Bioimpacts最新文献

Introduction: Signal transducer and activator of transcriptions (STATs) factors as critical proteins in cell signaling regulate diverse biological processes such as differentiation and proliferation of cells. STATs have been shown to play distinct roles in modulating immune responses mediated by innate and adaptive immune cell subsets due to their significant roles in cytokine signaling.

Methods: In the current study, we review recent studies on the contribution of individual STAT proteins to cytokine signaling, development, and activity of diverse immune cells that constitute the whole immune system and help its performance against endogenous or exogenous agents with a particular focus on meaningful STAT factor in each of innate and adaptive immune cells' subsets to clarify their function in favor of the tumor or against it.

Results: Dysregulation of signaling pathways in the immune cells is associated with various immune disorders, such as the inability of immune system cells in the effective destruction of cancerous cells. Increase of knowledge about these pathways' functions is essential to understand how they can be effectively targeted to eliminate tumors.

Conclusion: The majority of immune cells use the Jak/STAT signaling pathway, which is one of the most important signaling pathways with a role in induction of proper immune responses. Since each of the STAT factors has a specific role in diverse immune cells' subsets, appropriate targeting of them can be a promising strategy for patients who suffer from immune system disorders; specifically it can be beneficial as an approach for cancer immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) stands as the fourth leading cause of cancer-related deaths, primarily attributable to its resistance to chemotherapy, resulting in a nearly universal fatality rate. Despite the promise exhibited by numerous drugs in preclinical studies, their subsequent failure in clinical trials underscores the inherent limitations of conventional two-dimensional cell culture models commonly employed in early drug screening endeavors. The inadequacies of two-dimensional (2D) models prompted the exploration of three-dimensional (3D) culture systems, which more faithfully recapitulate the native tumor microenvironment. These 3D systems have distinct advantages over 2D models in morphology, proliferation, drug response, and protein expression. Among these 3D platforms, tumor organoids and spheroids, generated through different methodologies, have emerged as next-generation models that closely mirror aspects of pancreatic tumor biology. This comprehensive review scrutinizes pancreatic cancer spheroids' techniques, tissue sources, and applications, offering a nuanced analysis of their advantages and limitations. By comparing these distinct 3D culture systems, researchers gain valuable insights to inform the selection of optimal model designs aligned with their specific experimental objectives. The utilization of these advanced models holds significant promise for enhancing the clinical relevance of both in vitro and in vivo cancer research, thereby contributing to the development of improved therapeutics against pancreatic cancer.

Introduction: Fatty acid binding protein 5 (FABP5) exhibits heightened expression levels in triple-negative breast cancer. The inhibitor of FABP5, Stony Brook fatty acid-binding protein inhibitor 26 (SBFI-26), has demonstrated the capacity to suppress cell proliferation, migration, and invasion. This study delves into the functional mechanism and impact of combining SBFI-26 with docetaxel in treating MDA-MB-231 cells of triple-negative breast cancer.

Methods: Various concentrations of docetaxel and SBFI-26 were chosen for individual or combined treatments. The effects of SBFI-26, docetaxel, or their combination on cell cycle arrest and apoptosis were assessed using flow cytometry. Western blotting was utilised to detect the expression of apoptosis-related proteins, namely cysteinyl aspartate-specific proteases 3 (Caspase3), B cell leukemia/lymphoma 2 (Bcl-2), and Bcl-2 associated X (Bax), while intracellular reactive oxygen species (ROS) levels were determined using a fluorescence spectrophotometer.

Results: The IC50 values for SBFI-26 and docetaxel in inhibiting MDA-MB-231 cells were determined to be 106.1 μM and 86.14 nM, respectively. Significantly, the combination treatment augmented the proportion of G1 phase (apoptotic) cells by 3.67-fold compared to the control group (P < 0.0001). Furthermore, the apoptosis rate in the combination group was 2.59-fold higher than that in the docetaxel group (P < 0.0001) and demonstrated a significant increase of 1.82-fold compared with the SBFI-26 group (P < 0.001). Analyses revealed a decrease in the protein expression of Bcl-2, while Bax and Caspase3 exhibited an increase in the combination group for MDA-MB-231 cells. Moreover, the combined treatment group demonstrated a 2.97-fold increase (P < 0.0001) in ROS fluorescence intensity compared to the control group, a noteworthy 1.39-fold increase (P < 0.01) compared to the SBFI-26 treatment group, and a substantial 1.70-fold increase (P < 0.0001) compared to the docetaxel treatment group.

Conclusion: These findings suggest that the co-administration of SBFI-26 with docetaxel effectively enhances apoptosis in triple-negative breast cancer MDA-MB-231 cells by elevating intracellular ROS levels.

