Cinnamaldehyde (CA), a natural small-molecule aldehyde compound, exhibits potent antitumor activity. However, its application is hindered by inherent drawbacks, including poor chemical stability and rapid metabolic clearance. To overcome these challenges, histidine (His) is used to construct an amphiphilic prodrug (His-CA) through a Schiff base conjugation with CA, which is subsequently co-assembled with cisplatin (CDDP) to form stable nanodrugs (His-CA@Pt/NPs). Under physiological conditions, this amphiphilic assembly significantly improves the aqueous dispersibility of CA, while Pt-mediated coordination cross-linking further reinforces the structural integrity of the nanodrugs. In an acidic microenvironment, the nanodrugs undergo charge reversal and structural dissociation, facilitating rapid drug release with cumulative rates reaching 98.48 +/- 1.10% for CDDP and 58.47 +/- 2.18% for CA. Mechanistically, CA induces mitochondrial dysfunction and amplifies oxidative stress, while both His and CA act synergistically to deplete intracellular glutathione (GSH) and tetrahydrofolate (THF), respectively. This dual depletion potently augments CDDP-mediated DNA damage. In vivo studies confirmed that His-CA@Pt/NPs prolong the circulation half-life of CDDP to 2.55 h and promote effective accumulation within tumor tissues. The nanodrugs not only achieve superior antitumor efficacy (72.81% inhibition) compared to mono- or combination drug therapy, but also significantly mitigate the systemic toxicity commonly associated with small-molecule agents. Therefore, this histidine-modification strategy successfully optimizes the physicochemical properties of CA and CDDP while enhancing chemotherapeutic outcomes, offering a versatile and promising platform for other therapeutic agents.
The sequence of physical treatments constitutes a critical but underutilized parameter in starch modification. This study systematically examines how the order of ultrasound (U) and autoclaving (H) governs the multi-scale structural reorganization and resultant functional properties of three chestnut starch varieties (Castanea henryi, C. seguinii, and C. mollissima). Structural and functional properties were analyzed using complementary techniques. HU treatment created a porous network, synergistically enhancing water absorption by 40% (from 210.7 to 295.0 g/g) and reducing syneresis after five freeze-thaw cycles from 23.0% to 10.4%. In contrast, UH treatment induced extensive gelatinization yet better preserved semi-crystalline order (relative crystallinity 16.5% vs. 18.2% for HU), resulting in a significant increase in resistant starch (RS) from 24.7% to 45.3% and thus significantly lower digestibility, with variety-dependent effects observed. This work establishes treatment sequence as a novel, tunable, and chemical-free green lever for the precise design of starch functionality.
Plant Polyphenols are important bioactive compounds with significant physiological activities. However, their poor targeting and rapid metabolism in vivo limit their practical application. Therefore, this study aims to design a polylactic acid-co-hydroxyacetic acid (PLGA) nanosystem for co-deliver NaHCO3 and pine needle polyphenols, thereby enhancing the bioavailability of polyphenols. SEM tests revealed that NaHCO3 decomposed into CO2 under weak acid conditions, accelerating the disintegration of PLGA particles and achieving controlled release of the active agents. In vitro cell experiments demonstrated that the nanosystem was non-toxic and could efficiently scavenge intracellular reactive oxygen species and alleviate mitochondrial damage. In vivo experiments confirmed that the PLGA nano-system could down-regulate the levels of inflammatory factors, thereby alleviating acute liver injury. Overall, this nano-codelivery system not only overcomes the limitations of PLGA carrier materials but also significantly enhances the biostability and bioactivity of pine polyphenols.
