Biomolecules最新文献_第3页

Melatonin MT1 Receptor Expression in Luminal Invasive Ductal Breast Carcinoma in Postmenopausal Women. 褪黑激素MT1受体在绝经后妇女腔内浸润性导管乳腺癌中的表达。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-15 DOI: 10.3390/biom15040581

Leda Pistiolis, Sahar Alawieh, Thorhildur Halldorsdottir, Anikó Kovács, Roger Olofsson Bagge

{"title":"Melatonin MT1 Receptor Expression in Luminal Invasive Ductal Breast Carcinoma in Postmenopausal Women.","authors":"Leda Pistiolis, Sahar Alawieh, Thorhildur Halldorsdottir, Anikó Kovács, Roger Olofsson Bagge","doi":"10.3390/biom15040581","DOIUrl":"https://doi.org/10.3390/biom15040581","url":null,"abstract":"Laboratory and animal studies indicate that melatonin exerts a negative impact on breast cancer progression and metastasis. These actions are both receptor-dependent and -independent. Of the two transmembrane melatonin receptors identified in humans, breast cancer expresses only MT1. The aim of this study was to investigate the expression of MT1 in hormone-receptor-positive, HER2-negative invasive ductal breast carcinoma in postmenopausal women and its possible correlations with clinicopathological parameters and survival. A total of 118 patients with luminal A/B primary breast cancer with or without axillary metastases were identified. The MT1 receptor expression was immunohistochemically assessed as a percentage of stained cells and a weighted index (WI) (percentage multiplied by staining intensity). Most tumor samples (84.7%) and metastasized lymph nodes (96%) stained positive for MT1, with varying intensity. No statistically significant correlations were found between the MT1 expression or the WI in the primary tumor and the patient and tumor characteristics, or the MT1 and WI in the metastasized lymph nodes. The survival analysis did not reveal a significant effect of MT1 expression or the WI on the risk of recurrence or survival.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Pangenomic Approach to Improve Population Genetics Analysis and Reference Bias in Underrepresented Middle Eastern and Horn of Africa Populations. 在代表性不足的中东和非洲之角人群中改进群体遗传学分析和参考偏差的全基因组学方法。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-15 DOI: 10.3390/biom15040582

Adrien Oliva, Rachel Foare, Peter Campbell, Natalie A Twine, Denis C Bauer, Angad Singh Johar

{"title":"A Pangenomic Approach to Improve Population Genetics Analysis and Reference Bias in Underrepresented Middle Eastern and Horn of Africa Populations.","authors":"Adrien Oliva, Rachel Foare, Peter Campbell, Natalie A Twine, Denis C Bauer, Angad Singh Johar","doi":"10.3390/biom15040582","DOIUrl":"https://doi.org/10.3390/biom15040582","url":null,"abstract":"Genomics plays a crucial role in addressing health disparities, yet most studies rely on the hg38 linear reference genome, limiting the potential of pangenomic approaches, particularly for underrepresented populations. In this study, we focus on characterising East African populations, particularly Somalis, by constructing a variation graph using Mozabites from the Human Genome Diversity Project (HGDP) given their ancestral affinity with Somalis. We evaluated the effectiveness of this graph-based reference in estimating effective population sizes (Ne) in Bedouins compared to the hg38 reference and examined its impact on allele frequencies and genome-wide association studies (GWAS). Applying a coalescent model to the graph-based reference produced a Ne estimate of approximately 17 for the Bedouin population, which was significantly lower than the estimate from the hg38 reference (approximately 79,000). Only the graph-based estimate fell within the 95% confidence interval in simulations, indicating improved accuracy. Moreover, graph variants exhibited significantly lower allele frequencies (p-value < 2.2 × 10-16), suggesting potential effects on the interpretation and power of GWAS. Notably, GWAS variants specific to Bedouins derived from the graph showed lower frequencies (p = 0.023) than those obtained from the linear reference. These findings suggest that a pangenomic approach, informed by populations with ancestral affinities such as the Mozabites, provides more accurate estimates of Ne and allele frequencies. This highlights the importance of pangenomic strategies to better capture genetic diversity in underrepresented populations, a critical step towards improving population genetics studies, personalised medicine, and equitable healthcare.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders. 外泌体生物标志物：恶性和非恶性疾病诊断和预后应用的综合概述。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-15 DOI: 10.3390/biom15040587

