Search Results (287)

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article

The combustion of biomass fuels releases alkali metals, which induce severe catalyst deactivation due to alkali metal (K) poisoning in low-temperature ammonia selective catalytic reduction (NH₃-SCR) systems. To address this issue, this study developed a series of heteropoly acid (HPA)-modified Ce/AC catalysts prepared via incipient wetness impregnation. The low-temperature NH₃-SCR performance (80–200 °C) of these catalysts was systematically evaluated, with particular emphasis on their denitrification activity and K-poisoning resistance. The silicotungstic-acid (TSiA)-modified Ce/Ac (TSiA-Ce/AC) catalyst showed an improvement (>20%) in NO conversion activity under the K poisoning condition. The superior K-poisoning resistance of the TSiA-Ce/AC catalyst was attributed to the high density of Brønsted acidic sites and the strong K binding affinity of TSiA, which together protected active sites and preserved the standard SCR reaction pathway under K contaminations. This study proposes a novel strategy for enhancing catalyst K resistance in low-temperature NH₃-SCR systems. Full article

Biodentine, a tricalcium silicate cement, has emerged as a retrograde root-end filling material to promote periapical lesion (PL) healing after apicoectomy. However, its underlying mechanisms remain unclear. This study tested the hypothesis that Biodentine stimulates the osteogenic differentiation of mesenchymal stromal cells (MSCs) derived from PLs. The Biodentine extract (B-Ex) was prepared by incubating polymerized Biodentine in RPMI medium (0.2 g/mL) for three days at 37 °C. B-Ex, containing both released microparticles and soluble components, was incubated with PL-MSCs cultured in either a basal MSC medium or suboptimal osteogenic medium. Osteogenic differentiation was assessed by Alizarin Red staining and the expression of 20 osteoblastogenesis-related genes. Non-cytotoxic concentrations of B-Ex stimulated the proliferation of PL-MSCs and induced their osteogenic differentiation in a dose-dependent manner, with a significantly enhanced effect in suboptimal osteogenic medium. B-Ex upregulated most early and late osteoblastic genes. However, the differentiation process was prolonged, as indicated by the delayed expression of wingless-type MMTV integration site family member 2 (WNT2), bone gamma-carboxyglutamate protein (BGLAP), bone morphogenic protein-2 (BMP-2), growth hormone receptor (GHR), and FOS-like 2, AP-1 transcription factor subunit (FOSL2), compared with their expression under optimal osteogenic conditions. The stimulatory effect of B-Ex was primarily calcium dependent, as it was reduced by 85% when B-Ex was treated with the calcium-chelating agent EGTA. In conclusion, Biodentine promotes the osteogenic differentiation of PL-MSCs in a calcium-dependent manner, supporting its stimulatory role in periapical healing. Full article

Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. Ramulus Mori alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. Full article

The aim of this study was to investigate the influence of solid dispersion (SD) formulation factors on improvement of the bioavailability and pharmacokinetic profile of clopidogrel after peroral administration using an in vitro–in silico approach. A clopidogrel-specific, physiologically based biopharmaceutical model (PBBM) was developed and validated to predict absorption and distribution of clopidogrel after peroral administration of the tested formulations. Clopidogrel solid dispersions were prepared using two polymers (poloxamer 407 and copovidone) and a drug-to-polymer ratio of 1:5 and 1:9. The results of the in vitro dissolution test under pH–media change conditions showed that the type and ratio of polymers notably influenced the release of clopidogrel from the SDs. It can be observed that an increase in the polymer content in the SDs leads to a decrease in the release of clopidogrel from the SDs. The predictive power of the constructed clopidogrel-specific PBBM was demonstrated by comparing the simulation results with pharmacokinetic data from the literature. The in vitro dissolution data were used as inputs for the PBBM to predict the pharmacokinetic profiles of clopidogrel after the peroral administration of SDs. SDs with copovidone (1:5) and poloxamer (1:9) showed the potential to achieve the highest drug absorption and bioavailability, with an improvement of over 100% compared to an immediate-release (IR) tablet. The sample with poloxamer (1:9) may have the potential to reduce inter-individual variability in clopidogrel pharmacokinetics due to absorption in the cecum and colon and associated lower first-pass metabolism in the liver. This suggests that distal intestine may be the targeted delivery site for clopidogrel, leading to improved absorption and bioavailability of the drug. This study has shown that an in vitro–in silico approach could be a useful tool for the development and optimization of clopidogrel formulations, helping in decision making regarding the composition of the formulation to achieve the desired pharmacokinetic profile. Full article

