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Anti-tyrosinase activity of Curcuma aromatica ethyl acetate extract: from lead diarylheptanoids to melanogenesis targets 姜黄乙酸乙酯提取物的抗酪氨酸酶活性:从二芳基七烷类铅到黑色素生成靶点
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-21 DOI: 10.1186/s43088-025-00673-3
Chau Dieu Bui, Thuan-Thien Dinh, Thang Truong Le, Thuan Van Tran, Chau Dao Minh Huynh, Tho Huu Le, Nhan Trung Nguyen, Mai Thanh Thi Nguyen, Hai Xuan Nguyen, Truong Nhat Van Do, Hieu Tran-Van

Background

Curcuma aromatica (C. aromatica), a traditional medicinal plant, holds promise for addressing oxidative stress and hyperpigmentation through its rich curcuminoid and polyphenol content. Building on our previous identification of five major diarylheptanoids in its extract, this study investigated the ability of C. aromatica to mitigate oxidative stress and modulate melanogenesis with insight into its bioactive compounds’ contributions.

Results

Spectrophotometric analysis of its ethyl acetate extract revealed significantly high phenolic content, with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays confirming strong antioxidative activity. Using B16 cells, the extract demonstrated non-toxic inhibition of melanin synthesis, reduced tyrosinase activity, and downregulated melanogenic proteins such as tyrosinase, related proteins, and microphthalmia-associated transcription factor (MITF). Gene Ontology and KEGG pathway enrichment analysis (GO-KEGG) along with molecular docking showed that five major diarylheptanoids strongly interacted with these proteins, modulating key pathways involved in pigmentation and beyond.

Conclusions

Together, these findings highlight C. aromatica’s dual action in combating oxidative stress and inhibiting melanogenesis, positioning it as a promising candidate for advancing medicinal chemistry approaches to hyperpigmentation and oxidative damage.

姜黄(C. aromatica)是一种传统药用植物,其丰富的姜黄素和多酚含量有望解决氧化应激和色素沉着。基于我们之前在其提取物中鉴定出的五种主要的二芳基七烷类化合物,本研究探讨了香茅减轻氧化应激和调节黑素形成的能力,并深入了解其生物活性化合物的贡献。结果乙酸乙酯提取物的酚类物质含量较高,2,2-二苯基-1-苦味酰肼(DPPH)和铁还原抗氧化能力(FRAP)测定证实其具有较强的抗氧化活性。使用B16细胞,提取物显示出对黑色素合成的无毒抑制,降低酪氨酸酶活性,下调黑色素生成蛋白,如酪氨酸酶、相关蛋白和小眼相关转录因子(MITF)。基因本体和KEGG途径富集分析(GO-KEGG)以及分子对接表明,五种主要的二芳基七烷类化合物与这些蛋白强烈相互作用,调节色素沉积等关键途径。综上所述,这些发现突出了香姜在抗氧化应激和抑制黑色素生成方面的双重作用,使其成为推进药物化学方法治疗色素沉着和氧化损伤的有希望的候选药物。
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引用次数: 0
Exploring the presence of Lernaea cyprinacea in Carasobarbus luteus fishes via molecular diagnosis 利用分子诊断方法探讨鲤科Lernaea在黄斑鱼中的存在
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-21 DOI: 10.1186/s43088-025-00676-0
Zahraa Isam Jameel, Zaman Salman Hamza

Background

Lernaea species, which are part of the genus Lernaea, are widespread parasites capable of infecting a wide range of freshwater fish. Their classification is exceedingly challenging and contentious due to a significant amount of intraspecific variability in morphology and substantial similarities between different species.

Aim of study

The aim of this study was to gather data and molecular diagnosis to the Lernaea species that infect Carasobarbus luteus in in the Shatt al-Hilla, Iraq.

Materials and methods

In this study conducted in Shatt- Hilla, Iraq between September 2023 and April 2024, 26 sample of Lernaea species were obtained from 150 fish sample exam belonging to Carasobarbus luteus. The larvae of Lernaea species were studied by molecular analysis done by primer design for 18S RNA and 28S RNA, PCR amplification, sequencing, and comparing gene loci of 18S RNA and 28S RNA of larvae isolated from Lernaea species.

Results

The sequencing of 18S RNA and 28S RNA revealed that all larval Lernaea from all infected fishes represented exactly one species of Lernaea cyprinacea parasite based upon comparing and identifying a percentage of the Gene Bank database. The genetic characteristics of L. cyprinacea in this study are available in the Gene Bank database, and they were deposited in the Gene Bank. Their accession numbers were demonstrated as LC830719, LC830720, LC830721, and LC830722.

Conclusion

This is the first molecular diagnostic research on L. cyprinacea parasite from Carasobarbus luteus in Iraq. It found all larval Lernaea were of one species. PCR assays and DNA analyses are important in the detection of parasites on fish.

