asadollah asadi

Context: 

The clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system is a groundbreaking gene-editing tool that shows great promise for modifying genomes. Derived from prokaryotic adaptive immune defense mechanisms, this technique has been used in research on human diseases, demonstrating remarkable therapeutic potential. Through CRISPR, specific genetic mutations in patients can be corrected during gene therapy, offering a solution for treating diseases that were previously untreatable using conventional methods. This review explores the recent progress and future prospects of the CRISPR system, focusing on its applications in medicine and stem cell engineering. Special emphasis is placed on medical applications, the latest target design or analysis tools for genome editing, advancements in stem cell engineering, and associated innovations and challenges.

Evidence Acquisition:

 This study reviewed articles indexed in ISI, SID, PubMed, and PubMed Central from 2007 to 2024.

Cas9, a key protein in CRISPR gene editing, is an endonuclease capable of targeting and cutting specific DNA sequences, guided by short RNA sequences. The gene editing process involves homology-directed repair (HDR), non-homologous end joining (NHEJ), and base editing pathways. Base editing, which modifies the epigenome without inducing DNA breaks, is gaining increasing attention. However, CRISPR still faces technical challenges, and the development of more efficient "super" CRISPR technology will likely require time. This article reviews the effectiveness, limitations, and applications of the CRISPR system.

CRISPR/Cas9 tools allow for the creation of precise models, leading to more effective treatment options for patients.

Recurrent seizures characterize epilepsy, a category of neurological disorder. Epileptic seizures can result in sudden changes in brain electrical activity. Piracetam is a cyclic aminobutyric acid derivative with neuroprotective effects. We aimed to evaluate piracetam's neuroprotective, anticonvulsant, and anti-anxiety effects in the pentylenetetrazole (PTZ) seizure rat model. To assess piracetam's anticonvulsant properties in the PTZ seizure model, the experimental groups received Piracetam at 30 or 100 mg/kg. The positive control group received diazepam (2 mg/kg), and the negative control group received only PTZ. Elevated plus maze and open field tests evaluated the anti-anxiety effects. The antioxidant effects of Piracetam on brain tissues were also examined. Open field test results revealed that crossing the line increased significantly in the Piracetam (30 and 100 mg/kg) and diazepam groups compared to the negative control group. In the plus maze test, the Piracetam groups showed more time spent in open arms than the control group. Also, diazepam significantly increased the time spent in open arms compared to the negative control group. Histological results showed structural changes in hippocampal neurons. Also, the antioxidant test showed Piracetam's antioxidant properties compared to the negative control group. Piracetam had anticonvulsant and neuroprotective effects in PTZ epileptic rats and inhibited or reduced seizures. Also, it had anti-anxiety and sedative effects. Neuroprotective effects of Piracetam may be due to the control of neurotransmitters such as cholinergic, serotonergic, noradrenergic, and glutamatergic systems. Piracetam might have neuroprotective, anti-epileptic, anti-anxiety, and antioxidant properties in PTZ epileptic rats. However, further studies are needed to confirm these results.

Tissue engineering is a multidisciplinary and interdisciplinary topic that involves the development of biological implants for tissue regeneration intending to improve or enhance tissue or organ function.

This study aimed to evaluate the mechanical and histological properties of decellularized rat pancreas scaffolds, as well as to investigate the viability of adipose mesenchymal stem cells (MSCs) on the said scaffold for use in regenerative medicine and tissue engineering.

This is an experimental study that was performed in the research laboratory of Mohaghegh Ardabili University. To prepare the scaffold, male Wistar rats were anesthetized with carbon dioxide. After dissecting the mice, their pancreases were isolated and immediately transferred to a phosphate-buffered saline (PBS) solution to prepare them for decellularization. The decellularized scaffolds were evaluated histologically and mechanically. After decellularization, lipid MSCs were injected into de-cell scaffolds in the third passage.

Examination of the results of histological evaluations showed that scaffolding was completely decellularized. These results were confirmed by Mason trichrome and Dapi staining (coloring). Specialized tissue assessments by electron microscopy showed that the collagen and elastin strands were relatively conserved in the extracellular matrix (ECM).

In general, the result of this research demonstrates the successful decellularization of pancreatic tissue, effective preservation of the ECM of the desired tissue, and the viability of the MSCs on the scaffold resulting from the decellularization of the tissue.

