Biomolecules最新文献

{"title":"Expression of FGF23 and α-KLOTHO in Normal Human Kidney Development and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).","authors":"Patricija Bajt, Anita Racetin, Nela Kelam, Nikola Pavlović, Petar Todorović, Marinela Jelinčić Korčulanin, Natalija Filipović, Ivana Kuzmić Prusac, Fila Raguž, Katarina Vukojević","doi":"10.3390/biom15060811","DOIUrl":"10.3390/biom15060811","url":null,"abstract":"<p><p>Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric renal failure, but the molecular mechanisms driving these conditions are not yet fully understood. Fibroblast Growth Factor 23 (FGF23) and its co-receptor α-KLOTHO play crucial roles in regulating calcium and phosphate homeostasis in adult kidneys, but their roles in kidney development and the pathogenesis of CAKUT remain unclear. Because of that, we analyzed the spatial and temporal expression of FGF23 and α-KLOTHO in normal fetal kidney development and CAKUT using an immunofluorescence technique. Our results demonstrate a dynamic pattern of FGF23 and α-KLOTHO expression in healthy kidney development, with FGF23 levels decreasing and α-KLOTHO levels increasing with gestational age. Also, we showed that FGF23 expression was significantly reduced in horseshoe (HKs) and duplex kidneys (DKs), while α-KLOTHO expression remained unchanged across all CAKUT conditions. Based on our results, we suggest that altered FGF23 expression in CAKUT contributes to disease pathogenesis and may represent a potential therapeutic target.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494419","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}

{"title":"A Natural Alkaloid, 6-Hydroxymethyldihydronitidine, Suppresses Tumor Progression by Co-Regulating Apoptosis, Ferroptosis, and FAK Pathways.","authors":"Haojing Jiang, Jiantong Hou, Jianliang Wang, Jing Xu, Yuanqiang Guo","doi":"10.3390/biom15060814","DOIUrl":"10.3390/biom15060814","url":null,"abstract":"<p><p>Cancer treatment remains a formidable challenge globally. Natural products, particularly natural alkaloids, have emerged as significant resources for the development of novel anti-tumor drugs due to their structural diversity and unique biological activities. Our team previously isolated an alkaloid, 6-hydroxymethyldihydrochelerythrine (6-HMDN), from <i>Zanthoxylum ailanthoides</i>. Subsequent in vitro and in vivo activity screenings, utilizing cell-based assays and a zebrafish xenograft model, revealed that 6-HMDN significantly inhibited the proliferation of HepG2 and MCF7 cells and effectively suppressed HepG2 cell migration. Mechanistic studies indicated that 6-HMDN induced tumor cell apoptosis by modulating the Bcl-2/Bax protein balance and activating the caspase cascade. Furthermore, 6-HMDN augmented intracellular reactive oxygen species (ROS) levels, thereby promoting ferroptosis, as evidenced by lipid ROS accumulation and glutathione (GSH) depletion. Additionally, 6-HMDN attenuated focal adhesion kinase (FAK) phosphorylation, leading to the inhibition of tumor cell migration. In vivo experiments further substantiated the capacity of 6-HMDN to effectively suppress tumor proliferation and metastasis. These findings demonstrate that 6-HMDN exhibits potent anti-tumor activity, exerting its effects through multiple mechanisms involving the regulation of apoptosis, ferroptosis, and the FAK signaling pathway. Therefore, 6-HMDN may be considered a promising candidate for anti-tumor drug development.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494314","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}

{"title":"Are Cannabis-Based Medicines a Useful Treatment for Neuropathic Pain? A Systematic Review.","authors":"Nawaf Almuntashiri, Basma M El Sharazly, Wayne G Carter","doi":"10.3390/biom15060816","DOIUrl":"10.3390/biom15060816","url":null,"abstract":"<p><p>Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1',1'-dimethylheptyl-Δ⁸-tetrahydrocannabinol-11-oic acid (CT-3), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), combinations of Δ⁹-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494341","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}

