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Exploring microbial diversity in the rhizosphere: a comprehensive review of metagenomic approaches and their applications. 探索根圈微生物多样性:元基因组学方法及其应用综述。
IF 2.6 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1007/s13205-024-04065-9
Bhumi Rajguru, Manju Shri, Vaibhav D Bhatt

The rhizosphere, the soil region influenced by plant roots, represents a dynamic microenvironment where intricate interactions between plants and microorganisms shape soil health, nutrient cycling, and plant growth. Soil microorganisms are integral players in the transformation of materials, the dynamics of energy flows, and the intricate cycles of biogeochemistry. Considerable research has been dedicated to investigating the abundance, diversity, and intricacies of interactions among different microbes, as well as the relationships between plants and microbes present in the rhizosphere. Metagenomics, a powerful suite of techniques, has emerged as a transformative tool for dissecting the genetic repertoire of complex microbial communities inhabiting the rhizosphere. The review systematically navigates through various metagenomic approaches, ranging from shotgun metagenomics, enabling unbiased analysis of entire microbial genomes, to targeted sequencing of the 16S rRNA gene for taxonomic profiling. Each approach's strengths and limitations are critically evaluated, providing researchers with a nuanced understanding of their applicability in different research contexts. A central focus of the review lies in the practical applications of rhizosphere metagenomics in various fields including agriculture. By decoding the genomic content of rhizospheric microbes, researchers gain insights into their functional roles in nutrient acquisition, disease suppression, and overall plant health. The review also addresses the broader implications of metagenomic studies in advancing our understanding of microbial diversity and community dynamics in the rhizosphere. It serves as a comprehensive guide for researchers, agronomists, and policymakers, offering a roadmap for harnessing metagenomic approaches to unlock the full potential of the rhizosphere microbiome in promoting sustainable agriculture.

根瘤菌圈是受植物根系影响的土壤区域,是植物与微生物之间复杂互动影响土壤健康、养分循环和植物生长的动态微环境。土壤微生物是物质转化、能量流动动态和生物地球化学复杂循环中不可或缺的角色。大量研究致力于调查不同微生物之间的丰度、多样性和错综复杂的相互作用,以及植物与根瘤菌圈中微生物之间的关系。元基因组学是一套功能强大的技术,已成为剖析根圈中复杂微生物群落基因库的变革性工具。这篇综述系统地介绍了各种元基因组学方法,从可以对整个微生物基因组进行无偏见分析的散弹元基因组学,到用于分类剖析的 16S rRNA 基因定向测序。对每种方法的优势和局限性都进行了严格的评估,使研究人员对其在不同研究环境中的适用性有了细致入微的了解。本综述的一个核心重点是根瘤元基因组学在包括农业在内的各个领域的实际应用。通过解码根瘤微生物的基因组内容,研究人员可以深入了解它们在养分获取、疾病抑制和植物整体健康方面的功能作用。该综述还探讨了元基因组研究在促进我们对根瘤菌层微生物多样性和群落动态的了解方面的广泛影响。它是研究人员、农学家和决策者的综合指南,为利用元基因组学方法释放根圈微生物组在促进可持续农业方面的全部潜力提供了路线图。
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引用次数: 0
Green synthesis of chitosan nanoparticles using Cassia fistula leaf extract: evaluation of antimicrobial, antioxidant, antibiofilm, and cytotoxic activities. 利用决明子叶提取物绿色合成壳聚糖纳米颗粒:抗菌、抗氧化、抗生物膜和细胞毒性活性评估。
IF 2.6 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1007/s13205-024-04073-9
Anusiya Ganesan, Jaiganesh Rengarajan

The emerging field of green synthesis within nanobiotechnology presents significant environmental and economic advantages compared to conventional methodologies. This study investigates the synthesis and application of chitosan nanoparticles (ChNPs) using Cassia fistula (CF) leaf extract as a sustainable, and bio-based approach. Characterization of CF-ChNPs confirmed effective bioconversion and also demonstrated significant antimicrobial activity. Notably, CF-ChNPs demonstrated a remarkable antimicrobial effect against Pseudomonas aeruginosa, with a zone of inhibition of 17 ± 0.2 mm surpassing the impact on other organisms tested. The CF-ChNPs exhibited an initial burst release of 28 ± 0.28% after 2 h, gradually achieving a controlled release of 76.3 ± 0.43% within 24 h. In addition, CF-ChNPs exhibited an antioxidant activity of 43.1 ± 0.48% and showed excellent antibiofilm activity against Staphylococcus aureus in comparison to other organisms. The cell viability assay results have confirmed that CF-ChNPs do not have any negative impact on the viability of L929 fibroblasts, further highlighting their potential as versatile nanomaterials for treating microbial infections and other therapeutic applications.

