Bioimpacts最新文献

Induced autoimmunity or autoinflammatory-like conditions as a rare vaccine-related adverse event have been reported following COVID-19 vaccination. Such inadvertent adverse reactions have raised somewhat concerns about the long-term safety of the developed vaccines. Such multifactorial phenomena may be related to the cross-reactivity between the viral-specific antigens with the host self-proteins through molecular mimicry mechanism and/or nonspecific bystander activation of the non-target antigen-independent immunity by the entities of the vaccine products. However, due to the low incidence of the reported/identified individuals and insufficient evidence, autoimmunity following the COVID-19 vaccination has not been approved. Thereby, it seems that further designated studies might warrant post-monitoring of the inevitable adverse immunologic reactions in the vaccinated individuals, especially among hypersensitive cases, to address possible immunological mechanisms induced by the viral vaccines, incorporated adjuvants, and even vaccine delivery systems.

Introduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. Methods: The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. Results: The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. Conclusion: The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines.

Introduction: Premature ovarian insufficiency (POI) is a challenging issue in terms of reproduction biology. In this study, therapeutic properties of bone marrow CD146⁺ mesenchymal stem cells (MSCs) and CD144⁺ endothelial cells (ECs) were separately investigated in rats with POI.

Methods: POI rats were classified into control POI, POI + CD146⁺ MSCs, and POI + CD144⁺ ECs groups. Enriched CD146⁺ MSCs and CD144⁺ ECs were directly injected into ovarian tissue (15 × 10⁴ cells/10 μL) in relevant groups. After 4 weeks, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were measured in blood samples. Ovarian tissues were collected and subjected to Hematoxylin-Eosin and Masson's trichrome staining. The expression of angp-2, vegfr-2, smad-2, -4, -6, and tgf-β1 was studied using qRT-PCR analysis. Histopathological examination indicated an increased pattern of atretic follicles in the POI group related to the control rats (P<0.0001).

Results: Data indicated that injection of POI + CD146⁺ MSCs and CD144⁺ ECs in POI rats reduced atretic follicles and increased the number of normal follicles (P<0.01). Along with these changes, the content of blue-colored collagen fibers was diminished after cell transplantation. Besides, cell transplantation in POI rats had the potential to reduce increased FSH, and LH levels (P<0.05). In contrast, E2 content was increased in POI + CD146⁺ MSCs and POI + CD144⁺ ECs groups compared to control POI rats, indicating restoration of follicular function. CD144⁺ (smad-2, and -4) and CD146⁺ (smad-6) cells altered the activity of genes belonging TGF-β signaling pathway. Unlike POI + CD146⁺ MSCs, aberrant angiogenesis properties were significantly down-regulated in POI + CD144⁺ ECs related to the control POI group (P<0.05).

Conclusion: The transplantation of bone marrow CD146⁺ and CD144⁺ cells can lead to the restoration of ovarian tissue function in POI rats via modulating different mechanisms associated with angiogenesis and fibrosis.

The molecular marker, cardiac troponin (cTn) is a complex protein that is attached to tropomyosin on the actin filament. It is an essential biomolecule in terms of the calcium-mediated regulation of the contractile apparatus in myofibrils, the release of which is an indication of the dysfunction of cardiomyocytes and hence the initiation of ischemic phenomena in the heart tissue. Fast and accurate analysis of cTn may help the diagnosis and management of acute myocardial infarction (AMI), for which electrochemical biosensors and microfluidics devices can be of great benefit. This editorial aims to highlight the importance of cTn as vital biomarkers in AMI diagnosis.

Introduction: Chronic exposure to methamphetamine (Meth) results in permanent central nervous system damage and learning and memory dysfunction. This study aimed at investigating the therapeutic effects of bone marrow mesenchymal stem cells (BMMSCs) on cognitive impairments in Meth addicted rats and comparing intravenous (IV) delivery with intranasal (IN) delivery of BMMSCs. Methods: Adult Wistar rats were randomly divided into 6 groups; Control; Meth-addicted; IV-BMMSC (Meth administered and received IV BMMSCs); IN-BMMSC (Meth administered and received IN BMMSCs); IV-PBS (Meth administered and received IV Phosphate-buffered saline (PBS); IN-PBS (Meth administered and received IN PBS). BMMSCs were isolated, expanded in vitro, immunophenotyped, labeled, and administered to BMMSCs-treated groups (2 × 10⁶ cells). The therapeutic effect of BMMSCs was measured using Morris water maze and Shuttle Box. Moreover, relapse-reduction was evaluated by conditioning place preference after 2 weeks following BMMSCs administration. The expression of brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) in rat hippocampus was assessed using immunohistochemistry method. Results: Administration of BMMSCs caused a significant improvement in the learning and memory functions of Meth-addicted rats and reduced the relapse (P<0.01). In behavioral tests, comparison of IV and IN BMMSC-treated groups did not show any significant difference. Administration of BMMSCs improved the protein level of BDNF and GDNF in the hippocampus, as well as causing behavioral improvement (P<0.001). Conclusion: BMMSC administration might be a helpful and feasible method to treat Meth-induced brain injuries in rats and to reduce relapse. BMMSCs were significantly higher in IV-treated group compared to the IN route. Moreover, the expression of BDNF and GDNF was higher in IN-treated rats compared with IV treated group.

