yadollah omidi

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.

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.

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.

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.

 Atherosclerosis is a complicated cascade of inflammatory processes, oxidative stress, and apoptosis, making it the most prevalent cardiovascular disease. The onset and progression of cardiovascular diseases are greatly influenced by oxidative stress. Targeting oxidative stress is an effective strategy for treating such diseases. Marrubiin is a bioactive furan labdane diterpenoid acts as a strong antioxidant to protect against oxidative damage. This study aimed to investigate the protective effects of marrubiin against oxidative stress and apoptosis in a cellular model of the vascular system.

 Human umbilical vein endothelial cells were treated with varying concentration of marrubiin and its IC50 value was determined. The antioxidant potential of marrubiin was assessed by measuring the intracellular level of glutathione (GSH) using a colorimetric technique. Since apoptosis plays a significant role in the plaque rupture, the study also evaluated the protective effects of marrubiin on the expression of key genes involved in apoptotic pathways.

 Cells treated with marrubiin showed increased GSH levels compared to cell therapy control cells, indicating marrubiin’s ability to counteract the effects of TNF-α’s on GSH levels. Furthermore real-time PCR analysis demonstrated that marrubiin upregulated Bcl-xl while downregulating caspase3 and Nox4 in treated cells. These findings suggest that marrubiin protects against apoptosis and oxidative stress.

 Based on our findings, marrubiin is recommended as a preventive/therapeutic treatment for diseases caused by elevated intracellular reactive oxygen species levels in cardiovascular diseases.

Epidermal growth factor receptor (EGFR) is a cell surface protein that plays a vital role in regulating cell growth and division. However, certain tumors, such as colorectal cancer (CRC), can exhibit an overexpression of EGFR, resulting in uncontrolled cell growth and tumor progression. To address this issue, therapies targeting and inhibiting EGFR activity have been developed to suppress cancer growth. Nevertheless, resistance to these therapies poses a significant obstacle in cancer treatment. Recent research has focused on comprehending the underlying mechanisms contributing to anti-EGFR resistance and identifying new targets to overcome this striking challenge. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. Emerging evidence suggests that lncRNAs may participate in modulating resistance to anti-EGFR therapies in CRC. Consequently, combining lncRNA targeting with the existing treatment modalities could potentially yield improved clinical outcomes. Illuminating the involvement of lncRNAs in anti-EGFR resistance mechanisms of cancer cells can provide valuable insights into the development of novel anti-EGFR therapies in several solid tumors.

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.

 Mesoporous silica nanoparticles (MSNPs) are considered innovative multifunctional structures for targeted drug delivery owing to their outstanding physicochemical characteristics.

 MSNPs were fabricated using the sol-gel method, and polyethylene glycol-600 (PEG600) was used for MSNPs modification. Subsequently, sunitinib (SUN) was loaded into the MSNPs, MSNP-PEG and MSNP-PEG/SUN were grafted with mucin 16 (MUC16) aptamers. The nanosystems (NSs) were characterized using FT-IR, TEM, SEM, DLS, XRD, BJH, and BET. Furthermore, the biological impacts of MSNPs were evaluated on the ovarian cancer cells by MTT assay and flow cytometry analysis.

 The results revealed that the MSNPs have a spherical shape with an average dimension, pore size, and surface area of 56.10 nm, 2.488 nm, and 148.08 m2g-1, respectively. The cell viability results showed higher toxicity of targeted MSNPs in MUC16 overexpressing OVCAR-3 cells as compared to the SK-OV-3 cells; that was further confirmed by the cellular uptake results. The cell cycle analysis exhibited that the induction of sub-G1 phase arrest mostly occurred in MSNP-PEG/SUN-MUC16 treated OVCAR-3 cells and MSNP-PEG/SUN treated SK-OV-3 cells. DAPI staining showed apoptosis induction upon exposure to targeted MSNP in MUC16 positive OVCAR-3 cells.

 According to our results, the engineered NSs could be considered an effective multifunctional targeted drug delivery platform for the mucin 16 overexpressing cells.

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.

 Biocompatible and biodegradable scaffolds based on natural polymers such as gelatin and chitosan (CS) provide suitable microenvironments in dental tissue engineering. In the present study, we report on the synthesis of injectable thermosensitive hydrogel (PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel) for osteogenic differentiation of human dental pulp stem cells (hDPSCs).

