Bioimpacts最新文献

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.

Introduction: Peptides from lactic acid bacteria provide health benefits and can inhibit the growth of pathogenic organisms. The present work aimed to isolate and characterize peptides with antibacterial activity from Lactobacillus plantarum 1407.

Methods: Peptides were isolated and purified from L. plantarum 1407. The effect of various physiological parameters on the antibacterial activity of the isolated peptides was analyzed. The mode of action of the peptides on indicator organisms was observed using transmission microscopy analysis and flow cytometry analysis.

Results: Antibacterial activity and mode of action of peptides isolated from L. plantarum 1407 against gram-positive and gram-negative bacteria have been studied. L. plantarum culture exhibited maximum antibacterial activity at 40 °C, pH 8, and 0.7% salt concentration. The cell-free supernatant (CFS) was concentrated using a 3 kDa ultrafiltration membrane and the peptide fractions (<3 kDa) were further fractionated using Sephadex G-25 gel filtration chromatography. The antibacterial activity of the eluted fractions (F1 to F4) was evaluated using flow cytometry and transmission electron microscopy. F3 fraction exhibited increased antibacterial activity than F1, F2, and F4 fractions against the indicator organisms. Cell membrane damage and leakage of cytoplasmic content of the bacterial cells treated with the antibacterial F3 fraction peptides were observed.

Conclusion: The active peptides from L. plantarum 1407 can be potentially used for the treatment of bacterial infections.

Cell culture-based technologies are widely utilized in various domains such as drug evaluation, toxicity assessment, vaccine and biopharmaceutical development, reproductive technology, and regenerative medicine. It has been demonstrated that pre-adsorption of extracellular matrix (ECM) proteins including collagen, laminin and fibronectin provide more degrees of support for cell adhesion. The purpose of cell imprinting is to imitate the natural topography of cell membranes by gels or polymers to create a reliable environment for the regulation of cell function. The results of recent studies show that cell imprinting is a tool to guide the behavior of cultured cells by controlling their adhesive interactions with surfaces. Therefore, in this review we aim to compare different cell cultures with the imprinting method and discuss different cell imprinting applications in regenerative medicine, personalized medicine, disease modeling, and cell therapy.

Cancer is one of the leading causes of death worldwide and one of the greatest challenges in extending life expectancy. The paradigm of one-size-fits-all medicine has already given way to the stratification of patients by disease subtypes, clinical characteristics, and biomarkers (stratified medicine). The introduction of next-generation sequencing (NGS) in clinical oncology has made it possible to tailor cancer patient therapy to their molecular profiles. NGS is expected to lead the transition to precision medicine (PM), where the right therapeutic approach is chosen for each patient based on their characteristics and mutations. Here, we highlight how the NGS technology facilitates cancer treatment. In this regard, first, precision medicine and NGS technology are reviewed, and then, the NGS revolution in precision medicine is described. In the sequel, the role of NGS in oncology and the existing limitations are discussed. The available databases and bioinformatics tools and online servers used in NGS data analysis are also reviewed. The review ends with concluding remarks.

Introduction: In this perspective review, we evaluated the clinical management of fatal fentanyl overdose in several routes of administration, concentrating on both legally prescribed and illegally produced formulations.

Methods: A literature search was conducted on Web of Science, PubMed, and Google Scholar databases, using the following keywords: fentanyl, illicit fentanyl, deaths, misuse, abuse, and naloxone. We included only articles whose abstracts were available in English. All articles were screened using their abstracts to determine their relevance to the current review.

Results: The gold standard for treating both acute and chronic pain is fentanyl, but abuse of the drug has exploded globally since the late 2000s. Fentanyl abuse has been shown to frequently result in serious harm and even death.

Conclusion: By educating patients and physicians, making rescue kits easily accessible, developing vaccines to prevent opioid addiction, and perhaps even creating new tamper-resistant fentanyl formulations, it may be possible to prevent fentanyl misuse, therapeutic errors, and the repercussions that follow.

Introduction: Pyridopyrimidines belong to a class of compounds characterized by the presence of nitrogen as heteroatoms. These compounds exhibit diverse biological effects, particularly showing promise as anticancer agents, including actions that inhibit CDK4/6.

Methods: We designed and synthesized a range of substituted thiazolo-pyridopyrimidines (4a-p). Computational ADME/T analysis and molecular docking were performed using the crystal structure of CDK4/6. Subsequently, we synthesized the top-scoring compounds, characterized them using IR, NMR, and Mass spectroscopy, and assessed their impact on MCF-7 and MDAMB-231 cell lines using the SRB assay. To further evaluate stability, molecular dynamics simulations were conducted for the two most promising compounds within the binding site.

Results: The docking scores indicated stronger interactions for compounds 4a, 4c, 4d, and 4g. As a result, these specific compounds (4a, 4c, 4d, and 4g) were chosen for synthesis and subsequent screening to assess their cytotoxic effects. Remarkably, compounds 4c and 4a exhibited the most promising activity in terms of their IC₅₀ values across both tested cell lines. Furthermore, molecular dynamics simulation studies uncovered an elevated level of stability within the 4c-6OQO complex.