Two selenized chitooligosaccharide (O-Se-COS and N,O-Se-COS) with different sites modification were synthesized to alleviate liver injury in vivo. Comparing to traditional COS, both selenized COS exhibited enhanced reducibility as well as antioxidant capacity in vitro. Furthermore, O-Se-COS demonstrated superior efficacy in reducing intracellular reactive oxygen species (ROS) and mitochondrial damage compared to N,O-Se-COS as its enhanced cellular uptake by the positive/negative charge interactions. Two mechanisms were proposed to explained these results: one is to enhance the enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which effectively scavenge free radicals; the other is to down-regulate intracellular cytochrome P450 (CYP2E1) levels, inhibiting carbon tetrachloride (CCl4)-induced peroxidation damage. In vivo studies further demonstrated the effective alleviation of CCl4-induced liver injury by selenized COS, with therapeutic efficacy observed in the following order: O-Se-COS > N,O-Se-COS > COS. Finally, hemolysis and histological tests confirmed the biosafety of both selenized COS. Taken together, these finding demonstrated that selenium has the potential to improve the biological activity of COS, and precise selenylation was more conducive to achieving the synergistic effect where 1 + 1>2.
Selenium (Se) is a beneficial trace element for plants, while zinc (Zn) is a vital micronutrient. Bletilla striata (Thunb.) Reichb. F. is widely recognized as a medicinal herb. In this study, Se and Zn were introduced to determine the medicinal properties of B. striata. The plant’s biomass, polysaccharides, Se and Zn contents, and the antioxidant properties of polysaccharide solutions were all examined. A notable increase in polysaccharide synthesis in B. striata tubers was observed following the application of 0.2 kg ha−1 of Se, and 1.0 kg ha−1 of Zn, either individually or in combination. Se and Zn content in polysaccharides were 3.33 to 3.77 mg kg−1 and 82.82 to 121.78 mg kg−1, at 1.0 kg ha−1 Se and 10.0 kg ha−1 Zn treatments, respectively. These values were 2.1–3.1 times and 1.8–2.8 times higher than those observed in control samples. Polysaccharide antioxidation has resulted in an increase in antioxidant activity as the concentration of polysaccharide solutions increased. The largest scavenging of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals and the most excellent reducing power of the polysaccharide solutions were observed when a mixture of Se and Zn was applied at a rate of 1.0 kg ha−1 and 10.0 kg ha−1. The individual application of Se at 1.0 kg ha−1 and Zn at 10.0 kg ha−1 also resulted in significant DPPH radicals scavenging and reduced power. These data suggested that Se-Zn enriched B. striata is a new source of Se and Zn supplementation and an antioxidant resource.
The optimal extraction process of phytoglycogen(PG)from sweet corn by ultrasound-assisted method was studied,and the physicochemical properties and biological activities of PG were evaluated in this paper.The effects of solid-liquid ratio,ultrasonic power and ultrasonic time on the yield of PG were investigated and the process parameters were further optimized by orthogonal experiment.Furthermore,the physicochemical properties of PG obtained by ultrasound-assisted method were investigated.Meanwhile,the antioxidation,cytotoxicity,apoptosis and hemolysis of PG were evaluated in vitro.The results showed that the optimal extraction conditions were as follows:Solid-liquid ratio of 1∶9(g/mL),ultrasonic power of 160 W and ultrasonic time of 80 min,the actual yield was 14.31%±0.38%.The PG particle size obtained by ultrasound-assisted method was lower than that obtained by traditional water extraction and alcohol precipitation method.In vitro antioxidant experiment showed that PG had a certain antioxidant capacity,especially it was more sensitive to DPPH free radicals,and the clearance rate reached 54.58%±1.39%at 20 mg/mL.The results of biosafety evaluation showed that the survival rate of mouse fibroblasts(3T3)was higher than 95%after incubation with different concentrations of PG for 24 or 48 h.Meanwhile,PG had no obvious apoptotic effect on cells,and the apoptotic rate was lower than 7%at the maximum concentration.After 2 h of co-incubation,the hemolysis rate caused by PG on red blood cells was also much lower than the national standard(5%),which confirmed that PG had good biocompatibility with normal cells and red blood cells.Overall,this study showed that ultrasound-assisted method could improve the yield and physicochemical properties of PG,and also confirmed that PG was a non-toxic natural nanoparticle,which had great application potential in drug or food factor delivery.