Mahda Delshad, Mohammad-Javad Sanaei, Mohammad Hossein Mohammadi, Amir Sadeghi, Davood Bashash

{"title":"Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders.","authors":"Mahda Delshad, Mohammad-Javad Sanaei, Mohammad Hossein Mohammadi, Amir Sadeghi, Davood Bashash","doi":"10.3390/biom15040587","DOIUrl":"https://doi.org/10.3390/biom15040587","url":null,"abstract":"Exosomes are small extracellular vesicles, ranging from 30 to 150 nm, that are essential in cell biology, mediating intercellular communication and serving as biomarkers due to their origin from cells. Exosomes as biomarkers for diagnosing various illnesses have gained significant investigation due to the high cost and invasive nature of current diagnostic procedures. Exosomes have a clear advantage in the diagnosis of diseases because they include certain signals that are indicative of the genetic and proteomic profile of the ailment. This feature gives them the potential to be useful liquid biopsies for real-time, noninvasive monitoring, enabling early cancer identification for the creation of individualized treatment plans. According to our analysis, the trend toward utilizing exosomes as diagnostic and prognostic tools has raised since 2012. In this regard, the proportion of malignant indications is higher compared with non-malignant ones. To be precise, exosomes have been used the most in gastrointestinal, thoracic, and urogenital cancers, along with cardiovascular, diabetic, breathing, infectious, and brain disorders. To the best of our knowledge, this is the first research to examine all registered clinical trials that look at exosomes as a diagnostic and prognostic biomarker.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Valproate Damaging Effect on Erythrocyte Metabolism as a Decisive Factor in the Development of Encephalopathy. 丙戊酸对红细胞代谢的破坏作用是脑病发展的决定性因素。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-15 DOI: 10.3390/biom15040588

Lyudmila Tikhonova, Eugene Maevsky, Carmina Montoliu, Elena Kosenko

{"title":"Valproate Damaging Effect on Erythrocyte Metabolism as a Decisive Factor in the Development of Encephalopathy.","authors":"Lyudmila Tikhonova, Eugene Maevsky, Carmina Montoliu, Elena Kosenko","doi":"10.3390/biom15040588","DOIUrl":"https://doi.org/10.3390/biom15040588","url":null,"abstract":"Background: Valproic acid (VPA) is a mainstay of treatment for epilepsy. Although VPA is generally considered well tolerated, it has serious adverse effects related to the pathological impact on cerebral perfusion and oxidative metabolism, leading to progressive encephalopathy. Erythrocytes directly deliver oxygen to the tissues. To understand how the brain pathology may be related to limited oxygenation, it is important to determine whether VPA-related changes occur in the intracellular erythrocyte metabolism responsible for the oxygen transport function.Methods: To determine whether different therapeutic VPA doses affect major metabolic pathways in rat erythrocytes, the activity of rate-limiting enzymes and levels of metabolites of glycolysis, the Rapoport-Luebering shunt, the pentose phosphate pathway and the antioxidant systems were measured.Results: Our data showed that VPA-induced G6PD inhibition leads to profound oxidative stress, increased MetHb formation and decreased 2,3-DPG and ATP levels in erythrocytes that underlie the loss of their oxygen transport function, thus being a cause of a brain energy crisis that precedes encephalopathy.Conclusions: The measurement of parameters in metabolic pathways modulating the redox-signaling and oxygen-carrying capacity of erythrocytes is needed for further elucidation of complex mechanisms underlying VPA-induced brain hypoperfusion and encephalopathy.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vitamin D and Acute Kidney Injury: A Reciprocal Relationship. 维生素D与急性肾损伤：相互关系。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-15 DOI: 10.3390/biom15040586

