Biochemistry and Biophysics Reports最新文献

{"title":"Coenzyme Q10 and rikkunshito prevent age-related changes in mouse otolith morphology and function","authors":"Keita Ueda ,&nbsp;Takao Imai ,&nbsp;Tadao Okayasu ,&nbsp;Tatsuhide Tanaka ,&nbsp;Kouko Tatsumi ,&nbsp;Akio Wanaka ,&nbsp;Tadashi Kitahara","doi":"10.1016/j.bbrep.2025.102033","DOIUrl":"10.1016/j.bbrep.2025.102033","url":null,"abstract":"<div><div>Otoliths play an important role in maintaining body balance, and age-related decline in theis function and morphological integrity can lead to falls. In recent years, the herbal medicine rikkunshito (RKT) and the antioxidant coenzyme Q10 (CoQ10) have been studied for their anti-aging properties; however, their effects on otoliths remain unknown. Therefore, we aimed to investigate whether RKT and CoQ10 can prevent age-related functional and morphological changes in otoliths. To this end, 30 male and 30 female 8-week-old C57BL6N mice were used in this study. The mice were divided into three groups: a control group, CoQ10 group (0.2 % CoQ10 special diet), and RKT group (3 % RKT special diet). At 80 weeks of age, micro-computed tomography (μCT) images were taken and analyzed for otolith volume and CT number. Furthermore, eye movements induced by the linear vestibulo-ocular reflex (LVOR) were analyzed to assess otolith function.</div></div><div><h3>Results</h3><div>revealed that the RKT group had a significantly smaller volume of the 3 dimensional utriclar CT model (male mice; p = 0.0281, Steel test) and a significantly higher utricular CT number (male mice; p = 0.0104, Dunnett test) than the control group. The RKT group had a significantly weaker LVOR (male mice; lateral 1.3G stimulation; p = 0.00681, Dunnett test) (male mice; longitudinal 1.3G stimulation; p = 0.0183, Dunnett test) (male mice; longitudinal 0.7G stimulation; p = 0.00322, Dunnett test) than the control group. The CoQ10 group exhibited a significantly stronger utricle-induced LVOR than the control group (female mice; lateral 0.7G stimulation; p = 0.0133, Steel test).</div><div>In conclusion, RKT prevented age-related utricular morphological changes, but did not prevent age-related otolith functional changes in male mice. CoQ10 prevented age-related utricular functional changes for low frequency stimulation in female mice.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102033"},"PeriodicalIF":2.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891788","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}

{"title":"RNA signaling in medicinal plants: An overlooked mechanism for phytochemical regulation","authors":"Esther Ugo Alum ,&nbsp;Chidozie Dennis Udechukwu ,&nbsp;David Chukwu Obasi","doi":"10.1016/j.bbrep.2025.102032","DOIUrl":"10.1016/j.bbrep.2025.102032","url":null,"abstract":"<div><h3>Background/objective</h3><div>Medicinal plants are invaluable sources of bioactive phytochemicals critical for global health. This mini review explores the role of RNA signaling in regulating phytochemical production in medicinal plants, highlighting its potential for optimizing their therapeutic potential.</div></div><div><h3>Methods</h3><div>This mini review integrates insights from recent studies published in Scopus and Web of Science (2019–2025) on RNA-mediated signaling, including small RNAs (sRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs).</div></div><div><h3>Results</h3><div>RNA signaling is revealed as a pivotal mechanism in secondary metabolite regulation, mediating stress-induced compound synthesis and environmental interactions. Notable findings include the role of siRNAs in activating alkaloid pathways and lncRNAs in regulating phenolic compound biosynthesis. RNA-directed DNA methylation and systemic RNA signaling further highlight its versatility in phytochemical regulation.</div></div><div><h3>Conclusion</h3><div>RNA signaling enhances medicinal plant research, unlocking therapeutic potential through bioactive compound production. The study calls for focused research to bridge knowledge gaps and translate laboratory findings into field applications.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102032"},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886815","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}