背景Lernaea是Lernaea属的一部分,是一种广泛存在的寄生虫,能够感染多种淡水鱼。它们的分类极具挑战性和争议性,因为在形态上有大量的种内变异性和不同物种之间的大量相似性。本研究的目的是收集伊拉克Shatt al-Hilla地区感染Carasobarbus luteus的Lernaea种的资料并进行分子诊断。材料与方法本研究于2023年9月至2024年4月在伊拉克Shatt- Hilla进行,从150条黄斑鱼样本中获得了26种Lernaea样本。采用18S RNA和28S RNA引物设计、PCR扩增、测序、18S RNA和28S RNA基因位点比对等方法对Lernaea幼虫进行分子分析。结果经18S RNA和28S RNA测序,所有感染鱼的Lernaea幼虫均为cyprinacea Lernaea寄生虫的一种。本研究的L. cyprinacea遗传特征已在Gene Bank数据库中找到,并已存入Gene Bank。它们的加入号分别为LC830719、LC830720、LC830721和LC830722。结论首次对伊拉克黄体卡拉巴斯寄生虫进行了分子诊断研究。结果表明,所有幼虫均为同一种。PCR和DNA分析是鱼类寄生虫检测的重要手段。
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引用次数: 0
Novel transferosome formulation of Vemurafenib for skin cancer management: biocompatible and scalable strategies Vemurafenib用于皮肤癌管理的新型转移体制剂:生物相容性和可扩展策略
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-19 DOI: 10.1186/s43088-025-00671-5
Tariq M. Aljarba, Aftab Alam, Ahmed Farag El Kirdasy

Due to challenges such as poor aqueous solubility and compromised oral bioavailability, delivering Vemurafenib via a topical route using a scalable and biocompatible carrier-based hydrogel. This study aims to develop and characterize Vemurafenib-loaded transferosomes for the management of skin cancer. A Vemurafenib-loaded transferosomal gel was developed and thoroughly analyzed using various techniques, including transmission electron microscopy, ultraviolet spectroscopy, dermatokinetic parameters, entrapment efficiency, stability assessment, in vitro release study, vesicle elasticity examination, and antioxidant assays. The in vitro release of formulations was analyzed using four models: Korsmeyer, Higuchi, first-order, and zero-order models. The transferosomes exhibited a typical size of 105 nm, with a zeta size of 106.31 nm and a polydispersity index of 0.2417. Among the models investigated for in vitro release analysis, the Higuchi model was found to be the most suitable for the transferosome formulation. Compared to the standard formulation, the Vemurafenib-loaded transferosomal gel achieved a significantly higher concentration of 140.45 µg/ml on the skin epidermis within just 1.5 h. Additionally, in two hours, the Vemurafenib-loaded transferosomal gel resulted in a greater concentration of 118.52 µg/ml in the skin dermis, surpassing the usual formulation. Furthermore, the group receiving twice-daily administration of Vemurafenib-loaded transferosomal gel exhibited minimal hyperkeratosis compared to other treatment groups. The (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) (MTT) assay showed a higher A-431 cell lines inhibition under vemurafenib Hydrogel formulation, i.e., 78.28%. This study offers compelling evidence for the effectiveness of the Vemurafenib transferosomal gel, demonstrating its enhanced skin absorption. The formulation shows considerable promise for further research and potential clinical application in skin cancer treatment.

由于水溶性差和口服生物利用度降低等挑战,使用可扩展和生物相容性的载体水凝胶通过局部途径给药Vemurafenib。本研究旨在开发和表征装载vemurafenib的转移体用于皮肤癌的治疗。开发了装载vemurafenib的转移体凝胶,并使用各种技术进行了全面分析,包括透射电子显微镜,紫外光谱,皮肤动力学参数,包裹效率,稳定性评估,体外释放研究,囊泡弹性检查和抗氧化分析。采用Korsmeyer模型、Higuchi模型、一阶模型和零阶模型对制剂的体外释放进行分析。转移体的典型尺寸为105 nm, zeta尺寸为106.31 nm,多分散性指数为0.2417。在体外释放分析的模型中,发现Higuchi模型最适合转移体配方。与标准配方相比,负载vemurafenab的转移体凝胶在1.5小时内在皮肤表皮上达到了140.45µg/ml的显著高浓度。此外,在2小时内,负载vemurafenab的转移体凝胶在皮肤真皮中的浓度达到了118.52µg/ml,超过了通常的配方。此外,与其他治疗组相比,每天接受两次载vemurafenib转移体凝胶治疗的组表现出最小的角化过度。(3-(4,5 -二甲基噻唑-2)- 2,5 -二苯基溴化四唑)(MTT)试验显示,vemurafenib水凝胶制剂对a -431细胞系的抑制率较高,为78.28%。这项研究为Vemurafenib转移体凝胶的有效性提供了令人信服的证据,证明其增强皮肤吸收。该制剂在皮肤癌治疗方面具有进一步研究和潜在临床应用的前景。
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引用次数: 0
Huperzine A: a natural acetylcholinesterase inhibitor with multifunctional neuroprotective effects 石杉碱A:天然乙酰胆碱酯酶抑制剂,具有多功能神经保护作用
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-16 DOI: 10.1186/s43088-025-00675-1
Suvaiv, Kuldeep Singh, Syed Misbahul Hasan, Arun Kumar, Abdullah khan, Mo. Shahanawaz, Syed Mehdi Hasan Zaidi, Kausal Verma

Background

Huperzine A, a naturally derived compound, has garnered interest for its capacity to inhibit cholinesterase with multifaceted neuroprotective effects and is obtained from Huperzia serrata (Chinese club moss plant). This review highlights its pharmacological potential in the treatment of neurodegenerative disorders, particularly Alzheimer’s disease (AD). Huperzine A was used in various neurological conditions in traditional Chinese treatments.

