Pub Date : 2026-01-06DOI: 10.1016/j.bbrep.2025.102432
Leyi Luo , Tong Zhang , Linlin Liang , Weixin Chen , Tao Wang , Wenke Chen , Haitao Xiao , Guangtao Zhang
Inflammatory bowel disease (IBD) is characterized by gut dysbiosis and impaired microbial metabolite signaling. Emerging evidence suggests that gut microbial metabolites, such as trace amines (tryptamine, phenethylamine, and tyramine), function as endogenous TAAR1 agonists and may contribute to IBD pathogenesis. Our study identified elevated fecal trace amine levels in ulcerative colitis (UC) patients and DSS-induced colitis mice. In vitro, exposure to these trace amines enhanced 5-HT secretion in QGP-1 cells and ex vivo mouse colonic tissues, and this effect could be blocked by the TAAR1 antagonist EPPTB. In vivo, EPPTB treatment significantly mitigated DSS-induced colitis, as demonstrated by reduced weight loss, improved disease activity index (DAI), preserved colon length, and attenuated histopathological damage. Moreover, TAAR1 blockade reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increased IκB-α expression, restored intestinal barrier integrity (upregulating occludin and ZO-1, while downregulating cclaudin-2), and lowered colonic 5-HT levels by suppressing TPH1 expression. These findings suggest that TAAR1 inhibition alleviates colitis by modulating 5-HT signaling, positioning it as a promising therapeutic target for IBD.
炎症性肠病（IBD）的特征是肠道生态失调和微生物代谢物信号受损。新出现的证据表明，肠道微生物代谢物，如微量胺（色胺、苯乙胺和酪胺），作为内源性TAAR1激动剂发挥作用，可能有助于IBD的发病。我们的研究发现溃疡性结肠炎（UC）患者和dss诱导的结肠炎小鼠粪便微量胺水平升高。在体外，暴露于这些微量胺可以增强QGP-1 细胞和离体小鼠结肠组织中5-HT的分泌，而这种作用可以被TAAR1拮抗剂EPPTB阻断。在体内，EPPTB治疗显著减轻了dss诱导的结肠炎，表现为体重减轻、疾病活动指数（DAI）改善、结肠长度保持和组织病理学损伤减轻。此外，TAAR1阻断可降低促炎因子（TNF-α、IL-6、IL-1β），增加i - κ b -α表达，恢复肠屏障完整性（上调occludin和ZO-1，下调claudin-2），并通过抑制TPH1表达降低结肠5-HT水平。这些发现表明，TAAR1抑制通过调节5-HT信号通路来缓解结肠炎，将其定位为IBD的一个有希望的治疗靶点。
{"title":"The TAAR1 antagonist EPPTB ameliorates colitis via serotonin inhibition","authors":"Leyi Luo , Tong Zhang , Linlin Liang , Weixin Chen , Tao Wang , Wenke Chen , Haitao Xiao , Guangtao Zhang","doi":"10.1016/j.bbrep.2025.102432","DOIUrl":"10.1016/j.bbrep.2025.102432","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is characterized by gut dysbiosis and impaired microbial metabolite signaling. Emerging evidence suggests that gut microbial metabolites, such as trace amines (tryptamine, phenethylamine, and tyramine), function as endogenous TAAR1 agonists and may contribute to IBD pathogenesis. Our study identified elevated fecal trace amine levels in ulcerative colitis (UC) patients and DSS-induced colitis mice. In vitro, exposure to these trace amines enhanced 5-HT secretion in QGP-1 cells and ex vivo mouse colonic tissues, and this effect could be blocked by the TAAR1 antagonist EPPTB. In vivo, EPPTB treatment significantly mitigated DSS-induced colitis, as demonstrated by reduced weight loss, improved disease activity index (DAI), preserved colon length, and attenuated histopathological damage. Moreover, TAAR1 blockade reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and increased IκB-α expression, restored intestinal barrier integrity (upregulating occludin and ZO-1, while downregulating cclaudin-2), and lowered colonic 5-HT levels by suppressing TPH1 expression. These findings suggest that TAAR1 inhibition alleviates colitis by modulating 5-HT signaling, positioning it as a promising therapeutic target for IBD.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102432"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938487","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 : 2026-01-06DOI: 10.1016/j.bbrep.2025.102416
C. Paquette, T. Charlton, N. Prowse, T. Fortin, H. Sun, S. Hayley
α-synuclein (α-syn) rich Lewy bodies are a prominent pathological feature of Parkinson's disease (PD), with intra-cellular accumulation occurring in neurons and possibly microglia. Tracking α-syn movement between the two different cell types is of critical importance in determining how pathology spreads. We hypothesized that the separate pre-treatment of either primary cortical neurons or microglia with exogenous α-syn preformed fibrils (PFFs) will foster a cytotoxic environment when co-cultured with the opposite naïve cell type. To this end, using real time live cell imaging, we found an accumulation of Alexa Fluor 488 labelled α-syn PFFs in both microglia and neurons. In the co-cultures, the labelled-PFFs showed differing patterns of spread to non-seeded cells. The PFF treatment also provoked cellular loss that increased with the passage of time and induced marked vacuolation and changes in microglial morphology. Microglia appeared to accumulate PFFs from morphologically compromised neurons and shifted to a predominately dystrophic and “foamy enlarged fried egg” morphology over time and was associated with a reduction in levels of the anti-inflammatory cytokine, interleukin-4 (IL-4). We currently provide a novel in vitro co-culture model that allows for tracking α−syn spread between primary cortical microglia and neurons.