{"title":"A case of early epileptic encephalopathy caused by new mutation at W218C in KCNQ2 and review literature","authors":"Juhua Yang ,&nbsp;Yuping Huang ,&nbsp;Zhijun Chen ,&nbsp;Jiaheng Peng ,&nbsp;Kangyu Li ,&nbsp;Lijuan Huang ,&nbsp;Jie Yang ,&nbsp;Chunhui Yang","doi":"10.1016/j.bbrep.2025.102008","DOIUrl":"10.1016/j.bbrep.2025.102008","url":null,"abstract":"<div><div>Early-onset epileptic encephalopathy (EOEE) is mainly characterized by early refractory epileptic seizures in infants with progressive brain dysfunction, accompanied by complex causes (such as perinatal brain injury, structural brain malformations and genetic metabolic diseases). Early identification and etiological treatment are critical. It has been reported that mutations in Potassium Voltage-Gated Channel Subfamily Q Member 2 (<em>KCNQ2</em>) can result in EOEE. This study analyzed the genetic defects and clinical phenotypes of a newborn with early epileptic encephalopathy. Whole exome gene detection identified a novel heterozygous point mutation p. W218C in <em>KCNQ2.</em> The pathogenic variant was located in the protein's S4S5 connection region and was identified as a harmful mutation by silico tools. The child's clinical phenotype finally manifested as West syndrome during the follow-up. The mentioned variation may lead to severe clinical manifestations and poor neurological prognosis. Whole exome gene detection provides clinicians with more information on neonatal epileptic encephalopathy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102008"},"PeriodicalIF":2.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886779","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}

{"title":"SLC16A3 (MCT4) expression in tumor immunity and Metabolism: Insights from pan-cancer analysis","authors":"Wenxing Du ,&nbsp;Bo Zang ,&nbsp;Yang Wo ,&nbsp;Shiwei Chen","doi":"10.1016/j.bbrep.2025.102034","DOIUrl":"10.1016/j.bbrep.2025.102034","url":null,"abstract":"<div><h3>Background</h3><div>SLC16A3, a highly expressed H + -coupled symporter, facilitates lactate transport via monocarboxylate transporters (MCTs), contributing to acidosis. Although SLC16A3 has been implicated in tumor development, its role in tumor immunity remains unclear.</div></div><div><h3>Methods</h3><div>A pan-cancer analysis was conducted using datasets from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, and Genotype-Tissue Expression projects. SLC16A3 expression patterns and associations with tumor progression, prognosis, immune checkpoints, and immune neoantigens were evaluated across 30 cancer types. Immune infiltration scores were analyzed using the Tumor Immune Estimation Resource dataset.</div></div><div><h3>Results</h3><div>SLC16A3 expression is differentially regulated in cancer versus healthy tissues, with elevated levels associated with poor prognosis and reduced overall survival in glioblastoma multiforme (HR = 1.88), low-grade gliomas (HR = 1.51), and lung adenocarcinoma (HR = 1.33). Notably, significant associations between SLC16A3 expression and poor outcomes were observed in 33 cancers, except for rectum adenocarcinoma, testicular germ cell tumors, pheochromocytoma and paraganglioma, and adrenocortical carcinoma. SLC16A3 expression was also strongly linked to immune checkpoints and neoantigens. Correlations with tumor-infiltrating immune cells were pronounced in prostate adenocarcinoma but absent in uterine carcinosarcoma and cervical squamous cell carcinoma. Gene set enrichment analysis (GSEA) revealed a pivotal role of SLC16A3 in tumor growth, metabolism, and immunity.</div></div><div><h3>Conclusion</h3><div>SLC16A3, the transporter facilitating the efflux of lactic acid, shows differential expression across various cancer types and exerts a critical effect on tumor development and immunity. Thus, SLC16A3 has promising potential as a prognostic marker, and its targeted manipulation can offer therapeutic advantages.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102034"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881448","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}