Chandrashekar Annamalai, Pragasam Viswanathan

{"title":"Vitamin D and Acute Kidney Injury: A Reciprocal Relationship.","authors":"Chandrashekar Annamalai, Pragasam Viswanathan","doi":"10.3390/biom15040586","DOIUrl":"https://doi.org/10.3390/biom15040586","url":null,"abstract":"Vitamin D is a sterol prohormone with no intrinsic biological activity. Calcitriol, the active form of vitamin D, is synthesized in the kidneys. It has well-known pleiotropic and cytoprotective properties. In addition to regulating parathyroid hormone secretion and enhancing gut calcium absorption, it exhibits antioxidant, anti-inflammatory, antiproliferative, and antineoplastic effects. However, the role of vitamin D in AKI is unclear, unlike in CKD. Thus, this review aimed to understand how dysregulated vitamin D homeostasis occurs in AKI, as well as to explore how vitamin D deficiency and excess influence AKI. A comprehensive literature search was conducted between January 2000 and June 2024 to uncover relevant works detailing vitamin D homeostasis in health as well as investigating the impact of vitamin D deficiency and excess in humans, animals, and in vitro cell models of AKI. According to the findings of this review, vitamin D appears to have a reciprocal relationship with AKI. Acute renal injury, among other factors, can cause hypo- or hypervitaminosis D. Conversely, AKI can also be caused by vitamin D deficiency and toxicity. Even though hypovitaminosis D is associated with AKI, it is uncertain how it impacts AKI outcomes in distinct clinical scenarios. Newer therapeutic options might emerge as a result of understanding these challenges. Vitamin D supplementation may ameliorate renal injury but needs further validation. Furthermore, hypervitaminosis D has also been implicated in AKI by causing hypercalcemia and hyperphosphatemia. It is crucial to avoid prolonged, uncontrolled, and unsupervised supraphysiological vitamin D administration, especially intramuscular injection.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Antiproliferative Effects of Grossheimin-Derived Aminoanalogues. 葛拉西明衍生的氨基酸类似物的合成及其抗增殖作用。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-14 DOI: 10.3390/biom15040578

Meruyert Ashimbayeva, Zsolt Szakonyi, Sergazy M Adekenov, Nikoletta Szemerédi, Gabriella Spengler, Tam Minh Le

引用次数: 0

Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease. 不仅仅是一种替代能源：酮体的多种生物学功能和HMGCS2与健康和疾病的相关性。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-14 DOI: 10.3390/biom15040580

Varshini V Suresh, Sathish Sivaprakasam, Yangzom D Bhutia, Puttur D Prasad, Muthusamy Thangaraju, Vadivel Ganapathy

{"title":"Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.","authors":"Varshini V Suresh, Sathish Sivaprakasam, Yangzom D Bhutia, Puttur D Prasad, Muthusamy Thangaraju, Vadivel Ganapathy","doi":"10.3390/biom15040580","DOIUrl":"https://doi.org/10.3390/biom15040580","url":null,"abstract":"Ketogenesis, a mitochondrial metabolic pathway, occurs primarily in liver, but kidney, colon and retina are also capable of this pathway. It is activated during fasting and exercise, by \"keto\" diets, and in diabetes as well as during therapy with SGLT2 inhibitors. The principal ketone body is β-hydroxybutyrate, a widely recognized alternative energy source for extrahepatic tissues (brain, heart, muscle, and kidney) when blood glucose is sparse or when glucose transport/metabolism is impaired. Recent studies have identified new functions for β-hydroxybutyrate: it serves as an agonist for the G-protein-coupled receptor GPR109A and also works as an epigenetic modifier. Ketone bodies protect against inflammation, cancer, and neurodegeneration. HMGCS2, as the rate-limiting enzyme, controls ketogenesis. Its expression and activity are regulated by transcriptional and post-translational mechanisms with glucagon, insulin, and glucocorticoids as the principal participants. Loss-of-function mutations occur in HMGCS2 in humans, resulting in a severe metabolic disease. These patients typically present within a year after birth with metabolic acidosis, hypoketotic hypoglycemia, hepatomegaly, steatotic liver damage, hyperammonemia, and neurological complications. Nothing is known about the long-term consequences of this disease. This review provides an up-to-date summary of the biological functions of ketone bodies with a special focus on HMGCS2 in health and disease.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis. 探讨肝X受体在动脉粥样硬化中脂质代谢和免疫中的作用。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-14 DOI: 10.3390/biom15040579