Findings

Acetylcholinesterase is responsible for the breakdown of acetylcholine, a neurotransmitter critical for cognitive functions such as memory, learning, and attention. Huperzine A exhibits neuroprotective effects by preserving acetylcholine levels, and also offers antioxidant and anti-inflammatory benefits. These pharmacological actions suggest a potential role in modifying disease progression in AD and vascular dementia (VD). Although preclinical and clinical studies have demonstrated promising cognitive benefits, discrepancies in outcomes still exist. While considered safe at therapeutic dosages, excessive intake may lead to adverse effects, e.g., nausea, diarrhea, and muscle cramps.

Conclusion

Research on its effectiveness in various neurological conditions is ongoing, and its use should be approached with caution and professional guidance.

石杉碱A是一种天然衍生化合物,因其抑制胆碱酯酶的能力和多方面的神经保护作用而引起了人们的兴趣,它是从石杉(中国的刺藓植物)中提取的。这篇综述强调了其在治疗神经退行性疾病,特别是阿尔茨海默病(AD)方面的药理潜力。石杉碱A在中医治疗中用于多种神经系统疾病。乙酰胆碱是一种神经递质,对记忆、学习和注意力等认知功能至关重要,而乙酰胆碱酯酶负责分解乙酰胆碱。石杉碱A通过保持乙酰胆碱水平表现出神经保护作用,还具有抗氧化和抗炎作用。这些药理作用提示在阿尔茨海默病和血管性痴呆(VD)中调节疾病进展的潜在作用。尽管临床前和临床研究已经证明了有希望的认知益处,但结果仍然存在差异。虽然在治疗剂量下被认为是安全的,但过量摄入可能导致不良反应,例如恶心、腹泻和肌肉痉挛。结论其治疗各种神经系统疾病的有效性研究仍在进行中,应谨慎使用,并在专业指导下使用。
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引用次数: 0
Insights into the regulatory role of the lncRNA H19 and miRNA-152 and their cross-talk with their target genes in glioblastoma lncRNA H19和miRNA-152在胶质母细胞瘤中的调控作用及其与靶基因的串扰
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-14 DOI: 10.1186/s43088-025-00670-6
M. A. Abdelsamed, N. A. Hasona, A. Lotfy, H. Y. Abdallah

Background

Glioblastoma is a highly aggressive subtype of glioma. The alteration of non-coding RNA (lncRNA H19 and microRNA-152) in glioblastoma tissues promotes cell proliferation, migration, and invasion, while the exact relationship with glioblastoma is still uncertain with their genes (PTEN, KRAS, and NDRG1). This study aimed to identify new potential biomarkers for early diagnosis and novel therapeutic targets.

Methods

In a descriptive cross-sectional study, we employed quantitative real-time PCR for expression of lncRNA H19, miRNA-152, and their target genes in 84 glioblastoma specimens compared to 35 control samples (low-grade glioma, astrocytic astrocytoma, normal brain tissues). Additionally, for differential expression profile, predictive significance, and survival analysis, receiver operating characteristic analysis and Kaplan–Meier survival plot were used.

Results

The expression levels of lncRNA H19 and miR-152 were significantly altered in glioblastoma patients compared to those with low-grade glioma and normal brain tissues. Moreover, KRAS and NDRG1 showed significant upregulation in glioblastoma. It was demonstrated that lncRNA H19 has diagnostic values with AUC > 0.7 that differentiated glioblastoma from non-cancerous lesions and low-grade glioma. Nevertheless, KRAS and NDRG1 with AUC > 0.9 and > 0.8, respectively, distinguished between glioblastoma and all other comparative groups including non-cancerous lesions, low-grade glioma, and astrocytic astrocytoma. Furthermore, poor overall survival was observed with a median survival rate of 15 months.

Conclusions

The long non-coding RNA H19, along with KRAS and NDRG1, has shown promise as biomarkers for differentiating between glioblastoma, lower-grade glioma, and non-malignant lesions.

Key points

  • The expression levels of the lncRNA H19 and miR-152 were significantly altered in Glioblastoma patients compared to those with Low Grade Glioma and normal brain tissues.

  • The lncRNA H19, along with the genes KRAS and NDRG1, have shown promise as biomarkers for differentiating between Glioblastoma, Low Grade Glioma, and normal brain tissues.

