Biochemical and biophysical research communications最新文献_第4页

Identification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy 8-（2-甲基苯基）- 9h -benzo[f]indeno[2,1-c]quinolin-9-one （C-5635020）作为乳腺癌治疗的新型选择性TGFβ RII激酶抑制剂的鉴定

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151225

Mesfer Al Shahrani, Mohammad Abohassan, Mohammad Alshahrani, Reem M. Gahtani, Prasanna Rajagopalan

Objective and significance

Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary. This study used computational modeling and molecular dynamics simulations to screen the ChemBridge small molecule library against TGFβ RII.

Methods

This study employed high-throughput virtual screening, molecular dynamics simulations, and binding free energy calculations to identify potential inhibitors targeting TGF-β RII. MDA-MB 231 and MCF-7 breast cancer cells were used in anti-proliferative, tans-endothelial migration, and flow cytometric assays for in vitro validations.

Results

We identified 8-(2-methylphenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a potent and selective inhibitor. Protein-ligand modeling analysis revealed that C-5635020 targets the kinase domain of TGFβ RII with superior binding affinities compared to the standard drug, staurosporine. Computational results suggest that C-5635020 selectively binds and inhibits TGFβ RII activity, thereby controlling cell proliferation in breast cancer. In vitro, experiments corroborated these predictions, where C-5635020 inhibited TGFβ RII and p-Smad 2/3 positive population in MDAMB-231 and MCF-7 cells. The compound dose-dependently inhibited cell proliferation, trans-endothelial migration, and increased apoptosis in both breast cancer cell lines.

Conclusion

The strong binding affinity, stability, and favorable thermodynamics of C-5635020 with established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical developments for breast cancer treatment.

目的与意义：转化生长因子-β (TGF-β)在乳腺发育过程中通过调节组织组成发挥关键作用。TGFβ II型受体（TGFβ RII）与乳腺癌有关，是一个有价值的治疗靶点。由于许多现有的TGFβ i /TGFβ RII抑制剂的脱靶副作用，有必要采用更有针对性的方法来发现药物。本研究采用计算建模和分子动力学模拟来筛选ChemBridge小分子文库对抗TGFβ RII。方法：采用高通量虚拟筛选、分子动力学模拟、结合自由能计算等方法，鉴定TGF-β RII靶向抑制剂。MDA-MB 231和MCF-7乳腺癌细胞用于抗增殖、反内皮迁移和流式细胞术检测，以进行体外验证。结果：我们鉴定出8-（2-甲基苯基）- 9h -苯并[f]indeno[2,1-c]喹啉-9-one （C-5635020）是一种有效的选择性抑制剂。蛋白质配体模型分析显示，与标准药物staurosporine相比，C-5635020靶向TGFβ RII的激酶结构域，具有更好的结合亲和力。计算结果表明，C-5635020选择性结合并抑制TGFβ RII活性，从而控制乳腺癌细胞增殖。体外实验证实了这些预测，其中C-5635020抑制MDAMB-231和MCF-7细胞中的TGFβ RII和p-Smad 2/3阳性群体。该化合物剂量依赖性地抑制两种乳腺癌细胞系的细胞增殖、跨内皮细胞迁移和增加细胞凋亡。结论：C-5635020具有较强的结合亲和力、稳定性和良好的热力学特性，具有良好的体外疗效，具有作为乳腺癌临床前和临床开发先导化合物的潜力。

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引用次数: 0

ESCRT elicits vacuolar fission in the absence of Vps4 in budding yeast 在芽殖酵母中没有Vps4的情况下，ESCRT诱导液泡裂变。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151244