 The CS-g-PNIPAAm was synthesized using the reaction of carboxyl terminated PNIPAAm with CS, which was then mixed with various amounts of gelatin solution in the presence of genipin as a chemical crosslinker to gain a homogenous solution. The chemical composition and microstructures of the fabricated hydrogels were confirmed by FT-IR and SEM analysis, respectively. To evaluate the mechanical properties (e.g., storage and loss modulus of the gels), the rheological analysis was considered. Calcium deposition and ALP activity of DPSCs were carried out using alizarin red staining and ALP test. While the live/dead assay was performed to study its toxicity, the real-time PCR was conducted to investigate the osteogenic differentiation of hDPSCs cultured on prepared hydrogels.

 The hydrogels with higher gelatin incorporation showed a slightly looser network compared to the other ones. The hydrogel with less gelatin indicates a rather higher value of G', indicating a higher elasticity due to more crosslinking reaction of amine groups of CS via a covalent bond with genipin. All the hydrogels contained viable cells with negligible dead cells, indicating the high biocompatibility of the prepared hydrogels for hDPSCs. The quantitative results of alizarin red staining displayed a significant rise in calcium deposition in hDPSCs cultured on prepared hydrogels after 21 days. Further, hDPSCs cultured on hydrogel with more gelatin displayed the most ALP activity. The expression of late osteogenic genes such as OCN and BMP-2 were respectively 6 and 4 times higher on the hydrogel with more gelatin than the control group after 21 days.

 The prepared PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel presented great features (e.g., porous structure, suitable rheological behavior, and improved cell viability), and resulted in osteogenic differentiation necessary for dental tissue engineering.

Poly(ethylene oxide) (PEO) is the most common polymer used in commercial abuse-deterrent tablets. Due to its vulnerability to high-temperature manipulation, we investigated abuse-deterrent capability and the toxicity of this polymer upon thermal treatments at 80°C and 180°C for 1 hour.

Tablets (200 mg PEO and 300 mg Avicel®) were directly compressed under 2000 lb. The thermally manipulated PEOs were evaluated for their viscosity, crushability, structural changes, and cell toxicity.

Our findings showed that 180°C-treated tablets underwent some degrees of oxidative degradation with profound toxicity in both mesenchymal stem cells and MG63 cells. The 180°C-treated tablets exhibited almost no resistance against crushing and were prone to abuse. While thermal processing of PEO at around its melting temperature is a common approach to enhance crush resistance of its dosage forms, thermal manipulation at close to the PEO’s oxidation temperature can lead to structural changes, dramatic loss of crush and extraction resistance, and significant cell toxicity.

Similar to the low molecular weight PEO, when thermally manipulated at its thermo-oxidative temperature, the high molecular weight PEO loses its deterrence performance and causes severe cell toxicity.

Despite the progress made in the diagnosis and treatment of cancer, it has remained the second cause of death in industrial countries. Cancer is a complex multifaceted disease with unique genomic and proteomic hallmarks. Optogenetics is a biological approach, in which the light-sensitive protein modules in combination with effector proteins that trigger reversibly fundamental cell functions without producing a long-term effect. The technology was first used to address some key issues in neurology. Later on, it was also used for other diseases such as cancer. In the case of cancer, there exist several signaling pathways with key proteins that are involved in the initiation and/or progression of cancer. Such aberrantly expressed proteins and the related signaling pathways need to be carefully investigated in terms of cancer diagnosis and treatment, which can be managed with optogenetic tools. Notably, optogenetics systems offer some advantages compared to the traditional methods, including spatial-temporal control of protein or gene expression, cost-effective and fewer off-target side effects, and reversibility potential. Such noticeable features make this technology a unique drug-free approach for diagnosis and treatment of cancer. It can be used to control tumor cells, which is a favorable technique to investigate the heterogeneous and complex features of cancerous cells. Remarkably, optogenetics approaches can provide us with outstanding tool to extend our understanding of how cells perceive, respond, and behave in meeting with complex signals, particularly in terms of cancer evasion from the anticancer immune system functions.

The current study, for the first time, suggests nature-made pollen grains (PGs) of Pistacia vera L. as a potential candidate for using as scaffolding building blocks with encapsulation capability of bioactive compounds, such as bone morphogenetic protein 4 (BMP4).

