Startseite Mesoporous silica nanoparticles as a drug delivery mechanism
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Mesoporous silica nanoparticles as a drug delivery mechanism

  • Wei Zhang EMAIL logo , Hongwei Liu , Xilong Qiu EMAIL logo , Fanjiao Zuo und Boyao Wang
Veröffentlicht/Copyright: 15. Mai 2024
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Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 19 Heft 1

Abstract

Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

Keywords: drug slow-release system; controlled drug release system; mesoporous silica nanoparticles; review

1 Introduction

Drug delivery systems (DDSs) represent significant advancements in contemporary pharmaceutical research, reflecting improvements in dosage forms and formulation development. These systems stand at the vanguard of current scientific and technological progress, characterized by substantial advancements in theoretical foundations, innovative formulation designs, manufacturing methodologies, and clinical applications [1–3]. DDSs have the potential to enhance medication bioavailability by increasing solubility and regulating the rates of degradation and absorption [4,5]. Furthermore, by modifying medication molecules with biocompatible compounds to prevent recognition by the body’s immune system, these systems offer the potential to minimize drug-related adverse effects during medical treatment [6]. Nanomaterials have recently shown immense potential for use in biomedical fields, owing to the rapid advancement of nanotechnology and their exceptional physicochemical properties. Nanomaterials are extensively employed across various fields, including drug delivery [7], disease diagnostics and therapy [8,9], tissue engineering repair [10,11], among others, and have earned considerable recognition in the materials science domain for their contributions to controlled drug release systems. This acclaim is due to their inherent properties, which include easy synthesis, tunable size, chemical durability, large specific surface area, uniform and adjustable pore sizes, biocompatibility, surface modifiability, and effective loading capacity for poorly soluble pharmaceutical agents [12–14]. The rapid release of medications containing mesoporous silica nanoparticles (MSNs) is primarily attributed to the open pores of the MSNs.

The review provides an overview of MSNs, highlighting their advantages, slow-release, and controlled drug release system along with their applications. Our goal is to summarize recent research progress in mesoporous silica and then offer insights into strategies for achieving desired chemical properties using this nanoplatform for future practical applications. We aim to stimulate new ideas and inspire continued efforts in this emerging research field [15–17].

2 Mesoporous silica nanomaterials

Mesoporous materials, characterized by a porous structure with pore sizes ranging from 2 to 50 nm, have seen significant advancements in recent years. This progress is particularly notable in the development of two-dimensional hexagonal mesoporous silica, various transition metal oxides not based on silicon, and diverse nanoparticle assemblies. The outcome of related research efforts is the discovery of innovative materials with promising applications [18,19].

A significant breakthrough occurred in 1992 when scientists at the American Mobile Company developed the MCM-41 series of novel mesoporous silicon materials. They utilized a cationic alkyl quaternary ammonium salt surfactant as a template, employing the concept of liquid crystal templates [20]. MCM-41 mesoporous silica, one of these materials, has garnered considerable interest within the biomedical research community. Its appeal lies in its robust structural integrity, extensive specific surface area, pores organized in a uniform hexagonal pattern, ease of surface functionalization and modification, adjustable pore diameters, and low cytotoxicity [21,22].

3 Mesoporous silica sustained-release drug systems

Leveraging MSNs as a delivery method allows for the loading of hydrophobic drugs into MSN pores using non-aqueous solvents. As these drug molecules transition from the pores to the cytoplasm, the phospholipid bilayer facilitates their entry into the hydrophobic intracellular environment. Notably, drugs such as camptothecin [23] and paclitaxel [24], known to be encapsulated within MSNs, are effectively released from these pores. Drawing on the biocompatibility and cell permeability of MSNs, Wang et al. succeeded in encapsulating the drug telmisartan in mesoporous silica. The integration of these two elements during the formulation process enhanced both the bioavailability and dissolution rate of telmisartan [25]. Compared to raw drug materials, this approach markedly improved both the drug dissolution rates and cumulative drug dissolution. To boost the bioavailability of medications with low solubility and enhance their permeability, Wang et al. embarked on a study aimed at examining the effects of different drug loading methods on drug loading efficiency and dissolution rates within MSNs. Qiu et al. demonstrated the successful synthesis of MSNs, dendritic mesoporous silica nanoparticles (DMSNs), and hollow mesoporous silica nanoparticles (HMSNs), with all three types exhibiting higher drug loading and encapsulation efficiency. Analysis based on the first-order release equation curve and Higuchi equation parameters revealed that the loaded puerarin exhibited sustained-release properties [26], Figure 1.