Most Naoshia Tasnin , Tsuneyuki Takuma , Yuka Takahashi , Takashi Ushimaru

In budding yeast, endosomal sorting complex required for transport (ESCRT) mediates microautophagy by vacuolar membrane invagination into the vacuolar lumen, followed by Vps4-assisted membrane constriction and abscission. Here, we show that ESCRT elicits vacuolar fission in the absence of Vps4 after nutrient starvation, although vacuolar fusion is facilitated in wild-type cells in these conditions. ESCRT mediated vacuolar membrane invagination in vps4Δ cells, thereby causing vacuolar fission. It is known that vacuolar fission requires phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and β-propellers that bind polyphosphoinositides (PROPPINs), PI(3,5)P2-binding proteins. However, PROPPIN, but not PI(3,5)P2, was dispensable for the ESCRT-mediated vacuolar fragmentation. Finally, we showed evidence that microlipophagy triggers vacuolar fission. Thus, disruption of the coordinated sequence of ESCRT–Vps4 operations in microautophagy leads to vacuolar fragmentation. This study provides insight into the ESCRT–Vps4 axis-dependent cellular disfunctions and related diseases.

在出芽酵母中，运输所需的内体分选复合体（ESCRT）通过空泡膜内陷到空泡腔中介导微自噬，然后是vps4辅助的膜收缩和脱落。在这里，我们证明了ESCRT在缺乏Vps4的营养饥饿后引发空泡裂变，尽管在这些条件下野生型细胞的空泡融合更容易。ESCRT介导vps4Δ细胞的空泡膜内陷，从而引起空泡裂变。众所周知，液泡裂变需要磷脂酰肌醇3,5-二磷酸（PI(3,5)P2）和β-螺旋桨结合多磷酸肌醇（PROPPINs）， PI(3,5)P2结合蛋白。然而，对于escrt介导的液泡破裂，PROPPIN而非PI(3,5)P2是必不可少的。最后，我们发现了微脂肪吞噬触发空泡裂变的证据。因此，微自噬中ESCRT-Vps4操作协调序列的破坏导致液泡断裂。这项研究为ESCRT-Vps4轴依赖性细胞功能障碍和相关疾病提供了见解。

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引用次数: 0

A novel therapeutic strategy for leukopenia: Miltefosine activates the Ras/MEK/ERK pathway to promote neutrophil differentiation 一种治疗白细胞减少的新策略：米替福辛激活Ras/MEK/ERK通路，促进中性粒细胞分化。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151239

Qinyao Li , Siyu He , Zhichao Li , Sheng Liu , Xinyue Mei , Xiao Qi , Gan Qiao , Jiesi Luo , Hongping Shen , Jing Zeng , Feihong Huang , Siqi Gong , Zhicheng Chen , Jianming Wu , Long Wang

Leukopenia, marked by diminished white blood cell (WBC) counts, presents significant challenges in the management of hematological malignancies and immunocompromised patients. This study evaluated the therapeutic potential of miltefosine (MFS), a phospholipid analogue, for treating leukopenia. In vitro studies using HL60 and NB4 cells revealed that MFS effectively promoted neutrophil differentiation and function, evidenced by the upregulation of surface markers CD11b, CD11c, CD14, and CD15, as well as enhanced bactericidal activity assessed through the NBT reduction assay. In a murine model of irradiation-induced leukopenia, MFS significantly restored both WBC and neutrophil counts, promoted neutrophil production, improved bone marrow (BM) cell proliferation, and mitigated radiation-induced apoptosis of BM cells while promoting the recovery of hematopoietic stem cells (HSCs). Transcriptomic analyses indicated that MFS mediated the regulation of key pathways, particularly the MAPK signaling pathway, which is vital for myeloid differentiation. A comprehensive integration of network pharmacology and RNA sequencing data identified common targets linking MFS to leukopenia, underscoring the critical role of the Ras/MEK/ERK signaling cascade in mediating MFS's effects. Furthermore, molecular docking and Western blot analyses confirmed MFS's interaction with and activation of Ras/MEK/ERK pathway, essential for facilitating neutrophil differentiation. Notably, pharmacological inhibition of ERK significantly diminished MFS-induced neutrophil differentiation. Collectively, these findings elucidate the molecular mechanisms underlying MFS-mediated therapy for leukopenia and provide a solid foundation for future clinical investigations.

