{"title":"Downregulation of ATP8B2 in atherosclerosis exacerbates foam cell-like pathological changes via impairing lysosomal membrane fusion.","authors":"Rui Bu, Weihao Zhao, Rui Liang","doi":"10.1007/s11033-025-10565-5","DOIUrl":"https://doi.org/10.1007/s11033-025-10565-5","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis, a major cause of global mortality, involves the transformation of macrophages into foam cells, which is a key pathological process. This study aims to elucidate the molecular mechanisms that contribute to foam cell formation and the progression of atherosclerosis.</p><p><strong>Methods and results: </strong>We performed a comprehensive bioinformatics analysis of transcriptome data to identify differentially expressed genes (DEGs) associated with atherosclerosis. Using the human acute monocytic leukemia cell line THP-1, we established in vitro models of macrophages and foam cells to simulate the atherosclerotic microenvironment. Functional studies were conducted using siRNA-mediated knockdown, real-time PCR, Western blotting, and immunofluorescence imaging. Our results showed that ATP8B2 was significantly down-regulated in atherosclerotic foam cells. The downregulation of ATP8B2 led to impaired lysosomal membrane fusion, evidenced by an increase in CD63-positive compartments without a change in CD63 protein levels. Additionally, under starvation conditions, there was a significant accumulation of autophagosomes, indicating a defect in the autophagy-lysosomal pathway.</p><p><strong>Conclusions: </strong>This study, for the first time, demonstrates that the downregulation of ATP8B2 exacerbates atherosclerosis by disrupting lysosomal membrane fusion, leading to lipid accumulation and foam cell formation. These findings provide novel insights into the pathogenesis of atherosclerosis and suggest that ATP8B2 could be a potential therapeutic target for the prevention or treatment of this disease.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"485"},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shih-Chun Lan, Ming-Der Perng, Yung-Yee Chang, Ying-Fa Chen, Min-Yu Lan
{"title":"Phenotypic and molecular characterization of a recurrent SPTAN1 mutation causing SPG91.","authors":"Shih-Chun Lan, Ming-Der Perng, Yung-Yee Chang, Ying-Fa Chen, Min-Yu Lan","doi":"10.1007/s11033-025-10582-4","DOIUrl":"10.1007/s11033-025-10582-4","url":null,"abstract":"<p><strong>Background: </strong>Spectrins are ubiquitous cytoskeleton proteins found in all metazoan cells. αII-spectrin, encoded by SPTAN1, is the pivotal protein responsible for organization of the axonal cytoskeleton. Monoallelic SPTAN1 mutations cause various inherited neurological diseases, including spastic paraplegia 91 (SPG91), a type of hereditary spastic paraplegia (HSP).</p><p><strong>Methods and results: </strong>We reported two patients with SPG91 caused by the SPTAN1 mutation c.55 C > T (p.Arg19Trp), who presented with lower limb spasticity and polyneuropathy. An analysis of the patients reported in the literature in addition to the present patients revealed that SPTAN1 p.Arg19Trp was specific for an HSP phenotype, with 35% of the combined patients with sensory‒motor polyneuropathy and 30% with cerebellar ataxia. In computational simulations, this variant was predicted to perturb the stability of αII/β spectrin heterotetramerization but did not destabilize the tetramerization domain of αII-spectrin.</p><p><strong>Conclusions: </strong>Our findings on genotype‒phenotype correlations and genetic effects on molecular characteristics may provide important insights into the exploration of αII-spectrin-related neurological diseases.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"476"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The MNS blood group system in Tunisian blood donors: common and rare alleles.","authors":"Mohamed Hichem Sellami, Eya Ghazouani, Sondess Hadj Fredj, Hamida Ferchichi, Manel Chaabane, Houda Kaabi, Taieb Messaoud, Slama Hmida","doi":"10.1007/s11033-025-10552-w","DOIUrl":"10.1007/s11033-025-10552-w","url":null,"abstract":"<p><strong>Background: </strong>The MNS blood group system is highly complex and characterized by the presence of major polymorphic antigens, namely MNS1/MNS2 and MNS3/MNS4. This study aims to examine the genetic basis of the common MNS antigens in Tunisian blood donors and discussed their importance in transfusion immunology.