与传统方法相比,纳米生物技术中新兴的绿色合成领域具有显著的环境和经济优势。本研究利用决明子(CF)叶提取物合成并应用壳聚糖纳米颗粒(ChNPs),这是一种可持续的生物方法。CF-ChNPs 的表征证实了其有效的生物转化性,同时还显示出显著的抗菌活性。值得注意的是,CF-ChNPs 对铜绿假单胞菌具有显著的抗菌效果,其抑制区为 17 ± 0.2 毫米,超过了对其他受试生物的影响。此外,CF-ChNPs 的抗氧化活性为 43.1 ± 0.48%,对金黄色葡萄球菌的抗生物膜活性也优于其他生物。细胞活力测定结果证实,CF-ChNPs 不会对 L929 成纤维细胞的活力产生任何负面影响,这进一步凸显了 CF-ChNPs 作为治疗微生物感染和其他治疗应用的多功能纳米材料的潜力。
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引用次数: 0
Stimulating action of sodium nitroprusside and vinasse on salicin and direct regeneration in Salix Safsaf Forssk. 硝普钠和甘蔗渣对水杨酸和 Salix Safsaf Forssk.
IF 2.6 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-19 DOI: 10.1007/s13205-024-04068-6
Rania Saber Yousef, Osama Konsowa Ahmed, Zeinab K Taha

The present study aimed to enhance salicin and direct regeneration in willow (Salix safsaf Forssk) using the sodium nitroprusside (SNP) regulation of nitric oxide (NO) and vinasse for its nutrition effect in culture medium. Internodes of Salix safsaf were cultured on Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA) (0.25 mg L-1) and different concentrations of SNP (0, 5, 10, 15, and 20 mg L-1) or vinasse (0, 5, 10, and 20%) to examine shoot regeneration, antioxidant defense enzyme activity, total phenolic compounds, flavonoids, and salicine contents. The reported data revealed that application of SNP at 15 mg L-1 and vinasse at 10% induced a significant effect in vitro Salix safsaf shoot regeneration. To confirm that, nitric oxide is required for auxin-mediated activation of cell division in a dose-dependent manner. A concentration of 15 mg L-1 SNP promotes regeneration and salicin accumulation (3162.16 mg/100 g) during signaling action. On the other hand, the cross talk effect of nitric oxide and vinasse combination in Salix safsaf significantly induced a synergistic effect on direct propagation more than vinasse alone. SNP significantly stimulates salicylate accumulation in a dose-dependent manner, but the data on the association of vinasse and SNP on salicylate up-regulation showed a significant reduction in salicin accumulation when SNP was combined with 10% vinasse, which directly affected the signaling action of SNP as secondary product stimulators. Vinasse's phenolic compounds affect directly on the reduction activity of SNP to suppress its signaling action, or indirectly by inhibiting the sequence cascade of the SNP signaling transduction process to decrease the accumulation of salicin contents. Data confirmed that vinasse and SNP stimulated the antioxidant enzymes activity throw quenching the stimulated reactive oxygen species that produced via SNP. Results show that modified media with SNP administration at 15 mg L-1 and the combination of vinasse at 10% and SNP at 15 mg L-1 are recommended for modifying tissue culture media for induced direct regeneration and salicin accumulation in tissue culture applications, which will be very useful for commercial salicin overproduction as a biological active ingredient in willows.