利用大米、小米、紫米和荞麦为基质进行蛹虫草固体发酵,采用氢化物-发生原子荧光法测定总硒含量,高效液相色谱分析基质中虫草素和腺苷含量,考马斯亮蓝和硫酸-苯酚法测定粗蛋白和粗多糖含量.在单因素试验的基础上,采用响应面法对营养米糊的工艺配方进行优化,以有机硒、虫草素、腺苷、多糖、蛋白质、感官评分为指标,对营养米糊的冲泡料液比和水温进行比较与分析.结果表明,蛹虫草菌丝能够在15 d完全侵染大米、小米、紫米和荞麦基质,总硒含量分别为(1.8±0.3)mg/kg、(1.7±0.4)mg/kg、(1.9±0.4)mg/kg和(1.7±0.5)mg/kg,其中硒形态主要为硒代蛋氨酸.谷物发酵基质中富含虫草素、腺苷、多糖和蛋白质.通过单因素试验确定发酵基质适宜干燥温度为50℃,干燥后富硒蛹虫草谷物基质的粒形完整、菌丝暴露表面呈金黄色.由单因素与响应面试验优化富硒蛹虫草营养米糊(以大米基质为例)的制备工艺配方为:富硒蛹虫草谷物基质添加量50.0%,奶粉添加量4.5%,冲泡水温80℃.该条件下制备的营养米糊富含蛹虫草特有清香,色泽诱人,口感香醇,丰富了米糊的加工种类.
Mono-chemotherapy is inefficient and easily cause drug-resistance in clinical cancer treatment. In this work, a borate ester linked α-tocopherol succinate (α-TOS) dimer was developed and self-assembled with doxorubicin (DOX) to obtain hybrid nanodrugs (2BOH-TOS/DOX) to improve the deficiency of mono-chemotherapy. Hybrid nanodrugs were highly sensitive to H2O2 and triggered quickly DOX release via H2O2 stimulation. In vitro tests verified that hybrid nanodrugs could increase intracellular DOX levels through inhibiting ATP-dependent drugs efflux, resulting in higher cell-killing in drug-resistant tumor cells. In addition, nanodrugs could amplify oxidative therapy by inducing reactive oxygen species (ROS) generation and depleting intracellular glutathione (GSH). Furthermore, 3D cells experiments revealed that nanodrugs could effectively accumulate and penetrate in sensitive/resistant tumor-like spheroids, achieving higher antitumor effect through the combination of chemo/oxidative therapy. Overall, this H2O2-sensitive nanodrugs was effective in reversing drug-resistance and synergistically treating tumors.
Poly(lactide-co-glycolide) (PLGA) is promising carrier material for drugs delivery in cancer therapy. However, the slow degradation and lack of targeting have greatly limited the clinical effectiveness of PLGA-based nano -medicines. Herein, we fabricated a hybrid nanosystem (3 P @ He/Pt-NPs) comprising of acid-sensitive polymer (mPOE-PLGA), active-targeting polymer (PBA-PLGA) and therapeutic agents (hemin+cisplatin) to combat these problems. In neutral environment, PEGylation can effectively improve the blood stability and circulation time of hybrid nanosystem. After reaching tumor regions, this nanosystem efficiently increased cellular uptake by dePEGylation and PBA-mediated active-targeting. Furthermore, encapsulated hemin could catalyze the oxygen bubbles generation, which remarkably increasing the drugs release rate. Subsequently, hybrid particles produced a higher cell-killing effect to lung cancer cells (A549) by the combination therapy (chemotherapy and chemo-dynamic therapy (CDT)). Importantly, cisplatin further amplified CDT effect by inducing H2O2 regeneration owing to the cascade enzymatic reactions, while hemin decreased intracellular glutathione (GSH) level, resulting in a low detoxification effect to cisplatin. Thus, hybrid particles could efficiently inhibit drug-resistant tumor growth and the inhibition rate reached 83.2%. Overall, this hybrid polymer nanosystem improve the drawbacks of PLGA-based nanocarriers, and can realize a cascading enhanced tumor treatment.
师范生教学技能培养是高等教育落实"立德树人"根本任务的重要组成部分,是造就党和人民满意的高素质、专业化、创新性教师队伍的重要举措.本文以安庆师范大学生命科学学院为例,创新性地提出了"一核三翼九措"的教学基本功培训模式,从教师队伍、教学基本功培训、名师讲坛、教学技能竞赛等方面,系统总结了生物学师范生教学技能培养的成功经验,以期为地方师范院校培养高质量的应用型师范人才发挥示范引领和推动作用.