胶质母细胞瘤是一种高度侵袭性的胶质瘤亚型。胶质母细胞瘤组织中非编码RNA (lncRNA H19和microRNA-152)的改变促进了细胞的增殖、迁移和侵袭,但与胶质母细胞瘤的确切关系仍不确定,与它们的基因(PTEN、KRAS和NDRG1)有关。本研究旨在寻找新的潜在的早期诊断生物标志物和新的治疗靶点。方法在描述性横断面研究中,采用实时荧光定量PCR检测84例胶质母细胞瘤标本中lncRNA H19、miRNA-152及其靶基因的表达,并与35例对照标本(低级别胶质瘤、星形细胞星形细胞瘤、正常脑组织)进行比较。此外,对于差异表达谱、预测意义和生存分析,使用受试者工作特征分析和Kaplan-Meier生存图。结果与低级别胶质瘤和正常脑组织相比,lncRNA H19和miR-152在胶质母细胞瘤患者中的表达水平显著改变。KRAS和NDRG1在胶质母细胞瘤中表达显著上调。结果表明,lncRNA H19具有AUC >; 0.7的诊断价值,可将胶质母细胞瘤与非癌性病变和低级别胶质瘤区分开来。然而,KRAS和NDRG1的AUC分别为>; 0.9和>; 0.8,可以区分胶质母细胞瘤和所有其他对照组,包括非癌性病变、低级别胶质瘤和星形细胞星形细胞瘤。此外,总生存期较差,中位生存期为15个月。结论长链非编码RNA H19,以及KRAS和NDRG1,有望作为区分胶质母细胞瘤、低级别胶质瘤和非恶性病变的生物标志物。与低级别胶质瘤和正常脑组织相比,lncRNA H19和miR-152在胶质母细胞瘤患者中的表达水平明显改变。lncRNA H19,以及KRAS和NDRG1基因,已经显示出作为区分胶质母细胞瘤、低级别胶质瘤和正常脑组织的生物标志物的前景。
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引用次数: 0
Phytochemical analysis and evaluation of inhibitory potential of Ricinus communis leaf extract against novel Bacillus pathogens 蓖麻叶提取物对新型芽孢杆菌病原菌抑制潜力的植物化学分析与评价
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-11 DOI: 10.1186/s43088-025-00666-2
Diptimayee Acharya, Puspanjali Parida, Himansu Sekhara Mohapatra, Subhasmita Mallik, Jatindra Nath Mohanty, Santi Lata Sahoo

Mastitis is a common and complex disease, mainly caused by aureus and non-aureus species, and Enterobacteriaceae. Recently, a new and serious group of Gram-positive bacteria, the sporulating bacilli, has emerged as a mastitis pathogen. The study aimed to identify and characterize novel Bacillus strains (HSM85, SLS01, and DA03) associated with bovine mastitis and to evaluate the antimicrobial efficacy of Ricinus communis (castor) leaf extract against these pathogens. In methodology, Bacillus strains were isolated from milk samples of mastitis-infected cows, and the antimicrobial activity of different solvent-based leaf extract fractions was assessed using MIC, MBC, killing and biofilm inhibition assays, and GC–MS analysis to identify bioactive compounds. In result we found, the chloroform (non-polar) fraction showed the highest antimicrobial activity, followed by the ethanol (polar) fraction. MIC and MBC values ranged from 25 to 200 and 25–400 µg/ml, respectively. Bacterial growth was significantly inhibited at ½ MIC, while control cells entered log phase within 4 h. Assays (MIC, MBC, MBC/MIC ≤ 4, killing, biofilm inhibition, and nucleic acid leakage) confirmed the bactericidal potential of Ricinus communis leaf extract against novel Bacillus strains. GC–MS analysis revealed 48–53 peaks across solvent extracts, identifying dominant compounds like phytol, phytyl palmitate, and tetracontane, with some solvent-specific presence. Ricinus communis leaf extract showed strong bactericidal activity against emerging Bacillus strains causing bovine mastitis, with the chloroform fraction showing the highest efficacy. Its bioactive compounds and multi-target properties suggest its potential as a natural alternative for managing mastitis in dairy cattle.

乳腺炎是一种常见而复杂的疾病,主要由金黄色菌和非金黄色菌以及肠杆菌科引起。最近,一种新的严重的革兰氏阳性菌,孢子杆菌,已经成为乳腺炎的病原体。本研究旨在鉴定与牛乳腺炎相关的新型芽孢杆菌(HSM85、SLS01和DA03),并评价蓖麻叶提取物对这些病原菌的抑菌效果。在方法上,从乳腺炎感染奶牛的乳样中分离出芽孢杆菌菌株,采用MIC、MBC、杀灭和生物膜抑制试验评估不同溶剂基叶提取物组分的抗菌活性,并采用GC-MS分析鉴定生物活性化合物。结果表明,氯仿(非极性)部位抗菌活性最高,其次为乙醇(极性)部位。MIC和MBC值分别为25 ~ 200µg/ml和25 ~ 400µg/ml。在½MIC时,细菌生长受到显著抑制,而对照细胞在4 h内进入对数相。MIC、MBC、MBC/MIC≤4、杀灭、生物膜抑制和核酸泄漏试验证实了蓖麻叶提取物对新型芽孢杆菌菌株的杀菌潜力。GC-MS分析在溶剂提取物中发现了48-53个峰,鉴定出主要化合物,如叶绿醇、棕榈酸植酯和四孔烷,并有一些溶剂特异性存在。蓖麻叶提取物对新出现的牛乳腺炎芽孢杆菌有较强的杀菌作用,其中氯仿部分效果最好。其生物活性化合物和多靶点特性表明其作为管理奶牛乳腺炎的天然替代品的潜力。
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引用次数: 0
Ginger oil microemulsion improves reproductive performance of male albino rats: sexual behavior, gross testicular measurements, spermatogenesis, and expression of sperm capacitation genes 姜油微乳改善雄性白化大鼠生殖性能:性行为、睾丸大体测量、精子发生和精子获能基因表达
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-09 DOI: 10.1186/s43088-025-00654-6
Enas K. Aziz, Nagwa I. Sherabia, Doaa A. Mansour, Mona A. Nasr, Eman Elhusseiny, Afaf A. Kishta, Ahmed E. Elweza, Hend Mohmed Abdel-Bar, Reda M. Korany, Basma A. Elshafey