{"title":"Live cell imaging of exogenous α-synuclein fibrils in primary microglia and neuron co-cultures","authors":"C. Paquette, T. Charlton, N. Prowse, T. Fortin, H. Sun, S. Hayley","doi":"10.1016/j.bbrep.2025.102416","DOIUrl":"10.1016/j.bbrep.2025.102416","url":null,"abstract":"<div><div>α-synuclein (α-syn) rich Lewy bodies are a prominent pathological feature of Parkinson's disease (PD), with intra-cellular accumulation occurring in neurons and possibly microglia. Tracking α-syn movement between the two different cell types is of critical importance in determining how pathology spreads. We hypothesized that the separate pre-treatment of either primary cortical neurons or microglia with exogenous α-syn preformed fibrils (PFFs) will foster a cytotoxic environment when co-cultured with the opposite naïve cell type. To this end, using real time live cell imaging, we found an accumulation of Alexa Fluor 488 labelled α-syn PFFs in both microglia and neurons. In the co-cultures, the labelled-PFFs showed differing patterns of spread to non-seeded cells. The PFF treatment also provoked cellular loss that increased with the passage of time and induced marked vacuolation and changes in microglial morphology. Microglia appeared to accumulate PFFs from morphologically compromised neurons and shifted to a predominately dystrophic and “foamy enlarged fried egg” morphology over time and was associated with a reduction in levels of the anti-inflammatory cytokine, interleukin-4 (IL-4). We currently provide a novel <em>in vitro</em> co-culture model that allows for tracking α−syn spread between primary cortical microglia and neurons.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102416"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938483","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}
Breast cancer is still one of the challenges of medical science, despite fast and remarkable advancements in diagnosis and new therapy approaches. This study aims to explore the individual effects of TLR7/8 agonists and to compare their cytotoxic properties with those of the chemotherapy drug doxorubicin on 4T1 breast cancer cells, as well as to evaluate their role in the modulation of immune checkpoint molecules.
Methods
4T1 cancer cells were treated with the TLR7/8 agonist R848 and doxorubicin for a duration of 48 h. First, the viability of the cells was assessed using the MTT method. The relative expression of mRNA for Gal-9, PD-L1, and PVR was analyzed with HPRT serving as a housekeeping gene. Finally, an apoptosis test was conducted to evaluate the cytotoxic effects of R848 and doxorubicin on 4T1 cells. And the wound healing assay was completed in order to assess the migratory potential of 4T1 cells after treatment with R848 and doxorubicin.
Results
The expression of the PVR and Gal-9 genes in the group treated with R848 showed a decrease compared to the control group, although this change was not statistically significant. In contrast, the expression of PD-L1 and PVR in the group treated with doxorubicin increased significantly when compared to both the control group and the R848 treated group. Additionally, the total apoptosis rate in both the R848 and doxorubicin treatment groups was significantly higher than that in the control group. After 24 h post-scratch, control 4T1 cells showed about 50 % wound closure, while R848 reduced it to 35 %. Doxorubicin lowered migration to under 10 %. By 48 h, control and R848 nearly closed the wound, unlike the DOX group.
Conclusion
R848 and doxorubicin possess anti-proliferative and pro-apoptotic effects on 4T1 cells, doxorubicin effectively induces cell death and boosts immune checkpoint gene expression, while R848 fosters early apoptosis without raising checkpoint ligand expression.