A key step in the success of tissue regeneration is the selection of suitable biomaterials for the preparation of extracellular matrix-mimicking scaffolds. Polycaprolactone (PCL) is used as a scaffold in regenerative therapy and drug delivery applications. The purpose of this study is to develop a PCL nano-scaffold enriched with piracetam and octreotide and to investigate its neuroprotective effects on neural progenitor cells.

First, drug-enriched nano scaffolds were prepared and their properties were evaluated with different tests. After preparing the electrospun nano-scaffold enriched with piracetam and octreotide drugs, PC12 cells with a density of 1 x 104 cells were planted in the wells of the 96-well plate. After 2 hours, H2O2 was added to the wells to achieve a final concentration of 57 mM. Cell viability was then determined 24 hours later using the MTT method.

The morphology of the scaffold and its chemical structure showed appropriate porosity. The biocompatibility of the scaffold, which was checked 24 hours after the cultivation of PC12 cells, showed an increase in the viability of the cells as well as the proper connection of the cells on the scaffold.

Our results demonstrated the biocompatibility and non-toxicity of the PCL scaffold, along with increased cell survival on PCL/piracetam and PCL/octreotide scaffolds.

Neurotransmitters are released from neurons and establish neural connections. These substances play an important role in the formation and connections of the nervous system. The amount of neurotransmitter increases at the same time as the synapse is formed. Neural communication is carried out with the help of a large number of synapses along with various types of neurotransmitters. Neurotransmitters can be defined as chemicals released from neurons that act on specific receptors. These substances can be expressed in large amounts during certain stages of development, but then remain in only a few synapses. In this study, we will review the types of neurotransmitters and the molecular mechanisms involved in their secretion, describing the importance of this topic in understanding and addressing neurological disorders.

Studying neurotransmitters and the molecular pathways involved in their production and release can be instrumental in treating and potentially preventing neurological disorders.

 Identifying protein interactions is one of the main challenges in the fields of biostructure and molecular biology. Despite extensive progress, the exact patterns of protein-protein interactions are still unknown. The main goal of this study is to computationally evaluate the interactions of fibronectin-1 in the extracellular matrix of decellularized trachea and integrins in adipose tissue stem cells in order to provide the most accurate possible visualization of these interactions and their role in biological processes.

 After decellularization of the sheep trachea through the detergent-enzyme method, histological evaluations and ultrastructure photography of the samples were done by scanning electron microscopy. Also, the simulations of fibronectin1 binding of extracellular matrix protein with integrin αvβ1 and α5β3 of stem cells derived from adipose tissue were investigated, and interaction energy analysis was applied to predict the structure of protein-protein complexes using the algorithms available in HDOCK and ClusPro servers.

 The findings indicated the preservation of extracellular matrix components and scaffold ultrastructure. Also, in order to find the most favorable connection states in terms of energy, some of them were reported as stable interactions among the top types of connections. This insight provides a valuable understanding of cell-matrix adhesion, migration, and signaling, with potential implications for therapeutic development.

 The prepared scaffolds are ideal for engineering applications for which computational analysis and experimental data have been used for visualization of stable connection states with energy efficiency between fibronectin and integrin. Also, more studies on cell adhesion modeling in connection with tissue engineering science can provide a suitable field for the development of regenerative medicine in further studies.

</span></span> Determining the concentration of hydrogen peroxide in liquids and biological samples is very important because of its effects on human health. This study aimed to design a new electrochemical biosensor based on hemoglobin to detect hydrogen peroxide in serum samples.</span></span></span></span></span></span>

</span></span> In this study, a basic science, a biosensor based on modifying the glassy carbon electrode surface with a nanocomposite consisting of cobalt oxide nanoparticles and multi-walled carbon nanotube functionalized with a carboxyl group (MWCNT/Co3</sub>O4</sub>) and hemoglobin stabilized on this nanocomposite was made as a biological recognition element.</span></span></span></span></span></span>

</span></span> In optimal conditions, the biosensor was used to measure different concentrations of hydrogen peroxide. The designed biosensor showed a wide linear response range from 10 μM to 500 μM, a detection limit of 0.512 μM, and high reproducibility and stability.</span></span></span></span></span></span>

</span></span> In this innovative research work, MWCNTs/Co3</sub>O4</sub> nanocomposite was used to make a diagnostic biosensor. The presented biosensor showed an acceptable performance in the measurement of hydrogen peroxide in serum samples and laboratory solutions.</span></span></span></span></span></span></div>
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 The issues associated with the limitation of appropriate autologous vessels for vascular reconstruction via bypass surgery highlight the need for new alternative strategies based on tissue engineering. The present study aimed to prepare decellularized scaffolds from ovine carotid using chemical decellularization method.