Background

The effectiveness of nanoparticles in enhancing male sexual performance is a topic of great attention these days. The research goal was to evaluate the potency of ginger oil (G-Oil) and ginger oil microemulsion (G-ME) on male rat fertility and reproductive performance. Thirty-five male albino rats were split up into five groups and delivered oral gavage three times a week for eight weeks: control (1 ml /kg bw distilled water), corn oil (1 ml /kg bw corn oil), ginger oil (75 mg/kg bw ginger oil in corn oil as a vehicle), ginger oil microemulsion at two doses (75 and 37.5 mg/kg bw, respectively). Assessments of sexual behavior, sperm quality, relative testes weight, serum sex hormones, testicular oxidant/antioxidant status, sperm capacitation markers, and histomorphology and immunohistochemical changes in both testicles and epididymis were utilized.

Results

The results revealed that G-ME administration, especially at a low dose (37.5 mg/kg bw), significantly (p < 0.05) improved sexual behavior, relative testes weight, serum testosterone, and activating antioxidant enzyme Superoxide dismutase (SOD) along with reducing malondialdehyde (MDA) content in testicular tissues, indicating its antioxidant activity. Moreover, G-ME had significantly (p < 0.001) higher expression of SPACA1 and CD59b genes, accompanied by improvements in sperm motility, count, and viability compared to the control group. Additionally, G-ME 37.5 mg/kg bw showed remarkable histological enhancements as spermatogenic cells and spermatozoa increased in seminiferous tubules and epididymis tubular lumen. Also, a stimulatory effect was detected on proliferating cells with increasing PCNA immunodepression in testicular and epididymal tissues.

Conclusions

Finally, the results obtained revealed the superiority of G-ME at a low dose of 37.5 mg/kg above the traditional G-Oil due to improvements in its physical properties, which resulted in increased ginger bioavailability and improved different rat fertility indices.

纳米颗粒在提高男性性能力方面的有效性是近年来备受关注的话题。本研究旨在评价姜油(G-Oil)和姜油微乳(G-ME)对雄性大鼠生育能力和生殖性能的影响。将35只雄性白化大鼠分为5组,每周灌胃3次,共8周:对照组(蒸馏水1 ml /kg bw)、玉米油(玉米油1 ml /kg bw)、姜油(以玉米油为载体的姜油75 mg/kg bw)、姜油微乳2剂量(分别为75和37.5 mg/kg bw)。评估性行为、精子质量、睾丸相对重量、血清性激素、睾丸氧化/抗氧化状态、精子获能标记物以及睾丸和附睾的组织形态学和免疫组织化学变化。结果G-ME给药,特别是低剂量(37.5 mg/kg bw),显著(p < 0.05)改善了大鼠的性行为、睾丸相对体重、血清睾酮,激活了抗氧化酶超氧化物歧化酶(SOD),降低了睾丸组织中丙二醛(MDA)的含量,表明其具有抗氧化活性。此外,与对照组相比,G-ME组的SPACA1和CD59b基因的表达显著(p < 0.001)增加,同时精子活力、数量和活力也有所改善。此外,37.5 mg/kg bw的G-ME显著增强了精管和附睾管腔的生精细胞和精子数量。此外,在睾丸和附睾组织中检测到对增殖细胞的刺激作用,增加了PCNA免疫抑制。结论低剂量(37.5 mg/kg)的G-ME具有明显的物理性能优势,提高了生姜的生物利用度,改善了大鼠的生育指标。
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引用次数: 0
Naringin from Citrus maxima peel: a potential therapeutic agent for breast cancer via PKM2 inhibition 柑橘皮柚皮苷:通过抑制PKM2治疗乳腺癌的潜在药物
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-05 DOI: 10.1186/s43088-025-00668-0
Flama Monteiro, Vijith Vittal Shetty, Ranjitha Acharaya, Sriram Naresh, Manne Munikumar, Shilpa S Shetty, Pradeep Nataranjan, Suchetha Kumari N

Introduction

An extensive array of medicinal plants has undergone investigation, underscoring the imperative for the continued screening of natural inhibitors with the potential to target cancer metabolism. The current research endeavor was directed toward evaluating the chemotherapeutic efficacy of peel extracts of Citrus maxima and its constituent flavonoid, Naringin (NA), in the context of breast cancer, specifically targeting the pyruvate kinase isozyme M2 (PKM2).

