International Journal of Molecular Sciences最新文献

{"title":"Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome","authors":"Anna Pańczyszyn, E. Boniewska-Bernacka, I. Wertel, Anna Sadakierska-Chudy, Anna Goc","doi":"10.3390/ijms25168652","DOIUrl":"https://doi.org/10.3390/ijms25168652","url":null,"abstract":"The number of infertile couples undergoing in vitro fertilisation (IVF) has increased significantly. The efficacy of this procedure is contingent upon a multitude of factors, including gamete quality. One factor influencing gamete quality is oxidative stress, which leads to telomere damage and accelerates cellular ageing. Identifying new biomarkers that can predict the success of assisted reproduction techniques is a current relevant area of research. In this review, we discuss the potential role of SIRT1, a protein known to protect against oxidative stress and telomeres, which are responsible for genome stability, as biomarkers of gamete quality and assisted reproduction technique outcomes.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Translational Variants of Major Proteins in Amyotrophic Lateral Sclerosis Provide New Insights into the Pathophysiology of the Disease","authors":"Léa Bedja-Iacona, Elodie Richard, S. Marouillat, C. Brulard, Tarek Alouane, S. Beltran, Christian R. Andres, H. Blasco, P. Corcia, C. Veyrat-Durebex, P. Vourc'h","doi":"10.3390/ijms25168664","DOIUrl":"https://doi.org/10.3390/ijms25168664","url":null,"abstract":"Post-translational modifications (PTMs) affecting proteins during or after their synthesis play a crucial role in their localization and function. The modification of these PTMs under pathophysiological conditions, i.e., their appearance, disappearance, or variation in quantity caused by a pathological environment or a mutation, corresponds to post-translational variants (PTVs). These PTVs can be directly or indirectly involved in the pathophysiology of diseases. Here, we present the PTMs and PTVs of four major amyotrophic lateral sclerosis (ALS) proteins, SOD1, TDP-43, FUS, and TBK1. These modifications involve acetylation, phosphorylation, methylation, ubiquitination, SUMOylation, and enzymatic cleavage. We list the PTM positions known to be mutated in ALS patients and discuss the roles of PTVs in the pathophysiological processes of ALS. In-depth knowledge of the PTMs and PTVs of ALS proteins is needed to better understand their role in the disease. We believe it is also crucial for developing new therapies that may be more effective in ALS.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription-Associated Metabolomic Analysis Reveals the Mechanism of Fruit Ripening during the Development of Chinese Bayberry","authors":"Li Sun, Shuwen Zhang, Zheping Yu, Xiliang Zheng, Senmiao Liang, Haiying Ren, Xingjiang Qi","doi":"10.3390/ijms25168654","DOIUrl":"https://doi.org/10.3390/ijms25168654","url":null,"abstract":"The ripening process of Chinese bayberries (Myrica rubra) is intricate, involving a multitude of molecular interactions. Here, we integrated transcriptomic and metabolomic analysis across three developmental stages of the Myrica rubra (M. rubra) to elucidate these processes. A differential gene expression analysis categorized the genes into four distinct groups based on their expression patterns. Gene ontology and pathway analyses highlighted processes such as cellular and metabolic processes, including protein and sucrose metabolism. A metabolomic analysis revealed significant variations in metabolite profiles, underscoring the dynamic interplay between genes and metabolites during ripening. Flavonoid biosynthesis and starch and sucrose metabolism were identified as key pathways, with specific genes and metabolites playing crucial roles. Our findings provide insights into the molecular mechanisms governing fruit ripening in M. rubra and offer potential targets for breeding strategies aimed at enhancing fruit quality.