</p><p><strong>Methods and results: </strong>A group of 229 Tunisian blood donors were genotyped for the major alleles GYPA*01, GYPA*02, GYPB*03 and GYPB*04 using the SSP-PCR method. A specific GYPA region was sequenced in some subjects to examine if there is a rare allele. The statistical analysis was done using the HaploView Software. The molecular analysis showed that 4 blood donors are probably carrier of a rare GYPA allele. Furthermore, it appeared that the GYPA*01 and GYPB*04 alleles; and the GYPA*01-GYPB*04 haplotype are predominant in this series. As for the phenotype, the study showed that the MNS:1,2,-3,4 type is the most frequent in recruited blood donors.</p><p><strong>Conclusions: </strong>Overall, the study showed a balanced distribution of the targeted alleles. Furthermore, the observed frequencies appeared to be in harmony with that reported in other populations. Considering the importance of these findings, we think that this work will be an important contribution to the field of public health and epidemiology.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"474"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the role of mitochondrial dysfunction and aging in COVID-19-Related neurological complications.","authors":"Prajakta Hingole, Priya Saha, Sourav Das, Chayanika Gundu, Ashutosh Kumar","doi":"10.1007/s11033-025-10586-0","DOIUrl":"10.1007/s11033-025-10586-0","url":null,"abstract":"<p><p>The COVID-19 pandemic, caused by SARS-CoV-2, posed a tremendous challenge to healthcare systems globally. Severe COVID-19 infection was reported to be associated with altered immunometabolism and cytokine storms, contributing to poor clinical outcomes and in many cases resulting in mortality. Despite promising preclinical results, many drugs have failed to show efficacy in clinical trials, highlighting the need for novel approaches to combat the virus and its severe manifestations. Mitochondria, crucial for aerobic respiration, play a pivotal role in modulating immunometabolism and neuronal function, making their compromised capability as central pathological mechanism contributing to the development of neurological complications in COVID-19. Dysregulated mitochondrial dynamics can lead to uncontrolled immune responses, underscoring the importance of mitochondrial regulation in shaping clinical outcomes. Aging further accelerates mitochondrial dysfunction, compounding immune dysregulation and neurodegeneration, making older adults particularly vulnerable to severe COVID-19 and its neurological sequelae. COVID-19 infection impairs mitochondrial oxidative phosphorylation, contributing to the long-term neurological complications associated with the disease. Additionally, recent reports also suggest that up to 30% of COVID-19 patients experience lingering neurological issues, thereby highlighting the critical need for further research into mitochondrial pathways to mitigate long-tern neurological consequences of Covid-19. This review examines the role of mitochondrial dysfunction in COVID-19-induced neurological complications, its connection to aging, and potential biomarkers for clinical diagnostics. It also discusses therapeutic strategies aimed at maintaining mitochondrial integrity to improve COVID-19 outcomes.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"479"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abbas Asoudeh-Fard, Fatemeh Faezi Sis, Babak Rahmani, Mana Kamranjam, Fatemeh Soltanmohammadi, Mohammad Zareian Jahromi, Asghar Parsai
{"title":"Inhibitory effects of tetraselmis algae extract on cervical cancer cell proliferation: a molecular and cellular approach.","authors":"Abbas Asoudeh-Fard, Fatemeh Faezi Sis, Babak Rahmani, Mana Kamranjam, Fatemeh Soltanmohammadi, Mohammad Zareian Jahromi, Asghar Parsai","doi":"10.1007/s11033-025-10551-x","DOIUrl":"10.1007/s11033-025-10551-x","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is the leading type of primary malignancy in the uterus, causing significant morbidity and mortality, particularly in developing countries. Traditional treatments often result in severe side effects and recurrence, highlighting the need for safer alternatives. This study investigates the anticancer potential of Tetraselmis suecica, a green microalga known for its bioactive compounds.