Materials and methods

Extracts from the peel of Citrus maxima were prepared and analyzed using liquid chromatography–mass spectrometry (LC–MS) to detect the presence of the bioactive compound, NA. The potential anti-proliferative effects of these peel extracts of Citrus maxima and NA were examined against human breast cancer cell lines utilizing an MTT assay. To investigate the distribution of the cell cycle, cell cycle analysis was conducted. The induction of apoptosis was ascertained using Annexin V-FITC through flow cytometry. The protein expression of PKM2 was analyzed using Western blotting. Molecular docking and dynamics simulations analysis were employed.

Results

Liquid chromatography–mass spectrometry (LC–MS) analysis confirmed the existence of NA within the extracts of Citrus maxima. Both the crude extracts and NA demonstrated a dose-dependent inhibition of breast cancer cell proliferation. Our findings indicate that these crude extracts and NA instigate both early and late apoptosis, in addition to causing cell cycle arrest in the G2/M phase. Immunoblotting studies further revealed that the expression of PKM2 protein was suppressed by both the crude extracts and NA. Computational analysis demonstrated stable binding affinity with Ser77, His78, and Lys207 of PKM2.

Conclusion

This investigation unveils the presence of NA within Citrus maxima extracts, exhibiting robust affinity for PKM2 via molecular docking and dynamics simulations. Extracts and NA dose-dependently inhibit breast cancer cell proliferation. Notably, PKM2 regulates cancer cell glycolysis, promising intricate therapeutic prospects for breast cancer.

一系列广泛的药用植物已经进行了研究,强调了继续筛选具有靶向癌症代谢潜力的天然抑制剂的必要性。目前的研究工作旨在评估柑橘皮提取物及其成分类黄酮柚皮苷(NA)在乳腺癌中的化疗效果,特别是针对丙酮酸激酶同工酶M2 (PKM2)。材料与方法制备柑橘皮提取物,采用液相色谱-质谱联用(LC-MS)检测其活性成分NA的存在。利用MTT法研究了柑橘皮提取物和NA提取物对人乳腺癌细胞株的潜在抗增殖作用。为了研究细胞周期的分布,我们进行了细胞周期分析。流式细胞术检测Annexin V-FITC对凋亡的诱导作用。Western blotting分析PKM2蛋白表达。采用分子对接和动力学模拟分析。结果液相色谱-质谱(LC-MS)分析证实了大黄柑提取物中NA的存在。粗提物和NA均表现出剂量依赖性的乳腺癌细胞增殖抑制作用。我们的研究结果表明,这些粗提取物和NA除了在G2/M期引起细胞周期阻滞外,还能促进早期和晚期细胞凋亡。免疫印迹研究进一步发现,粗提物和NA均能抑制PKM2蛋白的表达。计算分析表明,PKM2与Ser77、His78和Lys207具有稳定的结合亲和力。通过分子对接和动力学模拟,本研究揭示了NA在柑橘提取物中存在,对PKM2表现出强大的亲和力。提取物和NA剂量依赖性抑制乳腺癌细胞增殖。值得注意的是,PKM2调节癌细胞糖酵解,对乳腺癌具有复杂的治疗前景。
{"title":"Naringin from Citrus maxima peel: a potential therapeutic agent for breast cancer via PKM2 inhibition","authors":"Flama Monteiro,&nbsp;Vijith Vittal Shetty,&nbsp;Ranjitha Acharaya,&nbsp;Sriram Naresh,&nbsp;Manne Munikumar,&nbsp;Shilpa S Shetty,&nbsp;Pradeep Nataranjan,&nbsp;Suchetha Kumari N","doi":"10.1186/s43088-025-00668-0","DOIUrl":"10.1186/s43088-025-00668-0","url":null,"abstract":"<div><h3>Introduction</h3><p>An extensive array of medicinal plants has undergone investigation, underscoring the imperative for the continued screening of natural inhibitors with the potential to target cancer metabolism. The current research endeavor was directed toward evaluating the chemotherapeutic efficacy of peel extracts of <i>Citrus maxima</i> and its constituent flavonoid, Naringin (NA), in the context of breast cancer, specifically targeting the pyruvate kinase isozyme M2 (PKM2).</p><h3>Materials and methods</h3><p>Extracts from the peel of <i>Citrus maxima</i> were prepared and analyzed using liquid chromatography–mass spectrometry (LC–MS) to detect the presence of the bioactive compound, NA. The potential anti-proliferative effects of these peel extracts of <i>Citrus maxima</i> and NA were examined against human breast cancer cell lines utilizing an MTT assay. To investigate the distribution of the cell cycle, cell cycle analysis was conducted. The induction of apoptosis was ascertained using Annexin V-FITC through flow cytometry. The protein expression of PKM2 was analyzed using Western blotting. Molecular docking and dynamics simulations analysis were employed.</p><h3>Results</h3><p>Liquid chromatography–mass spectrometry (LC–MS) analysis confirmed the existence of NA within the extracts of <i>Citrus maxima</i>. Both the crude extracts and NA demonstrated a dose-dependent inhibition of breast cancer cell proliferation. Our findings indicate that these crude extracts and NA instigate both early and late apoptosis, in addition to causing cell cycle arrest in the G2/M phase. Immunoblotting studies further revealed that the expression of PKM2 protein was suppressed by both the crude extracts and NA. Computational analysis demonstrated stable binding affinity with Ser77, His78, and Lys207 of PKM2.</p><h3>Conclusion</h3><p>This investigation unveils the presence of NA within <i>Citrus maxima</i> extracts, exhibiting robust affinity for PKM2 via molecular docking and dynamics simulations. Extracts and NA dose-dependently inhibit breast cancer cell proliferation. Notably, PKM2 regulates cancer cell glycolysis, promising intricate therapeutic prospects for breast cancer.</p></div>","PeriodicalId":481,"journal":{"name":"Beni-Suef University Journal of Basic and Applied Sciences","volume":"14 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bjbas.springeropen.com/counter/pdf/10.1186/s43088-025-00668-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145162052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethyl acetate extract from red coralline macroalgae Mastophora rosea, rich in polyphenolic catechins, induces apoptosis and inhibits metastasis in melanoma cell line 红珊瑚巨藻的乙酸乙酯提取物含有丰富的多酚儿茶素,可诱导黑色素瘤细胞凋亡和抑制转移
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-02 DOI: 10.1186/s43088-025-00665-3
Eka Sunarwidhi Prasedya, Putu Bella Aprillia Saraswati, Ni Wayan Riyani Martyasari, Andri Frediansyah, Munawar Khalil, Sri Widyastuti

