are a novel area of research that has gained attention due to their potential implications in biomolecule transport and therapeutic applications. PEVs are lipid bilayer-enclosed structures that contain a diverse cargo of biomolecules such as proteins and lipids. Moreover, it is known that PEVs have a noticeable therapeutic potential for various conditions such as inflammation and oxidative stress. However, there are critical problems such as removing the endosomes and plant-derived biomolecules that decrease the standardization and therapeutic efficacy of PEVs. In our study, the aim was to characterize plant cell suspension-derived extracellular vesicles (PCSEVs) obtained from two different plant cell suspension cultures: <i>Stevia rebaudiana</i> and <i>Vaccaria hispanica</i>. These vesicles were isolated using ultrafiltration and characterized with nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM). The molecular composition of PCSEVs was profiled and the cellular uptake assay was performed. Our results demonstrated that PCSEVs have a spherical shape, less than 200 nm. In the fatty acid analysis, the primary components in PCSEVs were palmitic acid, linoleic acid, and cis-vaccenic acid. The protein content of <i>Stevia rebaudiana</i>-derived EVs (SDEVs) was largely associated with proteins involved in extracellular structures and functions. Conversely, <i>Vaccaria hispanica</i>-derived EVs (HDEVs) displayed a higher presence of cytosolic proteins. These findings contribute to the understanding of PCSEVs and open up potential avenues in extracellular vesicle research, pointing to promising prospects for future innovations in various fields.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-07-11DOI: 10.1002/biof.2089
Minglv Fang, Ying Liu, Xiaoyan Gao, Jing Yu, Xiaohui Tu, Xueying Mo, Huanhu Zhu, Yan Zou, Cheng Huang, Shengjie Fan
{"title":"Perillaldehyde alleviates polyQ-induced neurodegeneration through the induction of autophagy and mitochondrial UPR in Caenorhabditis elegans","authors":"Minglv Fang, Ying Liu, Xiaoyan Gao, Jing Yu, Xiaohui Tu, Xueying Mo, Huanhu Zhu, Yan Zou, Cheng Huang, Shengjie Fan","doi":"10.1002/biof.2089","DOIUrl":"10.1002/biof.2089","url":null,"abstract":"<p>Huntington's disease (HD) is a fatal neurodegenerative disease associated with autophagy disorder and mitochondrial dysfunction. Here, we identified therapeutic potential of perillaldehyde (PAE), a monoterpene compound obtained from <i>Perilla frutescens</i> (L.) Britt., in the <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) model of HD, which included lifespan extension, healthspan improvement, decrease in polyglutamine (polyQ) aggregation, and preservation of mitochondrial network. Further analyses indicated that PAE was able to induce autophagy and mitochondrial unfolded protein reaction (UPR<sup>mt</sup>) activation and positively regulated expression of associated genes. In <i>lgg-1</i> RNAi <i>C. elegans</i> or <i>C. elegans</i> with UPR<sup>mt</sup>-related genes knockdown, the effects of PAE treatment on polyQ aggregation or rescue polyQ-induced toxicity were attenuated, suggesting that its neuroprotective activity depended on autophagy and UPR<sup>mt</sup>. Moreover, we found that pharmacological and genetic activation of UPR<sup>mt</sup> generally protected <i>C. elegans</i> from polyQ-induced cytotoxicity. Finally, PAE promoted serotonin synthesis by upregulating expression of TPH-1, and serotonin synthesis and neurosecretion were required for PAE-mediated UPR<sup>mt</sup> activation and its neuroprotective activity. In conclusion, PAE is a potential therapy for polyQ-related diseases including HD, which is dependent on autophagy and cell-non-autonomous UPR<sup>mt</sup> activation.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-06-17DOI: 10.1002/biof.2084
Michael James Houghton, Eglantine Balland, Matthew James Gartner, Belinda Jane Thomas, Kanta Subbarao, Gary Williamson
{"title":"The flavonoid quercetin decreases ACE2 and TMPRSS2 expression but not SARS-CoV-2 infection in cultured human lung cells","authors":"Michael James Houghton, Eglantine Balland, Matthew James Gartner, Belinda Jane Thomas, Kanta Subbarao, Gary Williamson","doi":"10.1002/biof.2084","DOIUrl":"10.1002/biof.2084","url":null,"abstract":"<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike-ACE2 complex to facilitate virus entry. As rate-limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity and COVID-19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID-19 recovery. A range of cultured human cells were assessed for co-expression of ACE2 and TMPRSS2. Immortalized Calu-3 lung cells, cultured and matured at an air–liquid interface (Calu-3-ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (<i>N</i> = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu-3-ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS-CoV-2 infectivity, and the effects of pre- and co-treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose-dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu-3-ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu-3-ALIs, and this warrants further investigation. Calu-3-ALIs, but not PBECs, were successfully infected with SARS-CoV-2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu-3-ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1268-1286"},"PeriodicalIF":5.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-06-12DOI: 10.1002/biof.2088
Praveen Jaiswar, Mitali Bhate, Avadhesha Surolia
{"title":"Mitigation of experimental ER stress and diabetes mellitus induced peripheral neuropathy by autophagy promoter, 6-BIO","authors":"Praveen Jaiswar, Mitali Bhate, Avadhesha Surolia","doi":"10.1002/biof.2088","DOIUrl":"10.1002/biof.2088","url":null,"abstract":"<p>Neuropathy occurs due to damage to the peripheral/central nervous system either due to injury, disease, or drug usage. Increased endoplasmic reticulum (ER) stress is observed in neuropathy. ER stress also leads to a block in autophagy amplifying neuropathic pain. 6-Bromoindirubin-3′-oxime (6-BIO) is an inhibitor of GSK-3β which suppresses mTOR activity thereby increasing autophagy. Tunicamycin (TM)-mediated ER stress and diabetic rat models were used to elucidate the role of ER stress and autophagy in mitigation of neuropathic pain by 6-BIO. Pain was assessed by behavioral studies in ER stressed/diabetic rats having neuropathy. Western blotting, RT-PCR, and fluorescence microscopy were used to assess the level of autophagy and ER stress after TM and 6-BIO treatment in SH-SY5Y neurons. Intraplantar injection of TM in rats led to peripheral neuropathy which was reduced upon 6-BIO injection. 6-BIO also reduced pain in animals exhibiting diabetic peripheral neuropathy. Modulation in the markers of autophagy (p-mTOR, LC-3, and SQSTM1/p62) shows that 6-BIO induces autophagolysosome formation post TM treatment. Concomitantly, 6-BIO reduces ER stress and c-Fos expression—a neuronal activity and pain marker. Alleviation of pain by the inhibition of ER stress and increased formation of autolysosomes by 6-BIO can be harnessed for treating peripheral neuropathy.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"51 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioFactorsPub Date : 2024-05-31DOI: 10.1002/biof.2079
Jeong-hun Mok, Do Young Park, Jong Chul Han
{"title":"Differential protein expression and metabolite profiling in glaucoma: Insights from a multi-omics analysis","authors":"Jeong-hun Mok, Do Young Park, Jong Chul Han","doi":"10.1002/biof.2079","DOIUrl":"10.1002/biof.2079","url":null,"abstract":"<p>Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi-omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, <i>n</i> = 5), exfoliation glaucoma (XFG, <i>n</i> = 4), primary open-angle glaucoma (POAG, <i>n</i> = 11), and cataracts (control group, <i>n</i> = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data-independent acquisition and data-dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L-phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L-phenylalanine or C3, APOD, and L-valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"50 6","pages":"1220-1235"},"PeriodicalIF":5.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}