本研究旨在利用硝普钠(SNP)对一氧化氮(NO)的调节作用以及葡萄渣在培养基中的营养作用,提高柳树(Salix safsaf Forssk)的水杨素和直接再生能力。在添加了苄基腺嘌呤(BA)(0.25 mg L-1)和不同浓度 SNP(0、5、10、15 和 20 mg L-1)或蔗渣(0、5、10 和 20%)的 Murashige and Skoog(MS)培养基上培养沙柳的节间,以检测嫩枝再生、抗氧化防御酶活性、总酚类化合物、黄酮类化合物和盐碱含量。报告数据显示,施用 15 mg L-1 的 SNP 和 10%的甘蔗渣对沙柳的体外嫩枝再生有显著影响。为了证实这一点,需要一氧化氮以剂量依赖的方式激活由辅助素介导的细胞分裂。在信号作用过程中,15 mg L-1 SNP 浓度可促进再生和水杨素积累(3162.16 mg/100 g)。另一方面,一氧化氮和甘蔗渣在沙柳中的交叉效应比单独使用甘蔗渣更能显著地诱导直接传播的协同效应。一氧化氮能以剂量依赖的方式明显刺激水杨酸盐的积累,但关于甘蔗渣和一氧化氮对水杨酸盐上调的关联数据显示,当一氧化氮与 10%的甘蔗渣结合时,水杨酸盐的积累明显减少,这直接影响了一氧化氮作为次生产物刺激剂的信号作用。甘蔗渣中的酚类化合物直接影响 SNP 的还原活性,抑制其信号作用,或间接抑制 SNP 信号转导过程的级联序列,减少水杨酸含量的积累。数据证实,甘蔗渣和 SNP 能刺激抗氧化酶的活性,淬灭 SNP 产生的活性氧。结果表明,15 毫克/升 SNP 的改良培养基以及 10%的甘蔗渣和 15 毫克/升 SNP 的组合可用于改良组织培养基,以诱导组织培养应用中的直接再生和水杨素积累,这对作为柳树生物活性成分的水杨素的商业化过度生产非常有用。
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引用次数: 0
Biological roles of THRAP3, STMN1 and GNA13 in human blood cancer cells. THRAP3、STMN1 和 GNA13 在人类血癌细胞中的生物学作用。
IF 2.6 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-25 DOI: 10.1007/s13205-024-04093-5
Suliman A Alsagaby

Blood cancers, such as diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma (BL) and acute myeloid leukemia (AML), are aggressive neoplasms that are characterized by undesired clinical courses with dismal survival rates. The objective of the current work is to study the expression THRAP3, STMN1 and GNA13 in DLBCL, BL and AML, and to investigate if these proteins are implicated in the prognosis and progression of the blood cancers. Isolation of normal blood cells was performed using lymphoprep coupled with gradient centrifugation and magnetic beads. Flow-cytometric analysis showed high quality of the isolated cells. Western blotting identified THRAP3, STMN1 and GNA13 to be overexpressed in the blood cancer cells but hardly detected in normal blood cells from healthy donors. Consistently, investigations performed using genotype-tissue expression (GTEx) and gene expression profiling interactive analysis (GEPIA) showed that the three proteins had higher mRNA expression in various cancers compared with matched normal tissues (p ≤ 0.01). Furthermore, the up-regulated transcript expression of these proteins was a feature of short overall survival (OS; p ≤ 0.02) in patients with the blood cancers. Interestingly, functional profiling using gProfiler and protein-protein interaction network analysis using STRING with cytoscape reported THRAP3 to be associated with cancer-dependent proliferation and survival pathways (corrected p ≤ 0.05) and to interact with proteins (p = 1 × 10-16) implicated in tumourigenesis and chemotherapy resistance. Taken together, these findings indicated a possible implication of THRAP3, STMN1 and GNA13 in the progression and prognosis of the blood cancers. Additional work using clinical samples of the blood cancers is required to further investigate and validate the results reported here.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04093-5.