{"title":"Comparative effects of a TLR7/8 agonist and doxorubicin on immune checkpoint modulation and apoptosis in 4T1 breast cancer cells","authors":"Nazanin Joudaki , Mohsen Tehrani , Abolghasem ajami , Saeid Taghiloo","doi":"10.1016/j.bbrep.2025.102440","DOIUrl":"10.1016/j.bbrep.2025.102440","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is still one of the challenges of medical science, despite fast and remarkable advancements in diagnosis and new therapy approaches. This study aims to explore the individual effects of TLR7/8 agonists and to compare their cytotoxic properties with those of the chemotherapy drug doxorubicin on 4T1 breast cancer cells, as well as to evaluate their role in the modulation of immune checkpoint molecules.</div></div><div><h3>Methods</h3><div>4T1 cancer cells were treated with the TLR7/8 agonist R848 and doxorubicin for a duration of 48 h. First, the viability of the cells was assessed using the MTT method. The relative expression of mRNA for Gal-9, PD-L1, and PVR was analyzed with HPRT serving as a housekeeping gene. Finally, an apoptosis test was conducted to evaluate the cytotoxic effects of R848 and doxorubicin on 4T1 cells. And the wound healing assay was completed in order to assess the migratory potential of 4T1 cells after treatment with R848 and doxorubicin.</div></div><div><h3>Results</h3><div>The expression of the PVR and Gal-9 genes in the group treated with R848 showed a decrease compared to the control group, although this change was not statistically significant. In contrast, the expression of PD-L1 and PVR in the group treated with doxorubicin increased significantly when compared to both the control group and the R848 treated group. Additionally, the total apoptosis rate in both the R848 and doxorubicin treatment groups was significantly higher than that in the control group. After 24 h post-scratch, control 4T1 cells showed about 50 % wound closure, while R848 reduced it to 35 %. Doxorubicin lowered migration to under 10 %. By 48 h, control and R848 nearly closed the wound, unlike the DOX group.</div></div><div><h3>Conclusion</h3><div>R848 and doxorubicin possess anti-proliferative and pro-apoptotic effects on 4T1 cells, doxorubicin effectively induces cell death and boosts immune checkpoint gene expression, while R848 fosters early apoptosis without raising checkpoint ligand expression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102440"},"PeriodicalIF":2.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938384","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}
Although neurogenic pulmonary edema (NPE) often occurs after aneurysmal subarachnoid hemorrhage (SAH), the mechanism of NPE progression after SAH remains unclear. This study investigates whether pulmonary endothelial glycocalyx (PEG) impairment accompanies NPE after SAH. Accordingly, SAH was induced by endovascular perforation in male mice. The lung tissues of the mice were removed 24 h after SAH induction. The degree of pulmonary edema and lung injury, and the extent of PEG injury were assessed. Water content of lung tissue by the wet/dry method in the SAH group was significantly increased compared to that in the sham group (81.7 % vs. 78.8 %, P < 0.01), which suggested NPE following SAH. Lung injury score by hematoxylin and eosin staining in the SAH group, assessed using a semiquantitative scoring system, was also significantly worse than that in the sham group (7.1 vs. 1.2, P < 0.001). Scanning electron microscopy images clearly demonstrated that the moss-like glycocalyx lined the endothelial lumen without any interruption in sham mice, whereas those microstructures were severely devastated in SAH mice. Moreover, the fluorescence intensity of tomato lectin was significantly reduced in SAH mice compared to that in sham mice (13.3 vs. 30.7, P < 0.001), thereby indicating the loss of PEG. Our results indicate that PEG, which is essential for regulating vascular permeability, is severely impaired after experimental SAH. Maintaining the integrity of PEG is a promising therapeutic strategy for NPE after SAH.