Figure 1 Schematic representation of the formation of MSN (a), DMSN (b), and HMSN (c), respectively.
Figure 1

Schematic representation of the formation of MSN (a), DMSN (b), and HMSN (c), respectively.

4 Mesoporous silica controlled drug release system

MSNs possess a large specific surface area, excellent biocompatibility, and a stable skeletal structure, making them a viable option for drug delivery. This has spurred significant research interest. In 2004, Hernandez et al. ventured into the field of nanoscale-controlled valve mechanisms by introducing the groundbreaking concept of a nanovalve based on macrocyclic receptor molecules [27]. For the nanovalve to function as intended, three key components are necessary: a nanocontainer for carrying drugs, an actuator capable of moving chains in response to specific stimuli, and a suitable control strategy to govern this chain movement. Designing a DDS that responds to particular environmental stimuli is crucial for achieving controlled medication release within the body, thereby minimizing drug leakage and adverse effects on healthy tissues. Examples of stimuli include light [27], pH fluctuations [28], enzyme activity [29], redox reactions [30], and combinations of these factors [31].

4.1 Light-responsive controlled drug release systems

Leveraging light to trigger reactions offers numerous benefits, such as the ability for remote activation, non-invasiveness, precise control, and extensive applicability in the biomedical sector. UV-visible and near-infrared light serve as the primary light sources in DDS [32].

In a noteworthy experiment, Nguyen et al. utilized mesoporous silica coated with the photosensitive substance anthracene formic acid [33]. This molecule-coated surface was encased by a ring of tetravalent ionic cyclophane – CBPQT4+. Upon exposure to light, the photosensitive molecule formed a covalent bond with the CBPQT4+ ring, facilitating a light-induced electron transfer that ultimately resulted in the dissociation of the ring from the molecular bearing. This process enabled the development of a drug release mechanism responsive to light, simplifying the release of drug molecules from the mesoporous silica pores.

In a similar approach, Sierocki et al. incorporated azobenzene into the pores of mesoporous silica [34]. In its stable state, azobenzene adopts a trans configuration, which can be isomerized upon exposure to UV light. This exposure triggers the isomerization of azobenzene into the cis configuration. Further exposure to light at 450 nm induces continuous trans-cis and cis-trans photoisomerization of azobenzene. The oscillatory movements of the detached azobenzene head, resulting from this series of changes, trigger the release of drug molecules into the surrounding solution from the mesoporous silica pores.

Additionally, Li et al. employed host–guest interactions to attach trans-cinnamamide to the molecular bearing linked to the mesoporous silica surface, utilizing cucurbit[7]uril (CB[7]) [35]. Upon exposure to UV radiation at 300 nm, the trans-cinnamamide underwent isomerization into the cis structure. This isomerization induced spatial repulsion caused CB[7] to detach from the molecular bearing, thereby opening the mesoporous silica pores and allowing the release of drug molecules.

4.2 pH-responsive controlled drug release systems

pH-sensitive drug delivery methods are gaining prominence due to their capacity to release drugs in response to the varying acidic or alkaline environments present in different parts of the body, which have distinct pH levels [36,37]. This characteristic enhances therapeutic efficacy while minimizing adverse impacts on non-target tissues. A pH-responsive nanovalve system is designed to selectively release drugs at tumor sites, leveraging the pH differential between tumor tissues (typically pH 5.8–7.1) and normal tissues (pH 7.4) within the body’s microenvironment [38]. This targeted approach facilitates cancer treatment without negatively affecting healthy tissues.

Stoddart et al. explored the interaction of CB[6] with amino groups on the molecular bearings of mesoporous silica as a potential drug release method. This interaction allows for binding or detachment based on pH variations. Under neutral and acidic conditions, the CB[6] ring securely encases the molecular bearings adorned with bisquaternary ammonium groups on the mesoporous silica surface, effectively trapping drug molecules within the mesoporous silica pores. Under alkaline conditions, deprotonation of the molecular bearings occurs, breaking the CB[6] binding and thereby enabling the release of drug molecules from the mesoporous silica [38].