A modified method using KOH (5%, 25ºC) was developed to produce nonallergic hollow pollen grains (HPGs), confirmed by energy dispersive X-ray (EDX) analysis, field emission scanning electron microscopy (FESEM), and DNA and protein staining techniques. The in-vitro study was conducted on human adipose-derived mesenchymal stem cells (hAD-MSCs) to investigate the applicability of HPGs as bone scaffolding building blocks. Cytocompability was evaluated by FESEM, MTT assay, and gene expression analysis of apoptotic markers (BAX and BCL2). The osteoconductive potential of HPGs was assessed by alkaline phosphatase (ALP) activity measurement and gene expression analysis of osteogenic markers (RUNX2 and osteocalcin).

Findings demonstrated that HPGs can be considered as biocompatible compounds increasing the metabolic activities of the cells. Further, the bioactive nature of HPGs resulted in suitable cellular adhesion properties, required for a potent scaffold. The investigation of apoptotic gene expression indicated a reduced BAX/BCL2 ratio reflecting the protective effect of HPGs on hAD-MSCs. The increased ALP activity and expression of osteogenic genes displayed the osteoconductive property of HPGs. Moreover, the incorporation of BMP4 in HPGs initiated a synergistic effect on osteoblast maturation.

Owing to the unique compositional and surface nanotopographical features of the Pistacia vera L. HPG, this microscale architecture provides a favorable microenvironment for the bottom-up remodeling of bone.

Cell-based models play an important role in understanding the pathophysiology and etiology of auditory disorders. For the auditory system, models have primarily focused on restoring inner and outer hair cells. However, they have largely underrepresented the surrounding structures and cells that support the function of the hair cells.

In this article, we will review recent advancements in the evolution of cell-based models of auditory disorders in their progression towards three dimensional (3D) models and organoids that more closely mimic the pathophysiology in vivo.

With the elucidation of the molecular targets and transcription factors required to generate diverse cell lines of the components of inner ear, research is starting to progress from two dimensional (2D) models to a greater 3D approach. Of note, the 3D models of the inner ear, including organoids, are relatively new and emerging in the field. As 3D models of the inner ear continue to evolve in complexity, their role in modeling disease will grow as they bridge the gap between cell culture and in vivo models.

Using 3D cell models to understand the etiology and molecular mechanisms underlying auditory disorders holds great potential for developing more targeted and effective novel therapeutics.

Tumor endothelial marker 1 (TEM1) is expressed by tumor vascular endothelial cells in various cancers.

Here, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) PEGylated with polyethylene glycol (PEG) and functionalized with anti-TEM1 antibody fragment (78Fc) and loaded them with necroptosis-inducing agent shikonin (SHK) (78Fc-PLGA-SHK NPs).

The nanoformulation showed a smooth spherical shape (~120 nm; the ζ potential of –30 mV) with high drug entrapment and bioconjugation efficiencies (~92% and ~90%, respectively) and a sustained-release profile in serum. Having significant toxicity in vitro (e.g., MS1 and TC1 cells), the nanoformulation dramatically increased the cytotoxicity in the TC1 murine lung carcinoma subcutaneous and intravenous/metastatic models as aggressive tumor models. The injection of the 78Fc-PLGA-SHK NPs to the MS1-xenograft mice resulted in significantly higher accumulation and effects in the TEM1-positive tumor targets, while they were excreted via urine track without retaining in the liver/spleen. In the TC1 subcutaneous model, C57/BL6 mice treated with the 78Fc-PLGA-SHK NPs revealed a significant therapeutic effect. The mice, which were tumor-free after receiving the nanoformulation, were re-challenged with the TC1 cells to investigate the immune response. These animals became tumor-free a week after the injection of TC1 cells.

Based on these findings, we propose the 78Fc-PLGA-SHK NPs as a highly effective immunostimulating nanomedicine against the TEM1-expressing cells for targeted therapy of solid tumors including ovarian cancer.

A new microfluidic-based method with electrochemical detection was developed for the simultaneous quantification of acetaminophen (AP) and phenylephrine (PHE) pharmaceuticals in the human blood and pharmaceuticals (e.g. tablet and drop).

The separation was achieved on a SU8/glass microchip with a 100 µm Pt working electrode that was positioned out of the channel and 2-(N-morpholino) ethanesulfonic acid was used as a running buffer (pH 7, 10 mM). Home designed modulated high voltage power supply and dual time switcher was used for controlling the injection and separation of the analytes in the unpinched injection mode.