 Ovine carotid were decellularized with Triton X-100 and tri-n-butyl phosphate (TnBP) at 37 °C. Histological analysis, biochemical tests, biomechanical assay and biocompatibility assay were used to investigate the efficacy of decellularization.

 Decellularization method could successfully decellularize ovine carotid without leaving any cell remnants. Scaffolds showed minimal destruction of the three-dimensional structure and extracellular matrix, as well as adequate mechanical resistance and biocompatibility for cell growth and proliferation.

 Prepared acellular scaffold exhibited the necessary characteristics for clinical applications.

Context: 

Stem cells play a key role in tissue repair and regeneration due to their self-renewal properties. In recent years, the use of stem cells as an important and valuable treatment method has created a new hope for the treatment of diseases and disorders that were previously difficult to treat. In this review article, the introduction of stem cells and their capabilities for treatment, as well as the sources of stem cells and the use of these sources for the treatment of diseases, including the treatment of leukemia, have been discussed.

Evidence Acquisition: 

Extensive search in Google Scholar and PubMed using keywords related to the article and review of various articles published between 1957 and 2022 about stem cells and the use of these cells to treat diseases.

Recently, it has been proven that hematopoietic stem cells can be produced from pluripotent embryonic stem cells, and hematopoietic stem cells can make different blood cells. These findings help medical science in the treatment of various types of blood cancer. Also, during the conducted research, it has been determined that induced pluripotent stem cells(iPSCs) can be used in the treatment of various diseases, including leukemia.NOTCH, Wnt, TGF-B1 signaling pathways play an important role in the proliferation and differentiation of hematopoietic stem cells. Evidence shows that cancer stem cells have a high ability to create tumors. The presence of cancer stem cells has been reported in some patients, including those with acute myeloid leukemia.Also, the results of research conducted in recent years show that the SALL4 gene can be used in the treatment of leukemia.

The results of various researches show that treatment with stem cells, including hematopoietic stem cell transplantation, can be a suitable method for treating patients with leukemia.

Electrospinning is one of the methods that can be used to create nanofibers, and it is also one of the most versatile processes for synthesizing nanofibers. Depending on how closely their morphologies mirror the extracellular matrix of the body, some products may be ideal for use in tissue engineering applications. With the use of this technique, researchers were able to investigate the possibility of directly producing fibers from a cell solution that included a diverse range of cells. When it comes to bioink, natural biomaterials are significantly superior to synthetic polymers. The purpose of tissue engineering is to produce new organs and tissues that can be used in the therapeutic regeneration of individuals who have been injured. The building blocks of a tissue engineering structure are biomaterial scaffolds that have been functionally oriented, with cell cultures growing on top of them. Electrospun fibers differentiate themselves from other scaffolds used in tissue engineering because of their simplicity in manufacturing and their structural resemblance to the extracellular matrix.

The N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors that participate in excitatory postsynaptic signaling in the mammalian central nervous system. In the 1980s, octreotide first became available for the treatment of acromegaly. In acromegaly patients and healthy volunteers, somatostatin and its analogs, such as octreotide and lanreotide, dramatically decrease the release of GH. In this study, we investigated the effect of octreotide, which controls blood lipids, on one of the proteins involved in epilepsy. After examining the genes involved in epilepsy by the DisGeNET server, we selected the ionotropic glutamate receptor NMDA type subunit 2B gene with the symbol GRIN2B. The docking and molecular simulation process was done using the AutoDock Vina 1.2.0 algorithm under the Chimera user interface. The analysis of docking results has been done by the PDBsum and Protein-Ligand Interaction Profiler servers. The VMD program prepared the images. The Pocket Drug server detected eighteen packets. Only the molecular docking results of 5 out of 18 pockets were acceptable. The results of docking for eighteen pockets were found in the target protein after the simulations; 13 have fewer than 14 residues, and 5 have more than 14 residues. We selected the best 18 pockets (P35, P64), (P10, P14, P17).