Conclusion: By integrating insights from computational, in vitro, and molecular dynamics simulation findings, compound 4c emerges as a leading candidate for future investigations. The presence of a polar hydroxyl group at the C2 position of the 8-phenyl substitution on the pyridopyrimidine rings appears to contribute to the heightened activity of the compound. Further enhancements to cytotoxic potential could be achieved through structural refinements.

Introduction: Imidazo[1,2-a]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-a]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines.

Methods: We evaluated the interaction between imidazo[1,2-a]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways.

Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA.

Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines.

Introduction: Natural biopolymers are used for various purposes in healthcare, such as tissue engineering, drug delivery, and wound healing. Bacterial cellulose and chitosan were preferred in this study due to their non-cytotoxic, biodegradable, biocompatible, and non-inflammatory properties. The study reports the development of a magnetic bacterial cellulose-chitosan (BC-CS-Fe₃O₄) nanocomposite that can be used as a biocompatible scaffold for tissue engineering. Iron oxide nanoparticles were included in the composite to provide superparamagnetic properties that are useful in a variety of applications, including osteogenic differentiation, magnetic imaging, drug delivery, and thermal induction for cancer treatment.

Methods: The magnetic nanocomposite was prepared by immersing Fe₃O₄ in a mixture of bacterial cellulose-chitosan scaffold and then freeze-drying it. The resulting nanocomposite was characterized using FE-SEM and FTIR techniques. The swelling ratio and mechanical strength of the scaffolds were evaluated experimentally. The biodegradability of the scaffolds was assessed using PBS for 8 weeks at 37°C. The cytotoxicity and osteogenic differentiation of the nanocomposite were studied using human adipose-derived mesenchymal stem cells (ADSCs) and alizarin red staining. One-way ANOVA with Tukey's multiple comparisons test was used for statistical analysis.

Results: The FTIR spectra demonstrated the formation of bonds between functional groups of nanoparticles. FE-SEM images showed the integrity of the fibrillar network. The magnetic nanocomposite has the highest swelling ratio (2445% ± 23.34) and tensile strength (5.08 MPa). After 8 weeks, the biodegradation ratios of BC, BC-CS, and BC-CS-Fe₃O₄ scaffolds were 0.75% ± 0.35, 2.5% ± 0.1, and 9.5% ± 0.7, respectively. Magnetic nanocomposites have low toxicity (P < 0.0001) and higher osteogenic potential compared to other scaffolds.

Conclusion: Based on its high tensile strength, low water absorption, suitable degradability, low cytotoxicity, and high ability to induce an increase in calcium deposits by stem cells, the magnetic BC-CS-Fe₃O₄ nanocomposite scaffold can be a suitable candidate as a biomaterial for osteogenic differentiation.

Introduction: Botulinum neurotoxins (BoNTs) cause botulism and are the most potent natural toxins known. Immunotherapy with neutralizing monoclonal antibodies (MAbs) is considered to be the most effective immediate response to BoNT exposure. Hybridoma technology remains the preferred method for producing MAbs with naturally paired immunoglobulin genes and with preserved innate functions of immune cells. The affinity-matured human antibody repertoire may be ideal as a source for antibody therapeutics against BoNTs. In an effort to develop novel BoNT type A (BoNT/A) immunotherapeutics, sorted by flow cytometry plasmablasts and activated memory B cells from a donor repeatedly injected with BoNT/A for aesthetic botulinum therapy could be used due to obtain hybridomas producing native antibodies.

Methods: Plasmablasts and activated memory B-cells were isolated from whole blood collected 7 days after BoNT/A injection and sorted by flow cytometry. The sorted cells were then electrofused with the K6H6/B5 cell line, resulting in a producer of native human monoclonal antibodies (huMAbs). The 3 antibodies obtained were then purified by affinity chromatography, analyzed for binding by Western blot assay and neutralization by FRET assay.

Results: We have succeeded in creating 3 hybridomas that secrete huMAbs specific to native BoNT/A and the proteolytic domain (LC) of BoNT/A. The 1B9 antibody also directly inhibited BoNT/A catalytic activity in vitro.

Conclusion: The use activated plasmablasts and memory B-cells isolated at the peak of the immune response (at day 7 of immunogenesis) that have not yet completed the terminal stage of differentiation but have undergone somatic hypermutation for hybridization allows us to obtain specific huMAbs even when the immune response of the donor is weak (with low levels of specific antibodies and specific B-cells in blood). A BoNT/A LC-specific antibody is capable of effectively inhibiting BoNT/A by mechanisms not previously associated with antibodies that neutralize BoNT. Antibodies specific to BoNT LC can be valuable components of a mixture of antibodies against BoNT exposure.

COVID-19 is an RNA virus belonging to the SARS family of viruses and includes a wide range of symptoms along with effects on other body organs in addition to the respiratory system. The high speed of transmission, severe complications, and high death rate caused scientists to focus on this disease. Today, many different investigation types are performed on COVID-19 from various points of view in the literature. This review summarizes most of them to provide a useful guideline for researchers in this field. After a general introduction, this review is divided into three parts. In the first one, various transmission ways COVID-19 are classified and explained in detail. The second part reviews the used biological samples for the detection of virus and the final section describes the various methods reported for the diagnosis of COVID-19 in various biological matrices.