Bioimpacts最新文献

The biological actions of oestrogen are mediated by the oestrogen receptor α or β (ERα or ERβ), which are members of a broad nuclear receptor superfamily. Numerous in vivo and in vitro studies have demonstrated that loss of circulating oestrogen modulated by classical ERα and ERβ led to rapid changes in pancreatic β-cell and islet function, GLUT4 expression, insulin sensitivity and glucose tolerance, dysfunctional lipid homeostasis, oxidative stress, and inflammatory cascades. Remarkably, 17β-oestradiol (E2) can completely reverse these effects. This review evaluates the current understanding of the protective role of classical ER in critical pathways and molecular mechanisms associated with insulin resistance and type 2 diabetes mellitus (T2DM). It also examines the effectiveness of menopausal hormone therapy (MHT) in reducing the risk of developing T2DM in menopausal women. Clinical trials have shown the protective effects of MHT on glucose metabolism, which may be useful to treat T2DM in perimenopausal women. However, there are concerns about E2's potential side effects of obesity and hyperlipidaemia in menopausal women. Further studies are warranted to gain understanding and find other oestrogen alternatives for treatment of insulin resistance and T2DM in postmenopausal women.

Introduction: Microneedle patch is one of the fascinating drug delivery approaches that offers low invasiveness and a painless physical application to enhance the delivery of micro and macro-molecules into the skin.

Methods: Variable contents of chitosan and polyvinyl alcohol were used for the development of doxazosin mesylate containing sustained release microneedle patches via solvent casting technique. The prepared patches were evaluated for microscopic evaluation, mechanical strength, drug loading (%) and Fourier transform infrared spectroscopy (FTIR) etc. The skin penetration study was performed by using pig ear skin and results were captured through confocal microscopy. Ex-vivo release study and pharmacokinetic evaluation were also performed.

Results: Sharp needle tips with a height of 600µm and a base of 200µm were confirmed through microscopic examination. Optimized formulation (SRF-6) exhibited loading of 92.11% doxazosin mesylate with appreciable strength up to 1.94N force. Ex-vivo release studies revealed 87.24% release within 48 hours. Moreover, the pharmacokinetic parameters in case of optimized patch formulation (SRF-6) were markedly improved i.e. MRT (19.46 h), AUC (57.12 μg.h /mL), C_max (2.16 µg /mL), t_max (10.10 h) and t_1/2 (6.32 h) as compared to commercially available tablet. Biocompatibility of the developed patches was validated from skin irritation studies.

Conclusion: Results confirmed the successful fabrication of microneedle patch having sufficient strength and effective penetration ability into the skin to ensure controlled release of incorporated drug for the intended duration. It can be employed as an efficient carrier system for other therapeutics those are prone to bioavailability issues due to first pass effect after their oral administration.

Introduction: In tissue engineering, the interaction among three primary elements, namely cells, material scaffolds, and stimuli, plays a pivotal role in determining the fate of cells and the formation of new tissue. Understanding the characteristics of these components and their interplay through various methodologies can significantly enhance the efficiency of the designed tissue engineering system. In silico methods, such as molecular dynamics (MD) simulation, use mathematical calculations to investigate molecular properties and can overcome the limitations of laboratory methods in delivering adequate molecular-level information.

Methods: The studies that used molecular dynamics simulation, either alone or in combination with other techniques, have been reviewed in this paper.

Results: The review explores the use of molecular dynamics simulations in studying substrate formation mechanism and its optimization. It highlights MD simulations' role in predicting biomolecule binding strength, understanding substrate properties' impact on biological activity, and factors influencing cell attachment and proliferation. Despite limited studies, MD simulations are considered a reliable tool for identifying ideal substrates for cell proliferation. The review also touches on MD simulations' contribution to cell differentiation studies, emphasizing their role in designing engineered extracellular matrix for desired cell fates.

Conclusion: Molecular dynamics simulation as a non-laboratory tool has many capabilities in providing basic and practical information about the behavior of the molecular components of the cell as well as the interaction of the cell and its components with the surrounding environment. Using this information along with other information obtained from laboratory tools can ultimately lead to the advancement of tissue engineering through the development of more appropriate and efficient methods.

Introduction: Multimodal contrast agents play an important role in early diagnosis of diseases and monitoring the treatment outcomes by increasing the accuracy and clarity of images.

Methods: Herein, a one-step simple hydrothermal route is utilized to prepare the gadolinium-1,4 H₂BDC- metal-organic framework (Gd-BDC-MOF) nanoparticles decorated with gold nanoclusters. The physicochemical properties of bimetal nanostructures were evaluated, their safety and ability to enhance contrast in both CT and MR imaging were also examined.

Results: The spherical nano-sized Au decorated Gd bimetal nanostructures have an average diameter of 64 nm. The presence of both Au and Gd metals in the prepared nanostructure was confirmed using EDAX. The XRD pattern shows that, in the hydrothermal synthesis of two metals using a terephthalic acid linker, gold nanoclusters are decorated onto the gadolinium metal organic framework. The FTIR analysis confirmed the attachment of Gd to the carboxylate group of the organic linker. The bimetal nanostructure sample with a concentration of 40 mM showed similar X-ray attenuation to that of iodine at a concentration of 128 mM. At a magnetic field strength of 1.5 T, the longitudinal relaxivity value of the bimetal nanostructure was determined to be 13.635 mM^-1 s^-1. The MTT assay demonstrated the cytocompatibility and safety of the contrast agent synthesized for biomedical applications.