白细胞减少症，以白细胞计数减少为标志，在血液恶性肿瘤和免疫功能低下患者的治疗中提出了重大挑战。本研究评估了米替福辛（MFS）的治疗潜力，一种磷脂类似物，用于治疗白细胞减少症。利用HL60和NB4细胞进行的体外研究表明，MFS可以有效促进中性粒细胞的分化和功能，这可以通过上调表面标记物CD11b、CD11c、CD14和CD15来证明，并通过NBT还原实验来增强杀菌活性。在辐射诱导的白细胞减少小鼠模型中，MFS显著恢复白细胞和中性粒细胞计数，促进中性粒细胞产生，改善骨髓（BM）细胞增殖，减轻辐射诱导的BM细胞凋亡，同时促进造血干细胞（hsc）的恢复。转录组学分析表明，MFS介导了关键通路的调节，特别是对髓细胞分化至关重要的MAPK信号通路。网络药理学和RNA测序数据的全面整合确定了MFS与白细胞减少的共同靶点，强调了Ras/MEK/ERK信号级联在介导MFS作用中的关键作用。此外，分子对接和Western blot分析证实了MFS与Ras/MEK/ERK通路的相互作用和激活，这对促进中性粒细胞分化至关重要。值得注意的是，ERK的药理抑制显著减少了mfs诱导的中性粒细胞分化。总的来说，这些发现阐明了mfs介导的白细胞减少治疗的分子机制，为未来的临床研究提供了坚实的基础。

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引用次数: 0

Bradykinin attenuates NiSO4-induced autophagy in MIN6 cells and protects islet function in mice by regulating the PI3K/AKT/mTOR signaling pathway 缓激肽通过调节PI3K/AKT/mTOR信号通路，减弱niso4诱导的MIN6细胞自噬，保护小鼠胰岛功能。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151265

Zhuanping Wang , Hui Chen

Previous studies have shown that nickel sulfate (NiSO₄) increases autophagy in thyroid cells and tissues. As an important organ of the endocrine system, the pancreas not only contributes to the exocrine function of digestion but also has the endocrine function of regulating blood sugar. However, it remains unknown whether NiSO₄ increases pancreatic autophagy. Bradykinin (BK) is an important component of the kallikrein–kinin system (KKS) and has many biological functions, such as reducing autophagy. The purpose of the present study was to explore the effects of BK on NiSO₄-induced changes in pancreatic endocrine function. The present results demonstrate that NiSO₄ increases fasting blood glucose (FBG) within a certain range and decreases insulin levels in mice. Moreover, NiSO₄ triggers incomplete autophagy in MIN6 cells by upregulating microtubule-associated protein 1 light chain 3-II (LC3II) and Beclin 1 but downregulating p62. Mechanistically, NiSO₄ leads to abnormal activation of autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. Moreover, BK decreases FBG and increases insulin secretion in mice exposed to NiSO₄. Light microscopy and transmission electron microscopy (TEM) analyses revealed that BK pretreatment partially restores MIN6 cell viability and decreases the number of autophagic bodies. BK significantly upregulates the protein levels of LC3II and Beclin1 but downregulates p62 in NiSO₄-induced MIN6 cells. In addition, BK increases the levels of phosphorylated phosphatidylinositol 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT) and mammalian target of rapamycin (mTOR). Most of these effects of BK are reversed by treatment with the HOE140 B2R inhibitor. The present results suggested that BK ameliorates NiSO₄-induced pancreatic β-cell dysfunction through B2R-mediated activation of the PI3K/AKT/mTOR signaling pathway and inhibition of autophagy.