Introduction: Biocompatible and biodegradable scaffolds have gained tremendous attention because of their potential in tissue engineering. In this study, the aim was to reach a feasible setup from a ternary hybrid of polyaniline (PANI), gelatin (GEL), and polycaprolactone (PCL) to fabricate aligned and random nanofibrous scaffolds by electrospinning for tissue engineering purposes. Methods: Different setups of PANI, PCL, and GEL were electrospun. Then, the best aligned and random scaffolds were chosen. SEM imaging was done to observe nanoscaffolds before and after stem cell differentiation. Mechanical properties of the fibers were tested. Their hydrophilicity was measured using the sessile drop method. SNL Cells were then seeded onto the fiber, and MTT was performed to assess its toxicity. The cells were then differentiated. After osteogenic differentiation, alkaline phosphatase activity, calcium content assay, and alizarin red staining were done to check the validity of osteogenic differentiation. Results: The two chosen scaffolds had an average diameter of 300 ± 50 (random) and 200 ± 50 (aligned). MTT was performed and its results showed that the scaffolds were non-toxic to cells. After stem cell differentiation, alkaline phosphatase activity was performed, confirming differentiation on both types of scaffolds. Calcium content and alizarin red staining also confirmed stem cell differentiation. Morphological analysis showed no difference regarding differentiation on either type of scaffold. However, unlike on the random fibers, cells followed a specific direction and had a parallel-like growth pattern on aligned fibers. Conclusion: All in all, PCL-PANI-GEL fibers showed to be capable candidates for cell attachment and growth. Furthermore, they proved to be of excellent use in bone tissue differentiation.

Introduction: Fingolimod is a drug that is used to treat multiple sclerosis (MS). It has pH-dependent solubility and low solubility when buffering agents are present. Multi-spectroscopic and molecular modeling methods were used to investigate the molecular mechanism of Fingolimod interaction with human serum albumin (HSA), and the resulting data were fitted to the appropriate models to investigate the molecular mechanism of interaction, binding constant, and thermodynamic properties. Methods: The interaction of Fingolimod with HSA was investigated in a NaCl aqueous solution (0.1 mM). The working solutions had a pH of 6.5. Data was collected using UV-vis, fluorescence quenching titrations, FTIR, and molecular modeling methods. Results: According to the results of the fluorescence quenching titrations, the quenching mechanism is static. The apparent binding constant value (K_A = 4.26×10³) showed that Fingolimod is a moderate HSA binder. The reduction of the K_A at higher temperatures could be a result of protein unfolding. Hydrogen bonding and van der Waals interactions are the main contributors to Fingolimod-HSA complex formation. FTIR and CD characterizations suggested a slight decrease in the α-helix and β-sheets of the secondary structure of HSA due to Fingolimod binding. Fingolimod binds to the binding site II, while a smaller tendency to the binding site I was observed as well. The results of the site marker competitive experiment and the thermodynamic studies agreed with the results of the molecular docking. Conclusion: The pharmacokinetic properties of fingolimod can be influenced by its HSA binding. In addition, considering its mild interaction, site II binding drugs are likely to compete. The methodology described here may be used to investigate the molecular mechanism of HSA interaction with lipid-like drugs with low aqueous solubility or pH-dependent solubility.

Introduction: The present study was done to assess the effect of molecularly-targeted core/shell of iron oxide/gold nanoparticles (Fe₃O₄@AuNPs) on tumor radiosensitization of SKBr-3 breast cancer cells. Methods: Human epidermal growth factor receptor-2 (HER-2)-targeted Fe₃O₄@AuNPs were synthesized by conjugating trastuzumab (TZ, Herceptin) to PEGylated (PEG)-Fe₃O₄@AuNPs (41.5 nm). First, the Fe₃O₄@Au core-shell NPs were decorated with PEG-SH to synthesize PEG-Fe₃O₄@AuNPs. Then, the TZ was reacted to OPSS-PEG-SVA to conjugate with the PEG-Fe₃O₄@AuNPs. As a result, structure, size and morphology of the developed NPs were assessed using Fourier-transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy. The SKBr-3 cells were treated with different concentrations of TZ, Fe₃O₄@Au_, and TZ-PEG-Fe₃O₄@AuNPs for irradiation at doses of 2, 4, and 8 Gy (from X-ray energy of 6 and 18 MV). Cytotoxicity was assessed by MTT assay, BrdU assay, and flow cytometry. Results: Results showed that the targeted TZ-PEG-Fe₃O₄@AuNPs significantly improved cell uptake. The cytotoxic effects of all the studied groups were increased in a higher concentration, radiation dose and energy-dependent manner. A combination of TZ, Fe₃O₄@Au, and TZ-PEG-Fe₃O₄@AuNPs with radiation reduced cell viability by 1.35 (P=0.021), 1.95 (P=0.024), and 1.15 (P=0.013) in comparison with 8 Gy dose of 18 MV radiation alone, respectively. These amounts were obtained as 1.27, 1.58, and 1.10 for 8 Gy dose of 6 MV irradiation, respectively. Conclusion: Radiosensitization of breast cancer to mega-voltage radiation therapy with TZ-PEG-Fe₃O₄@AuNPs was successfully obtained through an optimized therapeutic approach for molecular targeting of HER-2.

Introduction: Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model.

Methods: Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.

Results: The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.

Conclusion: Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.