{"title":"Brusatol Inhibits Esophageal Squamous Cell Carcinoma Tumorigenesis Through Bad-Mediated Mitochondrial Apoptosis Induction and Anti-Metastasis by Targeting Akt1.","authors":"Yao Ji, Xinxin Zhu, Yi Shi, Rui Fang, Yimeng Sun, Yurong Ruan, Liying Zhou, Yuanyuan Ge, Qichao Luo, Junyan Zhang, Junting Ma","doi":"10.3390/biom15060812","DOIUrl":"10.3390/biom15060812","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy characterized by poor prognosis and a deficiency of effective therapies. Brusatol (Bru), a bioactive component derived from <i>Brucea javanica</i>, exhibits potent anti-tumor activity. However, the pro-apoptotic and anti-metastatic effects of Bru in ESCC remain unclear. ESCC cells were incubated with Bru. The apoptotic status and metastatic capacities of the cells was measured by the Annexin V-FITC/PI, and wound-healing and transwell assays. Potential targets of Bru in ESCC were identified. The mechanisms by which Bru exerts its effects in ESCC cells were explored. Additionally, the typical 4-NQO-induced ESCC mouse model was employed to examine the anti-tumor effect of Bru in vivo. In this study, Bru was found to trigger mitochondria-mediated cell apoptosis (approximately 5.9- and 3.3-fold increases in the level of apoptosis at high concentrations (80 nM) in the KYSE30 and KYSE450 cells) and inhibit metastasis (49% wound closure decreases at high concentrations (80 nM) in both cells, compared to that in the DMSO group) in ESCC cells. In vivo, Bru significantly suppressed ESCC tumorigenesis. Notably, Bru interacts with Akt1, leading to a reduction in the phosphorylation level of Akt1 at Ser473. Consequently, this not only induced dephosphorylation of Bad at the Ser136 residue to promote mitochondrial apoptosis but also inhibited metastasis in ESCC cells. Bru promoted Bad-mediated mitochondrial apoptosis and inhibited the ESCC cell metastasis by targeting Akt1. Our results suggest Bru is a novel Akt1 inhibitor for inhibiting the progression of ESCC.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494361","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}

{"title":"Sesquiterpenoid Hormones Farnesoic Acid and Methyl Farnesoate Regulate Different Gene Sets in Shrimp <i>Neocaridina davidi</i> Hepatopancreas.","authors":"Yehui Luan, Wenyan Nong, Wai Lok So, Jerome Ho Lam Hui","doi":"10.3390/biom15060815","DOIUrl":"10.3390/biom15060815","url":null,"abstract":"<p><p>Sesquiterpenoid hormones such as the juvenile hormone and methyl farnesoate (MF) are well known to respectively control the development and reproduction in insects and crustaceans (such as shrimp, crabs, and lobsters). In recent years, the sesquiterpenoid hormone farnesoic acid (FA) has also been identified in other non-insect/crustacean invertebrates; despite this, their regulatory roles remain poorly understood. Here, we carried out the in vitro treatments of MF and FA on the hepatopancreas of female adult shrimps <i>Neocaridina davidi</i>. Transcriptomic analyses revealed a total of 65 and 112 differentially expressed genes in the MF- and FA-treated hepatopancreas at 3 h post-treatment, respectively. Gene pathway enrichment analyses further suggested that the two sesquiterpenoid hormones regulate different sets of genes, with the gene pathway involved in pancreatic secretion enriched only in the FA-treated hepatopancreas. This study demonstrates the differential regulatory roles between sesquiterpenoid forms, which warrants further investigation into the functions of FA in crustaceans.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494477","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}

{"title":"The Future of Chronic Kidney Disease Treatment: Combination Therapy (Polypill) or Biomarker-Guided Personalized Intervention?","authors":"Sajjad Biglari, Harald Mischak, Joachim Beige, Agnieszka Latosinska, Justyna Siwy, Mirosław Banasik","doi":"10.3390/biom15060809","DOIUrl":"10.3390/biom15060809","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a global health burden that affects close to one billion individuals. As many healthcare systems struggle to accommodate existing patients, CKD incidence and related costs are projected to continue rising. Based on a systematic search, this narrative review offers an in-depth assessment of advances in CKD pharmacotherapy published between 2020 and 2025, with a specific emphasis on drug combinations. Various treatment approaches for CKD exist, many of them targeting different mechanisms. Therefore, combining multiple medications could provide patients with better outcomes, though this comes with the risk of increased adverse effects and unnecessary costs. Alternatively, using biomarkers presents an opportunity to ascertain the most appropriate treatments specifically tailored to an individual's molecular profile, thus personalizing CKD management. The second part of this review presents the current state-of-the-art methods to guide CKD therapy based on markers predicting treatment response. Collectively, this review presents possible pathways toward more effective CKD treatment.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494453","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}