先前的研究表明，硫酸镍（NiSO4）增加了甲状腺细胞和组织的自噬。胰腺作为内分泌系统的重要器官，除了具有消化的外分泌功能外，还具有调节血糖的内分泌功能。然而，NiSO4是否增加胰腺自噬仍不清楚。缓激肽（BK）是缓激肽-激肽系统（KKS）的重要组成部分，具有减少自噬等多种生物学功能。本研究旨在探讨BK对niso4诱导的胰腺内分泌功能变化的影响。本研究结果表明，NiSO4在一定范围内提高小鼠空腹血糖（FBG），降低胰岛素水平。此外，NiSO4通过上调微管相关蛋白1轻链3-II （LC3II）和Beclin 1，下调p62，触发MIN6细胞的不完全自噬。机制上，NiSO4通过抑制PI3K/AKT/mTOR信号通路导致自噬异常激活。此外，在暴露于NiSO4的小鼠中，BK降低了FBG并增加了胰岛素分泌。光镜和透射电镜（TEM）分析显示，BK预处理能部分恢复MIN6细胞活力，减少自噬体的数量。在niso4诱导的MIN6细胞中，BK显著上调LC3II和Beclin1蛋白水平，下调p62蛋白水平。此外，BK增加磷酸化磷脂酰肌醇3-激酶（P-PI3K）、磷酸化蛋白激酶B （P-AKT）和哺乳动物雷帕霉素靶蛋白（mTOR）的水平。用HOE140 B2R抑制剂治疗后，BK的这些作用大部分被逆转。本研究结果表明，BK通过b2r介导的PI3K/AKT/mTOR信号通路的激活和自噬的抑制，改善了niso4诱导的胰腺β细胞功能障碍。

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引用次数: 0

IGF2-IGF1R signaling inhibition delays the growth of IGF2-high colorectal cancer by modulating MDSCs IGF2-IGF1R信号抑制通过调节MDSCs延缓igf2高的结直肠癌的生长。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151230

Enjian Zhu , Ying Liu , Shuanglong Xie , Junlei Hou , Xuezhi Yang , Minhao Xu , Fei Yang , Zhaoxia Li , Bo Zhu , Haoran Zha

Approximately 22 % of human colorectal cancers (CRC) are characterized by IGF2 overexpression, and the tumor-promoting role of IGF2 has been widely reported. Despite promising preclinical results, IGF2 signaling inhibition therapy has exhibited limited efficacy in treating unselected patients with CRC. Recent evidence suggests that IGF2-high CRC are more sensitive to IGF2 signaling blockade therapy in immune-deficient mice, suggesting that IGF2-high CRC can benefit from IGF2 signaling blockade therapy. However, T cells are absent in immunodeficient mice, and the effect of blocking IGF2 signaling on T cell-mediated antitumor immunity remains unknown. Herein, using an implanted mouse tumor model in immunocompetent hosts, we report that PQ401, an IGF2-IGF1R inhibitor, significantly inhibited the growth of IGF2-high CRC cells. PQ401 treatment increased the infiltration and function of tumor-infiltrating CD4⁺ and CD8⁺ T cells in a T cell-extrinsic manner. Our findings suggest that myeloid-derived suppressor cells (MDSCs) highly express the IGF2 receptor IGF1R. Moreover, PQ401 treatment inhibits the suppressive function and recruitment of MDSCs, thereby promoting the anti-tumor activity of T cells. These results provide a potential therapeutic regimen for patients with IGF2-high CRC.

大约22%的人类结直肠癌（CRC）以IGF2过表达为特征，IGF2的促肿瘤作用已被广泛报道。尽管有很好的临床前结果，IGF2信号抑制疗法在治疗未选择的结直肠癌患者中显示出有限的疗效。最近的证据表明，在免疫缺陷小鼠中，IGF2高CRC对IGF2信号阻断治疗更敏感，这表明IGF2高CRC可以从IGF2信号阻断治疗中获益。然而，T细胞在免疫缺陷小鼠中缺失，阻断IGF2信号传导对T细胞介导的抗肿瘤免疫的影响尚不清楚。在此，我们利用免疫功能正常的小鼠植入肿瘤模型，报告了IGF2-IGF1R抑制剂PQ401显著抑制igf2 -高水平CRC细胞的生长。PQ401处理以T细胞外源性方式增加肿瘤浸润性CD4+和CD8+ T细胞的浸润和功能。我们的研究结果表明，髓源性抑制细胞（MDSCs）高度表达IGF2受体IGF1R。此外，PQ401治疗可以抑制MDSCs的抑制功能和募集，从而促进T细胞的抗肿瘤活性。这些结果为igf2高的结直肠癌患者提供了一种潜在的治疗方案。

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引用次数: 0

One-step transformation of CO2 to methane by Escherichia coli with a synthetic biomethanation module 利用合成生物甲烷化模块，由大肠杆菌一步将二氧化碳转化为甲烷。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151284