A key principle of guided bone regeneration (GBR) is the use of a barrier membrane to prevent cells from non-osteogenic tissues from interfering with bone regeneration in patients with hard tissue deficiencies. The aim of the study was to investigate whether the osteoinductive properties of bone-conditioned medium (BCM) obtained from cortical bone chips harvested at the surgical site can be transferred to a native bilayer collagen membrane (nbCM). BCM extracted within 20 or 40 min, which corresponds to a typical implant surgical procedure, and BCM extracted within 24 h, which corresponds to BCM released from the autologous bone chips in situ, contained significant and comparable amounts of TGF-β1, IGF-1, FGF-2, VEGF-A, and IL-11. Significant (p < 0.001) quantities of BMP-2 were only detected in the 24-h BCM preparation. The bioactive substances contained in the BCM were adsorbed to the nbCMs with almost 100% efficiency. A fast but sequential release of all investigated proteins occurred within 6–72 h, reflecting their stepwise involvement in the natural regeneration process. BCM-coated nbCM significantly (p < 0.05) increased the migratory, adhesive, and proliferative capacity of primary human bone-derived cells (hBC), primary human periodontal ligament cells (hPDLC), and an osteosarcoma-derived osteoblastic cell line (MG-63) compared to cells cultured on BCM-free nbCM. The high proliferative rates of MG-63 cells cultured on BCM-free nbCM were not further potentiated by BCM, indicating that BCM-coated nbCM has no detrimental effects on cancer cell growth. BCM-coated nbCM caused significant (p < 0.05) induction of early osteogenic marker gene expression and alkaline phosphatase activity, suggesting an important role of BCM-functionalized nbCM in the initiation of osteogenesis. The 24-h BCM loaded on the nbCM was the only BCM preparation that caused significant induction of late osteogenic marker gene expression. Altogether, our data define the pre-activation of collagen membranes with short-term-extracted BCM as a potential superior modality for treating hard tissue deficiencies via GBR. Full article

Background: Electronic cigarettes (ECIGs) have grown in popularity, particularly among adolescents and young adults. Flavored ECIG-liquids (E-liquids) are aerosolized by these ECIGs and inhaled into the respiratory system. Several studies have shown detrimental effects of E-liquids in airway tissues, revealing that flavoring agents may be the most irritating component. However, research on the effects of E-liquids on biological processes of the oral cavity, which is the first site of aerosol contact, is limited. Hence, this study focuses on the effects of E-liquid flavors on oral epithelial cells using the OKF6/TERT-2 cell line model. Methodology: E-liquid was prepared with and without flavors (tobacco, menthol, cinnamon, and strawberry). OKF6/TERT-2 oral epithelial cells, cultured at 37 °C and 5% CO₂, were exposed to 1% E-liquid ± flavors for 24 h. Outcomes determined include cell morphology, media pH, wound healing capability, oxidative stress, expression of mucin and tight junction genes, glycoprotein release, and levels of inflammatory cytokines (TNFα, IL-6, and IL-8). Results: Exposure to 1% flavored E-liquids negatively affect cellular confluency, adherence, and morphology. E-liquids ± flavors, particularly cinnamon, increase oxidative stress and production of IL-8, curtail wound healing recovery, and decrease glycoprotein release. Gene expression of muc5b is downregulated after exposure to E-liquids. In contrast, E-liquids upregulate occludin and claudin-1. Conclusions: This study suggests that ECIG use is not without risk. Flavored E-liquids, particularly cinnamon, result in pathophysiological responses of OKF6/TERT-2 cells. The dysregulation of inflammatory responses and cellular biology induced by E-liquids may contribute to various oral pathologies. Full article

