Pub Date : 2026-03-01Epub Date: 2025-11-27DOI: 10.1016/j.bbrep.2025.102387
Chenyang Wang , Xiaoshan Li , Changbing Wang , Yudan Ye , Mingqi Zhao , Min Guo , Tiantian Xu , Lu Kuang , Yuqing Yan , Wanli Liang , Xingui Tian , Bing Zhu
Severe adenovirus infections pose significant health challenges, particularly in immunocompromised individuals. This study characterizes the antiviral activity of dihydro-resveratrol (Dihydro-R) against adenovirus type 7 and reveals a SIRT1-dependent mechanism. Our study reveals that Dihydro-R effectively inhibits adenoviral replication across multiple cell lines through SIRT1 activation. Mechanistically, Dihydro-R suppresses the NF-κB and JAK/STAT pathways, leading to reduced expression of inflammatory factors. The critical role of SIRT1 in Dihydro-R's antiviral activity was confirmed through reverse validation using a SIRT1 inhibitor. Notably, Dihydro-R's antiviral effects correlate with SIRT1 upregulation, with A549 cells showing the strongest response. Time-course analysis demonstrates maximal inhibition of NF-κB and JAK/STAT pathways within 48 h of Dihydro-R treatment. Furthermore, Dihydro-R modulates the expression of key cytokines, including IL-8, IL-6, and IL-4, contributing to its anti-inflammatory properties. Our findings not only highlight Dihydro-R as a promising therapeutic candidate for adenovirus infections but also provide insights into SIRT1-targeted antiviral strategies. This study opens new avenues for developing natural compound-based therapies against adenoviral infections and potentially other viral diseases involving similar pathways.
{"title":"Dihydro-R demonstrates innate immunity against Adenovirus-7 by suppressing the NF-κB/JAK-STAT pathway in a SIRT1-dependent manner","authors":"Chenyang Wang , Xiaoshan Li , Changbing Wang , Yudan Ye , Mingqi Zhao , Min Guo , Tiantian Xu , Lu Kuang , Yuqing Yan , Wanli Liang , Xingui Tian , Bing Zhu","doi":"10.1016/j.bbrep.2025.102387","DOIUrl":"10.1016/j.bbrep.2025.102387","url":null,"abstract":"<div><div>Severe adenovirus infections pose significant health challenges, particularly in immunocompromised individuals. This study characterizes the antiviral activity of dihydro-resveratrol (Dihydro-R) against adenovirus type 7 and reveals a SIRT1-dependent mechanism. Our study reveals that Dihydro-R effectively inhibits adenoviral replication across multiple cell lines through SIRT1 activation. Mechanistically, Dihydro-R suppresses the NF-κB and JAK/STAT pathways, leading to reduced expression of inflammatory factors. The critical role of SIRT1 in Dihydro-R's antiviral activity was confirmed through reverse validation using a SIRT1 inhibitor. Notably, Dihydro-R's antiviral effects correlate with SIRT1 upregulation, with A549 cells showing the strongest response. Time-course analysis demonstrates maximal inhibition of NF-κB and JAK/STAT pathways within 48 h of Dihydro-R treatment. Furthermore, Dihydro-R modulates the expression of key cytokines, including IL-8, IL-6, and IL-4, contributing to its anti-inflammatory properties. Our findings not only highlight Dihydro-R as a promising therapeutic candidate for adenovirus infections but also provide insights into SIRT1-targeted antiviral strategies. This study opens new avenues for developing natural compound-based therapies against adenoviral infections and potentially other viral diseases involving similar pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102387"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-28DOI: 10.1016/j.bbrep.2025.102375
Franz Müller , Sonja Neuser , Gaurav Shrestha , Netra P. Neupane , Katharina J. Götze , Nicola Brunetti-Pierri , Gaetano Terrone , Alexandre Reymond , Koen L. van Gassen , Eva Brilstra , Katharina Steindl , Anais Begemann , Anita Rauch , Jonathan Rips , Duha Fahham , Tahsin Stefan Barakat , Olivier Patat , Jérémie Mortreux , Matthew Hoi Kin Chau , Jill A. Rosenfeld , Dmitrij Ljaschenko
UNC13s are presynaptic proteins essential for neurotransmitter release at chemical synapses. In this study, we present eleven patients from nine families with severe neurodevelopmental impairments, who carry rare, biallelic UNC13C single-nucleotide variants (SNVs). Six missense variants, each identified in compound heterozygosity in one of three of these patients, were introduced into the Drosophila melanogaster ortholog unc13 using a previously established CRISPR/Cas9-based method for rapid and scarless genomic modifications, hypothesising that they underlie the observed clinical manifestations. However, none of the introduced mutations influenced Mendelian ratios, negative geotaxis, or lifespan of the fruit flies. Interestingly, two variants located outside the gene regions encoding known UNC13C domains caused a decreased ethanol sensitivity in Drosophila, while the Thr1729Met substitution within the C1 domain resulted in increased ethanol sensitivity. Molecular dynamics simulations of the latter mutant gene product suggested that the altered protein conformation enhances exposure of the ethanol-binding site, thereby increasing sensitivity to ethanol. These findings reinforce previous evidence highlighting the critical role of the C1 domain in ethanol sensitivity. Given the involvement of the C1 domain in synaptic plasticity this result might implicate an influence of the Thr1729Met on synaptic function.