Kaori Endo-Umeda, Makoto Makishima

{"title":"Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis.","authors":"Kaori Endo-Umeda, Makoto Makishima","doi":"10.3390/biom15040579","DOIUrl":"https://doi.org/10.3390/biom15040579","url":null,"abstract":"Hypercholesterolemia causes atherosclerosis by inducing immune cell migration and chronic inflammation in arterial walls. Recent single-cell analyses reveal the presence of lipid-enriched foamy macrophages, as well as other macrophage subtypes, neutrophils, T cells, and B cells, in atherosclerotic plaques in both animal models and humans. These cells interact with each other and other cells, including non-immune cells such as endothelial cells and smooth muscle cells. They thereby regulate metabolic, inflammatory, phagocytic, and cell death processes, thus affecting the progression and stability of atherosclerotic plaques. The nuclear receptors liver X receptor (LXR)α and LXRβ are transcription factors that are activated by oxysterols and regulate lipid metabolism and immune responses. LXRs regulate cholesterol homeostasis by controlling cholesterol's transport, absorption, synthesis, and breakdown in the liver and intestine. LXRs are also highly expressed in tissue-resident and monocyte-derived macrophages and other immune cells, including both myeloid cells and lymphocytes, and they regulate both innate and adaptive immune responses. Interestingly, LXRs have immunosuppressive and immunoregulatory functions that are cell-type-dependent. In animal models of atherosclerosis, LXRs have been shown to be involved in both progression and regression phases. The pharmacological activation of LXR enhances cholesterol efflux from macrophages and promotes atherosclerosis progression. Deleting LXR in immune cells, especially myeloid cells, accelerates atherosclerosis by increasing monocyte migration, macrophage proliferation and activation, and neutrophil extracellular traps (NETs); furthermore, the deletion of hematopoietic LXRs impairs the regression of atherosclerotic plaques. Therefore, LXRs in immune cells may be a potent therapeutic target for atherosclerosis.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12024750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TSC-mTORC1 Pathway in Postnatal V-SVZ Neurodevelopment. TSC-mTORC1通路在出生后V-SVZ神经发育中的作用

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-12 DOI: 10.3390/biom15040573

David M Feliciano, Angelique Bordey

引用次数: 0

The B22 Dilemma: Structural Basis for Conformational Differences in Proinsulin B-Chain Arg22 Mutants. B22困境：胰岛素原b链Arg22突变体构象差异的结构基础

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-12 DOI: 10.3390/biom15040577

Srivastav Ranganathan, Anoop Arunagiri

{"title":"The B22 Dilemma: Structural Basis for Conformational Differences in Proinsulin B-Chain Arg22 Mutants.","authors":"Srivastav Ranganathan, Anoop Arunagiri","doi":"10.3390/biom15040577","DOIUrl":"https://doi.org/10.3390/biom15040577","url":null,"abstract":"Proinsulin has three distinct regions: the well-folded A- and B-chains and the dynamic disordered C-peptide. The highly conserved B-chain is a hotspot for diabetes-associated mutations, including the severe loss-of-function R(B22)Q mutation linked to childhood-onset diabetes. Here, we explore R(B22)'s role in proinsulin stability using AlphaFold-predicted structures and metadynamics simulations to achieve enhanced sampling of the free energy landscape. Our results show that R(B22) stabilizes proinsulin by interacting with N86. Substituting R(B22) with E or Q disrupts this interaction, increasing conformational flexibility. The R(B22)Q variant exhibits a flattened free energy landscape, favoring unfolded states. Additional substitutions, including Gly, Ala, Lys, Tyr, Asp, and Phe, destabilize proinsulin to varying extents by weakening hydrogen bonding. Disrupting the R(B22)-N86 interaction broadly reduces inter-chain contacts, raising the risk of aggregation-prone states. Given the link between R(B22) mutations and diabetes, our study provides crucial molecular insights into proinsulin instability. These findings highlight the role of key inter-domain (A-Chain-B-chain, B-Chain-C-peptide, and A-Chain-C-peptide) interactions in maintaining protein structures and the implications this has for understanding disease-associated proinsulin variants.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0