Conclusion: The fabricated bimetal nanostructure exhibits dose-dependent positive contrast enhancement in both MR and CT imaging techniques, making it a promising candidate for use as a contrast agent in medical applications.

Introduction: Probiotics are used to provide health benefits and can improve the immune response. They can also target cancer cells directly with anticancer effects through various mechanisms. In this study, Lactiplantibacillus plantarum (basonym: Lactobacillus plantarum) strain MCC 3016 and its postbiotic metabolites/cell free supernatant (CFS) were used against Cal27 oral cancer cells in vitro.

Methods: Standard assays were employed to investigate the effect of Lpb. plantarum on cell viability, proliferation, migration, and clonogenicity of Cal27 cells. The mechanism of action was assessed by measuring the levels of reactive oxygen species (ROS), interleukins (IL)-6 and IL-8, tumor necrosis factor-α (TNF-α), as well as the expression of Ki67, vascular endothelial growth factor (VEGF), p53 and caspase-3. Further, the effect of Lpb. plantarum and its CFS on the cytotoxicity of chemotherapy drug 5-fluorouracil (5-FU) was evaluated using cell viability assays.

Results: Cal27 cells treated with Lpb. plantarum and its CFS showed a significant decrease (P < 0.01) in cell viability, proliferation, migration, and clonogenicity, along with increased levels of ROS and induced apoptosis. It significantly reduced IL-6, IL-8, TNF-α, and VEGF levels and upregulated p53 and caspase-3 expression. The postbiotic metabolites also showed similar effects on Cal27 cells. Furthermore, the cytotoxic effect of 5-FU on Cal27 cells was enhanced by Lpb. plantarum and its CFS treatment.

Conclusion: Lpb. plantarum MCC 3016 and its postbiotic metabolites exhibited promising anticancer effects on oral cancer cells and improved drug efficacy, demonstrating their potential therapeutic value in oral cancer therapy.

Introduction: Schizophrenia involves cognitive deficits, including working memory impairments. Researches indicate tau protein abnormalities may contribute to cognitive dysfunction in schizophrenia. While transcranial direct current stimulation (tDCS) shows promise in improving cognitive function, its effects on tau protein and working memory in schizophrenia remain unclear.

Methods: Forty participants were randomly assigned to receive either tDCS or sham treatment in this randomized clinical trial. The tDCS group received anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 minutes, while the sham group received a placebo. Serum tau levels and working memory were assessed before and after using ELISA and the digit span task.

Results: The results showed that the tDCS group had a significantly higher increase in phosphorylated tau protein serum levels compared to the sham group (5.53 ± 3.67 vs. 1.49 ± 3.90, P < 0.05). There was no significant mean change difference in serum levels of total tau protein between the groups. Females displayed higher increase in both total tau (1.88 ± 0.66 vs. 1.43 ± 0.80, P = 0.664) and p-tau levels (4.92 ± 0.88 vs. 2.11 ± 0.64, P = 0.014). The tDCS group also showed significantly higher improvement in working memory than the sham group (P < 0.05). Correlations between tau changes and memory enhancements approached significance (r_{(total tau)} = 0.30; P = 0.051, r_(p-tau) = 0.27; P = 0.063).

Conclusion: These findings reveal the tDCS impact on tau markers, shedding light on the disorder's molecular pathways and sex influences. Enhanced memory, linked to tau changes, suggests its potential as a treatment indicator.

Chrysin, a natural phytochemical compound found in various plant sources, possesses diverse pharmacological benefits, including anticancer, antioxidant, antidiabetic, neuroprotective, cardioprotective, hepatoprotective, immunoregulatory, and anti-inflammatory properties. Despite its well-documented biological activities, chrysin's low water solubility and bioavailability hinder its clinical development. This review explores the application of nanocarriers as a strategic approach to overcome these challenges and enhance the delivery of chrysin. Nanocarriers, including polymer-based nanoparticles (NPs), lipid-based NPs, and inorganic nanocarriers, have shown promise in improving the solubility, bioavailability, and tumor-targeted delivery of chrysin. The paper discusses chrysin's anticancer effects on different types of human cancers, elucidating its impact on crucial signaling pathways involved in tumorigenesis. The review categorizes and analyzes various nanocarriers, providing insights into their structural properties and drug release profiles. Among the nanocarriers, polymer-based NPs, especially those utilizing PLGA, emerge as promising strategies for chrysin encapsulation, demonstrating improvements in drug release, stability, and bioavailability. Lipid-based NPs and inorganic nanocarriers also exhibit potential in enhancing chrysin delivery. The comprehensive insights provided contribute to a deeper understanding of chrysin's pharmacological properties and its potential clinical applications, offering valuable perspectives for future research and translation into clinical settings. The review underscores the importance of selecting suitable structures for chrysin encapsulation to enhance its physicochemical properties and anticancer effects, paving the way for innovative nanomedicine approaches in cancer therapy.