{"title":"Single nucleotide variants in UNC13C associated with neurodevelopmental disorders affect ethanol sensitivity in Drosophila","authors":"Franz Müller , Sonja Neuser , Gaurav Shrestha , Netra P. Neupane , Katharina J. Götze , Nicola Brunetti-Pierri , Gaetano Terrone , Alexandre Reymond , Koen L. van Gassen , Eva Brilstra , Katharina Steindl , Anais Begemann , Anita Rauch , Jonathan Rips , Duha Fahham , Tahsin Stefan Barakat , Olivier Patat , Jérémie Mortreux , Matthew Hoi Kin Chau , Jill A. Rosenfeld , Dmitrij Ljaschenko","doi":"10.1016/j.bbrep.2025.102375","DOIUrl":"10.1016/j.bbrep.2025.102375","url":null,"abstract":"<div><div>UNC13s are presynaptic proteins essential for neurotransmitter release at chemical synapses. In this study, we present eleven patients from nine families with severe neurodevelopmental impairments, who carry rare, biallelic <em>UNC13C</em> single-nucleotide variants (SNVs). Six missense variants, each identified in compound heterozygosity in one of three of these patients, were introduced into the <em>Drosophila melanogaster</em> ortholog <em>unc13</em> using a previously established CRISPR/Cas9-based method for rapid and scarless genomic modifications, hypothesising that they underlie the observed clinical manifestations. However, none of the introduced mutations influenced Mendelian ratios, negative geotaxis, or lifespan of the fruit flies. Interestingly, two variants located outside the gene regions encoding known UNC13C domains caused a decreased ethanol sensitivity in <em>Drosophila</em>, while the Thr1729Met substitution within the C<sub>1</sub> domain resulted in increased ethanol sensitivity. Molecular dynamics simulations of the latter mutant gene product suggested that the altered protein conformation enhances exposure of the ethanol-binding site, thereby increasing sensitivity to ethanol. These findings reinforce previous evidence highlighting the critical role of the C<sub>1</sub> domain in ethanol sensitivity. Given the involvement of the C<sub>1</sub> domain in synaptic plasticity this result might implicate an influence of the Thr1729Met on synaptic function.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102375"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-29DOI: 10.1016/j.bbrep.2025.102359
Jihao Shi, Lexi Wu, Chuwen Tian, Haotian Chen
Colorectal cancer (CRC) ranks among the most prevalent malignancies globally and is the third leading cause of cancer - related deaths. Despite advancements in diagnosis and treatment, prognosis for CRC patients, especially those with advanced or metastatic disease, remains difficult due to its heterogeneity. Mitochondria, central to cellular activity, and the mitochondrial unfolded protein response (UPRmt), a stress - responsive pathway, are involved in various physiological and pathological processes. Recent studies have emphasized the importance of UPRmt in cancer biology. In this research, we explored the role of UPR - related genes (MRGs) in CRC. Through analyzing transcriptional profiles and clinical data of CRC patients, we identified different molecular subtypes according to MRG expression, which were related to patient prognosis, immune cell infiltration, and drug sensitivity. We also developed a prognostic signature based on key MRGs with strong predictive power for patient survival and treatment response. Additionally, the study of the spatial distribution of MRGs in tumor tissues revealed their heterogeneous expression and potential influence on tumor biology. Overall, our findings clarify the role of UPR in CRC and highlight its potential as a target for personalized cancer therapy.