{"title":"Alpha-1 Antitrypsin Deficiency and Bronchial Asthma: Current Challenges.","authors":"José Luis Lopez-Campos, Belén Muñoz-Sánchez, Marta Ferrer-Galván, Esther Quintana-Gallego","doi":"10.3390/biom15060807","DOIUrl":"10.3390/biom15060807","url":null,"abstract":"<p><p>Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition classically associated with pulmonary emphysema and liver disease. However, the potential link between AATD and other respiratory diseases, particularly bronchial asthma, remains poorly understood and highly debated. This narrative review explores the current evidence regarding the epidemiological, clinical, and pathophysiological relationship between AATD and asthma. Data from prevalence studies show marked variability in the frequency of AATD-associated alleles among asthma patients, ranging from 2.9% to 25.4%, suggesting either a true association or selection biases. Conversely, asthma prevalence among AATD patients also varies widely, from 1.4% to 44.6%, with higher frequencies observed in countries with long-standing national registries. However, methodological inconsistencies and a lack of standardized diagnostic criteria limit the interpretation of these findings. Current evidence is insufficient to support a direct causal role for AATD mutations in asthma development, and no clear impact of AATD on asthma severity or prognosis has been established. Furthermore, there is no conclusive evidence that augmentation therapy is beneficial in asthma patients carrying AATD mutations. Despite these uncertainties, screening for AATD in selected asthma populations-especially those with severe or atypical phenotypes-may be warranted, as recommended by major respiratory societies. Future research should focus on large, well-powered, prospective studies that evaluate the potential pathophysiological interactions between AATD and specific asthma endotypes, particularly T2-low asthma. These efforts may help clarify the relevance of AATD mutations in asthma pathogenesis and identify potential therapeutic targets.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494323","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}

{"title":"Lactylation: From Molecular Insights to Disease Relevance.","authors":"Yao Xu, Lu Zhang, Dong Shang, Hong Xiang","doi":"10.3390/biom15060810","DOIUrl":"10.3390/biom15060810","url":null,"abstract":"<p><p>Lactylation, referring to the covalent coupling of the lactyl group with lysine residues, is a recently defined post-translational modification. It has been demonstrated that lactylation can alter protein transcription, thereby affecting the transmission of genetic information and ultimately exerting diverse effects on health and diseases. Here, we review the existing literature and summarize the characteristics and mechanisms of lactylation on both histone and non-histone proteins. We hope to explore lactylation targets for different diseases, thus providing potential clues for new therapeutic strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494383","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}

{"title":"Role of Nutritional Elements in Skin Homeostasis: A Review.","authors":"Nansong Jiang, Tao Quan, Ran Li, Yaoxing Chen, Ting Gao","doi":"10.3390/biom15060808","DOIUrl":"10.3390/biom15060808","url":null,"abstract":"<p><p>Skin aging is the most prominent phenotype of human aging and is the result from the interaction of genetic and environmental factors. Improving skin aging is essential for maintaining the normal physiological function of the skin and the mental health of the human body. Existing studies have proposed many theories of aging, such as the free radical theory, mitochondrial theory of aging, etc., and accordingly have also proposed appropriate interventions. It is worth noting that many nutrients contained in the skin itself play an important role in maintaining skin health. During the aging process, a decrease in the levels of these nutrients is closely related to a weakening of the related functions. Therefore, supplementing these nutrients offers potential therapeutic options for improving skin aging. In this review, we summarize the important roles of nutrients in the skin and their potential in anti-aging, with the expectation of providing a therapeutic basis and clinical reference for delaying skin aging.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494471","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}

{"title":"Non-Coding RNAs: lncRNA, piRNA, and snoRNA as Robust Plasma Biomarkers of Alzheimer's Disease.","authors":"Ruomin Xin, Elizabeth Kim, Wei Tse Li, Jessica Wang-Rodriguez, Weg M Ongkeko","doi":"10.3390/biom15060806","DOIUrl":"10.3390/biom15060806","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a leading cause of dementia worldwide. As current diagnostic approaches remain limited in sensitivity and accessibility, there is a critical need for novel, non-invasive biomarkers aiding early detection. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs), have emerged as promising candidates due to their regulatory roles in gene expression and association with diseases. In this study, we systematically profiled ncRNA expression from RNA sequencing data of 48 AD and 22 control blood tissue samples, aiming to evaluate their utility as biomarkers for AD classification. Differential expression analysis revealed widespread dysregulation of lncRNAs and piRNAs, with over 5000 lncRNAs and nearly 1000 piRNAs significantly upregulated in AD. Weighted gene co-expression network analysis (WGCNA) identified multiple ncRNA modules associated with the AD phenotype. Using supervised machine learning approaches, we evaluated the diagnostic potential of ncRNA expression profiles, including single-gene, multi-gene, and module-level models. Random Forest models trained on individual genes identified 121 ncRNAs with AUROC > 0.8. Feature importance analysis emphasized ncRNAs such as lnc-MYEF2-3, lnc-PRKACB2, and HBII-115 as major contributors to diagnostic accuracy. These findings support the potential of ncRNA signatures as reliable and non-invasive biomarkers for AD diagnosis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494438","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}