Background

The rise in global temperatures and subsequent increase in extreme heatwaves is implicated to have a significant contribution to the growing incidence of various skin diseases, particularly melanoma skin cancer. The existing therapeutic approaches for skin cancer such as chemotherapy induce significant adverse effects. This highlights the need for further development of novel medicinal substances from natural sources which has less side effects implications. Macroalgae, often known as seaweeds, are recognized for their diverse array of bioactive compounds, which have numerous potential applications. The red coralline macroalgae or seaweed Mastophora rosea is abundant in the tropical Indo-Pacific region, including Indonesia. However, little is known regarding the phytochemical profile and potent bioactivity of this unique seaweed. The objective of this study is to assess the phytochemical profile, antioxidant and cytotoxic activity of M. rosea in melanoma cell line.

Methodology

The dried macroalgae M. rosea sample was extracted using various solvents with differing polarities: ethanol, ethyl acetate (EA), and n-hexane. Subsequent biochemical evaluations included total phenolic content and antioxidant capability. Additionally, cytotoxic experiments were conducted using the mammalian melanoma cell line SK-MEL-2.

Results

The ANOVA results revealed that the EA solvent was the most efficient in producing extracts with high total phenolic content (368.81 ± 3.16 mg GAE/g). This high total phenolic content is accompanied by potent antioxidant capacity (IC50 = 99.52 ± 19.58 µg/mL). In addition, M. rosea EA extract is attributed with the presence of various polyphenolic catechins, such as gallic acid, gallocatechin, epigallocatechin (EGC), catechin, epicatechin, epigallocatechingallate (EGCG), and epicatechingallate (ECG). Furthermore, M. rosea EA shows strong cytotoxic activity against the melanoma cell line SK-MEL-2 (IC50 = 37.10 ± 0.85 µg/mL). In addition to the melanoma cell line, the M. rosea EA extract shows similar cytotoxicity in epithelial HeLa cells (IC50 = 34.32 ± 1.19 µg/mL) and low cytotoxicity in normal human dermal fibroblast cells (IC50 > 200 µg/mL).

Conclusion

The current results show that M. rosea could induce apoptosis and also suppress metastasis activity in SK-MEL-2 cells. Further characterization and isolation of the possible bioactive compounds are necessary to better comprehend its mechanism of action against melanoma. Nevertheless, this study indicates that more study needed to be done on various macroalgae regarding their phenolic components that may be beneficial for the development of novel therapeutic agents for cancer treatment.