Timely approvals and payments to the project participants are crucial for successful completion of construction projects. However, the construction industry faces persistent delays and non-payments to contractors. Despite the desirable benefits of automated payments and enhanced access to digitized data progress, most payment applications rely on centralized control mechanisms; inefficient procedures; and documentation that takes time to prepare, review, and approve. As such, there is a need for a reliable payment automation system that guarantees timely execution of payments upon the detection of completed works. Therefore, this study used a cutting-edge approach to automate construction payments by integrating blockchain-enabled smart contracts and scan-to-Building Information Modeling (BIM). In this approach, scan-to-BIM provides accurate, real-time building progress data, which serve as the source of verifiable off-chain data. A chain-link is then used to securely relay these data to the blockchain system. Blockchain-enabled smart contracts automate the execution of payments upon meeting contract conditions. The proposed approach was implemented on a real case study project. The actual site scan was captured using a photogrammetry 360° camera, which uses a combination of structured light and infrared depth sensing technology to capture 3D data and create detailed 3D models of spaces. This study leveraged accurate, real-time building progress data to automate payments using blockchain-enabled smart contracts upon work completion, thus reducing payment disputes by tying payments to verifiable construction progress, leading to faster release of payments. The findings show that this approach provides a transparent basis for payment, enhancing trust and allowing precise project progress tracking. Full article

Background/Objectives: Since 2008, following clinical studies conducted on children that revealed the ability of the β-adrenergic antagonist propranolol to inhibit capillary growth in infantile hemangiomas (IHs), its oral administration has become the first-line treatment for IHs. Although oral propranolol therapy at a dosage of 3 mg/kg/die is effective, it can cause systemic adverse reactions. This therapy is not necessarily applicable to all patients. Topical skin applications could help maintain a high drug concentration at local sites and also represent a characteristically easy method of administration for pediatric patients. Because no topical propranolol dosage forms are commercially available, such formulations may be prepared at hospitals and pharmacies. Methods: In the present study, we identified a simple method for preparing topical propranolol hydrochloride formulations at 1% w/w with five commercial ready-to-use bases and evaluated the pharmaceutical profiles. The physical stability of the extemporaneous formulations was predicted by performing an accelerated centrifuge test and assessed by visual inspection after one month storage at 25 °C. The chemical stability of the drug in the five formulations was assessed by using a high-performance liquid chromatography (HPLC) method. In vitro drug-release and permeability experiments were conducted through synthetic membranes and the outer pavilion of a pig’s ear by utilizing Franz-type diffusion cells. Results: The results indicated that the release of the drug was significantly influenced by the internal structure and physicochemical properties of each base. Conclusions: Specifically, the formulations prepared with the hydrophilic bases could be easily prepared and yield satisfactory results, representing a potential effective therapy for IHs in pediatric patients. Full article

Niobium pentoxide (T-Nb₂O₅) is a promising anode material for dual-ion batteries due to its high lithium capacity and fast ion storage and release mechanism. However, T-Nb₂O₅ suffers from the disadvantages of poor electrical conductivity and fast cycling capacity decay. Herein, a nitrogen-doped three-dimensional porous carbon (RMF) was prepared for loading niobium pentoxide to construct a composite system with excellent electrochemical performance. The obtained T-Nb₂O₅/RMF composites have a well-developed pore structure and a high specific surface area of 1568.5 m² g⁻¹, which could effectively increase the contact area between the material and electrolyte, improving the electrode reaction and lithium-ion transfer diffusion. Nitrogen doping increased surface polarity, creating more active sites and accelerating the electrode reaction rate. The introduction of T-Nb₂O₅ imparted high power density and excellent cycling stability to the battery. The composites exhibited good electrochemical performance when used as dual-ion battery anode, with a stable cycle life of 207.2 mA h g⁻¹ at 1 A g⁻¹ current density after 650 cycles and great rate performance of 181.5 mA h g⁻¹ at 5A g⁻¹ was also obtained. This work provides the possibility for applying T-Nb₂O₅/RMF as an anode for a high-performance dual-ion battery. Full article