Yang et al. investigated a pH-responsive, mesoporous silica-based drug release system functionalized with column[5] aryl hydrocarbon (CP[5]A) [39]. In this system, rotaxane molecules on the mesoporous silica surface are encased by electron-rich CP[5]A, effectively retaining drug molecules within the pores of the mesoporous silica under alkaline or neutral conditions. However, in acidic environments, CP[5]A dissociates from the rotaxane molecules, facilitating the easier release of drug molecules from the mesoporous silica.

Oiu et al. developed a method for delivering paclitaxel using carboxymethyl chitosan (CMCS)-functionalized dendritic fibrous nano-silica (DFNS). DFNS, characterized by a three-dimensional dendritic structure, was synthesized using a double-template method. A pH-responsive, nanoloaded vehicle system was then prepared by grafting CMCS onto DFNS through a covalent binding reaction. In vitro cellular experiments indicated that CMCS-DFNS significantly enhanced drug uptake efficiency in breast cancer MCF-7 cells. Crucially, in vivo and cellular pharmacokinetic results demonstrated that CMCS-DFNS could prolong circulation time and increase the relative bioavailability of paclitaxel. Therefore, this pH-responsive DDS holds potential for the delivery of anti-tumor drugs and offers a new pathway for enhancing the bioavailability of other compounds with low inherent bioavailability [40], Figure 2.

Figure 2 Schematic illustration of the synthesis process of CMCS-DFNS@PTX and the pH-responsive release.
Figure 2

Schematic illustration of the synthesis process of CMCS-DFNS@PTX and the pH-responsive release.

4.3 Enzyme-responsive controlled drug release systems

The variability in enzymes across different tissues in the human body highlights the importance of employing biomolecules as gatekeepers for controlled drug release within mesoporous systems in silico. E.g., a range of biomolecules – including antigen–antibody interactions [41], hybridized single-stranded DNA [42], enzymes [43], sugars [44], ribose [45–48], and proteins [49] have been engineered to function as gating elements at the entrances of mesoporous silica structures. This approach confers a high level of specificity, precision, and efficiency on the resultant mesoporous silica drug release systems.

In 2008, Stoddart et al. introduced a mesoporous silica drug release system designed to respond to enzymatic stimulation [50]. In this system, α-cyclodextrin (α-CD) wraps around the polyethylene glycol molecular bearings on the surface of the mesoporous silica, forming a bond with the upper ester linkage and thus securing drug molecules within the mesoporous silica pores. Upon introduction of porcine heparan esterase, which catalyzes the enzymatic hydrolysis of the ester bond, the molecular bearings break apart. This causes α-CD to detach from them, thereby facilitating the release of the drug from the pores.

Yang et al. developed organic–inorganic hybrid nanomaterials that leverage supramolecular interactions between hosts and guests. These materials not only showcase excellent biocompatibility but also exceptional controlled release capabilities in response to specific external stimuli. The release mechanisms, precisely regulated by cup-shaped aromatic-based nanogate systems enable the responsive release of acetylcholine – a neurotransmitter – into the environment. This approach facilitates timed, targeted, and quantifiable controlled release, exemplifying a significant advancement in the field of DDSs [51].

4.4 Redox-responsive controlled drug release systems

Recently, notable progress has been made in the development of controlled drug release systems that react to alterations in the body’s redox environment. Studies have shown that the unique reducing conditions present within tumors act as a distinct trigger for the decomposition of redox-responsive delivery systems inside tumor cells, enabling the release of encapsulated medication. These redox-responsive systems present several benefits, such as stability in normal tissues and enhanced therapeutic efficacy compared to other controlled release mechanisms. Consequently, this can significantly diminish the toxicity and adverse effects associated with both the drugs and the nanocarriers [30,52].

