Biolmpacts
Volume:13 Issue: 2, Mar 2023

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.

 Immune checkpoint inhibitors (ICIs) have provided noteworthy benefits in multiple cancer patients. However, the efficacy of monotherapy of ICIs was very limited. In this study, we endeavored to explore whether losartan can modulate the solid tumor microenvironment (TME) and improve the therapeutic efficacy of anti-PD-L1 mAb in 4T1 mouse breast tumor model and the underlying mechanism.

 The tumor-bearing mice were treated with control agents, losartan, anti-PD-L1 mAb or the dual agents. The blood and tumor tissues were respectively used for ELISA and immunohistochemical analysis. CD8-depletion and lung metastatic experiments were performed.

 Compared to control group, losartan inhibited the expression of alpha-smooth muscle actin (α-SMA), deposition of collagen I in the tumor tissues. The concentration of transforming growth factor-β1 (TGF-β1) in the serum was low in the losartan treated group. Although losartan alone was ineffective, the combination of losartan and anti-PD-L1 mAb elicited dramatic antitumor effect. Immunohistochemical analysis revealed that there were more intra-tumoral infiltration of CD8+ T cells and increased granzyme B production in the combination therapy group. In addition, the size of spleen was smaller in the combination therapy group, compared to monotherapy. The CD8-depleting Abs abrogated the antitumor efficacy of losartan and anti-PD-L1 mAb in vivo. The combination of losartan and anti-PD-L1 mAb significantly inhibited 4T1 tumor cells lung metastatic in vivo.

 Our results indicated that losartan can modulate the tumor microenvironment, and improve the efficacy of anti-PD-L1 mAb.

 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.

 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.

 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).

 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.

 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.

 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.

 According to the results of the fluorescence quenching titrations, the quenching mechanism is static. The apparent binding constant value (KA = 4.26×103) showed that Fingolimod is a moderate HSA binder. The reduction of the KA 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.

 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.

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.

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.

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.

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.

 Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs).

 Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy.

 Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys.

 Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).

The approach for drug delivery has impressively developed with the emergence of nanosuspension, particularly the targeted nanoemulsions (NEs). It can potentially improve the bioavailability of drugs, enhancing their therapeutic efficiency. This study aims to examine the potential role of NE as a delivery system for the combination of docetaxel (DTX), a microtubule-targeting agent, and thymoquinone (TQ) in the treatment of human ductal carcinoma cells T47D.

NEs were synthesized by ultra-sonication and characterized physically by dynamic light scattering (DLS). A sulforhodamine B assay was performed to evaluate cytotoxicity, and a flow cytometry analysis for cell cycle, apoptosis, autophagy, and cancer stem cell evaluations. A quantitative polymerase chain reaction further assessed the epithelial-mesenchymal transition gene expirations of SNAIL-1, ZEB-1, and TWIST-1.

The optimal sizes of blank-NEs and NE-DTX+TQ were found at 117.3 ± 8 nm and 373 ± 6.8 nm, respectively. The synergistic effect of the NE-DTX+TQ formulation significantly inhibited the in vitro proliferation of T47D cells. It caused a significant increase in apoptosis, accompanied by the stimulation of autophagy. Moreover, this formulation arrested T47D cells at the G2/M phase, promoted the reduction of the breast cancer stem cell (BCSC) population, and repressed the expression of TWIST-1 and ZEB-1.

Co-delivery of NE-DTX+TQ may probably inhibit the proliferation of T47D via the induction of apoptosis and autophagy pathways and impede the migration by reducing the BCSC population and downregulating TWIST-1 expression to decrease the epithelial-to-mesenchymal transition (EMT) of breast cancer cells. Therefore, the study suggests the NE-DTX+TQ formula as a potential approach to inhibit breast cancer growth and metastasis.

In late December 2019, a sudden severe respiratory illness of unknown origin was reported in China. In early January 2020, the cause of COVID-19 infection was announced a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Examination of the SARS-CoV-2 genome sequence revealed a close resemblance to the previously reported SARS-CoV and coronavirus Middle East respiratory syndrome (MERS-CoV). However, initial testing of drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. One of the key strategies to fight the virus is to look at how the immune system works against the virus, which has led to a better understanding of the disease and the development of new therapies and vaccine designs.

This review discussed the innate and acquired immune system responses and how immune cells function against the virus to shed light on the human body's defense strategies.

Although immune responses have been revealed critical to eradicating infections caused by coronaviruses, dysregulated immune responses can lead to immune pathologies thoroughly investigated. Also, the benefit of mesenchymal stem cells, NK cells, Treg cells, specific T cells, and platelet lysates have been submitted as promising solutions to prevent the effects of infection in patients with COVID-19.

It has been concluded that none of the above has undoubtedly been approved for the treatment or prevention of COVID-19, but clinical trials are underway better to understand the efficacy and safety of these cellular therapies.