{"title":"Identification of GABBR2 as a diagnostic marker and its association with Aβ in Alzheimer's disease","authors":"Huijun Li ,&nbsp;Yawei Fan ,&nbsp;Chan Chen ,&nbsp;Yuzhong Xu ,&nbsp;Xiong Wang ,&nbsp;Wei Liu","doi":"10.1016/j.bbrep.2025.102035","DOIUrl":"10.1016/j.bbrep.2025.102035","url":null,"abstract":"<div><h3>Background</h3><div>Synaptic dysfunction and synapse loss occur in Alzheimer's disease (AD). The current study aimed to identify synaptic-related genes with diagnostic potential for AD.</div></div><div><h3>Methods</h3><div>Differentially expressed genes (DEGs) were overlapped with phenotype-associated module selected through weighted gene co-expression network analysis (WGCNA), and synaptic-related genes. The overlapped hub genes were further processed using machine learning algorithms, intersected with module gene from protein-protein interaction (PPI) network constructed with DEGs, to yield co-hub genes. The diagnostic potentials of the co-hub genes were examined by receiver operating characteristic (ROC) analysis. Correlation between co-hub genes with clinical features and immune cell infiltration was analyzed. Finally, the expression of co-hub genes was analyzed in several datasets and validated in AD transgenic mice.</div></div><div><h3>Results</h3><div>A total of three co-hub genes were identified, including MAP1B, L1CAM, and GABBR2. GABBR2 showed area under the curve (AUC) values of 0.98, 0.81, and 0.88 in the training and two external validation datasets. GABBR2 was negatively correlate with beta- and gamma-secretase activities, and infiltration of natural killer T cells and effector memory CD8 T cells. Finally, GABBR2 was validated to be downregulated in AD transgenic mice, aligning with bioinformatic findings. GABBR2 overexpression in N2a/APP cells increased ADAM10 while decreased of BACE1, leading to upregulation of sAPPα while downregulation of sAPPβ.</div></div><div><h3>Conclusion</h3><div>In conclusion, GABBR2 acts as a novel biomarker for the diagnosis of AD and negatively correlated with Aβ in AD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102035"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879203","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}

{"title":"High-resolution transcriptome analysis on a mouse model of neonatal hypoxic-ischemic encephalopathy using single-nucleus RNA-seq","authors":"Nao Wakui ,&nbsp;Takashi Shimbo ,&nbsp;Morifumi Hanawa ,&nbsp;Tomomi Kitayama ,&nbsp;Yukari Yamamoto ,&nbsp;Yuya Ouchi ,&nbsp;Kotaro Saga ,&nbsp;Aiko Okada ,&nbsp;Kazuya Mimura ,&nbsp;Katsuto Tamai ,&nbsp;Masayuki Endo","doi":"10.1016/j.bbrep.2025.102026","DOIUrl":"10.1016/j.bbrep.2025.102026","url":null,"abstract":"<div><div>Neonatal hypoxic-ischemic encephalopathy (HIE) encompasses brain injuries resulting from dysregulated oxygen or blood flow to the brain before, during, or immediately after birth. During the acute phase, neuronal damage is driven by excitotoxicity, with permanent injury manifesting over the subsequent hours. Treatment options have limited efficacy, requiring deeper insights into HIE pathogenesis. Recent advances in single-cell RNA sequencing have enabled molecular investigations of diverse diseases. However, the large size of certain cells, such as neurons, has posed challenges in studying conditions where neuronal damage is central. Thus, we employed single-nucleus RNA sequencing to evaluate damages in a mouse model of HIE and found pronounced changes in the hippocampus with significantly reduced neuronal populations. We observed the characteristic activation of hippocampal microglia, confirmed by immunostaining in the HIE model. These alterations were specific to combined hypoxic-ischemic conditions and were not observed with hypoxia or ischemia alone. These findings provide insights into the molecular and anatomical impact of HIE and highlight the hippocampus as a critical focus for understanding disease mechanisms and therapeutic development.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102026"},"PeriodicalIF":2.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879213","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}