Ze-Peng Wen , Chong Sha , Said Nawab , Zi-Jie Lu , Yang-Chun Yong

The biomethanation process is widely recognized as a significant approach to mitigating carbon dioxide emissions while simultaneously generating methane. However, only a few microorganisms that required intricate culturing conditions were identified for biomethanation. Here, Escherichia coli that featured easy cultivation and versatile chassis was genetically modified for biomethanation for the first time. The nif-related gene cluster with methanogenic capability from Rhodopseudomonas palustris was systematically analyzed, cloned, and integrated into a synthetic biomethanation module. As a result, E. coli BL21 (DE3) and Rosetta (DE3) carrying this synthetic biomethanation module exhibited significant methane production activity, with methane yields reaching 50 nmol/mL and 159 nmol/mL, respectively. This finding provided a simple route to construct synthetic strain for biomethanation, which would advance the fundamental research and be beneficial to further harness the power of biomethanation for practical application.

生物甲烷化过程被广泛认为是减少二氧化碳排放同时产生甲烷的重要方法。然而，只有少数需要复杂培养条件的微生物被确定为生物甲烷化。在这里，大肠杆菌具有易于培养和多功能底盘的特点，首次进行了生物甲烷化基因改造。系统分析、克隆了古红假单胞菌具有产甲烷能力的nif相关基因簇，并将其整合到合成生物甲烷化模块中。结果表明，携带该合成生物甲烷化模块的大肠杆菌BL21 （DE3）和Rosetta （DE3）具有显著的产甲烷活性，产甲烷量分别达到50 nmol/mL和159 nmol/mL。这一发现为构建生物甲烷化合成菌株提供了一条简单的途径，有助于推进生物甲烷化的基础研究，并有利于进一步利用生物甲烷化的力量进行实际应用。

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引用次数: 0

β‐Caryophyllene attenuates oxidative stress and inflammatory response in LPS induced acute lung injury by targeting ACE2/MasR and Nrf2/HO-1/NF-κB axis β-石竹烯通过靶向ACE2/MasR和Nrf2/HO-1/NF-κB轴减轻LPS诱导的急性肺损伤的氧化应激和炎症反应。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151286

Pakter Niri , Achintya Saha , Subramanyam Polopalli , Mohit Kumar , Sanghita Das , Bidisha Saha , Danswrang Goyary , Yangchen Doma Bhutia , Sanjeev Karmakar , Sumit Kishor , Saidur Rahaman , Pronobesh Chattopadhyay

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), is a clinical syndrome that can cause pulmonary edema, inflammation, oxidative stress, and immunological dysregulations. β‐Caryophyllene (BCP), a natural bicyclic sesquiterpene, possesses a variety of pharmacological properties and has the potential to be a therapeutic agent. This study aimed to comprehend the effect of BCP on Nrf2/HO-1/NF-κB and ACE2/MasR axis in a rat model of ALI by lipopolysaccharide (LPS) and the underlying mechanisms during this process. The study also examined pulmonary edema, BALF, and cytokine production to investigate inflammation and oxidative stress. In the LPS group, Western blot analysis showed decreased Nrf2/HO-1 and ACE2/MasR, including increased lung edema, elevated vascular permeability, neutrophil infiltration in BALF, increased cytokine levels, and histological changes. In comparison to the LPS group, BCP dramatically reduced lung edema, vascular permeability, and histological changes. Additionally, by lowering malondialdehyde and myeloperoxidase activity in lung tissues, it also reduced oxidative stress. BCP boosted IL-10 production and decreased the levels of pro-inflammatory cytokines and neutrophil infiltration. BCP administration decreased VEGF-A and SP-D expression, subsequently lowering NF-κB activation and cytokine production. Further, BCP altered ACE2 expression, indicating its involvement by activating the ACE2/Angiotensin (1–7)/MasR axis. In addition, BCP could stimulate the Nrf2/HO-1 anti-oxidant axis to suppress NF-κB and reduce inflammation. BCP modulation of the ACE2/MasR and Nrf2/HO-1/NF-κB axis impedes the course of ALI by influencing immunological response including but not limited to oxidative stress, the influx of neutrophils, and cytokine production. Hence, BCP may act as a potential candidate for management of ALI.