教师在教育教学的过程中,适时渗透新时代生态文明理念,有助于学生树立保护环境的社会责任意识.微视频应用于课堂教学,化抽象知识为具体,有利于开阔学生视野,激发其学习兴趣,提高教学效率.本文以"生态系统的物质循环"为例,将微视频应用于具体的教学环节中,旨在帮助学生树立人与自然和谐共生的理念.
本文以天然壳聚糖为骨架,分别以二甲基马来酸酐和肉桂醛为亲/疏水组分合成双亲性大分子前药,并进一步组装成纳米前药以用于肿瘤治疗.采用核磁、红外以及透射电镜等方法检测纳米前药的结构、尺寸、电荷以及形貌等特性,并探讨了该纳米颗粒的稳定性和pH刺激响应性;此外,从细胞摄取、细胞毒性、活性氧生成、线粒体损伤、细胞凋亡等方面深入评价纳米前药在治疗乳腺癌方面的潜力及其机制.结果表明,纳米前药呈现球形结构,粒径约160nm,分散均一,CMC值较低,在生理条件下能维持较高的稳定性.此外,该纳米颗粒具备双重pH敏感性,可以在不同pH梯度刺激下分别实现电荷翻转和药物控释,从而提高胞内有效药物浓度并导致更高的肿瘤细胞杀伤效应.抗癌作用机制研究证实了该纳米前药能够诱导线粒体损伤、活性氧生成以及细胞色素c释放,从而加快肿瘤细胞凋亡.总体上讲,本研究不仅极大地提高了肉桂醛的生物学活性,同时也为天然活性分子在纳米医学方面的应用提供了理论与技术参考.
The effective delivery and targeted release of drugs within tumor cells are critical factors in determining the therapeutic efficacy of nanomedicine. To achieve this objective, a conjugate of maltose (Mal) and bovine serum albumin (BSA) was synthesized by the Maillard reaction and self-assembled into nanoparticles with active-targeting capabilities upon pH/heating induction. This nanoparticle could be effectively loaded with doxorubicin (DOX) to form stable nanodrugs (Mal-BSA/DOX) that were sensitive to low pH or high glutathione (GSH), thereby achieving a rapid drug release (96.82 % within 24 h). In vitro cell experiments indicated that maltose-modified BSA particles efficiently enhance cellular internalization via glucose transporters (GLUT)-mediated endocytosis, resulting in increased intracellular DOX levels and heightened expression of γ-H2AX. Consequently, these results ultimately lead to selective tumor cells death, as evidenced by an IC50 value of 3.83 μg/mL in HepG2 cells compared to 5.87 μg/mL in 293t cells. The efficacy of Mal-BSA/DOX in tumor targeting therapy has been further confirmed by in vivo studies, as it effectively delivered a higher concentration of DOX to tumor tissue. This targeted delivery approach not only reduces the systemic toxicity of DOX but also effectively inhibits tumor growth (TGI, 75.95 %). These findings contribute valuable insights into the advancement of targeting-albumin nanomedicine and further support its potential in tumor treatment.
STSE教育理念涵盖了科学、技术、社会和环境4个维度,是一种面向未来的教育模式.它要求教师在教学过程中将自然科学的科学和技术与社会科学的社会和环境有机融合,从而不断提升学生的科学和人文素养.本文以微生物学课程中"病毒的繁殖方式"为例,通过图片、动画、问题、案例等教学方式,将STSE教育理念融入课堂教学,使学生既掌握了病毒繁殖过程的基本知识,又对病毒知识的实践应用理解得更为深入,更提升了学生的社会责任感和环境意识.STSE教育理念有助于帮助学生树立正确的三观,最终落实高等教育"立德树人"的根本任务.