Spinal cord injury is a disease related to the central nervous system that leads to impaired sensory and motor functions, loss of axon, cell body and glial cell support. Currently, the treatment of spinal injuries is limited to physiotherapy, occupational therapy, and surgery. However, current treatment methods cannot fully and effectively regenerate damaged nerve fibers and improve nerve function. Neural tissue engineering has focused on building biomimetic scaffolds inspired by the complex structure of the spinal cord together with cells to repair spinal cord lesions. In recent years, the 3D bioprinting technique has been used to make highly specialized and complex biological models, such as the spinal cord. Bioprinting is done by placing bioink on a substrate in layers. The additive approach of bioprinting enables the construction of fine 3D tissue models with precise control over the spatial position of cells.

The application of 3D bioprinting technology in the field of making cell-rich scaffolds and in vivo studies in spinal cord injury models indicate the bright prospects of this technology in the field of treating spinal lesions. However, to completely simulate the spinal cord tissue and improve the nerve function of the spinal cord after injury, it is necessary to conduct more research with different cells, biomaterials, and spinal cord injury models. In this review article, the method of 3D bioprinting, the types of printing techniques in spinal cord tissue engineering, and the studies conducted in line with the application of bioprinting in the treatment of spinal cord injuries are discussed.

 The goal of tissue engineering is to create biological solutions that restore, maintain, and improve the function of damaged tissue. Scaffolds are structures based on extracellular matrix materials that have undergone various treatments.

 This study aimed to prepare polycaprolactone/silymarin and polycaprolactane/tragacanth scaffolds and compare the morphology and viability of PC12 cell lines.

 A 7% polycaprolactane solution (dissolved in acetic acid) was mixed with a 0.9% silymarin solution to prepare the polycaprolactane scaffold and silymarin loading, and a 7% polycaprolactane solution was mixed to prepare the polycaprolactane and tragacanth scaffold. Tragacanth solution was mixed at a concentration of 0.7% by weight, and then two scaffolds were prepared by electrospinning. The morphology of the scaffolds was studied by scanning electron microscopy (SEM), and the chemical structure of the scaffolds was studied by ATR-FTIR spectroscopy. The biocompatibility of the scaffolds and cell survival of PC12 cells was investigated by MTT assay.

 The morphology of the scaffolds and their chemical structure showed good porosity and successful loading of silymarin onto PCL and a suitable combination of tragacanth with PCL. The biocompatibility of the scaffolds was evaluated at 24, 48, and 72 hours after PC12 cell culture. Cell survival was found to increase on polycaprolactane/silymarin scaffolds compared to polycaprolactane/tragacanth.

 From the results of this study, loading polycaprolactane scaffold with silymarin increases the proliferation and survivability of PC12 cells compared to polycaprolactane/supporting scaffold, which may be a good candidate for neural tissue engineering.

Tissue engineering is a set of methods that can replace or repair damaged tissues with natural or artificial tissue. Tragacanth is a natural polymer that has excellent biological properties such as biodegradability and biocompatibility. Silymarin biochemically has cleansing and antioxidant properties and also has anti-inflammatory effects. The aim of this study is the production of polycaprolactone (PCL) / tragacanth / silymarin nanoscaffold and to investigate the biocompatibility of dental cells on it.

To create a polycaprolactone /tragacanth nanoscaffold and add silymarin to it, acetic acid was used to dissolve 7 percent of the polycaprolactone, 0.7 weight percent of the tragacanth solution, and 0.9 percent of the silymarin solution. The scaffold was then created using an electrospinning machine. Scanning electron microscope (SEM) analysis and FTIR analysis were used to analyze the scaffold's chemical structure and shape, respectively.

The scaffold's correct porosity and the successful loading of silymarin on it were revealed by analyzing the scaffold's morphology and chemical composition. The biocompatibility of the scaffold was investigated 24, 48 and 72 hours after the cultivation of dental cells, and the results showed an increase in cell viability and proper attachment of cells on the scaffold.

The findings of this study demonstrated that silymarin loading on the polycaprolactone/catira scaffold improves dental cell proliferation and survival. This scaffold may therefore be a good choice for tissue engineering.