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Skin Exposure to Benzo[a]pyrene in Rat Model: Insights into Epidermal Cell Function and Draining Lymph Node Cell Response","authors":"Anastasija Malešević, Dina Tucović, Jelena Kulaš, Ivana Mirkov, Dusanka Popovic, Maja Čakić Milošević, Aleksandra Popov Aleksandrov","doi":"10.3390/ijms25168631","DOIUrl":"https://doi.org/10.3390/ijms25168631","url":null,"abstract":"The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin’s reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin’s response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ss4368: Pathogen-Associated Molecular Pattern for Inducing Plant Cell Death and Resistance to Phytophthora capsici","authors":"Ziwen He, Shufang Peng, Qingqing Yin, Yuanyuan Huang, Ting Deng, Yiwei Luo, Ningjia He","doi":"10.3390/ijms25168674","DOIUrl":"https://doi.org/10.3390/ijms25168674","url":null,"abstract":"Plant recognition of pathogen-associated molecular patterns (PAMPs) is pivotal in triggering immune responses, highlighting their potential as inducers of plant immunity. However, the number of PAMPs identified and applied in such contexts remains limited. In this study, we characterize a novel PAMP, designated Ss4368, which is derived from Scleromitrula shiraiana. Ss4368 is specifically distributed among a few fungal genera, including Botrytis, Monilinia, and Botryotinia. The transient expression of Ss4368 elicits cell death in a range of plant species. The signaling peptides, three conserved motifs, and cysteine residues (C46, C88, C112, C130, and C148) within Ss4368 are crucial for inducing robust cell death. Additionally, these signaling peptides are essential for the protein’s localization to the apoplast. The cell death induced by Ss4368 and its homologous protein, Bc4368, is independent of the SUPPRESSOR OF BIR1-1 (SOBIR1), BRI1-ASSOCIATED KINASE-1 (BAK1), and salicylic acid (SA) pathways. Furthermore, the immune responses triggered by Ss4368 and Bc4368 significantly enhance the resistance of Nicotiana benthamiana to Phytophthora capsici. Therefore, we propose that Ss4368, as a novel PAMP, holds the potential for developing strategies to enhance plant resistance against P. capsici.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal Dysbiosis, Tight Junction Proteins, and Inflammation in Rheumatoid Arthritis Patients: A Cross-Sectional Study","authors":"A. Mucientes, J. M. Lisbona-Montañez, N. Mena-Vázquez, Patricia Ruiz-Limón, S. Manrique-Arija, Aimara García-Studer, F. Ortiz-Márquez, Antonio Fernández-Nebro","doi":"10.3390/ijms25168649","DOIUrl":"https://doi.org/10.3390/ijms25168649","url":null,"abstract":"Recent studies point to intestinal permeability as an important factor in the establishment and development of rheumatoid arthritis (RA). Tight junctions (TJs) play a major role in intestinal homeostasis. The alteration of this homeostasis is related to RA. Furthermore, RA patients present dysbiosis and a lower microbiota diversity compared to healthy individuals. A cross-sectional study including RA patients and sex- and age-matched healthy controls was performed. The quantification of TJ proteins was carried out by ELISA. Gut microbiota was evaluated by NGS platform Ion Torrent S. The inflammatory variables included were DAS28, CRP, inflammatory cytokines (IL-6, IL-1, TNF-α) and oxidised LDL. Claudin-1 levels showed significant differences between groups. Results evidenced a correlation between claudin-1 values and age (r: −0.293; p < 0.05), IL6 (r: −0.290; p < 0.05) and CRP (r: −0.327; p < 0.05), and between zonulin values and both age (r: 0.267; p < 0.05) and TNFα (r: 0.266; p < 0.05). Moreover, claudin-1 and CRP levels are related in RA patients (β: −0.619; p: 0.045), and in patients with high inflammatory activity, the abundance of the genus Veillonella is positively associated with claudin-1 levels (β: 39.000; p: 0.004).","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141926690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prognostic and Predictive Utility of CDX2 in Colorectal Cancer","authors":"Wei Yen Chan, Wei Chua, K. Wilkinson, Chandika Epitakaduwa, Hiren Mandaliya, J. Descallar, T. L. Roberts, Therese M Becker, W. Ng, Cheok Soon Lee, S. H. Lim","doi":"10.3390/ijms25168673","DOIUrl":"https://doi.org/10.3390/ijms25168673","url":null,"abstract":"Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I–IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2’s relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mycobacterial Biofilm: Mechanisms, Clinical Problems, and