</p><p><strong>Methods: </strong>HeLa cervical cancer cells and HUVEC were treated with varying concentrations of T. suecica (25, 50, 75, and 100 mg/ml) for 24 h. Cell viability was assessed using the MTT assay, and gene expression related to apoptosis (Bax, Bcl-2, Caspases-3, -8, -9, PTEN, and AKT) was evaluated via real-time PCR for HeLa cells. Apoptosis was quantified using Annexin-V/PI double-staining for HeLa cells as well. The effect on HUVEC cells was assessed only by the MTT assay.</p><p><strong>Results: </strong>Treatment with T. suecica significantly reduced HeLa cell viability to 25% at 75 mg/ml and increased the expression of pro-apoptotic genes while decreasing anti-apoptotic markers. Apoptotic cell populations rose markedly, indicating that T. suecica induces apoptosis through both intrinsic and extrinsic pathways. However, no significant effect on cell viability or apoptosis was observed in HUVEC cells, suggesting that T. suecica selectively targets cancer cells without affecting normal endothelial cells.</p><p><strong>Conclusions: </strong>T. suecica exhibits promising anticancer properties and may serve as a novel therapeutic agent for cervical cancer, warranting further research into its mechanisms and therapeutic applications. The selective activity on cancer cells and lack of toxicity to normal cells such as HUVECs further supports its potential for targeted cancer therapy.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"473"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaya Bharati, Satish Kumar, Bijoy Mukut Buragohain, Diptesh Das, Salam Jayachitra Devi, N H Mohan, Vivek Kumar Gupta
{"title":"Identification of differentially expressed genes and pathways in the post-ovulatory ampulla of cyclic pigs through a transcriptomics approach.","authors":"Jaya Bharati, Satish Kumar, Bijoy Mukut Buragohain, Diptesh Das, Salam Jayachitra Devi, N H Mohan, Vivek Kumar Gupta","doi":"10.1007/s11033-025-10605-0","DOIUrl":"10.1007/s11033-025-10605-0","url":null,"abstract":"<p><strong>Background: </strong>Information on global transcriptomic changes in the porcine ampulla after ovulation is crucial for understanding of oviductal physiology at the molecular level. The objective of the present study was to investigate the differentially expressed genes (DEGs) and signalling pathways regulating the functionality of ampulla in pigs post-ovulation.</p><p><strong>Methods and results: </strong>The RNA-sequencing of the post-ovulatory ampulla (POA) and early luteal ampulla (ELA) tissues was conducted using Illumina NextSeq2000. The R package NOISeq was used to obtain significantly differentially expressed genes (DEGs) with the probability of differential expression (1-FDR) value ≥ 0.95 and log<sub>2</sub> fold change (log<sub>2</sub>FC) ≥ 1, which revealed 817 DEGs (657 up- and 160 down-regulated) in the POA vs. ELA group comparison. These DEGs were functionally annotated with various gene ontology terms like sterol biosynthetic process, growth, cell migration, and Reactome pathways like signal transduction, metabolism, and cell cycle, indicating key role of these molecular events in POA. The WNT, TNFR2 non-canonical NF-kB, and hedgehog signalling pathways along with the activation of the immune system process, were enriched in the POA vs. ELA group, which indicates their role in cell-cell interactions and cell fate determination in remodelling the oviductal microenvironment during transition from estrogen to progesterone domination. The highly connected upregulated hub genes ESR1, RAD51, YARS1, TYMS and CDK2 can be regarded as key regulatory factors in synchronizing the changes in POA at the molecular level in the oviduct.</p><p><strong>Conclusion: </strong>The present study revealed several DEGs, signalling pathways and novel modulatory factors associated with the ampullary physiology during early embryonic development in the POA, which may influence fertility and litter size in pigs.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"481"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of thrombomodulin in pterygium: implications for inflammation and disease progression.","authors":"Yu-Kuei Lee, Chun-Chieh Lai, I-Chen Peng, Yi-Hsun Huang","doi":"10.1007/s11033-025-10588-y","DOIUrl":"10.1007/s11033-025-10588-y","url":null,"abstract":"<p><strong>Background: </strong>Pterygium is a chronic inflammatory condition of conjunctiva. Thrombomodulin (TM) is a glycoprotein involved in the regulation of inflammation. This study investigated TM expression in primary and recurrent pterygium compared to normal conjunctiva, along with its role in pterygium pathogenesis and potential as a therapeutic target for inflammation control.