弥漫大 B 细胞淋巴瘤(DLBCL)、伯基特淋巴瘤(BL)和急性髓性白血病(AML)等血癌都是侵袭性肿瘤,其特点是临床过程不理想,生存率低。本次研究的目的是研究 THRAP3、STMN1 和 GNA13 在 DLBCL、BL 和 AML 中的表达,并探讨这些蛋白是否与血癌的预后和进展有关。研究人员使用淋巴捕获器、梯度离心和磁珠分离正常血细胞。流式细胞仪分析表明分离的细胞质量很高。免疫印迹检测发现,THRAP3、STMN1 和 GNA13 在血癌细胞中过表达,但在健康捐献者的正常血细胞中几乎检测不到。同样,利用基因型-组织表达(GTEx)和基因表达谱交互分析(GEPIA)进行的研究表明,与匹配的正常组织相比,这三种蛋白质在各种癌症中的 mRNA 表达量更高(p ≤ 0.01)。此外,这些蛋白的转录表达上调是血癌患者总生存期(OS)缩短的一个特征;p ≤ 0.02。有趣的是,使用 gProfiler 进行的功能分析和使用 STRING 与 cytoscape 进行的蛋白-蛋白相互作用网络分析显示,THRAP3 与癌症依赖性增殖和生存途径相关(校正后 p ≤ 0.05),并与肿瘤发生和化疗耐药性相关蛋白相互作用(p = 1 × 10-16)。综上所述,这些发现表明 THRAP3、STMN1 和 GNA13 可能与血癌的进展和预后有关。要进一步研究和验证本文报告的结果,还需要使用血癌临床样本开展更多工作:在线版本包含补充材料,可在10.1007/s13205-024-04093-5上查阅。
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引用次数: 0
Upcycling of tea processing waste into kombucha-derived bioactive cellulosic composite for prospective wound dressing action. 将茶叶加工废料升级再造为从昆布茶中提取的生物活性纤维素复合材料,用于伤口敷料。
IF 2.6 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-27 DOI: 10.1007/s13205-024-04095-3
Baishali Dey, Sivaraman Jayaraman, Paramasivan Balasubramanian

The aim of the study was to utilize kombucha-derived bacterial cellulosic sheet [KBC], formed as a by-product of fermented, sugared black tea (in the presence of a symbiotic culture of bacteria and yeast), for potential wound dressing applications. KBC was functionalized using aqueous and ethanolic extracts of different phytochemical agents using two ex-situ methods- casting and impregnation. It was observed that casted KBC functionalized with ethanolic extract of Turmeric (1.2% w/w) yielded a maximum zone of inhibition (24.37 ± 0.42 mm) against Pseudomonas aeruginosa. The hemocompatibility test confirmed the composite's biocompatible nature as the percentage hemocompatibility was found to be less than 5%. The MTT assay established its viability and anti-cancerous properties with Turmeric extract loaded KBC showing higher efficiency compared to Tulsi extract. FTIR analysis and SEM imaging confirmed the functionalization of cellulose sheets and the change in morphology. The contact angle analysis showed improved hydrophilic properties of the sheets for absorbing wound exudates, and the water absorption study revealed maximum absorptivity of up to 321.20 ± 6.23%. Thus, it can be concluded from the study that tea processing waste can be reused to produce a value-added product that can act as an efficient, cost-effective biomaterial for wound dressing applications.

该研究旨在利用昆布茶衍生的细菌纤维素薄片 [KBC](在细菌和酵母共生培养的情况下)作为发酵糖渍红茶的副产品,用于潜在的伤口敷料应用。采用两种原位方法--浇铸法和浸渍法,利用不同植物化学制剂的水提取物和乙醇提取物对 KBC 进行了功能化处理。结果表明,用姜黄乙醇提取物(1.2% w/w)制成的功能化 KBC 对铜绿假单胞菌的抑制区最大(24.37 ± 0.42 mm)。血液相容性测试证实了该复合材料的生物相容性,其血液相容性低于 5%。MTT 试验证实了 KBC 的活力和抗癌特性,与涂尔西提取物相比,负载姜黄提取物的 KBC 表现出更高的效率。傅立叶变换红外光谱分析和扫描电镜成像证实了纤维素片的功能化和形态变化。接触角分析表明,纤维素片在吸收伤口渗出物方面具有更好的亲水性,吸水率研究表明,最大吸水率可达 321.20 ± 6.23%。因此,这项研究得出结论,茶叶加工废料可以再利用,生产出高附加值的产品,作为一种高效、经济的生物材料用于伤口敷料。
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引用次数: 0
Cytotoxic activity of callus extract from Vachellia farnesiana (L) Wight & Arn. Vachellia farnesiana (L) Wight & Arn.
IF 2.8 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-18 DOI: 10.1007/s13205-024-04085-5
José Alejandro Domínguez-Colín, Leticia Buendía-González, Carmen Hernández-Jaimes, Francisco Cruz-Sosa, Juan Orozco-Villafuerte