虽然神经源性肺水肿（NPE）常发生在动脉瘤性蛛网膜下腔出血（SAH）后，但SAH后NPE进展的机制尚不清楚。本研究探讨SAH后肺内皮糖萼（PEG）损伤是否伴随NPE。因此，雄性小鼠血管内穿孔可诱发SAH。小鼠在SAH诱导后24 h切除肺组织。评估肺水肿、肺损伤程度及PEG损伤程度。经干湿法测定，SAH组肺组织含水量明显高于sham组（81.7 % vs. 78. %,P <； 0.01），提示SAH后肺组织发生NPE。使用半定量评分系统评估SAH组苏木精和伊红染色肺损伤评分，SAH组的肺损伤评分也明显低于sham组（7.1 vs. 1.2, P <； 0.001）。扫描电镜图像清楚地显示，假手术小鼠的内皮腔内排列着苔藓样的糖萼，没有任何中断，而SAH小鼠的这些微结构严重破坏。此外，与假手术小鼠相比，SAH小鼠的番茄凝集素荧光强度显著降低（13.3 vs. 30.7, P <； 0.001），表明PEG丢失。我们的研究结果表明，实验性SAH后，对调节血管通透性至关重要的PEG严重受损。维持PEG的完整性是一种很有前途的治疗SAH后NPE的策略。
{"title":"Pulmonary edema following subarachnoid hemorrhage is associated with impairment of pulmonary vascular endothelial glycocalyx","authors":"Nozomi Sasaki , Yusuke Egashira , Hideshi Okada , Chihiro Takada , Shinomi Sasaibe , Masaki Kumagai , Yoshiki Kuse , Shinsuke Nakamura , Hirofumi Matsubara , Yukiko Enomoto , Toru Iwama , Tsuyoshi Izumo , Hideaki Hara , Masamitsu Shimazawa","doi":"10.1016/j.bbrep.2025.102420","DOIUrl":"10.1016/j.bbrep.2025.102420","url":null,"abstract":"<div><div>Although neurogenic pulmonary edema (NPE) often occurs after aneurysmal subarachnoid hemorrhage (SAH), the mechanism of NPE progression after SAH remains unclear. This study investigates whether pulmonary endothelial glycocalyx (PEG) impairment accompanies NPE after SAH. Accordingly, SAH was induced by endovascular perforation in male mice. The lung tissues of the mice were removed 24 h after SAH induction. The degree of pulmonary edema and lung injury, and the extent of PEG injury were assessed. Water content of lung tissue by the wet/dry method in the SAH group was significantly increased compared to that in the sham group (81.7 % vs. 78.8 %, <em>P</em> < 0.01), which suggested NPE following SAH. Lung injury score by hematoxylin and eosin staining in the SAH group, assessed using a semiquantitative scoring system, was also significantly worse than that in the sham group (7.1 vs. 1.2, <em>P</em> < 0.001). Scanning electron microscopy images clearly demonstrated that the moss-like glycocalyx lined the endothelial lumen without any interruption in sham mice, whereas those microstructures were severely devastated in SAH mice. Moreover, the fluorescence intensity of tomato lectin was significantly reduced in SAH mice compared to that in sham mice (13.3 vs. 30.7, <em>P</em> < 0.001), thereby indicating the loss of PEG. Our results indicate that PEG, which is essential for regulating vascular permeability, is severely impaired after experimental SAH. Maintaining the integrity of PEG is a promising therapeutic strategy for NPE after SAH.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102420"},"PeriodicalIF":2.2,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797520","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}
Spatial transcriptomic technology enables resolving a tumor microenvironment heterogeneity of colorectal cancer (CRC) tissue samples. However, there is limited evidence regarding the relative strengths and weaknesses of different CRC sample types and preservation methods, including formalin-fixed paraffin-embedded (FFPE), fresh frozen (FF) and snap frozen (SF). Here, we examine gene expression profiles in 36 tissue areas, FFPE, FF and SF samples, derived from a patient with stage IV CRC, using spatial analysis of the whole transcriptome. The tissue samples obtained from surgical resection of the cancer were subjected to a detailed histological evaluation and spatial transcriptomics analysis to compare the quality of the sample between different preservation methods. Spatial transcriptomic analysis demonstrated that FFPE tissue samples offered improved resolution of cellular morphology in the tumor microenvironment, facilitating greater detail of gene expression and cell types. In contrast, gene expression analysis of FF and SF tissues embedded in optimal cutting temperature compound revealed a high level of CRC gene expression. FFPE, FF and SF samples shared a significant overlap among the top 300 genes that were strongly associated with key biological processes in CRC. In summary, the spatial analysis of the whole transcriptome across FFPE, FF and SF CRC tissues revealed intratumoral heterogeneity and highlighted key transcriptomic signatures, suggesting the specific value of different tissue preservation methods in the profiling of CRC.