The injection was carried out using +750 V for 7 seconds, and the separation and detection voltages were set at +1000 V and +0.9 V, respectively. Critical parameters such as detection potential, buffer concentration, injection, and separation voltage were studied in terms of their effects on the resolution, peak height, and migration times. For each analyte, the correlation coefficients were over 0.99 (n=6). The developed microchip was able to detect AP and phenylephrine simultaneously with the limit of detection of 7.9 and 5.2 (µg/mL) respectively for PHE and AP and excellent linear range of 10-200 (µg/mL). The recovery of the drugs ranged from 96% to 103%, while the repeatability of the method through inter- and intra-day was lower than 7%.

The developed method offers several advantages, including easy sample pretreatment process, simplicity, very fast analysis compared to other typical chromatographic methods. Thus, the proposed microfluidic-based method is proposed to be used as a time- and cost-effective monitoring method for the analysis of AP and PHE.

To be fully functional, pharmaceutical, and biomedical research centers need to be transformed to become innovative research and development (R&D) hubs. Such transformation, however, is a dynamic complex matter.

To establish an innovative R&D hub, a simple and concise manifesto is conceptualized for the nonlinear dynamic transformation towards an innovative research hub to reinforce the transition of the 2nd generation R&D centers.

Interdisciplinary research is the most demanded field of research to overcome various multi-sided health issues. To become an innovative R&D hub, pharmaceutical centers must function as a small-scale physical infrastructure to support the inter-communication of scientists and provide specific technological needs to promote the related innovation and entrepreneurship with advanced business plans and prototypes. Given that a success paradigm within an unorderly surrounding setting has already been condemned to fail, the orderly integration of nested systems and groups should be carefully implemented towards a shared vision with formal and tacit agreements among all parties, including academia, industry, and finance team.

To achieve a fully functional innovative R&D hub, a “know-how” approach with the systems thinking mindset within all the parties is of paramount necessity. The healthier the order of the whole working system is, the more effective will be the encompassed entitles and players. However, systems should have several checkpoints to enhance clarity and evade discrepancy and divergence. Since the medication is a highly trusted and needed public enterprise, the drug discovery and development paradigm should be practiced at the highest speed with maximum transparency and accountability.

Cell aggregation of threedimensional (3D) culture systems (the socalled spheroids) are designed as in vitro platform to represent more accurately the in vivo environment for drug discovery by using semi-solid media. The uniform multicellular tumor spheroids can be generated based on the interaction of cells with extracellular matrix (ECM) macromolecules such as collagen and integrin. This study aimed to investigate the possible interactions between the cellulose family and collagen using both in vitro and in silico approaches.

The 3D microtissue of JIMT-1 cells was generated using hanging drop method to study the effects of charge and viscosity of the medium containing cellulose family. To determine the mode of interaction between cellulose derivatives (CDs) and collagen-integrin, docking analysis and molecular simulation were further performed using open source web servers and chemical simulations (GROMACS), respectively.

The results confirmed that the addition of CDs into the 3D medium can promote the formation of solid spheroids, where methylcellulose (MC) yielded uniform spheroids compared to carboxymethyl cellulose (CMC). Moreover, the computational analysis showed that MC interacted with both integrin and collagen, while sodium carboxymethyl cellulose (NaCMC) only interacted with collagen residues. The stated different behaviors in the 3D culture formation and collagen interaction were found in the physicochemical properties of CDs.

Based on in vitro and in silico findings, MC is suggested as an important ECMmimicking entity that can support the semi-solid medium and promote the formation of the uniform spheroid in the 3D culture.

This biography highlights the scientific trajectory of Professor Mohammad A. Rafi, Ph.D., who, in particular, has greatly advanced the field of neurodegenerative disorders during his long and successful tenure at Jefferson Medical College, Thomas Jefferson University. This Editorial recognizes, above all, Professor Rafi's significant contributions to the study of lysosomal storage disorders as they relate to Krabbe Disease.

Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 293,241 deaths worldwide since its emergence in late 2019 (updated May 13, 2020). COVID-19 is caused by a novel emerged coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens.

In this study, we have targeted spike (S) glycoprotein, as an important surface antigen to identify its B- and T-cell immunodominant regions. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover the most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020).

The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations.

These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in preclinical studies.

Attributable to some critical features especially the similarity of the protein synthesis machinery between humans and microalgae, these microorganisms can be utilized for the expression of many recombinant proteins. However, low and unstable gene expression levels prevent the further development of microalgae biotechnology towards protein production.