The in vitro cultures of Vachellia farnesiana (L) Wight & Arn. have demonstrated cytotoxic activity through callus extract on the HeLa cell line. Explants excised from in vitro-grown seedlings from seeds of two different locations were inoculated on Murashige and Skoog (MS) culture media containing various concentrations of N-6 benzyladenine (BA) or kinetin with 2,4-dichlorophenoxyacetic acid (2,4-D). Optimal efficiency in friable callus induction (100%) was achieved in leaf explants cultured on MS media containing 2.32 µM BA + 13.57 µM 2,4-D. Plant tissues (callus and leaf) were extracted and subjected to quantitative phytochemical analysis, revealing the highest total alkaloid and phenolic content in leaf extracts from Queretaro adult specimens (339.5 ± 20.9 mg atropine equivalents (AE) per g dry extract (DE) and 158.4 ± 12.5 mg gallic acid equivalents (GAE) per g DE, respectively). In contrast, callus cultures exhibited significantly higher total triterpene content (356–381 mg ursolic acid equivalents (UAE) per g DE) compared to leaf extracts (208–243 mg UAE/g DE). Both leaf and callus extracts displayed cytotoxic activity against the HeLa cell line, with a significantly lower half-maximal inhibitory concentration (IC50) for leaf extracts (28–32 µg/mL) compared to callus cultures (43–66 µg/mL), suggesting that alkaloids were primarily responsible for the cytotoxic activity. Furthermore, this study provides valuable insights into the controlled production of bioactive compounds with cytotoxic activity, with callus serving as a rich source.

Vachellia farnesiana (L) Wight & Arn.的体外培养物通过胼胝体提取物对 HeLa 细胞系显示出细胞毒性活性。从两个不同地点的种子离体生长的秧苗上摘取的外植体被接种到含有不同浓度的 N-6 苄基腺嘌呤(BA)或 2,4-二氯苯氧乙酸(2,4-D)的木拉昔和斯库格(MS)培养基上。在含有 2.32 µM BA + 13.57 µM 2,4-D 的 MS 培养基上培养的叶片外植体可获得最佳的易碎胼胝体诱导效率(100%)。提取植物组织(胼胝体和叶片)并进行定量植物化学分析后发现,克雷塔罗(Queretaro)成株标本的叶片提取物中生物碱和酚类总含量最高(分别为每克干提取物(DE)339.5 ± 20.9 毫克阿托品当量(AE)和每克干提取物(DE)158.4 ± 12.5 毫克没食子酸当量(GAE))。相比之下,胼胝体培养物的总三萜含量(356-381 毫克熊果酸当量(UAE)/克 DE)明显高于叶提取物(208-243 毫克 UAE/ 克 DE)。叶片和胼胝体提取物对 HeLa 细胞系都具有细胞毒性活性,叶片提取物的半最大抑制浓度(IC50)(28-32 µg/mL)明显低于胼胝体培养物(43-66 µg/mL),这表明生物碱是细胞毒性活性的主要原因。此外,这项研究为控制生产具有细胞毒性活性的生物活性化合物提供了宝贵的见解,而胼胝体则是一个丰富的来源。
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引用次数: 0
Betanin-encapsulated starch nanoparticles: synthesis and cytotoxic effect on colon cancer 白桦脂素包裹的淀粉纳米颗粒:合成及其对结肠癌的细胞毒性作用
IF 2.8 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-16 DOI: 10.1007/s13205-024-04078-4
Suhail Ahmad Bhat, Sathyapriya Chandramohan, Guguloth Sai Krishna, Chandansri Hiranmaya, Sankar Pajaniradje, Anjali Suresh Nair, Debabrata Mohanty, Rukkumani Rajagopalan