Introduction: This study aimed to investigate the feasibility of preparation of sustained-release chlorpheniramine maleate (CPM) pellets based on Compritol® as a lipid matrix and evaluation of the affecting factors on pellet properties.

Methods: Using the D-optimal experimental design, different pellet formulations containing various amounts of CPM, Compritol® and Avicel were prepared by the wet extrusion-spheronization method. Then the pellets were cured at 40, 65 and 90 °C for 4 and 8 h to study the effect of the thermal process. The physicomechanical properties of the pellets were investigated in terms of particle size distribution, pelletization yield, mechanical strength, aspect ratio and sphericity. To investigate the possible interaction of CPM and Compritol®, as well as to evaluate the morphology and surface characteristics of the pellets DSC and SEM were used, respectively. Also, to investigate the drug release rate from pellets the dissolution test was carried out and mean dissolution time (MDT) was calculated to compare different formulations.

Results: The results showed that the curing process up to 65 °C improves the strength of the pellets. However, increasing the curing temperature from 65 to 90 °C and also increasing the curing time from 4 to 8 h did not have a significant effect on the strength of the pellets but increased the drug release rate of pellets. Increasing the amount of the drug or decreasing Compritol® in the matrix of pellets leads to a larger particle size with greater mechanical strength. All formulations of the pellets had an aspect ratio and sphericity of about 1.1 and 0.9 respectively, which indicates the spherical shape of the pellets as shown by SEM. DSC thermograms indicate the reduction of the crystallinity or the change of the crystalline form of the drug to amorphous during the pelletization process.

Conclusion: The results revealed the feasibility of preparing lipid-based sustained-release matrix pellets using the wet extrusion-spheronization method. The optimal formulation in terms of physicomechanical properties and release rate was the formulation containing 8% CPM, 67% Compritol® and 25% Avicel, which were dried at 40 ° C for 4 h and released about 90% of the drug within 12 h.

Adaptive inflammation consists of multiple cellular changes and molecular reactions to protect host cells against several pathological conditions. Along with the activation of varied immune cells, the production and secretion of cytokines arrays can regulate the progression of inflammatory response in a paracrine manner. Among different molecular cascades, Toll-like receptors (TLRs) are activated in response to several pathological conditions and damage signals. It has been indicated that extracellular vesicles, especially exosomes (Exos) are key bioshuttles with specific cargoes and are involved in cell-to-cell communication. The role of Exos in the initiation, progression, and cession of inflammation has been previously addressed in terms of cytokine transmission. Whether and how the activation of TLRs can alter the Exo biogenesis and angiogenesis potential in immune cells and endothelial cells (ECs) remains to be elucidated. Here, the cross-talk between the TLRs, Exo biogenesis, and angiogenesis has been highlighted.

Introduction: In the modern era, the use of biomaterials in orthopaedics has revolutionised the healthcare sector. Traditionally, some non-biodegradable materials such as titanium and stainless steel are used as biomaterials. However, issues such as toxicity, poor tissue adhesion, and stress-shielding effect can occur with non-biodegradable materials for bone fracture fixation. Several biodegradable materials have been developed to resolve these issues but have not yet been appropriately industrialized for implant applications. These substances can be classified into metals, ceramics, and polymers, which can be blended to create composites that enhance biocompatibility and biomechanical characteristics.

Methods: This study began by contrasting the biocompatibility and mechanical compatibility among various alloys: biodegradable low entropy (BLE) alloys, biodegradable medium entropy (BME) alloys, biodegradable high entropy (BHE) alloys, and non-biodegradable medium entropy (NBME) alloys. Additionally, the design morphology of bio-implants like plates, screws, and others was inspected. Moreover, a meta-analysis was conducted to optimize the design of biomaterials, ensuring appropriate biocompatibility and degradation rate. A subsequent statistical analysis was executed to determine the optimal material concentration for bio-implant alloy creation.

Results: Initially, in this paper, the advantages of biodegradable materials over conventional non-biodegradable materials are discussed and bibliometric analysis is done to show recent research contributions in the field of biomedical implant application. Then compared biocompatibility and mechanical compatibility among BLE alloys, BME alloys, BHE alloys, NBME alloys. Furthermore, investigated the design morphology of bio-implants such as plates and screws. Also presented a meta-analysis for design optimization of biomaterials to meet suitable biocompatibility and biodegradation rates and presented a statistical analysis among them, which helps to select the appropriate material concentration for bio-implant alloy formation.

Conclusion: It was observed that in biodegradable materials, tensile strength is in the pattern of NBME > BHE > BME > BLE, and the degradation rate is in the pattern of BME > NBME > BHE > BLE. This study suggests that biodegradable materials (BLE and BME) are a much better choice than non-biodegradable materials in orthopaedic applications. It was also observed that a Biodegradable locking compression plate (BLCP) can provide the necessary strength and performance. Further, the systematic meta-analysis presented herein furnishes crucial data to researchers, guiding them in enhancing the efficiency of diverse biomaterials and optimizing their designs.