急性肺损伤（ALI）及其严重形式急性呼吸窘迫综合征（ARDS）是一种可引起肺水肿、炎症、氧化应激和免疫失调的临床综合征。β-石竹烯（BCP）是一种天然双环倍半萜，具有多种药理特性，具有潜在的治疗价值。本研究旨在了解BCP对脂多糖（LPS） ALI大鼠模型中Nrf2/HO-1/NF-κB和ACE2/MasR轴的影响及其机制。该研究还检查了肺水肿、BALF和细胞因子的产生，以调查炎症和氧化应激。在LPS组，Western blot分析显示Nrf2/HO-1和ACE2/MasR降低，包括肺水肿增加，血管通透性升高，BALF中中性粒细胞浸润，细胞因子水平升高，组织学改变。与LPS组相比，BCP显著降低了肺水肿、血管通透性和组织学变化。此外，通过降低肺组织中的丙二醛和髓过氧化物酶活性，它还可以减少氧化应激。BCP促进IL-10的产生，降低促炎细胞因子水平和中性粒细胞浸润。BCP可降低VEGF-A和SP-D的表达，从而降低NF-κB的活化和细胞因子的产生。此外，BCP改变了ACE2的表达，表明其通过激活ACE2/血管紧张素(1-7)/MasR轴参与。BCP还能刺激Nrf2/HO-1抗氧化轴抑制NF-κB，减轻炎症反应。BCP调节ACE2/MasR和Nrf2/HO-1/NF-κB轴通过影响免疫反应（包括但不限于氧化应激、中性粒细胞的涌入和细胞因子的产生）阻碍ALI的进程。因此，BCP可能作为ALI治疗的潜在候选。

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引用次数: 0

Engineering mRNA vaccine with broad-spectrum protection against SARS-cov-2 variants 对SARS-cov-2变体具有广谱保护的工程mRNA疫苗

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151224

Shuang Du , Liu Yang , Xingguang Chen , Yonghao Chen , Liang Weng , Hui Huang , Silin Pang

Herd immunity through mass vaccination is an effective method for preventing infectious diseases. However, the emerging SARS-CoV-2 variants, with their frequent mutations, largely evade the immune response and protection induced by COVID-19 vaccines. Here, we designed messenger RNAs encoding mutant epitopes of the spike protein shared among various COVID-19 variants. These mRNAs were encapsulated in lipid nanoparticles to formulate a vaccine named ‘mPANVAX@COVID'. Post-vaccination, this approach elicited effective immunity against multiple SARS-CoV-2 variants, including Delta and Omicron, and demonstrated good safety. This study suggests a novel direction for the design of broadly protective vaccines.

通过大规模疫苗接种进行群体免疫是预防传染病的有效方法。然而，新出现的频繁突变的SARS-CoV-2变体在很大程度上逃避了COVID-19疫苗诱导的免疫反应和保护。在这里，我们设计了编码各种COVID-19变体共享的刺突蛋白突变表位的信使rna。这些mrna被包裹在脂质纳米颗粒中，形成一种名为“mPANVAX@COVID”的疫苗。接种疫苗后，该方法可对多种SARS-CoV-2变体（包括Delta和Omicron）产生有效免疫，并显示出良好的安全性。本研究为广泛保护性疫苗的设计提供了新的方向。

引用次数: 0

Topology-based protein classification: A deep learning approach 基于拓扑的蛋白质分类：一种深度学习方法。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151240

Aliye Sadat Hashemi, Iosif I. Vaisman

Utilizing Artificial Intelligence (AI) in computational biology techniques could offer significant advantages in alleviating the growing workloads faced by structural biologists, especially with the emergence of big data. In this study, we employed Delaunay tessellation as a promising method to obtain the overall structural topology of proteins. Subsequently, we developed multi-class deep neural network models to classify protein superfamilies based on their local topology. Our models achieved a test accuracy of approximately 0.92 in classifying proteins into 18 well-populated superfamilies. We believe that the results of this study hold substantial value since, to the best of our knowledge, no previous studies have reported the utilization of protein topological data for protein classification through deep learning and Delaunay tessellation.