{"title":"Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells","authors":"Ali Rafat ,&nbsp;Khadijeh Dizaji Asl ,&nbsp;Zeinab Mazloumi ,&nbsp;Mehdi Talebi ,&nbsp;Hojjatollah Nozad Charoudeh","doi":"10.1016/j.bbrep.2025.102027","DOIUrl":"10.1016/j.bbrep.2025.102027","url":null,"abstract":"<div><h3>Background</h3><div>Recent trends in developing new treatments for cancers, highlight the use of immune cells particularly Natural Killer (NK) cells, as promising therapeutic strategies. While NK cells exhibit significant anti-tumor effects, their effectiveness is often limited. This study investigated the impact of BIBR1532, a human telomerase reverse transcriptase (hTERT) inhibitor, on improving the cytotoxicity of NK cells against Acute Myeloid Leukemia (AML) cells.</div></div><div><h3>Methods</h3><div>Primary AML cells and Kg-1a cell lines were cultured and treated with the half-maximal inhibitory concentration (IC50) of BIBR1532 for 48 h. The treated cells were then co-cultured with NK cells, after which cytotoxicity, cell proliferation, and apoptosis were assessed using Annexin V/7-AAD and Ki-67 expression analysis. Finally, apoptosis-related genes and proteins, hTERT gene and caspase 3/7 activity were studied.</div></div><div><h3>Results</h3><div>The Telomerase Inhibition (TI) in primary AML and Kg-1a cells with IC50 values of 38.75 μM and 57.64 μM, respectively, sensitized the AML cells and enhanced the anti-proliferative effects of NK cells. The combination of BIBR1532 and NK cells led to increased apoptosis, as indicated by the upregulation of the Bax and Bad genes, an increased Bax/Bcl-2 ratio, caspase 3/7 activity, Bax protein and a downregulation of mRNA expression levels of Bcl-2, Bcl-xl and decreased Bcl-2 protein.</div></div><div><h3>Conclusion</h3><div>The findings of this study demonstrate that the concurrent application of BIBR1532 and NK cells promotes apoptosis and reduces proliferation by targeting apoptosis-related genes and proteins such as Bax and Bcl-2.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102027"},"PeriodicalIF":2.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876905","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}

{"title":"NMDA Receptors: Next therapeutic targets for Tinnitus?","authors":"Chenhao Che,&nbsp;Yongzhen Wu,&nbsp;Shan Sun","doi":"10.1016/j.bbrep.2025.102029","DOIUrl":"10.1016/j.bbrep.2025.102029","url":null,"abstract":"<div><div>Tinnitus, a common otological symptom, lacks clinically approved pharmacological treatments, highlighting an urgent unmet need. This review explores the potential role of NMDARs, key glutamate receptors in the auditory system, in tinnitus pathophysiology, including excitotoxicity, synaptic plasticity, and neuropathic pain. Alterations in NMDAR variants with different subunit compositions during development have also been implicated in the onset of tinnitus. Clinical trials of NMDAR antagonists, such as acamprosate, caroverine, neramexane, and AM-101, have shown promising results, though none are yet approved. These findings highlight the need for further research on NMDARs to advance the development of next-generation targeted pharmacological therapies for tinnitus.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102029"},"PeriodicalIF":2.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876904","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}

{"title":"Metabolism of sphingolipids in a rat spinal cord stenosis model","authors":"Baasanjav Uranbileg ,&nbsp;Yoko Hoshino ,&nbsp;Mariko Ezaka ,&nbsp;Makoto Kurano ,&nbsp;Kanji Uchida ,&nbsp;Yutaka Yatomi ,&nbsp;Nobuko Ito","doi":"10.1016/j.bbrep.2025.102025","DOIUrl":"10.1016/j.bbrep.2025.102025","url":null,"abstract":"<div><h3>Background</h3><div>Lumbar spinal canal stenosis (LSCS) plays a crucial role in neurogenic claudication and neuropathic pain. Recent studies suggest that changes in sphingolipid metabolism are linked to neuropathic pain. To explore the association between sphingolipids and LSCS, we measured the levels of sphingolipids and sphingolipid-associated molecules in an animal model of cauda equina compression (CEC), a typical type of LSCS.</div></div><div><h3>Methods</h3><div>By placing silicon blocks within the lumbar epidural space, CEC model were constructed in which motor disfunction had already been confirmed in our previous study. Quantitative measurements of various sphingolipids were conducted using LC-MS/MS in spinal cord and cerebrospinal fluid (CSF) samples on days 1, 7, and 28 following insertion of silicon blocks. Additionally, gene expression was analyzed in spinal cord tissue.</div></div><div><h3>Results</h3><div>In the CEC model, there was a significant increase ceramide levels in the CSF with upregulation of ceramide synthase 1 in the spinal cord tissue samples on day 1. Further, S1P levels in the CSF increased on day 7 and in the spinal cord significantly increased on day 28, and there was an increase in mRNA expression levels of sphingosine kinases (SphK)1 on days 1,7, and 28, while SphK2 on days 7 and 28. Regarding S1P receptors, there was an increase in mRNA expression levels of S1P1 on days 1,7, and 28 and S1P3 on day1.</div></div><div><h3>Conclusion</h3><div>The production and activation of the sphingolipid signaling pathway could play a pivotal role in neuropathic pain related to LSCS.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102025"},"PeriodicalIF":2.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876903","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}