Trans-anethole is a steroidogenic plant derivative. Adiponectin secretion and dopamine release is lower in patients suffer from polycystic ovary syndrome (PCOS). In the present study the effects of interaction of trans-anethole and L-dopa were investigated on serum concentration of adiponectin in PCOS model rats. Following estradiol valerate- induced PCOS, forty-five PCOS rats in 9 groups received saline, trans-anethole (50 mg/kg), L-dopa (100 mg/kg), sulpride (10 mg/kg), SCH23390 hydrochloride (1 mg/kg) or simultaneous injections of these drugs via intraperitoneal injection. Five intact rats received saline. Blood samples were collected via tail vein. Serum concentration of adiponectin was determined by ELISA. Mean serum concentration of adiponectin significantly decreased in PCOs rats compared to intact group. Adiponectin concentration in PCOS rats receiving trans- anethole or L-dopa significantly increased compared to PCOS group. Simultaneous injections SCH23390 hydrochloride and sulpride inhibit the stimulatory effects of L-dopa on serum concentration of adiponectin via exerting synergistic effects. Simultaneous injections of trans- anethole and L-dopa synergistically caused a significant increase in serum concentration of adiponectin compared to PCOS group. Trans-anethole as a steroidogenic plant derivative, may be an effective agent for increasing the activity of dopaminergic neurons and controlling the metabolic complication derived of decreased levels of adiponectin secretion in PCOS.

Demineralized bone matrix (DBM) is an allograft bone composed of native insoluble bone morphogenetic proteins and plays important roles in skeletal development, osteogenesis, and differentiation of mesenchymal stem cells. The osteoinductive capabilities of Allogenic DBM make it a potential drug delivery system for preventive treatment in various anatomical sites. In this study, the cytotoxic and teratogenic effects of DBM nanoparticles, on Wharton’s jelly mesenchymal stem cells and chicken embryos were evaluated. 

DBM nanoparticles were injected into fertile eggs at doses of 10, 20, 40, 80, and 100 µM / egg. Then morphological, histological, and skeletal malformations were evaluated. Cytotoxic effects of DBM nanoparticles on Wharton’s jelly mesenchymal stem cells were also assessed using MTT test.

Results showed that the fetal growth abnormality occurred only in embryos treated at the highest dose tested (i.e., 100 µM / egg) and MTT test showed no cytotoxicity in low concentration. 

These results indicated that nanoparticles do not have significant toxic effects on chick embryos and cultured stem cells. Only high doses of DBM nanoparticles reduce growth in embryos and cultured cells.

Micronutrients are one of the major groups of nutrients required by the body. Vitamins and minerals are considered micronutrients that are vital for growth, immune function, brain development, and many other important functions. they also play a role in preventing and fighting diseases. Malnutrition (undernutrition) is caused by a lack of nutrients and is the leading cause of death in the world. Biofortification of staple crops with micronutrients has been proposed as a potential technique for combating malnutrition by enriching target food crops. Iron deficiency is one of the most frequent dietary problems worldwide, affecting both industrialized and developing nations. Iron deficiency anemia is a condition in which the blood doesn’t have enough healthy red blood cells. It may be due to blood loss, lack of red blood cell production, and high rates of red blood cell destruction, but it leads to reduced oxygen flow to the body’s organs and causes fatigue, skin pallor, shortness of breath, light-headedness, dizziness, or a fast heartbeat. Nanotechnology is the creation and use of innovative structures, materials, and systems in a variety of disciplines, including agriculture, food, and medicine. The study and management of matter at sizes of 1 to 100 nanometers is known as nanotechnology. It can help with everything from food production to manufacturing, and it can make a big impact on food quality and safety, and also the health benefits of foods. While nanotechnology may be the greatest technique to reduce anemia’s effects while also boosting iron bioavailability in the blood, it has some negative effect on the body that depends on the duration of exposure and the level of intake. In this paper, we discuss how micronutrient deficiencies and anemia can be prevented by using nano techniques as well as how they impact the human body.

The regeneration of nerve defects and nerve damage is considered as most difficult clinical issue worldwide. Current treatments for regenerating nerves following trauma restrict nerve recovery because of intricate neural structures and some inhibitory factors at the injured site. Researchers have constructed innovative three-dimensional (3D) scaffolds with complicated structures using bioprinting to overcome nerve tissue regeneration difficulties. The therapeutic potential of this method for application to both the central and peripheral nervous systems was assessed. This study provides an overview of recent advancements in 3D bioprinting development and their medicinal potential for the nervous system.