{"title":"Unraveling the role of mitochondrial unfolded protein response in colorectal cancer","authors":"Jihao Shi, Lexi Wu, Chuwen Tian, Haotian Chen","doi":"10.1016/j.bbrep.2025.102359","DOIUrl":"10.1016/j.bbrep.2025.102359","url":null,"abstract":"<div><div>Colorectal cancer (CRC) ranks among the most prevalent malignancies globally and is the third leading cause of cancer - related deaths. Despite advancements in diagnosis and treatment, prognosis for CRC patients, especially those with advanced or metastatic disease, remains difficult due to its heterogeneity. Mitochondria, central to cellular activity, and the mitochondrial unfolded protein response (UPR<sup>mt</sup>), a stress - responsive pathway, are involved in various physiological and pathological processes. Recent studies have emphasized the importance of UPR<sup>mt</sup> in cancer biology. In this research, we explored the role of UPR - related genes (MRGs) in CRC. Through analyzing transcriptional profiles and clinical data of CRC patients, we identified different molecular subtypes according to MRG expression, which were related to patient prognosis, immune cell infiltration, and drug sensitivity. We also developed a prognostic signature based on key MRGs with strong predictive power for patient survival and treatment response. Additionally, the study of the spatial distribution of MRGs in tumor tissues revealed their heterogeneous expression and potential influence on tumor biology. Overall, our findings clarify the role of UPR in CRC and highlight its potential as a target for personalized cancer therapy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102359"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-11DOI: 10.1016/j.bbrep.2025.102405
Mohammad Jahanpanah, Abtin Ghasempour, Diana Mokhtari, Shirin Eshghi, Mahsa Mousakhan Bakhtiari, Mohammad Taha Salmanifard Ardestani, Leila Jafari, Maryam Behfar, Amir Ali Hamidieh
The exact etiology of Acute Lymphoblastic Leukemia (ALL) is not yet fully understood. Inherited genetic abnormalities and exposure to environmental risk factors are implicated in pathogenesis of ALL patients. Over the past two decades, epigenetic factors like microRNAs (miRs) have been in the spotlight and shown to have a pivotal role in the pathogenicity of ALL. MiRs are a group of small non-coding single-stranded RNAs (∼22 nucleotides) involved in post-transcriptional regulation of gene expression. MiR-181a has been shown to have a dual behavior in different types of cancers. This dual behavior of miR-181a shows that it should be investigated in a disease-specific manner. In this study, 24 studies were reviewed in different sections including the expression pattern of miR-181a, its target genes, and its potential as a biomarker in ALL from January 2000 to March 2025. Results of the reviewed studies conclusively indicate that miR-181a-5p is upregulated in pediatric ALL patients compared to normal control groups, and miR-181a-5p acts as an oncomir in pediatric ALL patients. Nevertheless, there are only a few studies in adults with inconclusive results. Furthermore, miR-181a-5p might be the upstream activator of the leukemic T-cell proliferation by having direct and indirect effects on several genes. Recent studies indicate that this miR can be implemented in diagnosing and classifying central nervous system (CNS) involvement in ALL patients, which is a devastating challenge in the field of hematology-oncology.
{"title":"MicroRNA-181a in acute lymphoblastic leukemia: expression pattern, target genes and its potential as a biomarker","authors":"Mohammad Jahanpanah, Abtin Ghasempour, Diana Mokhtari, Shirin Eshghi, Mahsa Mousakhan Bakhtiari, Mohammad Taha Salmanifard Ardestani, Leila Jafari, Maryam Behfar, Amir Ali Hamidieh","doi":"10.1016/j.bbrep.2025.102405","DOIUrl":"10.1016/j.bbrep.2025.102405","url":null,"abstract":"<div><div>The exact etiology of Acute Lymphoblastic Leukemia (ALL) is not yet fully understood. Inherited genetic abnormalities and exposure to environmental risk factors are implicated in pathogenesis of ALL patients. Over the past two decades, epigenetic factors like microRNAs (miRs) have been in the spotlight and shown to have a pivotal role in the pathogenicity of ALL. MiRs are a group of small non-coding single-stranded RNAs (∼22 nucleotides) involved in post-transcriptional regulation of gene expression. MiR-181a has been shown to have a dual behavior in different types of cancers. This dual behavior of miR-181a shows that it should be investigated in a disease-specific manner. In this study, 24 studies were reviewed in different sections including the expression pattern of miR-181a, its target genes, and its potential as a biomarker in ALL from January 2000 to March 2025. Results of the reviewed studies conclusively indicate that miR-181a-5p is upregulated in pediatric ALL patients compared to normal control groups, and miR-181a-5p acts as an oncomir in pediatric ALL patients. Nevertheless, there are only a few studies in adults with inconclusive results. Furthermore, miR-181a-5p might be the upstream activator of the leukemic T-cell proliferation by having direct and indirect effects on several genes. Recent studies indicate that this miR can be implemented in diagnosing and classifying central nervous system (CNS) involvement in ALL patients, which is a devastating challenge in the field of hematology-oncology.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102405"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-09DOI: 10.1016/j.bbrep.2026.102486
Okechukwu Paul-Chima Ugwu , Melvin Nnaaemeka Ugwu , Hope Onohuean , Hilal Ahmad Rather , Ibe Michael Usman
Background
Medicinal plants produce specialised (secondary) metabolites including alkaloids, terpenoids, flavonoids and phenolics that underpin pharmaceuticals, nutraceuticals and traditional therapeutics. Although enzyme-encoding genes and transcription factors are established regulators of these pathways, accumulating evidence indicates that noncoding RNAs (ncRNAs) provide additional, and in some contexts decisive, regulatory control.