Graphical abstract

全球气温的上升和随之而来的极端热浪的增加被认为对各种皮肤疾病,特别是黑色素瘤皮肤癌的发病率不断上升有重要贡献。现有的治疗皮肤癌的方法,如化疗,会引起明显的不良反应。这突出表明需要进一步从天然来源开发副作用较小的新型药用物质。大型藻类,通常被称为海藻,因其多种生物活性化合物而被公认,具有许多潜在的应用前景。红珊瑚大藻或海草在热带印度洋-太平洋地区,包括印度尼西亚,是丰富的。然而,人们对这种独特海藻的植物化学特征和有效的生物活性知之甚少。本研究的目的是评估玫瑰红支原体在黑色素瘤细胞系中的植物化学特征、抗氧化和细胞毒活性。方法采用不同极性溶剂乙醇、乙酸乙酯和正己烷提取大藻样品。随后的生化评价包括总酚含量和抗氧化能力。此外,利用哺乳动物黑色素瘤细胞系SK-MEL-2进行了细胞毒性实验。结果方差分析结果表明,EA溶剂提取的总酚含量最高(368.81±3.16 mg GAE/g);这种高总酚含量伴随着强大的抗氧化能力(IC50 = 99.52±19.58µg/mL)。此外,玫瑰玫瑰提取物还含有多种多酚儿茶素,如没食子酸、没食子儿茶素、没食子儿茶素(EGC)、儿茶素、表儿茶素、没食子儿茶素(EGCG)和表儿茶素(ECG)。此外,玫瑰草提取物对黑色素瘤细胞系SK-MEL-2具有较强的细胞毒活性(IC50 = 37.10±0.85µg/mL)。除黑色素瘤细胞系外,玫瑰荆芥提取物对上皮HeLa细胞具有相似的细胞毒性(IC50 = 34.32±1.19µg/mL),对正常人真皮成纤维细胞具有较低的细胞毒性(IC50 > 200µg/mL)。结论玫红色念珠菌对SK-MEL-2细胞具有诱导凋亡和抑制转移活性的作用。为了更好地了解其抗黑色素瘤的作用机制,有必要进一步表征和分离可能的生物活性化合物。然而,这项研究表明,需要对各种大型藻类的酚类成分进行更多的研究,这些研究可能有助于开发新的癌症治疗药物。图形抽象
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引用次数: 0
Bag Valve Mask with Ventilation Indicator (BVM-VI) prototype for ventilation rhythm in Basic Life Support 基本生命支持中通气节律的带通气指示器的袋式阀面罩(BVM-VI)原型
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-08-01 DOI: 10.1186/s43088-025-00664-4
Pratama Yulianto, Endang Triyanto, Ridlwan Kamaluddin, Adhe Akbar Azanni

Background

Bag valve mask (BVM) are a practical choice for emergency medical personnel to treat out-of-hospital cardiac arrest (OHCA). However, the use of currently available conventional BVM still often results in overventilation in cases of cardiac arrest or respiratory failure. Globally, 79% of hyperventilation events occur during Basic Life Support (BLS) with BVM. This study aims to produce a prototype BVM-VI.

Method

The prototyping method of Research and Development design was chosen as the primary method, followed by black box testing with clinical, practical, and academic experts, and ended with limited scale testing with 10 users.

Result

BVM-VI is the result of combining conventional BVM with a portable indicator light module to signal ventilation actions. Expert assessment using the black box test method with CVI analysis resulted in a content validity score of 100%. A limited study conducted by nursing students using a survey method showed reliability with an Intraclass Correlation Coefficient (ICC) of 0.769.

Conclusion

BVM-VI became the initial prototype for developing a ventilation aid with breathing rhythm adjustment in BLS.

背景袋式瓣膜面罩(BVM)是急救医务人员治疗院外心脏骤停(OHCA)的实用选择。然而,在心脏骤停或呼吸衰竭的情况下,使用目前可用的传统BVM仍然经常导致过度通气。在全球范围内,79%的过度通气事件发生在BVM的基本生命支持(BLS)期间。本研究的目的是制造一个BVM-VI原型机。方法采用研发设计的原型法作为主要方法,然后进行临床、实践和学术专家的黑盒测试,最后进行10名用户的有限规模测试。结果tbvm - vi是将传统BVM与便携式指示灯模块相结合的结果,指示通风动作。专家评价采用黑盒检验法结合CVI分析,内容效度评分为100%。用调查法对护生进行的一项有限研究显示信度,班级内相关系数(ICC)为0.769。结论bvm - vi是开发具有呼吸节律调节功能的BLS通气辅助设备的雏形。
{"title":"Bag Valve Mask with Ventilation Indicator (BVM-VI) prototype for ventilation rhythm in Basic Life Support","authors":"Pratama Yulianto,&nbsp;Endang Triyanto,&nbsp;Ridlwan Kamaluddin,&nbsp;Adhe Akbar Azanni","doi":"10.1186/s43088-025-00664-4","DOIUrl":"10.1186/s43088-025-00664-4","url":null,"abstract":"<div><h3>Background</h3><p>Bag valve mask (BVM) are a practical choice for emergency medical personnel to treat out-of-hospital cardiac arrest (OHCA). However, the use of currently available conventional BVM still often results in overventilation in cases of cardiac arrest or respiratory failure. Globally, 79% of hyperventilation events occur during Basic Life Support (BLS) with BVM. This study aims to produce a prototype BVM-VI.</p><h3>Method</h3><p>The prototyping method of Research and Development design was chosen as the primary method, followed by black box testing with clinical, practical, and academic experts, and ended with limited scale testing with 10 users.</p><h3>Result</h3><p>BVM-VI is the result of combining conventional BVM with a portable indicator light module to signal ventilation actions. Expert assessment using the black box test method with CVI analysis resulted in a content validity score of 100%. A limited study conducted by nursing students using a survey method showed reliability with an Intraclass Correlation Coefficient (ICC) of 0.769.</p><h3>Conclusion</h3><p>BVM-VI became the initial prototype for developing a ventilation aid with breathing rhythm adjustment in BLS.</p></div>","PeriodicalId":481,"journal":{"name":"Beni-Suef University Journal of Basic and Applied Sciences","volume":"14 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bjbas.springeropen.com/counter/pdf/10.1186/s43088-025-00664-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Beni-Suef University Journal of Basic and Applied Sciences
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