采用荧光光谱技术考察了浓度、温度和pH对天然胶原和酰化胶原分子聚集行为的影响.结果表明,天然胶原与酰化胶原分子在277和293 nm处分别出现了归属于苯丙氨酸(phenylalanine,Phe)和酪氨酸(tyro-sine,Tyr)的特征荧光峰.与天然胶原相比,酰化胶原分子在360~400 nm处出现了归属于Tyr激发态的宽峰,表明其聚集程度强于天然胶原.随着浓度的增加,天然胶原与酰化胶原分子的聚集程度增加,导致荧光强度逐渐增大;然而随着温度的升高,Phe和Tyr的荧光量子产率逐渐降低,同时天然胶原与酰化胶原分子不断解聚集直至出现无规卷曲构造,导致荧光强度不断降低;随pH升高,天然胶原与酰化胶原分子聚集程度先增加后降低,在等电点附近,聚集程度最大.二维荧光光谱数据表明,浓度影响下,天然胶原分子的Phe和酰化胶原分子的Tyr激发态优先响应;温度影响下,天然胶原分子的Tyr和酰化胶原分子的Tyr聚集态优先响应;pH影响下,天然胶原分子的Tyr和酰化胶原分子的Tyr激发态优先响应.
Efficient intracellular drugs delivery and accumulation are the key determinant for overcoming tumor multidrug resistance (MDR). To realize this purpose, dual-pH responsive chitosan nanoparticles (DCCA/DOX-NPs) were fabricated to treat MDR tumor in human breast cancer (MCF-7/ADR). The particles were firstly sensitive to tumor extracellular pH 6.5, contributing to the surface charge reversal (6.32 -> 11.45 mV) by the cleavage of beta-carboxylic amide, which greatly increased cellular uptake efficiency. DCCA/DOX-NPs further responded to lower intracellular pH 5.0, thereby triggering DOX and cinnamaldehyde (CA) release by the cleavage of Schiff base. Cells assays verified that dual-pH sensitive particles caused higher toxicity in MDR tumor cells. Furthermore, the particles could overcome tumor resistance by decreasing intracellular levels of ATP and PARP-1, eventually receiving stronger antitumor efficiency in vivo (84.94%). Overall, this amphiphilic chitosan nanosystem with various bioactivities could work as an alternative promising for treating MDR tumor.
生物化学是生物科学类专业的核心课程,其在教学中的地位不言而喻.然而,生物化学知识纷繁复杂,加之知识点分散、零碎,使其难以激发学生的学习兴趣.随着国家对美育教学的大力提倡,将美育融入生物化学教学已成为研究热点.文章从生物化学的实际教学出发,重点挖掘了教材、课堂教学和课后教学的美育因子,以期激发学生的学习兴趣,达到以美促学、以美启智的目的.
Protein modification by active aldehydes is associated with ageing and some chronic diseases, and it is closely related to food quality and safety. In this study, the modification of bovine serum albumin (BSA) using trans,trans-2,4-decadienal at various concentrations (0-10 mm) is investigated. The results show that the changes in the number of free amino groups and arginine residues, carbonyl formation, aggregation characteristics, and fluorescent lipofuscin-like pigments (LFLP) fluorescence are more severe at (E,E)-2,4-decadienal concentrations of 4-10 mm, whereas the conformational changes are more significant at low concentrations (0.1-2 mm). In the BSA modified by 1-10 mm (E,E)-2,4-decadienal, the microenvironment of tryptophan residues to become more hydrophobic, the structure became compact, hydrophobic binding sites decreases, molecular weight and particle size increases, and covalently cross-linked heterogeneous aggregates increases. At the same time, the relationship between the oxidation parameters and samples is explained using principal component analysis and hierarchical cluster analysis. Practical Applications: (E,E)-2,4-decadienal is highly electrophilically active with biomacromolecules. However, compared to the widely studied malonaldehyde (MDA), acrolein (ACR), 4-hydroxynonenal (HNE), and 4-oxo-trans-2-nonenal (ONE)-protein adducts, research on the modification of a protein by (E,E)-2,4-decadienal is insufficient, and the chemical nature of (E,E)-2,4-decadienal-protein adducts is not clear. This study may be useful for extending our understanding of the specific role of (E,E)-2,4-decadienal in the formation of modified proteins during the occurrence of chronic diseases and provides a theoretical reference for food quality and safety problems caused by protein carbonylation during processing and storage.