{"title":"Heterohybridomas producing human immunoglobulin light chains using CD138-selected bone marrow cells","authors":"P. Zhou ,&nbsp;X. Ma ,&nbsp;S. Scalia ,&nbsp;D. Toskic ,&nbsp;X. Wu ,&nbsp;T. Fogaren ,&nbsp;Nancy Coady Lyons ,&nbsp;Luis del Pozo-Yauner ,&nbsp;R.L. Comenzo","doi":"10.1016/j.bbrep.2025.102017","DOIUrl":"10.1016/j.bbrep.2025.102017","url":null,"abstract":"<div><h3>Background</h3><div>Light chain research is hampered by lack of mammalian cell lines producing human light chains (FLC). Therefore, we used heterohybridoma (HH) technology to produce clones making FLC thereby providing tools to study light chain behavior.</div></div><div><h3>Methods</h3><div>Marrow CD138+ cells from patients with multiple myeloma (MM) and polyclonal gammopathy (PG) were selected, fused with B5-6 T cells and cultured in hypoxanthine-aminopterin-thymidine medium (HAT). HH clones were selected based on ELISA for human immunoglobulins and flow cytometry for intracellular (IC) FLC. We compared marrow cell counts and HH yields by diagnosis, evaluated clones making only FLC by flow and by dimer/monomer (D/M) ratios in vitro and in vivo, and sequenced FLC genes with RT-PCR.</div></div><div><h3>Results</h3><div>Marrows from 13 patients with active disease, 10 MM and 3 PG, were no different in mononuclear or CD138-selected cell counts. HH FLC clones (7 λ, 1 κ) were obtained from 5/10 MM and 2/3 PG; one PG case produced 2 HH FLC clones (one λ and one κ). Of the 10 MM cases, 8 had high risk cytogenetic features and 4 of the 8 produced HH clones while of the 3 PG cases 2 had negative cytogenetics and 1 had loss of IgH identified and produced an HH clone. Mononuclear (MNC) and CD138-selected cell numbers were markedly higher in the samples that enabled productive fusions. Median MFI for the 8 HH clones by IC flow for FLC was 9849 (range, 5344–27451) and median percentage of cells IC positive was 88 % (69–95). Medians of in vitro and in vivo FLC production were 47 μg/mL (9–80) per million cells after 2 days of culture and 66.4 μg/mL (16–1100) in NOD-SCID γ (NSG) mice 14 days after intraperitoneal (IP) implants of 2 × 10⁶ HH cells. Dimer/monomer ratio medians were 0.575 (0.08–0.939) in vitro and 0.91 (0.82–2.7) in vivo, values that were correlated (R² = 0.565) by two-tailed paired <em>t</em>-test with <em>P</em> &lt; 0.05.</div></div><div><h3>Conclusions</h3><div>B5-6 T HH producing human FLC were obtained from 50 % of MM and PG cases. High numbers of MNC and CD138+ cells enabled productive fusions. The HH clones produced FLC with easily appreciated dimers and monomers in vitro and in vivo. With IP in vivo implants after 2 weeks more dimers were seen than in short term cultures in vitro. These HH clones will be made available for study of FLC metabolism and testing of therapeutics designed to abrogate FLC production or enable FLC clearance in vivo.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"42 ","pages":"Article 102017"},"PeriodicalIF":2.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858972","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}