Introduction: To date, different strategies have been used for co-transplantation of cell-loaded biomaterials for bone tissue regeneration. This study aimed to investigate the osteogenic properties of adipose-derived-mesenchymal stem cell (AD-MSC) sheets combined with nanofibrous poly-caprolactone (PCL) mat and Gelfoam in rats with calvarial bone defect.

Methods: Calvarial critical-size defects were induced in male rats. Animals were classified into Control, Gelfoam, Gelfoam/PCL nanofiber, Gelfoam/AD-MSC sheet, and Gelfoam/PCL nanofiber/AD-MSC sheet groups. After 3 months, rats were sacrificed and the regeneration rate was evaluated.

Results: Almost all groups showed bone regeneration properties, but the volume of newly formed bone was higher in groups that received Gelfoam/AD-MSC and Gelfoam/PCL nanofiber/AD-MSC sheets (P < 0.05). The application of Gelfoam/PCL nanofiber/AD-MSC sheets not only increased bone thickness, bone volume/total bone volume (BV/TV) ratio, strong Hounsfield Unit (HU), but also led to the formation of ossified connective tissue with wrinkled patterns.

Conclusion: The current study indicated that the Gelfoam/PCL nanofiber/AD-MSC sheet provides a suitable platform for effective osteogenesis in calvarial bone defects.

Introduction: Peptides are promising and attractive anti-wrinkle active ingredients, amongst which glycyl-histidyl-lysine peptide (GHK) is one of the most broadly promoted peptide for topical application. This simple sequence of amino acid residues not only has the capability of tissue regeneration and the enhancement of collagen and glycosaminoglycans synthesis but also is able to increase nerve outgrowth and angiogenesis. Consequently, GHK has several properties, from wound healing to prevention/reduction wrinkles. GHK-Cu and Pal-GHK are metal complex and palmitoylated derivatives of GHK, respectively. Although GHK-Cu and Pal-GHK are widely used in anti-wrinkle products available on the cosmetic market, the published information on their skin permeability, effectiveness, physicochemical properties and so on is insufficient.

Methods: This review aims to highlight whether GHK is sufficiently effective on wrinkle prevention/reduction. Apart from the effectiveness, another question that is tried to be answered is whether skin permeability of GHK allows it to act as an anti-wrinkle peptide at its site of action? Skin permeation enhancement methods employed so far are also reviewed.

Results: Based on cellular studies, undoubtedly, GHK can be considered as an anti-wrinkle ingredient. Although GHK-Cu and Pal-GHK have been of interest as effective peptides to be incorporated in the anti-wrinkle products, there is a surprising absence of clinical studies using them. Metal complexation and chemical modification with a hydrophobic moiety increase permeability of this peptide. Besides, cell penetrating peptides seem promising to increase skin permeation of GHK and its derivatives. Skin pretreatment with microneedles also has the potential to be further studied for permeation enhancement of such peptides. As peptide ingredients, their formulation may encounter some challenges, mainly due to their hydrophilic (high aqueous solubility and low partition coefficient) and unstable nature.

Conclusion: Although GHK-Cu and Pal-GHK are effective and relatively skin permeable, their permeability could be successfully increased using permeation enhancement methodologies.

Introduction: Presently, the development of effective vaccines against SARS-CoV-2 is absolutely necessary, especially regarding the emergence of new variants that cause increasing morbidity and fatalities.

Methods: In the present study we designed a mosaic vaccine targeting the mutational spike protein of COVID-19 using a bioinformatics approach. Various immunoinformatics tools were utilized to provide the highest potential for a mosaic vaccine that could activate immune responses against COVID-19.

Results: The evaluation of the constructed vaccine revealed that it is antigenic and immunogenic as well as nonallergenic. The physicochemical properties also show promising characteristics, including being highly stable and hydrophilic. As expected, the vaccine shows strong interactions with several important receptors including angiotensin-converting enzyme 2 (ACE2), Toll-like receptor 3 (TLR3) and TLR8 by the lowest energy level, docking score and binding free energy. The vaccine binds to receptors via certain amino acids using various types of binding including salt bridges, hydrogen bonds, and other means. As shown in computationally derived models, the interactions promote activation of the immune response by eliciting the release of various cytokines, antibodies, memory B and T cells, as well as increasing of natural killer cell and dendrite cell counts.

Conclusion: Therefore, the novel designed mosaic vaccine could be considered as a potential vaccine candidate for immediate production to stem the continuing and tragic effects of the COVID-19 pandemic. However, several advanced experimental studies should be conducted to ensure and verify the effectivity and safety against SARS‑CoV‑2 in vivo.