{"title":"Comparative spatial whole transcriptome analysis of matched frozen and formalin-fixed paraffin-embedded colorectal cancer tissues","authors":"Kullanist Thanormjit , Thanawat Suwatthanarak , Tantip Arigul , Amphun Chaiboonchoe , Onchira Acharayothin , Piroon Jenjaroenpun , Vitoon Chinswangwatanakul , Pariyada Tanjak","doi":"10.1016/j.bbrep.2025.102413","DOIUrl":"10.1016/j.bbrep.2025.102413","url":null,"abstract":"<div><div>Spatial transcriptomic technology enables resolving a tumor microenvironment heterogeneity of colorectal cancer (CRC) tissue samples. However, there is limited evidence regarding the relative strengths and weaknesses of different CRC sample types and preservation methods, including formalin-fixed paraffin-embedded (FFPE), fresh frozen (FF) and snap frozen (SF). Here, we examine gene expression profiles in 36 tissue areas, FFPE, FF and SF samples, derived from a patient with stage IV CRC, using spatial analysis of the whole transcriptome. The tissue samples obtained from surgical resection of the cancer were subjected to a detailed histological evaluation and spatial transcriptomics analysis to compare the quality of the sample between different preservation methods. Spatial transcriptomic analysis demonstrated that FFPE tissue samples offered improved resolution of cellular morphology in the tumor microenvironment, facilitating greater detail of gene expression and cell types. In contrast, gene expression analysis of FF and SF tissues embedded in optimal cutting temperature compound revealed a high level of CRC gene expression. FFPE, FF and SF samples shared a significant overlap among the top 300 genes that were strongly associated with key biological processes in CRC. In summary, the spatial analysis of the whole transcriptome across FFPE, FF and SF CRC tissues revealed intratumoral heterogeneity and highlighted key transcriptomic signatures, suggesting the specific value of different tissue preservation methods in the profiling of CRC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102413"},"PeriodicalIF":2.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797522","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 : 2025-12-15DOI: 10.1016/j.bbrep.2025.102412
Dan Jiang , Dongfei Fang , Zicen Wang , Huanqi Cun , Baoxia Fang , Fuchao Chen
Purpose
To optimize the preparation methods of three intravenous poorly soluble antibacterial drugs (oxacillin sodium, cefmetazole sodium, and ciprofloxacin hydrochloride) and investigate their compatibility and stability in infusion.
Methods
Taking the variety of solvents, volume of initial solvent, and oscillation time as influencing factors, and with the count of particulate matter and content uniformity in the preparation solution as the evaluation indices, the L9(34) orthogonal test was used to optimize the preparation methods of three intravenous insoluble antibacterial drugs. Simulate clinical drug concentrations, mix each drug separately with 0.9 % sodium chloride (0.9 % NS) and 5 % glucose (5 % GS), and take samples at different time points under room temperature and refrigerator conditions to determine their appearance, pH value, and relative percentage of drug content.
Results
The optimal preparation method for oxacillin sodium was as follows: it was pre-dissolved in 8 mL of 0.9 % NS and shaken for 90 s before dilution and preparation. The optimal preparation method for cefmetazole sodium was as follows: it was pre-dissolved in 8 mL of 5 % GS, and shaken for 120 s before dilution and preparation. The optimal preparation method for ciprofloxacin hydrochloride was as follows: it was pre-dissolved in 18 mL of 5 % GS, and oscillation for 120 s before dilution and preparation. The three drugs were combined with 0.9 % NS and 5 % GS, respectively, and remained relatively stable within 24 h.
Conclusion
Optimal selection of the variety of solvents, the volume of the initial solvent, and the oscillation time in preparing poorly soluble antibiotics can improve the quality of the intravenous infusion. Stability experiments confirmed that the three drugs can remain stable for 24 h, ensuring safety during clinical intravenous infusion.
{"title":"Optimization design of solution preparation methods of three poorly soluble drugs of clinical use in infusions on orthogonal test and evaluation of stability study","authors":"Dan Jiang , Dongfei Fang , Zicen Wang , Huanqi Cun , Baoxia Fang , Fuchao Chen","doi":"10.1016/j.bbrep.2025.102412","DOIUrl":"10.1016/j.bbrep.2025.102412","url":null,"abstract":"<div><h3>Purpose</h3><div>To optimize the preparation methods of three intravenous poorly soluble antibacterial drugs (oxacillin sodium, cefmetazole sodium, and ciprofloxacin hydrochloride) and investigate their compatibility and stability in infusion.</div></div><div><h3>Methods</h3><div>Taking the variety of solvents, volume of initial solvent, and oscillation time as influencing factors, and with the count of particulate matter and content uniformity in the preparation solution as the evaluation indices, the L<sub>9</sub>(3<sup>4</sup>) orthogonal test was used to optimize the preparation methods of three intravenous insoluble antibacterial drugs. Simulate clinical drug concentrations, mix each drug separately with 0.9 % sodium chloride (0.9 % NS) and 5 % glucose (5 % GS), and take samples at different time points under room temperature and refrigerator conditions to determine their appearance, pH value, and relative percentage of drug content.