Here, we designed a novel "Gained Agrobacterium-2A plasmid for microalgae expression" (named GAME plasmid) for the production of the human interleukin-2 using three model microalgae, including Chlamydomonas reinhardtii, Chlorella vulgaris, and Dunaliella salina. The GAME plasmid harbors a native chimeric hsp70/Int-1/rbcS2 promoter, the microalgae specific Kozak sequence, a novel hybrid 2A peptide, and Int-1 and Int-3 of the rbcS2 gene in its expression cassette.

The obtained data confirmed that the GAME plasmid can transform the microalgae with high transformation frequency. Molecular and proteomic analyses revealed the stable and robust production of the hIL-2 by the GAME plasmid in the microalgae. According to the densimetric analysis, the microalgae can accumulate the produced protein about 0.94% of the total soluble protein content. The ELISA data confirmed that the produced hIL-2 possesses the same conformation pattern with the acceptable biological activity found naturally in humans.

Most therapeutic proteins need post-translational modifications for their correct conformation, biological function, and half-life. Accordingly, microalgae could be considered as a cost-effective and more powerful platform for the production of a wide range of recombinant proteins such as antibodies, enzymes, hormones, and vaccines.

Colorectal cancer (CRC) is one of the main health burden worldwide, which can cause major economic and physiological problems along with relatively high rate of mortality. It is important to develop new methods for the localized delivery of recombinant protein therapeutics, in large part due to the failure of conventional therapies in most cases. Since E. coli Nissle 1917 (EcN) does not produce any virulence factors, here we used these bacteria with the light-activated promoter system to deliver therapeutic agents in the desired location and time.

In this study, Staphylococcus aureus alpha hemolysin (SAH), after codon usage optimization, was cloned into blue light activating vector (pDawn) and transferred to EcN strain. Then, the functionality and cytotoxicity of secreted alpha hemolysin was evaluated in the SW480 colon cancer cell line by using different experiments, including blood agar test, flow cytometry analysis, and DAPI staining.

Our findings revealed that EcN can produce functional SAH under the blue light irradiation against SW480 cancer cells. Moreover, cytotoxicity assays confirmed the dose- and time-dependent toxicity of this payload (SAH) against SW480 cancer cells.

Based on our results, EcN is proposed as an appropriate light-activated vehicle for delivery of anticancer agents to the target cancer cells/tissues.

Chemotherapies used to treat colon cancer might often fail due to the emergence of chemoresistance and side effects. Escherichia coli Nissle 1917 (EcN) is a beneficial probiotic, whose molecular mechanisms in the prevention of colon cancer are yet to be fully understood. The present study assessed the anti-cancer effects of EcN treatments in human colorectal cancer, HT-29 cell line, with the analysis of related mechanisms. The co-culture conditioned-media (CM) of EcN with adenocarcinoma HT-29 cells and heat-inactivated bacteria (HIB) were applied for the treatment of the HT-29 cells. To study the inhibition potential of CM and HIB on cancer cells, various cellular/molecular analyses were implemented, including DAPI-staining and DNA ladder assays, flow cytometry and Real-time quantitative PCR (qPCR), as well as Western blotting analyses. Our results indicated that EcN could elicit apoptotic impacts on the colon cancer HT-29 cells by up-regulating PTEN and Bax and down-regulating AKT1 and Bcl-xL genes. Based on our findings, EcN is proposed as a useful supplemental probiotic treatment against colon cancer.

Gastric cancer is considered the second prevalent cause of death around the world. This type of cancer is generally induced by Helicobacter pylori which could colonize within the gastric mucosa of the infected cases. To date, triple antibiotic therapy has routinely been utilized for controlling the H. pylori-induced infection. However, this strategy has been unsuccessful, in large part because of issues such as occurring point mutations in the H. pylori genome that can induce resistance to the antibiotics administered. Recently, it has been shown that different probiotics may have strong anti-cancer effects, in which they are capable of inhibiting H. pylori by both immunological and non-immunological mechanisms. Here, we aimed at finding possible anti-cancer impacts of the probiotic bacterium Lactobacillus plantarum on gastric cancer, AGS cells.

The anti-cancer effects of the conditioned media of the locally isolated L. plantarum on the AGS cells were evaluated by different analyses such as flow cytometry, DNA ladder assay, DAPI staining, and RT-PCR.

Our findings showed that the conditioned media of L. plantarum can inhibit both H. pylori and AGS cells through up-/down-regulation of PTEN, Bax, TLR4, and AKT genes. The exudates of the probiotic L. plantarum bacteria can increase the expression of PTEN, Bax, and TLR4, and also decrease the expression of AKT gene.