Objective
To synthesise and critically appraise evidence on how plant ncRNAs microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate secondary metabolism in medicinal plants, and to map translational opportunities and unresolved gaps.
Methods
We conducted a narrative review with a systematic synthesis across PubMed/MEDLINE, Scopus, Web of Science Core Collection, CAB Abstracts and AGRICOLA, supplemented by Google Scholar screening using SANRA.
Results
Across medicinal and non-model plant systems, miRNAs repeatedly target transcription factors that control biosynthetic pathways (e.g., MYB/bHLH/WRKY families) and, in some cases, key enzymes (e.g., PAL/CHS/DFR modules), thereby supporting stress-responsive and developmentally timed reprogramming of metabolite profiles. siRNAs contribute through RNA-directed DNA methylation (RdDM) and regulation of transposons and gene clusters. lncRNAs modulate chromatin accessibility and function as scaffolds or decoys, including as competing endogenous RNA (ceRNA) ‘sponges’, whereas circRNAs are emerging as relatively stable regulatory hubs that may influence miRNA availability and stress-associated transcriptional states. Evidence quality varies across ncRNA classes and species, and mechanistic validation in medicinal plants remains inconsistent.
Conclusions
ncRNAs constitute a multilayer regulatory system shaping the ‘phytochemical economy’ of medicinal plants. Progress towards translation will require standardised ncRNA annotation resources, rigorous causal validation, and integrated multi-omics study designs to support precision metabolic engineering and sustainable phytochemical production.
{"title":"Noncoding RNAs and the phytochemical economy: Molecular regulators of secondary metabolism in medicinal plants","authors":"Okechukwu Paul-Chima Ugwu , Melvin Nnaaemeka Ugwu , Hope Onohuean , Hilal Ahmad Rather , Ibe Michael Usman","doi":"10.1016/j.bbrep.2026.102486","DOIUrl":"10.1016/j.bbrep.2026.102486","url":null,"abstract":"<div><h3>Background</h3><div>Medicinal plants produce specialised (secondary) metabolites including alkaloids, terpenoids, flavonoids and phenolics that underpin pharmaceuticals, nutraceuticals and traditional therapeutics. Although enzyme-encoding genes and transcription factors are established regulators of these pathways, accumulating evidence indicates that noncoding RNAs (ncRNAs) provide additional, and in some contexts decisive, regulatory control.</div></div><div><h3>Objective</h3><div>To synthesise and critically appraise evidence on how plant ncRNAs microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate secondary metabolism in medicinal plants, and to map translational opportunities and unresolved gaps.</div></div><div><h3>Methods</h3><div>We conducted a narrative review with a systematic synthesis across PubMed/MEDLINE, Scopus, Web of Science Core Collection, CAB Abstracts and AGRICOLA, supplemented by Google Scholar screening using SANRA.</div></div><div><h3>Results</h3><div>Across medicinal and non-model plant systems, miRNAs repeatedly target transcription factors that control biosynthetic pathways (e.g., MYB/bHLH/WRKY families) and, in some cases, key enzymes (e.g., PAL/CHS/DFR modules), thereby supporting stress-responsive and developmentally timed reprogramming of metabolite profiles. siRNAs contribute through RNA-directed DNA methylation (RdDM) and regulation of transposons and gene clusters. lncRNAs modulate chromatin accessibility and function as scaffolds or decoys, including as competing endogenous RNA (ceRNA) ‘sponges’, whereas circRNAs are emerging as relatively stable regulatory hubs that may influence miRNA availability and stress-associated transcriptional states. Evidence quality varies across ncRNA classes and species, and mechanistic validation in medicinal plants remains inconsistent.</div></div><div><h3>Conclusions</h3><div>ncRNAs constitute a multilayer regulatory system shaping the ‘phytochemical economy’ of medicinal plants. Progress towards translation will require standardised ncRNA annotation resources, rigorous causal validation, and integrated multi-omics study designs to support precision metabolic engineering and sustainable phytochemical production.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102486"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-02-09DOI: 10.1016/j.bbrep.2026.102485
Han Mo , Hui Li , Jiadong Wu , Liu Yi , Fenglan He , Qingmei Huang , Xian Zhang , Qian Yang , Tianmu Chen , Xianfeng Zhou
Objectives
This study aimed to elucidate the global epidemic trends and evolutionary characteristics of nine major non-polio enterovirus serotypes (CVA2, CVA4, CVA6, CVA10, CVA16, CVB3, CVB5, EV-A71, and EV-D68) through genomic data mining, focusing on their spatiotemporal distribution and evolutionary dynamics.