在计算生物学技术中利用人工智能（AI）可以为减轻结构生物学家面临的日益增长的工作量提供显着的优势，特别是随着大数据的出现。在这项研究中，我们采用Delaunay镶嵌作为一种有前途的方法来获得蛋白质的整体结构拓扑。随后，我们开发了基于局部拓扑结构的多类深度神经网络模型来对蛋白质超家族进行分类。我们的模型在将蛋白质分类为18个人口稠密的超家族方面取得了约0.92的测试精度。我们认为，这项研究的结果具有很大的价值，因为据我们所知，之前没有研究报道过通过深度学习和Delaunay镶嵌利用蛋白质拓扑数据进行蛋白质分类。

引用次数: 0

Effects of in vitro simulated digestion on the hypoglycaemic capacity of wheat bran-soluble dietary fibre 体外模拟消化对小麦麸溶性膳食纤维降血糖能力的影响。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-01 DOI: 10.1016/j.bbrc.2024.151267

Wenliang Zhao, Yi Lyu , Ling Xiong, Luanfeng Wang, Fang Wang, Haizhao Song, Xinchun Shen

Wheat bran-soluble dietary fibre (WB-SDF) is known for its hypoglycaemic properties and its potential to control postprandial blood glucose levels in individuals with hyperglycaemia. However, the digestive process may alter its glucose-lowering potential. This study investigated the effects of in vitro simulated digestion on the hypoglycaemic efficacy of WB-SDF. The hypoglycaemic effects of WB-SDF were determined by examining its glucose-binding capacity, glucose dialysis retardation index and ability to inhibit glucose uptake and transport in Caco-2 cells. Structural changes after digestion were analysed via polysaccharide conformation analysis, microstructure observation and particle size measurements to evaluate their impacts on hypoglycaemic efficacy. Results indicate that WB-SDF and digested wheat bran-dietary fibre significantly decreased glucose adsorption and α-glucosidase activity compared with the control group in Caco-2 cells. However, simulated digestion resulted in a relatively smaller reduction in α-glucosidase activity compared with the WB-SDF treatment group. The massive loss of surface laminar structure, reduction of –OH groups and partial glycosidic bond breakage in digested wheat bran-dietary fibre after digestion led to reduced glucose adsorption capacity and glucose dialysis retardation index. Moreover, the reduction in particle size after digestion enhanced the inhibition of glucose transport–related gene expression in Caco-2 cells. Thus, although digestion weakens the glucose adsorption of WB-SDF, it improves its ability to inhibit glucose transport, highlighting the intricate interplay between structural modifications and hypoglycaemic efficacy.

小麦麸皮可溶性膳食纤维（WB-SDF）以其降糖特性和控制高血糖患者餐后血糖水平的潜力而闻名。然而，消化过程可能会改变其降血糖的潜力。本研究探讨体外模拟消化对WB-SDF降血糖作用的影响。通过检测WB-SDF的葡萄糖结合能力、葡萄糖透析迟缓指数和抑制Caco-2细胞葡萄糖摄取和转运的能力来确定其降糖作用。通过多糖构象分析、微观结构观察和粒度测量等方法分析消化后的结构变化，评价其对降糖功效的影响。结果表明，与对照组相比，WB-SDF和消化的麦麸-膳食纤维显著降低了Caco-2细胞对葡萄糖的吸附和α-葡萄糖苷酶活性。然而，与WB-SDF处理组相比，模拟消化导致α-葡萄糖苷酶活性下降相对较小。消化后的麦麸-膳食纤维表面层流结构大量丢失，-OH基团减少，部分糖苷键断裂，导致葡萄糖吸附能力降低，葡萄糖透析迟缓指数下降。此外，消化后颗粒大小的减小增强了Caco-2细胞中葡萄糖转运相关基因表达的抑制。因此，虽然消化削弱了WB-SDF对葡萄糖的吸附，但它提高了其抑制葡萄糖运输的能力，突出了结构修饰与降糖功效之间复杂的相互作用。

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引用次数: 0