</div></div><div><h3>Results</h3><div>The optimal preparation method for oxacillin sodium was as follows: it was pre-dissolved in 8 mL of 0.9 % NS and shaken for 90 s before dilution and preparation. The optimal preparation method for cefmetazole sodium was as follows: it was pre-dissolved in 8 mL of 5 % GS, and shaken for 120 s before dilution and preparation. The optimal preparation method for ciprofloxacin hydrochloride was as follows: it was pre-dissolved in 18 mL of 5 % GS, and oscillation for 120 s before dilution and preparation. The three drugs were combined with 0.9 % NS and 5 % GS, respectively, and remained relatively stable within 24 h.</div></div><div><h3>Conclusion</h3><div>Optimal selection of the variety of solvents, the volume of the initial solvent, and the oscillation time in preparing poorly soluble antibiotics can improve the quality of the intravenous infusion. Stability experiments confirmed that the three drugs can remain stable for 24 h, ensuring safety during clinical intravenous infusion.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102412"},"PeriodicalIF":2.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797524","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 : 2025-12-15DOI: 10.1016/j.bbrep.2025.102415
Sukyoung Han , Myeongwoo Jung , Seungyeon Ryu , Seongho Cha , Hyosun Tak , Seung Min Jeong , Eun Kyung Lee
We investigated HuD (ELAVL4), a neuronal RNA-binding protein with emerging endocrine functions, as a regulator of GLP-1 biogenesis in intestinal L-cells. Using absolute qPCR and immunofluorescence, we found that HuD was significantly expressed in the GLUTag cells derived from mice intestinal L-cell line and was co-localized with GLP-1-positive cells in the small intestine of mice. RNA interference-mediated HuD knockdown reduced both GLP-1 immunoreactivity and levels. Mechanistically, RNA immunoprecipitation and biotinylated 3′UTR pull-down demonstrated that HuD binds to the mRNAs of the Gcg and Pcsk1 (PC1/3) genes. The levels of the proglucagon (∼17 kDa) and PC1/3 proteins decreased without significant changes in their mRNAs, suggesting post-transcriptional control. Metabolic stress converged on this module: palmitate decreased proglucagon/PC1/3 in GLUTag cells, and a high-fat diet reduced GLP-1 and PC1/3 signals in the mouse intestine. Interestingly, zinc sulfate partially restored proglucagon and PC1/3 levels following palmitate treatment. These findings reveal a HuD–Gcg/Pcsk1 axis is crucial for GLP-1 biogenesis and which is susceptible to lipotoxic stress.
{"title":"RNA binding protein HuD regulates the biosynthesis of glucagon-like peptide 1 in intestinal L-cells","authors":"Sukyoung Han , Myeongwoo Jung , Seungyeon Ryu , Seongho Cha , Hyosun Tak , Seung Min Jeong , Eun Kyung Lee","doi":"10.1016/j.bbrep.2025.102415","DOIUrl":"10.1016/j.bbrep.2025.102415","url":null,"abstract":"<div><div>We investigated HuD (ELAVL4), a neuronal RNA-binding protein with emerging endocrine functions, as a regulator of GLP-1 biogenesis in intestinal L-cells. Using absolute qPCR and immunofluorescence, we found that HuD was significantly expressed in the GLUTag cells derived from mice intestinal L-cell line and was co-localized with GLP-1-positive cells in the small intestine of mice. RNA interference-mediated HuD knockdown reduced both GLP-1 immunoreactivity and levels. Mechanistically, RNA immunoprecipitation and biotinylated 3′UTR pull-down demonstrated that HuD binds to the mRNAs of the <em>Gcg</em> and <em>Pcsk1</em> (PC1/3) genes. The levels of the proglucagon (∼17 kDa) and PC1/3 proteins decreased without significant changes in their mRNAs, suggesting post-transcriptional control. Metabolic stress converged on this module: palmitate decreased proglucagon/PC1/3 in GLUTag cells, and a high-fat diet reduced GLP-1 and PC1/3 signals in the mouse intestine. Interestingly, zinc sulfate partially restored proglucagon and PC1/3 levels following palmitate treatment. These findings reveal a HuD–<em>Gcg</em>/<em>Pcsk1</em> axis is crucial for GLP-1 biogenesis and which is susceptible to lipotoxic stress.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102415"},"PeriodicalIF":2.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797523","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}
Understanding the mechanical properties of cells is crucial for gaining insights into their physiological and pathological states. This study focuses on the mechanical behavior of human mammary epithelial cells (MCF-10) and human breast cancer cells (MCF-7), emphasizing mechanical frequencies, finite element modeling (FEM), and nonlinear dynamics of the cells.
Methods
Cells were cultured and subjected to mechanical testing using Atomic Force Microscopy (AFM) and Magnetic Tweezer Cytometry (MTC). The elastic and viscoelastic properties were analyzed, and FEMs were developed to simulate cell behavior under various mechanical stimuli. The nonlinear dynamic behavior was examined using the Duffing model, and chaos was assessed using the Largest Lyapunov exponent (LLE).