Design
We employed a data mining framework integrating programming, phylogenetic analysis, Bayesian evolutionary modeling, and selection pressure assessment. Over 40,000 genomic sequences from GenBank were analyzed to reconstruct temporal phylogenies, estimate evolutionary rates, and characterize amino acid variability in the capsid protein VP1. Seasonal decomposition and spatial-temporal trend modeling were applied to evaluate epidemic patterns across the six WHO regions.
Results
Key findings include [1]: Distinct biennial or triennial epidemic cycles for EV-D68 and clear seasonal peaks for HFMD-associated serotypes [2]; A preliminary observation termed the “60% Transcendence” phenomenon, where once cumulative VP1 nucleotide mutations reach approximately 60%, the cumulative non-synonymous amino acid mutations begin to exceed this threshold [3]; Evidence of episodic positive selection at critical VP1 codons, suggesting immune-driven evolution [4]; Divergent trends in relative genetic diversity, with EV-A71, CVA16, and CVA6 showing sustained expansion, while the diversity of CVB5 and EV-D68 declined sharply during the COVID-19 pandemic.
Conclusions
This study provides valuable insights into the changing landscape of global enterovirus infections and underscores the critical role of genomic epidemiology in tracking their spread. Sustained research in this field is essential for developing effective strategies to prevent and control enterovirus-related diseases worldwide.
{"title":"Global distribution and evolution of nine major non-polio enteroviruses revealed by genomic data mining","authors":"Han Mo , Hui Li , Jiadong Wu , Liu Yi , Fenglan He , Qingmei Huang , Xian Zhang , Qian Yang , Tianmu Chen , Xianfeng Zhou","doi":"10.1016/j.bbrep.2026.102485","DOIUrl":"10.1016/j.bbrep.2026.102485","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to elucidate the global epidemic trends and evolutionary characteristics of nine major non-polio enterovirus serotypes (CVA2, CVA4, CVA6, CVA10, CVA16, CVB3, CVB5, EV-A71, and EV-D68) through genomic data mining, focusing on their spatiotemporal distribution and evolutionary dynamics.</div></div><div><h3>Design</h3><div>We employed a data mining framework integrating programming, phylogenetic analysis, Bayesian evolutionary modeling, and selection pressure assessment. Over 40,000 genomic sequences from GenBank were analyzed to reconstruct temporal phylogenies, estimate evolutionary rates, and characterize amino acid variability in the capsid protein VP1. Seasonal decomposition and spatial-temporal trend modeling were applied to evaluate epidemic patterns across the six WHO regions.</div></div><div><h3>Results</h3><div>Key findings include [1]: Distinct biennial or triennial epidemic cycles for EV-D68 and clear seasonal peaks for HFMD-associated serotypes [2]; A preliminary observation termed the “60% Transcendence” phenomenon, where once cumulative VP1 nucleotide mutations reach approximately 60%, the cumulative non-synonymous amino acid mutations begin to exceed this threshold [3]; Evidence of episodic positive selection at critical VP1 codons, suggesting immune-driven evolution [4]; Divergent trends in relative genetic diversity, with EV-A71, CVA16, and CVA6 showing sustained expansion, while the diversity of CVB5 and EV-D68 declined sharply during the COVID-19 pandemic.</div></div><div><h3>Conclusions</h3><div>This study provides valuable insights into the changing landscape of global enterovirus infections and underscores the critical role of genomic epidemiology in tracking their spread. Sustained research in this field is essential for developing effective strategies to prevent and control enterovirus-related diseases worldwide.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102485"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muscle atrophy is a growing concern, particularly in older adults and people with sedentary lifestyles. Because treatment options are limited, extensive research is crucial to discover novel therapeutic agents. Thus, we investigated the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) and its parent compound, 4-hydroxy-3-methoxycinnamic acid (HMCA), on dexamethasone (Dex)-induced muscle atrophy in C57BL/6J female mice. Dex injection (10 mg/kg body weight [BW] in mice for 10 consecutive days negatively affected body weight, gastrocnemius and tibialis anterior muscle mass, myofiber cross sectional area (CSA) and level of myosin heavy chain (MyHC) protein. Atrogin-1 and muscle ring finger protein-1, two major muscle atrophy-associated ubiquitin ligases, were significantly increased following Dex administration, along with their upstream regulators forkhead box O3a (FoxO3a) and Krüppel-like factor 15 (KLF15). Furthermore, Dex-induced oxidative stress by increasing malondialdehyde and advanced oxidation protein products in plasma and skeletal muscle. Intriguingly, HMPA and HMCA administration (50 mg/kg BW) for 21 days effectively prevented the attenuation of muscle mass, myofiber CSA and MyHC protein levels and suppressed ubiquitin ligase expression by ameliorating the upstream transcriptional factors FoxO3a and KLF15. Moreover, increased oxidative stress and oxidative stress-sensitive casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) ubiquitin ligase induced by Dex were effectively diminished by HMPA/HMCA administration. These observations suggest that HMPA and HMCA may be potential in vivo therapeutic agents that attenuate muscle atrophy by reversing atrophy-mimicking genes, oxidative stress, and related anomalies.