Breast cancer is a common clinical malignant tumor that seriously threatens women’s physical and mental health. Chemotherapy, as the first choice of breast cancer treatment, has limited its application in the clinic due to problems of poor stability, short half-life, and serious toxic side effects. With the emergence of nanotechnology, inorganic materials to prepare mesoporous silica nanoparticles (MSNs) have been widely used in anti-tumor drug carriers. However, their slow degradation rate limits their application in the biomedical field. Therefore, developing low-toxicity MSNs with good biocompatibility, biodegradability, and rapid release at the tumor site is a key scientific issue to be addressed. Here, we prepared DOX-loaded Ca-Mg-doped MSNs by electrostatic adsorption to obtain Ca-Mg@DOX@MSNs with suitable particle sizes and zeta potential, and the incorporation of calcium and magnesium also led to an increase in the degradation rate under acidic conditions and an accelerated release, which reduced the toxicity of DOX and promoted cellular uptake with good anti-tumor effects. This study provides a new idea for the clinical treatment of breast cancer. Full article

Aging disrupts multiple homeostatic processes, including autophagy, a cellular process for the recycling and degradation of defective cytoplasmic structures. Acute treatment with the autophagy inhibitor chloroquine blunts the maximal forces generated by the diaphragm muscle, but the mechanisms underlying neuromuscular dysfunction in old age remain poorly understood. We hypothesized that chloroquine treatment increases the presynaptic retention of the styryl dye FM 4-64 following high-frequency nerve stimulation, consistent with the accumulation of unprocessed bulk endosomes. Diaphragm-phrenic nerve preparations from 24-month-old male and female C57BL/6 × 129 J mice were incubated with FM 4-64 (5 µM) and either chloroquine (50 µM) or vehicle during 80 Hz phrenic nerve stimulation. Acute chloroquine treatment significantly decreased FM 4-64 intensity at diaphragm neuromuscular junctions following 80 Hz phrenic nerve stimulation, consistent with disrupted synaptic vesicle recycling. A similar reduction was evident in regions with the greatest FM 4-64 fluorescence intensity, which most likely surround synaptic vesicle release sites. In the absence of nerve stimulation, chloroquine treatment significantly increased FM 4-64 intensity at diaphragm neuromuscular junctions. These findings highlight the importance of autophagy in regulating presynaptic vesicle retrieval (including vesicle recycling and endosomal processing) and support the role of autophagy impairments in age-related neuromuscular dysfunction. Full article

Due to their high biocompatibility, biodegradability, and facile surface functionalization, phospholipid vesicles as carriers have garnered significant attention in the realm of disease diagnosis and treatment. On the one hand, phospholipid vesicles can function as probes for the detection of various diseases by encapsulating nanoparticles, thereby enabling the precise localization of pathological changes and the monitoring of disease progression. On the other hand, phospholipid vesicles possess the capability to selectively target and deliver therapeutic agents, including drug molecules, genes and immune modulators, to affected sites, thereby enhancing the sustained release of these agents and improving therapeutic efficacy. Recent advancements in nanotechnology have led to an increased focus on the application of phospholipid vesicles in drug delivery, biological detection, gene therapy, and cell mimics. This review aims to provide a concise overview of the structure, characteristics, and preparation techniques of phospholipid vesicles of varying sizes. Furthermore, we will summarize the latest research developments regarding their use as nanomedicines and gene carriers in disease treatment. Additionally, we will elucidate the potential of phospholipid vesicles in facilitating the internalization, controlled release, and targeted delivery of therapeutic substrates. Through this review, we aspire to enhance the understanding of the evolution of phospholipid vesicles within the biological field, outline prospective research, and address the forthcoming challenges associated with phospholipid vesicles in disease diagnosis and treatment. Full article