The trachea is a respiratory organ, which connects the larynx to the main flageolet and the lungs, made up of cartilaginous rings and a mucosal layer-lined tube characterized by smooth muscle and connective tissue. Tissue engineering is one of the most promising and potent therapeutic approaches for curing long-segment tracheal stenosis. This study reviewed articles indexed in scientific databases including ISI, SID, PubMed, and PubMed Central between 1993 and 2022. Although three-dimensional scaffolds are a new therapeutic approach, they have opened up new avenues for renovating pathologically problematic tissues. This review article discusses the anatomy of the trachea and therapeutic approaches such as tissue engineering to construct tracheal cartilage to replace the damaged trachea. Next, we concisely review the recent advances in stem cell biology in scaffolds and their interplay with growth factors to optimize an engineered tracheal epithelium.

One of the functions of RNA editing is to change the RNA sequence without changing the genomic DNA sequence and changing the fate of cellular RNA. Therefore, studying the clinical application of RNA editing for targeted therapies is necessary.

All articles related to the subject of the study were searched in the Scopus, PubMed/Medline, ISI Web of Knowledge, and Google Scholar database.

The changes that occur within the RNA editing are A to I base replacement by adenosine deaminase (ADAR) on RNA and C to U replacement by the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide1 (APOBEC1). Recently, the role of RNA editing in human diseases has been reported.

RNA editing can be used as a new strategy to identify new disease biomarkers and more personalized treatments for various diseases.

In the last few years, researchers have regarded gene therapy as one of the most essential approaches to treating diseases such as cancer and a variety of genetic disorders. In this research, the capability of FeCo-Chitosan nanoparticles for gene delivery into the MCF-7 cells was investigated.

To this purpose, FeCo-Chitosan/DNA nanoparticles was prepared. Then, the physicochemical properties such as the morphology, size, zeta potential and their magnetic properties of nanoparticles were evaluated. In addition, the biological properties of the nanoparticles, such as biocompatibility, DNA protection, DNA release, and gene transfer capability to MCF-7 cells were investigated.

The results showed that the FeCo-Chitosan / DNA nanoparticles had a spherical structure with an average size of about 200 nm. The zeta potential of the FeCo-Chitosan/DNA complex increased with increasing the concentration of FeCo-Chitosan nanoparticles in FeCo-Chitosan/DNA complex. Electrophoretic analysis confirmed that the FeCo-Chitosan/DNA nanoparticles could protect DNA from nuclease degradation and ultrasound damages. The results of MTT test also showed that FeCo-Chitosan nanoparticles have high biocompatibility. The ability of the FeCo-Chitosan/DNA nanoparticles to deliver genes to MCF-7 cells were examined using fluorescent microscopy and flow cytometry.

The fluorescence microscopy and flow cytometry analysis showed that FeCo-Chitosan nanoparticles have the ability to transfer and release DNA safely to MCF-7 cells. These results also showed that efficiency of gene transfer was increased with increasing the concentration of the FeCo-Chitosan in FeCo-Chitosan/DNA complex.

Insulin is a big hormone (five,808 Da) generally produced with the aid of the pancreas. Insulin receptors (IR) are found in neurons and glial cells. Insulin resistance has been related to increased plasma insulin levels, glucose intolerance, elevated insulin-like growth factor-1 (IGF-I), glucose and free fatty acids, body mass index, and an elevated risk for colorectal cancers. Proinflammatory cytokines, boom components, and hormones secreted by adipocytes play a key role in colorectal cancer etiology. Acetyl-CoA acetyltransferase (ACAT1) mediates insulin-precipitated cell proliferation and metastatic outcomes in colorectal cancer cells. Therefore, miRNAs might serve as a biological connection between metabolic changes linked to obesity and the beginning and progression of colorectal cancer (CRC). Furthermore, these findings shed new light on weight problems as a CRC danger component in which miRNA dysregulation potentially plays a role. The role of IGFs in colorectal cancer is investigated by examining the association of two genetic polymorphisms in IGFBP-3 (a G → C single nucleotide polymorphism) and IGF-1 (a cytosine-adenosine dinucleotide repeat) with colorectal cancer risk in addition to the possibility of the other interventions, including physical activity, body mass index (BMI), and the use of postmenopausal hormones. These factors can exert their effects by modifying IGF-1 and the related binding proteins (IGFBP). Furthermore, the IGFBP-3 genotype can lead to a substantial effect modifier in the association between colorectal cancer and risk factors.  It has been found that functional polymorphisms in the pathway of insulin genes, including IGFBPI, INSR, INS, and insulin receptor substrate 1 and 2 (IRS1 and IRS2), can be related to CRC.