{"title":"Protective effects of 3-(4-hydroxy-3-methoxyphenyl) propionic acid against dexamethasone-induced muscle atrophy: modulation of associated genes and oxidative stress in female mice","authors":"Anayt Ulla , Honomi Ogura , Md Mizanur Rahman , Saya Nakamura , Yuka Ichiba , Haruka Tsuda , Takayuki Uchida , Hiroyuki Kayaki , Yosuke Nishitani , Susumu Yoshino , Hiroshige Kuwahara , Toshiro Matsui , Takeshi Nikawa","doi":"10.1016/j.bbrep.2026.102483","DOIUrl":"10.1016/j.bbrep.2026.102483","url":null,"abstract":"<div><div>Muscle atrophy is a growing concern, particularly in older adults and people with sedentary lifestyles. Because treatment options are limited, extensive research is crucial to discover novel therapeutic agents. Thus, we investigated the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) and its parent compound, 4-hydroxy-3-methoxycinnamic acid (HMCA), on dexamethasone (Dex)-induced muscle atrophy in C57BL/6J female mice. Dex injection (10 mg/kg body weight [BW] in mice for 10 consecutive days negatively affected body weight, gastrocnemius and tibialis anterior muscle mass, myofiber cross sectional area (CSA) and level of myosin heavy chain (MyHC) protein. Atrogin-1 and muscle ring finger protein-1, two major muscle atrophy-associated ubiquitin ligases, were significantly increased following Dex administration, along with their upstream regulators forkhead box O3a (FoxO3a) and Krüppel-like factor 15 (KLF15). Furthermore, Dex-induced oxidative stress by increasing malondialdehyde and advanced oxidation protein products in plasma and skeletal muscle. Intriguingly, HMPA and HMCA administration (50 mg/kg BW) for 21 days effectively prevented the attenuation of muscle mass, myofiber CSA and MyHC protein levels and suppressed ubiquitin ligase expression by ameliorating the upstream transcriptional factors FoxO3a and KLF15. Moreover, increased oxidative stress and oxidative stress-sensitive casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) ubiquitin ligase induced by Dex were effectively diminished by HMPA/HMCA administration. These observations suggest that HMPA and HMCA may be potential <em>in vivo</em> therapeutic agents that attenuate muscle atrophy by reversing atrophy-mimicking genes, oxidative stress, and related anomalies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102483"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A systematic understanding of the metabolic components in cigar tobacco leaves (CTLs) from different ecological regions remains limited. This study aimed to clarify the substance differences between CTLs from Yunnan and major foreign production areas and to identify potential discriminant metabolites. A total of 25 CTL samples were collected from four production areas in Yunnan and five different foreign countries. The metabolic profiles were comprehensively characterized using continuous flow analysis, ion chromatography, GC-MS, and UPLC-MS/MS. The results revealed that Yunnan CTLs were characterized by a lower sugar-nicotine ratio and significantly higher contents of starch, pectin, and lignin compared to foreign samples. Phenolic acids, alkaloids, flavonoids, amino acids and derivatives, terpenoids, and lipids were identified as the primary components across all CTLs. A total of 398 differential metabolites (248 volatile and 150 non-volatile) were identified, predominantly from the classes of amino acids and derivatives, alkaloids, terpenoids, and lipids. From these, 12 metabolites were selected as potential candidates for distinguishing CTL origin. KEGG enrichment and MetOrigin analyses indicated that the differential metabolites were mainly involved in the biosynthesis of alkaloids, amino acids, flavonoids, lipids, and terpenes, with these pathways being significantly influenced by microorganism and enzyme-mediated carbon and nitrogen coupling metabolism. This exploratory study provides a metabolic foundation for improving production techniques and for the analysis of style-defining substances in Yunnan CTLs.