Results
MCF-10 cells exhibited higher stiffness than MCF-7 cells. The mechanical frequencies of both cell types were determined, and significant differences were observed at higher frequencies. FEM simulations provided detailed insights into the stress distribution and deformation patterns within cells. The nonlinear analysis revealed chaotic behavior at specific frequencies, particularly in the range of 22–36 kHz.
Conclusion
Identifying the mechanical frequencies and responses of cancer cells, including their nonlinear and chaotic behaviors, can inform the development of noninvasive therapeutic strategies. Further research is required to refine these models and explore the potential of mechanical forces in cancer treatment.
{"title":"How do vibration stimulation frequencies affect the nonlinear dynamics and mechanical characterization of breast cancer cells?","authors":"Ashkan Heydarian , Dornaz Milani , Hamidreza Mortazavy Beni , Mehrafarin Babaee , Hamid Reza Goudarzi","doi":"10.1016/j.bbrep.2025.102414","DOIUrl":"10.1016/j.bbrep.2025.102414","url":null,"abstract":"<div><h3>Introduction</h3><div>Understanding the mechanical properties of cells is crucial for gaining insights into their physiological and pathological states. This study focuses on the mechanical behavior of human mammary epithelial cells (MCF-10) and human breast cancer cells (MCF-7), emphasizing mechanical frequencies, finite element modeling (FEM), and nonlinear dynamics of the cells.</div></div><div><h3>Methods</h3><div>Cells were cultured and subjected to mechanical testing using Atomic Force Microscopy (AFM) and Magnetic Tweezer Cytometry (MTC). The elastic and viscoelastic properties were analyzed, and FEMs were developed to simulate cell behavior under various mechanical stimuli. The nonlinear dynamic behavior was examined using the Duffing model, and chaos was assessed using the Largest Lyapunov exponent (LLE).</div></div><div><h3>Results</h3><div>MCF-10 cells exhibited higher stiffness than MCF-7 cells. The mechanical frequencies of both cell types were determined, and significant differences were observed at higher frequencies. FEM simulations provided detailed insights into the stress distribution and deformation patterns within cells. The nonlinear analysis revealed chaotic behavior at specific frequencies, particularly in the range of 22–36 kHz.</div></div><div><h3>Conclusion</h3><div>Identifying the mechanical frequencies and responses of cancer cells, including their nonlinear and chaotic behaviors, can inform the development of noninvasive therapeutic strategies. Further research is required to refine these models and explore the potential of mechanical forces in cancer treatment<strong>.</strong></div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102414"},"PeriodicalIF":2.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797525","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 : 2025-12-14DOI: 10.1016/j.bbrep.2025.102407
Ce Shi , Lei Chen , Jinshuang Li , Tingting Shi , Chun Yang , Liguo Zhao
Osteoporosis, a prevalent metabolic bone disorder, exhibits an age-related increase in incidence, profoundly impacting patients’ quality of life. Recent studies have underscored the fundamental role of mitochondria in bone metabolism, emphasizing the intricate link mitochondrial dysfunction and the viability and functionality of bone cells. Beyond their role in energy production, mitochondria are critical in modulating cellular apoptosis, oxidative stress, and calcium ion homeostasis, all of which are essential for maintaining bone health. Emerging evidence suggests that mitochondrial dysfunction plays an integral role in the pathogenesis of osteoporosis, yet significant challenges persist in this field. This review seeks to elucidate the critical role of mitochondria in osteoporosis research, examine their intricate relationship with bone metabolism, and synthesize current research advances alongside future directions. Ultimately, it aims to offer novel insights for the prevention and treatment of osteoporosis.