</p><p><strong>Methods and results: </strong>Pterygium (10 primary, 10 recurrent) and normal conjunctiva specimens were collected from 20 patients who underwent pterygium excision. TM expression was analyzed using immunofluorescence, western blotting, and real-time quantitative polymerase chain reaction (RT-PCR). Inflammatory markers, including interleukin-6 (IL-6), high mobility group box 1 (HMGB1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and matrix metalloproteinase-1 (MMP-1), were measured. The results showed significantly lower TM expression in pterygium tissues (p < 0.01), with higher TM levels in the head region compared to the body, suggesting a localized inflammatory response. Additionally, macrophage marker F4/80 and neutrophil marker NIMP-R14 were elevated in pterygium tissues. Western blot and RT-PCR confirmed significantly reduced TM expression (p < 0.0001) in primary and recurrent pterygium, with recurrent cases showing even lower levels (p < 0.05). Elevated IL-6, HMGB1, VEGF, bFGF, and MMP-1 levels suggest a strong association between TM downregulation and increased inflammation.</p><p><strong>Conclusions: </strong>TM downregulation in pterygium (particularly in recurrent cases) may contribute to chronic inflammation and disease progression. Upregulation of TM at the pterygium head may represent a localized protective response against inflammation. TM supplementation should be explored as a novel therapeutic strategy to mitigate inflammation in pterygium.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"477"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elaheh Najafi, Farhad Pourfarzi, Mohammad Mazani, Abbas Yazdanbod, Kosar Rezagholizadeh, Aliakbar Fazaeli
{"title":"Paraoxonase 1 polymorphisms and their relationship with gastric cancer risk: a biochemical perspective on oxidative stress.","authors":"Elaheh Najafi, Farhad Pourfarzi, Mohammad Mazani, Abbas Yazdanbod, Kosar Rezagholizadeh, Aliakbar Fazaeli","doi":"10.1007/s11033-025-10563-7","DOIUrl":"10.1007/s11033-025-10563-7","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a significant global health issue, with oxidative stress playing a pivotal role in its pathogenesis. Paraoxonase 1 (PON1), an enzyme with antioxidant properties, may modulate oxidative stress and cancer susceptibility. This study examined the association between two PON1 polymorphisms, rs662 (Q192R) and rs854560 (L55M), and their effects on GC risk and oxidative stress markers.</p><p><strong>Methods: </strong>The study included 250 histopathologically confirmed GC patients and 210 healthy controls. PON1 polymorphisms were genotyped, and biochemical markers-including PON1 and arylesterase (ARE) activities, total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)-were quantified.</p><p><strong>Results: </strong>The genotype frequencies of rs854560 and rs662 differed significantly between GC patients and controls. The rs854560 polymorphism was linked to GC risk in co-dominant and dominant inheritance models, while rs662 was associated in co-dominant, dominant, and recessive models. PON1 and ARE activities were significantly reduced in GC patients compared to controls (p = 0.001 and p < 0.001, respectively). TAC was higher in controls (p = 0.006), whereas TOS and OSI showed non-significant trends toward elevation in the GC group (p = 0.093 and p = 0.181, respectively). Genotype stratification revealed significant variations in PON1, ARE, TAC, TOS, and OSI levels across rs854560 and rs662 variants.</p><p><strong>Conclusion: </strong>Our findings indicate that genetic polymorphisms in PON1, specifically rs662 and rs854560, influence susceptibility to gastric cancer by altering oxidative stress markers. These findings provide insights into how PON1 genetic variations affect oxidative stress and contribute to cancer risk.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"472"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milad Kashi, Abbas Farahani, Azam Ahmadi, Aref Shariati, Majid Akbari