{"title":"Comparative metabolomic of cigar tobacco leaves: A preliminary investigation of potential discriminatory metabolites between Yunnan and Foreign","authors":"Gaokun Zhao, Guanghui Kong, Mengxia Li, Yuping Wu, Heng Yao, Wei Li, Huachan Xia, Guanghai Zhang","doi":"10.1016/j.bbrep.2026.102461","DOIUrl":"10.1016/j.bbrep.2026.102461","url":null,"abstract":"<div><div>A systematic understanding of the metabolic components in cigar tobacco leaves (CTLs) from different ecological regions remains limited. This study aimed to clarify the substance differences between CTLs from Yunnan and major foreign production areas and to identify potential discriminant metabolites. A total of 25 CTL samples were collected from four production areas in Yunnan and five different foreign countries. The metabolic profiles were comprehensively characterized using continuous flow analysis, ion chromatography, GC-MS, and UPLC-MS/MS. The results revealed that Yunnan CTLs were characterized by a lower sugar-nicotine ratio and significantly higher contents of starch, pectin, and lignin compared to foreign samples. Phenolic acids, alkaloids, flavonoids, amino acids and derivatives, terpenoids, and lipids were identified as the primary components across all CTLs. A total of 398 differential metabolites (248 volatile and 150 non-volatile) were identified, predominantly from the classes of amino acids and derivatives, alkaloids, terpenoids, and lipids. From these, 12 metabolites were selected as potential candidates for distinguishing CTL origin. KEGG enrichment and MetOrigin analyses indicated that the differential metabolites were mainly involved in the biosynthesis of alkaloids, amino acids, flavonoids, lipids, and terpenes, with these pathways being significantly influenced by microorganism and enzyme-mediated carbon and nitrogen coupling metabolism. This exploratory study provides a metabolic foundation for improving production techniques and for the analysis of style-defining substances in Yunnan CTLs.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102461"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-16DOI: 10.1016/j.bbrep.2026.102447
Lijun Su , Nan Qu , Lili Chen , Yuying Lin , Huiwen Mo , Yanlan Huang
Objective
This study aimed to investigate whether the NLRP3 inflammasome modulates the Th17/Treg cell balance in experimental autoimmune myocarditis (EAM).
Methods
BALB/c mice were immunized subcutaneously with purified cardiac myosin heavy chain-α to induce EAM, injected NLRP3 inhibitor (MCC950) or PBS into the EAM mice by intraperitoneal injection. Splenic CD4+ T cells were isolated for in vitro culture. Myocardial inflammation was evaluated by HE staining. Th17/Treg ratios were analyzed by flow cytometry in cardiac tissue and cultured cells. RORγt and Foxp3 mRNA expression was measured by RT-PCR and IL-17/IL-10 levels by ELISA.
Results
Our study demonstrates that NLRP3 inhibition significantly attenuates myocardial inflammatory cell infiltration and preserves cardiac architecture in EAM mice. The EAM group exhibited significantly increased Th17/Treg ratios and RORγt mRNA expression in myocardial tissue compared to both MCC950-treated and control groups while demonstrating markedly decreased Foxp3 mRNA levels. In vitro experiments using cultured CD4+ T cells revealed substantially higher Th17 cell proportions, RORγt expression, and IL-17 secretion in the EAM group versus MCC950-treated cells, accompanied by significantly reduced Treg cell frequencies, Foxp3 mRNA levels, and IL-10 production.
Conclusion
During the pathogenesis of experimental autoimmune myocarditis (EAM), the NLRP3 inflammasome promotes Th17 cell differentiation while suppressing Treg cell development. Inhibition of the NLRP3 inflammasome restores the Th17/Treg balance and mitigates myocardial injury. These findings suggest that the NLRP3 inflammasome is a critical signaling hub in modulating immune responses in EAM. Targeting NLRP3 may represent a novel immunotherapeutic strategy for myocarditis.