Colorectal cancer (CRC) is a common and life-threatening neoplastic disease that continues to pose a formidable challenge to global health. The present work was performed to evaluate the anticancer properties of betanin and betanin (BT) loaded starch nanoparticles (S-BT). The BT and S-BT were characterized by DLS, SEM, UV spectroscopy, XPS and FTIR. The cytotoxic effect was assessed by MTT and LDH assay. The apoptotic potential of BT and S-BT was assessed by DCFDA, Rh123, AO/EB and DAPI staining methods. Cell cycle arrest was depicted using flow cytometry. The antimetastatic potential of BT and S-BT was evaluated by wound healing assay. The S-BT showed a spherical morphology with a size of 175 nm. The betanin contained SNPs were found to have strong encapsulation efficiency and favorable release profiles. Both BT and S-BT exhibited cytotoxicity in SW480 cells but S-BT displayed increased cytotoxicity when compared to BT alone. Loss of mitochondrial membrane potential, nuclear fragmentation, chromatin condensation and generation of ROS, all indicative of apoptotic mode of cell death, were revealed by fluorescence imaging. The cells were arrested in the G2M phase. Moreover, both BT and S-BT were able to inhibit the migratory potential of SW480 cells. Overall, our results indicated that both BT and S-BT were able to induce anticancer effects; and, S-BT was found to have increased therapeutic efficacy when compared to BT alone.

大肠癌(CRC)是一种常见的危及生命的肿瘤性疾病,对全球健康仍构成严峻挑战。本研究旨在评估甜菜宁和甜菜宁(BT)负载淀粉纳米颗粒(S-BT)的抗癌特性。通过 DLS、SEM、紫外光谱、XPS 和傅立叶变换红外光谱对 BT 和 S-BT 进行了表征。细胞毒性效应通过 MTT 和 LDH 试验进行评估。用 DCFDA、Rh123、AO/EB 和 DAPI 染色法评估了 BT 和 S-BT 的凋亡潜能。细胞周期停滞采用流式细胞仪进行描述。伤口愈合试验评估了 BT 和 S-BT 的抗转移潜力。S-BT 呈球形,大小为 175 nm。研究发现,含有甜菜宁的 SNP 具有很强的封装效率和良好的释放特性。在 SW480 细胞中,BT 和 S-BT 都表现出细胞毒性,但与单独使用 BT 相比,S-BT 表现出更强的细胞毒性。荧光成像显示线粒体膜电位丧失、核破碎、染色质凝结和 ROS 生成,所有这些都表明细胞凋亡模式。细胞停滞在 G2M 期。此外,BT 和 S-BT 都能抑制 SW480 细胞的迁移潜能。总之,我们的研究结果表明,BT 和 S-BT 都能诱导抗癌作用;与单独使用 BT 相比,S-BT 的疗效更高。
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引用次数: 0
Computational screening of chemical constituents derived from berry fruits as allosteric caspace-3/-7 inhibitors 计算筛选从浆果中提取的化学成分作为同工酶 Caspace-3/-7 抑制剂
IF 2.8 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-16 DOI: 10.1007/s13205-024-04067-7
Waseem Ahmad Ansari, Mohsin Ali Khan, S. M. Mahfooz Hasan, Zainab Siddiqui, Saheem Ahmad, Mohd Shahnawaz Khan, Mohammad Faheem Khan

With the aim of finding the plant-derived allosteric inhibitors of caspase-3/-7, we conducted computational investigations of bioactive compounds present in various berry fruits. In a molecular docking study, perulactone demonstrated excellent binding affinity scores of −12.1 kcal/mol and −9.1 kcal/mol for caspase 7 and 3, respectively, whereas FDA-approved allosteric inhibitors (DICA and FICA) were found to show lower docking scores (−5.6 and −6.1 kcal/mol) against caspase 7 while (−5.0 and −5.1 kcal/mol) for caspase 3, respectively. MD simulations were used to validate the binding stability of perulactone in the active sites of caspase-7/-3, and the results showed outstanding stability with lower ligand RMSDs of 1.270–3.088 Å and 2.426–9.850 Å against the targeted receptor. Furthermore, we performed MMGBSA free binding energy, where the perulactone values of ΔGBind were determined to be −63.98 kcal/mol and −66.32 kcal/mol for both receptors (3IBF and 1NME), which are significantly better than the −45.16 kcal/mol and −39.51 kcal/mol for DICA as well as −26.37 kcal/mol and −15.50 kcal/mol for FICA, respectively. The drug resemblance of perulactone was effectively evaluated by ADMET. Thus, our findings indicated that perulactone could be an orally administered therapeutic candidate for regulating apoptosis in a variety of disorders. However, there may be an urgent need to study using in vitro and in vivo experiments.