Zink et al. developed molecular bearings known as rotaxanes, which were attached to the surface of mesoporous silicon. These rotaxanes featured a bistable state with two attachment sites: tetrathiafulvalene (TTF) and dioxynaphthalene (DNP). A CBPQT4+ ring, serving as a valve molecule, was positioned around the molecular bearings in their bistable state, demonstrating a strong affinity for TTF. In the absence of an oxidizing reagent, CBPQT4+ remained attached to the TTF site, distanced from the mesoporous silica pore, thus allowing the ingress or egress of drug molecules. Upon the introduction of Fe(ClO4)3·6H2O, TTF was oxidized to TTF2+, prompting the CBPQT4+ to migrate to the DNP site close to the pore entrance, effectively encapsulating the drug molecules within. The subsequent reduction of TTF to its original state by ascorbic acid caused CBPQT4+ to revert to the DNP site, facilitating controlled drug release [53].

Zink et al. further innovated by modifying the surface of mesoporous silicon with ferrocene dicarboxylic acid and β-cyclodextrin (β-CD) to engineer nanovalves. Upon application of an oxidizing voltage via cyclic voltammetry, the resulting positively charged oxidized ferrocenyl salt disrupted the stable inclusion complex formation with β-CD. This process led to the oxidation of the ferrocenyl dicarboxylic acid, prompting β-CD to detach, which in turn facilitated the release of drug molecules contained within the pore channels.

Zhao et al. utilized electrostatic interactions to attach negatively charged single-stranded DNA to positively charged disulfide bonds on the surface of mesoporous silicon. The introduction of reducing agents such as dithiothreitol and glutathione resulted in the cleavage of the disulfide bonds, enabling the single-stranded DNA to detach and thereby release the drug. Importantly, the intracellular concentration of the reducing agent glutathione is significantly higher (up to 10 mM) compared to extracellular concentrations (less than 10 µM). This difference in glutathione levels makes mesoporous silica an ideal storage microenvironment outside cells, offering considerable promise for the targeted delivery of therapeutic drugs, particularly in cancer treatment [54].

5 Challenges and opportunities

Leveraging the distinctive attributes of MSNs, multifunctional MSN nanocomposites emerge as potent agents for diverse applications. Nonetheless, significant opportunities remain to enhance the commercial production of MSNs. To boost yield, the development of new materials and synthetic strategies is crucial, particularly with a focus on efficiently synthesizing ultra-large-sized MSNs. Moreover, concerted efforts are required to ingeniously design smart theranostics that facilitate highly effective therapy under remote control and to establish correlations between experimental outcomes and therapeutic efficacy. This approach will pave the way for real-time monitoring of therapeutic results, thereby advancing personalized theranostics. The ongoing development of MSN-based theranostics for biomedical applications remains a vibrant and critical area of research. Continued in-depth investigation into MSNs promises to yield exciting and promising advancements for the chemistry and biomedicine communities by contributing novel discoveries and addressing existing challenges. Interdisciplinary collaboration is paramount to further refine the performance of MSN-based theranostics and ensure their successful clinical implementation.

6 Future trends

In conclusion, our review has highlighted recent advancements in MSNs that have led to the creation of novel smart materials with extensive applications across various fields. MSNs have been endowed with numerous advantageous properties, establishing them as superior solid supports for constructing intelligent machinery. Significant strides have been made in developing biocompatible nanocarriers capable of controlled entrapment and release of cargo molecules in response to a wide array of internal and external stimuli. Consequently, MSNs hold a promising future in the pharmaceutical industry, presenting a broad spectrum of potential applications.

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Acknowledgments

The authors would like to acknowledge the support from Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

  1. Funding information: This work was supported by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A).

  2. Author contributions: Wei Zhang and Hongwei Liu writed the paper. Wei Zhang and Fanjiao Zuo performed the literature search. Xilong Qiu and Boyao Wang critically revised the work.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: Data sharing is not applicable for this article as no datasets were generated or analyzed during the current study.

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Received: 2024-01-05
Revised: 2024-03-19
Accepted: 2024-03-21
Published Online: 2024-05-15

© 2024 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
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  50. Mesoporous silica nanoparticles as a drug delivery mechanism
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  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
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  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
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  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
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  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
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  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
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  213. Special Issue on Multi-omics
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https://doi.org/10.1515/biol-2022-0867
Schlagwörter für diesen Artikel
drug slow-release system; controlled drug release system; mesoporous silica nanoparticles; review
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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Heruntergeladen am 27.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0867/html
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