{"title":"NLRP3 inflammasome regulates Th17/Treg cell balance in experimental autoimmune myocarditis","authors":"Lijun Su , Nan Qu , Lili Chen , Yuying Lin , Huiwen Mo , Yanlan Huang","doi":"10.1016/j.bbrep.2026.102447","DOIUrl":"10.1016/j.bbrep.2026.102447","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate whether the NLRP3 inflammasome modulates the Th17/Treg cell balance in experimental autoimmune myocarditis (EAM).</div></div><div><h3>Methods</h3><div>BALB/c mice were immunized subcutaneously with purified cardiac myosin heavy chain-α to induce EAM, injected NLRP3 inhibitor (MCC950) or PBS into the EAM mice by intraperitoneal injection. Splenic CD4<sup>+</sup> T cells were isolated for in vitro culture. Myocardial inflammation was evaluated by HE staining. Th17/Treg ratios were analyzed by flow cytometry in cardiac tissue and cultured cells. RORγt and Foxp3 mRNA expression was measured by RT-PCR and IL-17/IL-10 levels by ELISA.</div></div><div><h3>Results</h3><div>Our study demonstrates that NLRP3 inhibition significantly attenuates myocardial inflammatory cell infiltration and preserves cardiac architecture in EAM mice. The EAM group exhibited significantly increased Th17/Treg ratios and RORγt mRNA expression in myocardial tissue compared to both MCC950-treated and control groups while demonstrating markedly decreased Foxp3 mRNA levels. In vitro experiments using cultured CD4<sup>+</sup> T cells revealed substantially higher Th17 cell proportions, RORγt expression, and IL-17 secretion in the EAM group versus MCC950-treated cells, accompanied by significantly reduced Treg cell frequencies, Foxp3 mRNA levels, and IL-10 production.</div></div><div><h3>Conclusion</h3><div>During the pathogenesis of experimental autoimmune myocarditis (EAM), the NLRP3 inflammasome promotes Th17 cell differentiation while suppressing Treg cell development. Inhibition of the NLRP3 inflammasome restores the Th17/Treg balance and mitigates myocardial injury. These findings suggest that the NLRP3 inflammasome is a critical signaling hub in modulating immune responses in EAM. Targeting NLRP3 may represent a novel immunotherapeutic strategy for myocarditis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102447"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-03DOI: 10.1016/j.bbrep.2025.102394
Jiafang Cui, Ling Shen, Bing Han
Circular RNAs (circRNAs) are a class of covalently closed, non-coding RNA molecules characterized by their exceptional stability and tissue-specific expression. Once considered splicing artifacts, they have emerged as pivotal regulators in cellular pathophysiology, particularly within the central nervous system (CNS), where they are highly abundant. This review synthesizes the current understanding of the biogenesis, molecular functions, and regulatory roles of circRNAs in major CNS disorders, underscores their significant potential as next-generation diagnostic and prognostic biomarkers, as well as promising therapeutic targets. Moving from bench to bedside, the review critically examines the burgeoning landscape of circRNA-based therapeutics. We assess the promise and limitations of current delivery platforms, including exosomes and lipid nanoparticles (LNPs), with special attention to the formidable challenge of traversing the blood-brain barrier (BBB). To conclude, we outline the prevailing challenges and future perspectives, emphasizing that the development of more sensitive detection methods and optimized delivery systems is paramount to translating the immense potential of circRNAs into tangible clinical solutions for CNS diseases.
{"title":"CircRNAs: Novel biomarkers and therapeutic targets for diseases of the central nervous system","authors":"Jiafang Cui, Ling Shen, Bing Han","doi":"10.1016/j.bbrep.2025.102394","DOIUrl":"10.1016/j.bbrep.2025.102394","url":null,"abstract":"<div><div>Circular RNAs (circRNAs) are a class of covalently closed, non-coding RNA molecules characterized by their exceptional stability and tissue-specific expression. Once considered splicing artifacts, they have emerged as pivotal regulators in cellular pathophysiology, particularly within the central nervous system (CNS), where they are highly abundant. This review synthesizes the current understanding of the biogenesis, molecular functions, and regulatory roles of circRNAs in major CNS disorders, underscores their significant potential as next-generation diagnostic and prognostic biomarkers, as well as promising therapeutic targets. Moving from bench to bedside, the review critically examines the burgeoning landscape of circRNA-based therapeutics. We assess the promise and limitations of current delivery platforms, including exosomes and lipid nanoparticles (LNPs), with special attention to the formidable challenge of traversing the blood-brain barrier (BBB). To conclude, we outline the prevailing challenges and future perspectives, emphasizing that the development of more sensitive detection methods and optimized delivery systems is paramount to translating the immense potential of circRNAs into tangible clinical solutions for CNS diseases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102394"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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