Glaucoma is a serious eye disease characterized by elevated intraocular pressure, which can ultimately lead to blindness, making it the second leading cause of blindness worldwide, following cataracts. The condition is associated with various risk factors and primarily affects the optic nerve. To treat glaucoma, a range of approaches, both traditional and innovative, have been employed. Recently, there has been a significant focus on nanoemulsions as a promising avenue for treatment. This review underscores the advantages of using oil-in-water nanoemulsions for ocular drug delivery, showcasing their superiority in terms of enhanced bioavailability and stability compared with other dispersion systems. This review also delves into the limitations inherent in traditional drug formulations, elucidates the mechanisms governing drug release, explores the pivotal role of surfactants, and examines the landscape of granted patents in this domain. By addressing these critical aspects, the review offers invaluable insights into the treatment of glaucoma, shedding light on innovative approaches that hold great promise in the fight against this debilitating eye condition. During our search, it was noticed that despite the existence of commendable research in the field of ocular nanoemulsions, particularly in the context of glaucoma along with granted patents, the commercialized nanoemulsion formulations for glaucoma is not yet exist.

University rankings offer some benefits but also come with significant drawbacks. While they can encourage healthy competition, they often lead to unethical practices and prioritize short- term gains over long-term educational purposes. Relying on biased metrics like citations and journal impact factors is a major flaw, potentially misrepresenting the true value of scholarly work. The foremost focus of universities should be on educating proficient students, advancing dependable knowledge, and addressing societal needs. Annual rankings based on one year's criteria and output prove impractical, as research outcomes and educational impact require more time to materialize. It is crucial to consider abandoning or reevaluating ranking systems to prevent biased, financially-driven approaches from causing harm. An internal assessment, gauging satisfaction levels within the university community and the quality of education provided, could offer a more effective approach to ranking universities. Acknowledging the negative impact of journal rankings took decades. It is imperative to avoid subjecting educational systems to similarly detrimental effects from university rankings. The most effective method for ranking universities is through an internal system that takes into account the satisfaction levels of university community members regarding their work conditions and overall institution, as well as whether students are acquiring the education and skills they seek.

Introduction: Pro-inflammatory responses have an important role in developing coronavirus disease 2019 (COVID-19). L-carnitine (LC) has been known to possess anti-inflammatory, anticoagulant, and antiviral effects. So, we aimed to evaluate the efficacy of LC in hospitalized patients with moderate-to-severe COVID-19.

Methods: This double-blind, placebo-controlled, randomized clinical trial was conducted on hospitalized patients with moderate to severe COVID-19. The patients were randomized (1:1) to receive LC (n = 50) at a dose of 20 mg/kg or matching placebo (n = 51) from normal saline once daily for 14 days or until hospitalization and standard care. The primary outcome was hospital mortality and disease severity according to the World Health Organization's clinical progression scale. We also assessed the free carnitine level at baseline and the end of the study. C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), and improvement of respiratory conditions were chosen as secondary outcomes.

Results: From 104 patients who met the inclusion criteria, 101 individuals' data were analyzed. The LC group showed a significant reduction in LDH levels (P = 0.003), although CRP, ferritin, and D-dimer levels did not significantly differ from the placebo group. Also, no significant difference was observed in disease severity, oxygenation status, hospital mortality, or hospital stay between the two groups. Additionally, there was no increase in serum-free carnitine levels in the LC group (P > 0.05 for all).

Conclusion: The results of the current study did not support the superiority of LC over placebo in improving oxygenation, decreasing mortality, and hospital stay, as well as CRP, ferritin, and D-dimer in moderate to severe COVID-19 patients.

Trial registration: IRCT20170609034406N10; https://en.irct.ir/trial/60306.

Introduction: The discovery of gene editing techniques has opened a new era within the field of biology and enabled scientists to manipulate nucleic acid molecules. CRISPR-Cas9 genome engineering has revolutionized this achievement by successful targeting the DNA molecule and editing its sequence. Since genomic changes are the basis of the birth and growth of many tumors, CRISPR-Cas9 method has been successfully applied to identify and manipulate the genes which are involved in initiating and driving some neoplastic processes.

Methods: By review of the existing literature on application of CRISPR-Cas9 in cancer, different databases, such as PubMed and Google Scholar, we started data collection for "CRISPR-Cas9", "Genome Editing", "Cancer", "Solid tumors", "Hematologic malignancy" "Immunotherapy", "Diagnosis", "Drug resistance" phrases. Clinicaltrials.gov, a resource that provides access to information on clinical trials, was also searched in this review.

Results: We have defined the basics of this technology and then mentioned some clinical and preclinical studies using this technology in the treatment of a variety of solid tumors as well as hematologic neoplasms. Finally, we described the progress made by this technology in boosting immune-mediated cell therapy in oncology, such as CAR-T cells, CAR-NK cells, and CAR-M cells.

Conclusion: CRISPR-Cas9 system revolutionized the therapeutic strategies in some solid malignant tumors and leukemia through targeting the key genes involved in the pathogenesis of these cancers.