为了找到源自植物的 Caspase-3/-7 异位抑制剂,我们对各种浆果中的生物活性化合物进行了计算研究。在分子对接研究中,perulactone 与 caspase 7 和 caspase 3 的结合亲和力得分分别为 -12.1 kcal/mol 和 -9.1 kcal/mol,而 FDA 批准的异位抑制剂(DICA 和 FICA)与 caspase 7 的对接得分较低(-5.6 和 -6.1 kcal/mol),与 caspase 3 的对接得分分别为 -5.0 和 -5.1 kcal/mol。我们利用 MD 模拟验证了 perulactone 在 caspase-7/-3 活性位点的结合稳定性,结果显示其具有出色的稳定性,与目标受体的配体 RMSD 值较低,分别为 1.270 至 3.088 Å 和 2.426 至 9.850 Å。此外,我们还进行了 MMGBSA 自由结合能测定,结果显示两种受体(3IBF 和 1NME)的 Perulactone ΔGBind 值分别为 -63.98 kcal/mol 和 -66.32 kcal/mol,明显优于 DICA 的 -45.16 kcal/mol 和 -39.51 kcal/mol 以及 FICA 的 -26.37 kcal/mol 和 -15.50 kcal/mol。通过 ADMET 有效评估了 Perulactone 的药物相似性。因此,我们的研究结果表明,秘鲁内酯可作为一种口服候选疗法,用于调节多种疾病的细胞凋亡。不过,目前可能还迫切需要进行体外和体内实验研究。
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引用次数: 0
Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of Tamarindus indica using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice 利用网络药理学方法预测罗望子水醇提取物抗抑郁潜力的分子靶点,并评估其在小鼠慢性不可预测轻度应激模型中的疗效
IF 2.8 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-13 DOI: 10.1007/s13205-024-04081-9
Vishnusai Beere, Khushboo Choudhary, Priya Bisht, Amita Rai, Nitesh Kumar

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects. Tamarindus indica (TI) is a plant that grows in the shape of a tree. Network pharmacology of TI revealed the key targets MAPK, D1-6, 5HT, DAT, MAO, COMT, PKA, PKC, AKT, and VMAT, which are linked to prominent key pathways such as dopaminergic and serotonergic. The cell viability assays on SH-Sy5y cells indicated a favourable safety profile with an IC50 of 573.99 µg/ml and further, the in vivo efficacy was observed through Chronic Unpredictable Mild Stress (CUMS) model in mice. The hydroalcoholic extract of TI demonstrated antidepressant effects, significantly reducing immobility time in the Tail Suspension Test (TST) and Forced Swim Test (FST). Additionally, locomotor activity, assessed via the Open Field Test (OFT), was significantly increased in the treatment group compared to CUMS mice. Biochemical analyses revealed elevated Brain Derived Neurotropic Factor (BDNF), decreased cortisol levels, and reduced catechol-O-methyltransferase (COMT) concentration in TI-treated (50 mg/kg) groups. These findings underscore the potential of TI as a natural antidepressant, offering a promising avenue for further therapeutic development in depression management. The current study did not evaluate the level of neurotransmitters in the brain, which will be evaluated in future studies.