{"title":"Antibacterial and antibiofilm efficacy of eugenol, carvacrol, and cinnamaldehyde against colistin-resistant Klebsiella pneumoniae.","authors":"Milad Kashi, Abbas Farahani, Azam Ahmadi, Aref Shariati, Majid Akbari","doi":"10.1007/s11033-025-10564-6","DOIUrl":"10.1007/s11033-025-10564-6","url":null,"abstract":"<p><strong>Background: </strong>Colistin-resistant Klebsiella pneumoniae (CR K. pneumoniae) is considered one of the bacteria with the highest levels of antibiotic resistance, necessitating the discovery of alternative therapeutic strategies. This study aimed to evaluate the ability of eugenol, carvacrol, and cinnamaldehyde to inhibit CR K. pneumoniae and the biofilm community of this bacterium.</p><p><strong>Method: </strong>The minimum inhibitory concentration (MIC) and antibiofilm effects of compounds were assessed using broth macrodilution and microtiter plate assays, respectively. Time-kill assays determined the bactericidal effects of natural compounds on CR K. pneumoniae isolates. Protein and nucleic acid leakage were examined to assess metabolic disruption and cell membrane integrity. Real-time PCR was used to evaluate the effect of natural compounds on the expression of biofilm-related genes (mrkA, treC, and luxS).</p><p><strong>Results: </strong>In the disk diffusion test, the inhibition zones of eugenol, carvacrol, and cinnamaldehyde were 15 ± 1, 29 ± 2, and 30 ± 1 mm, respectively. The MIC of eugenol, carvacrol, and cinnamaldehyde were 260, 119, and 128 µg/mL, respectively. The time-kill assay demonstrated the rapid bactericidal effects of eugenol, carvacrol, and cinnamaldehyde at 2× MIC, with kill times of 6, 2, and 3 h, respectively. At the MIC, the kill times were 12, 10, and 12 h, respectively. These compounds significantly released proteins and nucleic acids from the treated bacteria. They also inhibited biofilm formation and disrupted mature biofilms. Furthermore, mrkA and treC expression levels were significantly reduced in the presence of eugenol and cinnamaldehyde.</p><p><strong>Conclusion: </strong>These natural compounds demonstrated significant antibacterial and antibiofilm activity against CR K. pneumoniae, emerging as a promising natural alternative for treatment.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"480"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingxuan Hu, Qingzhen He, Yang Cui, Wenbing Ding, Hualiang He, Hongshuai Gao, Qiao Gao, Lin Qiu, Youzhi Li
{"title":"RNA interference knockdown of the nuclear receptor HR3 suppresses vitellogenesis in Chilo suppressalis.","authors":"Jingxuan Hu, Qingzhen He, Yang Cui, Wenbing Ding, Hualiang He, Hongshuai Gao, Qiao Gao, Lin Qiu, Youzhi Li","doi":"10.1007/s11033-025-10550-y","DOIUrl":"10.1007/s11033-025-10550-y","url":null,"abstract":"<p><strong>Background: </strong>Developmental and reproductive processes are the most critical physiological processes in insects, with the insect hormone 20-hydroxyecdysone (20E, the major active form of ecdysone) playing a central regulatory role in key developmental events such as embryonic development, larval molting, metamorphosis, and reproduction. As an early-late gene within the ecdysone-mediated genetic regulatory network, the orphan nuclear receptor HR3, which exhibits characteristics of both early and late genes, serves as a critical regulator of insect metamorphosis and development. However, the precise molecular mechanisms underlying HR3's function in the reproduction of non-model insects remain poorly understood.</p><p><strong>Methods and results: </strong>We cloned Chilo suppressalis HR3 (CsHR3) and phylogenetic analysis demonstrates that CsHR3 shares the highest sequence homology with its ortholog in Ostrinia furnacalis. Spatiotemporal expression profiling revealed that CsHR3 expression peaked during day 4 of the female pupal stage, with the highest tissue-specific expression observed in the heads of female pupae. RNA-interference (RNAi) mediated silencing of CsHR3 resulted in delayed oocyte maturation, reduced yolk deposition, and decreased fecundity. Concurrently, transcriptional levels of key genes involved in yolk formation vitellogenin (Vg), 20E and juvenile hormones (JH) signaling pathways, including chitin synthase 1 (CHS1), were significantly downregulated in the CsHR3-knockdown group.</p><p><strong>Conclusion: </strong>These findings collectively demonstrate that CsHR3 plays an essential role in the reproductive regulation of C. suppressalis, potentially mediating transcriptional control of 20E and JH pathway-related genes and chitin biosynthesis-related targets. This study not only advances the understanding of reproductive regulation in Lepidoptera but also highlights HR3 as a potential molecular target for pest management strategies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"478"},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}