Background: The clinical efficacies of anticancer drugs are limited by non-selective toxic effects on healthy tissues and low bioavailability in tumor tissue. Therefore, the development of vehicles that can selectively deliver and release drugs at the tumor site is critical for further improvements in patient survival. Methods: We prepared a CEC nano-drug delivery system, CEC@ZIF-8, with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta potential, infrared (IR), x-ray diffraction (XRD), and transcriptome analysis, and examined the in vitro cytotoxicity and cellular uptake properties of CEC@ZIF-8 using cervical cancer cells. Lastly, we established a TC-1 tumor-bearing mouse model and evaluated its in vivo anti-cervical cancer activity. Results: The CEC@ZIF-8 nano-delivery system had favorable biocompatibility, heat stability, and pH responsiveness, with a CEC loading efficiency of 12%, a hydrated particle size of 174 ± 5.8 nm, a zeta potential of 20.57 mV, and slow and massive drug release in an acidic environment (pH 5.5), whereas release was 6% in a neutral environment (pH 7.4). At the same time, confocal imaging and cell viability assays demonstrated greater intracellular accumulation and more potent cytotoxicity against cancer cells compared to free CEC. The mechanism was analyzed by a series of transcriptome analyses, which revealed that CEC@ZIF-8 NPs differentially regulate the expression levels of 1057 genes in cancer cells, and indicated that the enriched pathways were mainly cell cycle and apoptosis-related pathways via the enrichment analysis of the differential genes. Flow cytometry showed that CEC@ZIF-8 NPs inhibited the growth of HeLa cells by arresting the cell cycle at the G0/G1 phase. Flow cytometry also revealed that CEC@ZIF-8 NPs induced greater apoptosis rates than CEC, while unloaded ZIF-8 had little inherent pro-apoptotic activity. Furthermore, the levels of reactive oxygen species (ROS) were also upregulated by CEC@ZIF-8 NPs while ROS inhibitors and caspase inhibitors reversed CEC@ZIF-8 NPs-induced apoptosis. Finally, CEC@ZIF-8 NPs also reduced the growth rate of xenograft tumors in mice without the systemic toxicity observed with cisplatin treatment. Conclusions: The CEC@ZIF-8 nano-drug delivery system significantly enhanced the anti-cervical cancer effect of CEC both in vivo and in vitro, providing a more promising drug delivery system for clinical applications and tumor management. At the same time, this work demonstrates the clinical potential of CEC-loaded ZIF-8 nanoparticles for the selective destruction of tumor tissues. Full article

Immunization against Gonadotropin-Releasing Hormone (GnRH) has been successfully explored and developed for the parenteral inoculation of animals, aimed at controlling fertility, reducing male aggressiveness, and preventing boar taint. Although effective, these vaccines may cause adverse reactions at the injection site, including immunosuppression and inflammation, as well as the involvement of laborious and time-consuming procedures. Oral vaccines represent an advancement in antigen delivery technology in the vaccine industry. In this study, a Salmonella enterica serovar Typhimurium (S. Typhimurium) mutant lacking the pathogenicity island 2 (S. Typhimurium ΔSPI2) was used as a vehicle and mucosal adjuvant to deliver two genetic constructs in an attempt to develop an oral immunological preparation against gonadotropin hormone-releasing hormone (GnRH). S. Typhimurium ΔSPI2 was transformed to carry two plasmids containing a modified GnRH gene repeated in tandem (GnRXG/Q), one under eukaryotic expression control (pDNA::GnRXG/Q) and another under prokaryotic expression control (pJexpress::GnRXG/Q). A group of three male BALB/c mice were orally immunized and vaccination-boosted 30 days later. The oral administration of S. Typhimurium ΔSPI2 transformed with both plasmids was effective in producing antibodies against GnRXG/Q, leading to a decrease in serum testosterone levels and testicular tissue atrophy, evidenced by a reduction in the transverse tubular diameter of the seminiferous tubules and a decrease in the number of layers of the seminiferous epithelium in the testes of the inoculated mice. These results suggest that S. Typhimurium ΔSPI2 can be used as a safe and simple system to produce an oral formulation against GnRH and that Salmonella-mediated oral antigen delivery is a novel, yet effective, alternative to induce an immune response against GnRH in a murine model, warranting further research in other animal species. Full article