Treatments","authors":"Xining Liu, Junxing Hu, Wenzhen Wang, Hanyu Yang, Erning Tao, Yufang Ma, Shanshan Sha","doi":"10.3390/ijms25147771","DOIUrl":"https://doi.org/10.3390/ijms25147771","url":null,"abstract":"Tuberculosis (TB) remains a threat to human health worldwide. Mycobacterium tuberculosis (Mtb) and other nontuberculous mycobacteria (NTM) can form biofilms, and in vitro and animal experiments have shown that biofilms cause serious drug resistance and mycobacterial persistence. Deeper investigations into the mechanisms of mycobacterial biofilm formation and, consequently, the exploration of appropriate antibiofilm treatments to improve the efficiency of current anti-TB drugs will be useful for curing TB. In this review, the genes and molecules that have been recently reported to be involved in mycobacterial biofilm development, such as ABC transporter, Pks1, PpiB, GroEL1, MprB, (p)ppGpp, poly(P), and c-di-GMP, are summarized. Biofilm-induced clinical problems, including biofilm-related infections and enhanced virulence, as well as their possible mechanisms, are also discussed in detail. Moreover, we also illustrate newly synthesized anti-TB agents that target mycobacterial biofilm, as well as some assistant methods with high efficiency in reducing biofilms in hosts, such as the use of nanoparticles.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Dong et al. Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis. Int. J. Mol. Sci. 2016, 17, 943","authors":"Yonghui Dong, Hui Liu, Xuejun Zhang, Fei Xu, Liang Qin, Peng Cheng, Hui Huang, Fengjing Guo, Qing Yang, Anmin Chen","doi":"10.3390/ijms25147757","DOIUrl":"https://doi.org/10.3390/ijms25147757","url":null,"abstract":"The journal retracts the article “Inhibition of SDF-1α/CXCR4 Signalling in Subchondral Bone Attenuates Post-Traumatic Osteoarthritis” [...]","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergic Effect of the Antimicrobial Peptide ToAP2 and Fluconazole on Candida albicans Biofilms","authors":"Jhones do Nascimento Dias, Fabián Andrés Hurtado Erazo, L. J. Bessa, Peter Eaton, José R S A Leite, H. C. Paes, A. Nicola, I. Silva-Pereira, Patrícia Albuquerque","doi":"10.3390/ijms25147769","DOIUrl":"https://doi.org/10.3390/ijms25147769","url":null,"abstract":"Candida albicans is one of the agents of invasive candidiasis, a life-threatening disease strongly associated with hospitalization, particularly among patients in intensive care units with central venous catheters. This study aimed to evaluate the synergistic activity of the antifungal peptide ToAP2 combined with fluconazole against C. albicans biofilms grown on various materials. We tested combinations of different concentrations of the peptide ToAP2 with fluconazole on C. albicans biofilms. These biofilms were generated on 96-well plates, intravenous catheters, and infusion tubes in RPMI medium at two maturation stages. Scanning electron microscopy and atomic force microscopy were employed to assess the biofilm structure. We also evaluated the expression of genes previously proven to be involved in C. albicans biofilm formation in planktonic and biofilm cells after treatment with the peptide ToAP2 using qPCR. ToAP2 demonstrated a synergistic effect with fluconazole at concentrations up to 25 µM during both the early and mature stages of biofilm formation in 96-well plates and on medical devices. Combinations of 50, 25, and 12.5 µM of ToAP2 with 52 µM of fluconazole significantly reduced the biofilm viability compared to individual treatments and untreated controls. These results were supported by substantial structural changes in the biofilms observed through both scanning and atomic force microscopy. The gene expression analysis of C. albicans cells treated with 25 µM of ToAP2 revealed a decrease in the expression of genes associated with membrane synthesis, along with an increase in the expression of genes involved in efflux pumps, adhesins, and filamentation. Our results highlight the efficacy of the combined ToAP2 and fluconazole treatment against C. albicans biofilms. This combination not only shows therapeutic potential but also suggests its utility in developing preventive biofilm tools for intravenous catheters.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}