自 20 世纪 90 年代以来,心理障碍的发病率急剧上升,给全球健康造成了巨大的负担,抑郁症患者平均每周损失 6 个小时,占所有缺勤工作日的 20% 以上。目前的抗抑郁药物虽然对某些人有效,但疗效有限,而且有饮食限制和不良反应,包括肝损伤和高血压。自然疗法具有良好的治疗潜力,且副作用极小。罗望子(Tamarindus indica,TI)是一种长成树形的植物。TI 的网络药理学揭示了 MAPK、D1-6、5HT、DAT、MAO、COMT、PKA、PKC、AKT 和 VMAT 等关键靶点,这些靶点与多巴胺能和血清素能等主要关键通路相关联。对 SH-Sy5y 细胞进行的细胞存活率检测表明,该药物具有良好的安全性,其 IC50 值为 573.99 µg/ml;此外,还通过慢性不可预测轻度应激(CUMS)模型对小鼠进行了体内疗效观察。TI 的水醇提取物具有抗抑郁作用,能显著缩短尾悬试验(TST)和强迫游泳试验(FST)中的静止时间。此外,与 CUMS 小鼠相比,通过开阔地试验(OFT)评估的治疗组小鼠的运动活动明显增加。生化分析表明,TI(50 毫克/千克)治疗组的脑衍生神经营养因子(BDNF)升高,皮质醇水平降低,儿茶酚-O-甲基转移酶(COMT)浓度降低。这些发现凸显了 TI 作为天然抗抑郁剂的潜力,为进一步开发抑郁症治疗方法提供了一个前景广阔的途径。目前的研究没有评估大脑中神经递质的水平,这将在今后的研究中进行评估。
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引用次数: 0
Virtual screening and molecular dynamics simulations of phytochemicals targeting cofactor-independent phosphoglycerate mutase in antimicrobial-resistant Mycoplasma genitalium 针对抗微生物生殖支原体中不依赖于辅助因子的磷酸甘油酸突变酶的植物化学物质的虚拟筛选和分子动力学模拟
IF 2.8 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-09-11 DOI: 10.1007/s13205-024-04082-8
Krishnendu Barik, Pranabesh Mandal, Praffulla Kumar Arya, Durg Vijay Singh, Anil Kumar

Mycoplasma genitalium (M. genitalium) poses a significant challenge in clinical treatment due to its increasing antimicrobial resistance. This study investigates alternative therapeutic approaches by targeting the cofactor-independent phosphoglycerate mutase (iPGM) enzyme with phytochemicals derived from ethnobotanical plants. In silico screening identified several promising inhibitors, with 2-carboxy-D-arabinitol demonstrating the highest binding affinity (− 9.77 kcal/mol), followed by gluconic acid (− 9.03 kcal/mol) and citric acid (− 8.68 kcal/mol). Further analysis through molecular dynamics (MD) simulations revealed insights into the binding mechanisms and stability of these phytochemicals within the iPGM active site. The MD simulations indicated initial fluctuations followed by stability, with intermittent spikes in RMSD values. The lowest RMSF values confirmed the stability of the ligand–protein complexes. Key residues, including Ser-61, Arg-188, Glu-62, Asp-397, and Arg-260, were found to play crucial roles in the binding and retention of inhibitors within the active pocket. These findings suggest that the identified phytochemicals could serve as novel antimicrobial agents against M. genitalium by effectively inhibiting iPGM activity.

生殖支原体(M. genitalium)对抗菌药的耐药性不断增加,给临床治疗带来了巨大挑战。本研究利用从民族植物中提取的植物化学物质,针对不依赖辅助因子的磷酸甘油酸突变酶(iPGM)酶,研究了替代治疗方法。硅学筛选确定了几种有前景的抑制剂,其中 2-羧基-D-阿拉伯糖醇的结合亲和力最高(- 9.77 kcal/mol),其次是葡萄糖酸(- 9.03 kcal/mol)和柠檬酸(- 8.68 kcal/mol)。通过分子动力学(MD)模拟进行的进一步分析揭示了这些植物化学物质在 iPGM 活性位点内的结合机制和稳定性。MD 模拟表明,最初的波动随后趋于稳定,RMSD 值出现间歇性峰值。最低的 RMSF 值证实了配体-蛋白质复合物的稳定性。研究发现,包括 Ser-61、Arg-188、Glu-62、Asp-397 和 Arg-260 在内的关键残基对抑制剂在活性口袋中的结合和保留起着至关重要的作用。这些研究结果表明,所发现的植物化学物质可有效抑制 iPGM 的活性,从而成为针对 M. genitalium 的新型抗菌剂。
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引用次数: 0
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3 Biotech
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