Various factors may result in peripheral nerve injury leading to permanent functional loss. Here, we review the role of calcium and potassium ions in peripheral nerve regeneration and repair. This narrative review of the literature collected its data by searching Google Scholar, PubMed, Elsevier, Springer, Wiley, EBSCO, Scopus, and Science Direct. Publications were searched with no particular time restriction from 1997 to 2021, including all types of study. About 100 relevant papers were found from 1997, 77 of which were selected for this study. Both beta subunits of sodium channels are expressed in peripheral neurons, and drugs that affect those channels may facilitate nerve repair. Riluzole is a sodium/glutamate antagonist which has recently entered clinical trials for spinal cord injury. Riluzole's neuroprotective effects are due to sodium channel blockade and, subsequently, the prevention of Ca2+ overflow. Besides, 4-aminopyridine (4-AP) is a neurotransmitter of potassium channel blockers that increases the rate of functional improvement following peripheral nerve damage by promoting remyelination. Verapamil is a calcium channel blocker that stimulates an endogenous anti-inflammatory response and reduces pro-inflammatory processes, thus causing pain modulation. Inhibition of ROCKs accelerate the regeneration and functional restoration after spinal-cord damage in mammals, and inhibition of the Rho/ROCK pathway has been additionally proven efficacious in animal models of stroke, inflammatory and demyelinating diseases, Alzheimer’s disease, and neuropathic ache. Therefore, the neurite outgrowth of surviving neurons is necessary for nerve regeneration to reinnervate target tissue after nerve damage. One of the critical components of the damage response process is a local translation in axons, and it is critical for the regenerative outcome. On the other hand, it provides new axonal regrowth molecules and induces signals returning to the cell's soma to partake in regenerative pathways and survival.

Tissue engineering is a growing field to repair and replace the defective function of damaged tissue or organ, and today it is proposed as a new treatment to replace conventional transplant methods. For this purpose, polymeric biomaterials (scaffolds) and living cells are used. The purpose of this study is to fabricate polycaprolactan (PCL) nanoscaffold and load silymarin on the nanoscaffold to check the biocompatibility and proliferation ability of pc12 cells on it.

In order to prepare polycaprolactan nanoscaffold and load silymarin on it, 7% polycaprolactan solution (dissolved in acetic acid) was mixed with silymarin solution with a concentration of 0.9% (weight percent), and then the scaffold was prepared using electrospinning device. The morphology of the scaffold was evaluated by scanning electron microscope (SEM) and the chemical structure of the scaffold was evaluated by ATR-FTIR spectroscopy. Toxicity of the scaffold and cell survival of PC12 cells were investigated by MTT test and SEM microscope respectively.

Examining the morphology of the scaffold and its chemical structure showed the appropriate porosity of the scaffold and the successful loading of silymarin on the PCL scaffold. The toxicity of the scaffold was investigated 24, 48 and 72 hours after the cultivation of PC12 cells, and the results showed an increase in cell viability and proper attachment of cells on the scaffold.

The results of this research showed that the loading of silymarin on polycaprolactan scaffold increases the proliferation and survival of PC12 cells. Therefore, this scaffold can be a suitable candidate for nerve tissue engineering.

The peripheral nervous system has an innate ability to regenerate itself, and several factors, including neurotrophic factors, play an important role in this process. Neurotrophic factors are molecules that affect the peripheral nervous system and play a vital role in nerve protection, growth, and regeneration. In severe injuries, internal nerve repair is not very effective. Given current treatments have many limitations and side effects. The use of some natural and herbal stimulants seems to have fewer side effects and accelerate the regeneration of the peripheral nerve. Therefore, it is important to pay attention to the role of neurotrophic factors and study the therapeutic effects of natural stimulants in the regeneration of peripheral nerves.

Neurotrophic factors could play an important role in repairing and supporting peripheral nerves. Moreover, the use of some natural stimulants as herbal medicines, due to less side effects, provide a suitable environment for the regeneration of peripheral nerves.