In agreement with different reports, our results proved the anti-cancer effects of the locally isolated L. plantarum through some immunological cell signaling pathways. Accordingly, it seems the probiotics could be considered as at least a complementary treatment for different types of malignancies.

Currently, drug-induced reactive oxygen species (ROS) mediating apoptosis pathway have extensively been investigated in designing effective strategies for colorectal cancer (CRC) chemotherapy. Bovine pancreatic ribonuclease A (RNase A) represents a new class of cytotoxic and nonmutagenic enzymes, and has gained more attention as a potential anticancer modality; however, the cytosolic ribonuclease inhibitors (RIs) restrict the clinical application of this enzyme. Nowadays, nanotechnology-based diagnostic and therapeutic systems have provided potential solutions for cancer treatments.

In this study, the gold nanoparticles (AuNPs) were synthesized, stabilized by polyethylene glycol (PEG), functionalized, and covalently conjugated with RNase A. The physicochemical properties of engineered nanobiomedicine (AuNPs-PEG-RNase A) were characterized by scanning electron microscope (SEM), dynamic light scattering (DLS), and UV-vis spectrum. Then, its biological impacts including cell viability, apoptosis, and ROS production were evaluated in the SW-480 cells.

The engineered nanobiomedicine, AuNPs-PEG-RNase A, was found to effectively induce apoptosis in SW-480 cells and result in a significant reduction in cancer cell viability. Besides, the maximum production of ROS was obtained after the treatment of cells with an IC50 dose of AuNPsPEG-RNase A.

Based on the efficient ROS-responsiveness and the anticancer activity of RNase A of the engineered nanomedicine, this nanoscaled biologics may be considered as a potential candidate for the treatment of CRC.

Testis-specific gene antigen 10 (TSGA10) is a less-known gene, which is involved in the vague biological paths of different cancers. Here, we investigated the TSGA10 expression using different concentrations of glucose under hypoxia and also its interaction with the hypoxia-inducible factor 1 (HIF-1). The breast cancer MDA-MB-231 and MCF-7 cells were cultured with different concentrations of glucose (5.5, 11.0 and 25.0 mM) under normoxia/hypoxia for 24, 48, and 72 hours and examined for the HIF-1α expression and cell migration by Western blotting and scratch assays. The qPCR was employed to analyze the expression of TSGA10. Three-dimensional (3D) structure and the energy minimization of the interacting domain of TSGA10 were performed by MODELLER v9.17 and Swiss-PDB viewer v4.1.0/UCSF Chimera v1.11. The UCSF Chimera v1.13.1 and Hex 6.0 were used for the molecular docking simulation. The Cytoscape v3.7.1 and STRING v11.0 were used for protein-protein interaction (PPI) network analysis. The HIF-1a related hypoxia pathways were obtained from BioModels database and reconstructed in CellDesigner v4.4.2. The increased expression of TSGA10 was found to be significantly associated with the reduced metastasis in the MDA-MB-231 cells, while an inverse relationship was seen between the TSGA10 mRNA level and cellular migration but not in the MCF-7 cells. The C-terminal domain of TSGA10 interacted with HIF-1α with high affinity, resulting in PPI network with 10 key nodes (HIF-1α, VEGFA, HSP90AA1, AKT1, ARNT, TP53, TSGA10, VHL, JUN, and EGFR). Collectively, TSGA10 functional expression alters under the hyper-/hypo-glycemia and hypoxia, which indicates its importance as a candidate bio-target for the cancer therapy.

Aptamers (Aps) are short single-strand nucleic acids exhibiting unique 3D structure which facilitate their targeting potential against various cancer molecular markers (CMMs). Such features of Aps not only make them as suitable targeting agents in targeted drug delivery systems (DDSs) but also candidate them as macromolecules that inhibit the interaction of the target protein with other proteins. On the other hand, the conjugation of Aps with another therapeutic molecule such as antisense oligonucleotide (AS-ODN), siRNA/miRNA, Ap, toxins, chemotherapeutic agents, DNAzyme/Ribozymes provide hopeful strategy to eradicate the malignancies and overcome the off-target unwanted side effects. Such prominent features of Aps make them a promising treatment modality to overcome the tumor complexity and heterogeneity and consequently hired toward personalized therapy of cancer by using bispecific Ap-based therapeutics.