{"title":"The pivotal role of mitochondria in osteoporosis: From pathogenesis to future therapies","authors":"Ce Shi , Lei Chen , Jinshuang Li , Tingting Shi , Chun Yang , Liguo Zhao","doi":"10.1016/j.bbrep.2025.102407","DOIUrl":"10.1016/j.bbrep.2025.102407","url":null,"abstract":"<div><div>Osteoporosis, a prevalent metabolic bone disorder, exhibits an age-related increase in incidence, profoundly impacting patients’ quality of life. Recent studies have underscored the fundamental role of mitochondria in bone metabolism, emphasizing the intricate link mitochondrial dysfunction and the viability and functionality of bone cells. Beyond their role in energy production, mitochondria are critical in modulating cellular apoptosis, oxidative stress, and calcium ion homeostasis, all of which are essential for maintaining bone health. Emerging evidence suggests that mitochondrial dysfunction plays an integral role in the pathogenesis of osteoporosis, yet significant challenges persist in this field. This review seeks to elucidate the critical role of mitochondria in osteoporosis research, examine their intricate relationship with bone metabolism, and synthesize current research advances alongside future directions. Ultimately, it aims to offer novel insights for the prevention and treatment of osteoporosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102407"},"PeriodicalIF":2.2,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797519","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 : 2025-12-14DOI: 10.1016/j.bbrep.2025.102408
Enver Saka , Sakina Yagi , Bengusu H. Akgul , Eulogio J. Llorent-Martínez , Evren Yildiztugay , Ismail Koyuncu , Meltem Cayci , Ismail Yapıcı , Ilhami Gulcin , Yimao Wu , Meng-Yao Li , Gokhan Zengin
Studies evaluating the chemical constituents and pharmacological potential of Paracaryum species (family Boraginaceae) were limited. The current study was designed to investigate, for the first time, the chemical profile, antioxidant, enzyme-inhibitory, and cytotoxic properties of P. hedgei Aytaç & R.R. Mill. Roots extracts recorded the highest total phenolic content (24.72–91.16 mg GAE/g). About 33 compounds were identified, and the aerial parts extracts were dominated by rosmarinic acid, rutin, and sagerinic acid. In general, the root extracts exhibited greater antioxidant activity than the extracts from the aerial parts. Among the solvents, The 70 % EtOH extract of roots showed the highest antiradical (DPPH: 207.90 mg TE/g; ABTS: 238.08 mg TE/g), ion-reducing (FRAP: 384.99 mg TE/g; CUPRAC: 615.27 mg TE/g), and total antioxidant activities (3.21 mmol TE/g), whereas the EtOAc and aqueous extracts from the aerial parts demonstrated the best chelating capacity. The enzyme inhibition varied according to the plant parts examined and the solvents employed for extraction. The EtOAc extract of the roots exerted the highest inhibitory effect towards the human carbonic anhydrase II (IC50: 2.32 μg/ml). The cytotoxicity of the extracts was tested against three cancer cell lines (HELA, A549, and HCT-116) and one healthy cell line (HEK-293). Specifically, the EtOAC extracts showed cytotoxic effects on HELA cells sourced from aerial parts (IC50: 106.30 μg/ml) and on HCT-116 cells sourced from roots (IC50: 96.82 μg/ml). Molecular docking results provided additional support for the enzyme inhibition capabilities of the extracts. Combined network pharmacology and molecular docking analyses revealed that phenolic acids from P. hedgei exert anti-cancer effects on cervical and colorectal adenocarcinoma by modulating key pathways, including retinoic acid metabolism, steroid biosynthesis, and inflammatory responses. These findings can provide a scientific starting point for the pharmaceutical potential of P. hedgei, and it can be considered a valuable source of natural bioactive compounds for functional nutraceutical and pharmaceutical applications.
对琉璃苣属植物化学成分和药理潜力的评价研究有限。本研究旨在首次研究刺猬草Aytaç &； R.R. Mill的化学特征、抗氧化、酶抑制和细胞毒性。根提取物总酚含量最高（24.72 ~ 91.16 mg GAE/g）。共鉴定出33个化合物，其中以迷迭香酸、芦丁和sagerium酸为主。总体而言，根提取物的抗氧化活性高于地上部分提取物。在溶剂中,70 % EtOH根的提取物显示最高的反激进主义的(DPPH: 207.90 毫克 TE / g, abt: 238.08 毫克 TE / g), ion-reducing(收紧:384.99 毫克 TE / g, CUPRAC: 615.27 毫克 TE / g),和总抗氧化活动(3.21 更易 TE / g),而层与水提取物的天线部分展示了最好的螯合能力。酶的抑制作用根据所检测的植物部位和提取溶剂的不同而不同。根中乙酸乙酯提取物对人碳酸酐酶ⅱ的抑制作用最强（IC50: 2.32 μg/ml）。对三种癌细胞系（HELA、A549和HCT-116）和一种健康细胞系（HEK-293）进行了细胞毒性试验。其中，EtOAC提取物对来源于地根的HELA细胞（IC50: 106.30 μg/ml）和来源于根的HCT-116 细胞（IC50: 96.82 μg/ml）具有细胞毒作用。分子对接结果为该提取物的酶抑制能力提供了额外的支持。结合网络药理学和分子对接分析发现，刺蒺藜酚酸通过调节视黄酸代谢、类固醇生物合成和炎症反应等关键通路，对子、结直肠腺癌具有抗癌作用。这些发现可以为刺猬草的药用潜力提供一个科学的起点，它可以被认为是功能性营养保健和制药应用的天然生物活性化合物的宝贵来源。
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