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نشریه دانشجویی INFINITY

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INFINITY

The first and only English student magazine for medical laboratory sciences

No.5- August 2024

Director-in-Charge: Mahdieh Sadat Hosseini Nezhad

Editor-in-chief: Nazanin Zeinab Arefipour

نشریه دانشجویی INFINITY

Infinity:

No.5- August 2024

Concessionaire: scientific Association of Medical Laboratory sciences_varastegan Institute for Medical Sciences

ISSN: 320/8232

Director-in-Charge: Mahdieh Sadat Hosseini Nezhad

Editor-in-chief: Nazanin Zeinab Arefipour

Cover designer: Zeynab Mirnezhad

Editors: Mahdieh Sadat Hosseini Nezhad, Nazanin Zeinab Arefipour

Authors: Zeynab Mirnezhad, Hossein Rayat Pisheh, Melika Hosseinpour, Arezoo Ezanlo, Ali Ahmadi, Setareh Eskandari, Nastaran Tavabaki, Maryam Rohbakhsh Faalnezhad, Nazanin Zeinab Arefipour, Mahdieh Sadat Hosseini Nezhad

سخن سردبیر

Editor-in-chief

When I see a new cell under the microscope, it feels like discovering a new planet through a telescope because, in the world of medical laboratory sciences, there's always a new planet waiting to be discovered and this infinite world plays a pivotal role in healthcare, encompassing disciplines such as clinical biochemistry, microbiology, hematology, immunology, genetics, and medical biotechnology. Each article featured in this magazine represents a critical exploration of disease mechanisms, diagnostic techniques, therapeutic strategies, and advancements in medical technology.

I invite you all to join us in this endeavor. Whether you're a student researcher eager to share your findings or a reader curious about the latest breakthroughs, Infinity is here to inspire and inform. Let's embark on this journey together, where curiosity meets discovery and each page of Infinity brings us closer to unraveling the mysteries of laboratory sciences.

Thank you to our dedicated authors and reviewers for their invaluable contributions.

نازنین زینب عارفی پور

Nazanin Zeinab Arefipour

Editor-in-Chief, Infinity

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Director-in-Charge

Reaching the fifth edition of the only English-language journal in the field of laboratory sciences is a testament to the tireless efforts of the authors' team and all those who have supported us along the way.
In today's fast-paced world, we have always strived to contribute a small part to enhancing the knowledge and awareness of our country's scientific community in the laboratory sciences field by providing up-to-date and practical scientific articles.
Finally, we cordially invite all professors, students, researchers, and those interested in the life sciences to collaborate with us on future journal issues.
Sincerely,

مهدیه حسینی نژاد

Mahdieh Sadat Hosseini Nezhad

Director-in-Charge

Human icon

Biochemistry

The role of Metformin in the fight against Colorectal Cancer

Test tube icon

Hematology

-Antibacterial Capacity of chitosan in wound healing -Gene therapy for Hemophilia B with etranacogene dezaparvovec

Syringe icon

Immunology

- Mesenchymal stem cells and their application in transplantation therapies

microb icon

Microbiology

- A new antibiotic that has nothing to do with good bacteria

DNA icon

Genetics & Biotechnology

- Investigation of the Role of Effective Gene Therapy in Lung Cancer Control and Recovery
-Potential use of cancer cells as expression systems in pharmaceutical biotechnology
-Spatial Transcriptomics in Neuroscience and Neurological Disorders

اعلان

News

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part 1

Biochemistry

-The role of Metformin in the fight against Colorectal Cancer

Biochemistry

The role of metformin in the fight against Colorectal Cancer

Introduction:

Colorectal cancer (CRC) remains a significant global health concern, with a high incidence and mortality rate. The disease arises from the uncontrolled growth of abnormal cells in the colon or rectum, often progressing slowly over several years. Early detection and effective treatment strategies are crucial for improving patient outcomes and reducing the burden of colorectal cancer on the healthcare systems.
Metformin, a widely prescribed medication for managing type 2 diabetes, has garnered attention for its potential role in cancer prevention and treatment. Studies have suggested that metformin may exert anti-cancer effects through various mechanisms, including the inhibition of cell proliferation, induction of apoptosis, and modulation of cellular metabolism. Its well-established safety profile, affordability, and widespread availability make metformin an appealing candidate for repurposing in oncology.

The fundamental mechanisms contributing to the protective effects of metformin in CRC:

Metformin has been shown to induce a temporary cell cycle arrest in colorectal cancer (CRC) cells. It effectively diminishes the expression of CRC stem cell markers, particularly CD44 and LGR5, thereby attenuating the stemness associated with CRC. This stemness is a critical determinant in the initiation, progression, and metastasis of colorectal cancer. Furthermore, metformin enhances the radiosensitivity of CRC cells and diminishes their capacity for DNA repair, even in P53-deficient CRC cells. It facilitates the differentiation of CRC cells while concurrently reducing their stemness. The drug induces cell cycle arrest in the G0/G1 or G2/M phases. Additionally, metformin amplifies the anti-cancer effects of various chemotherapeutic agents. It also inhibits DNA replication and proliferation in resistant CRC cells by downregulating the expression of the mini-chromosome maintenance protein complex (M-CM), which functions as a DNA helicase.

Research also indicates that metformin is capable of downregulating c-Myc and IGFR1 in colorectal cancer (CRC) cells. c-Myc plays a pivotal role in the reprogramming of gene expression in CRC, influencing various processes such as cellular proliferation, invasion, migration, immune evasion, chemoresistance, and the facilitation of the Warburg effect, which is defined by the process of aerobic glycolysis. The activation of c-Myc is mediated by the KRAS gene through downstream signaling pathways, including Wnt/β-catenin and MEK/ERK. Notably, cancer cells exhibit a preference for glucose fermentation to lactate over aerobic glycolysis, even when mitochondrial function remains intact. Furthermore, KRAS mutations are linked to the silencing of MATE1, a protein involved in the extrusion of multidrugs and toxins. The stimulation of IGFR1 enhances CRC cell proliferation via the PI3K/AKT/mTORC1 signaling pathway. Metformin exerts its effects by inhibiting critical proliferative pathways, namely PI3K/AKT, MEK/ERK, and Wnt/β-catenin, in CRC cells through an AMPK-dependent mechanism.

Epithelial-mesenchymal transition (EMT) plays a critical role in the migration and metastasis of cancer cells. Research indicates that metformin exerts an inhibitory effect on the metastasis of colorectal cancer (CRC) cells by interfering with the EMT process. Specifically, metformin reduces the expression of vimentin while enhancing the expression of E-cadherin, which collectively diminishes the invasive and metastatic capabilities of CRC cells. Additionally, vascular endothelial growth factor (VEGF) is recognized as a pivotal factor in intra-tumor angiogenesis, facilitating the growth and metastasis of CRC cells. Metformin has been shown to decrease VEGF expression in CRC cells. Furthermore, metformin also downregulates the expression of hypoxia-inducible factor 1α (HIF-1α) in these cells.

The other possible mechanism of action (MoA) of metformin is the inhibition of mitochondrial respiratory complex I, which leads to the activation of 5'-AMP-activated protein kinase (AMPK) in a serine/threonine-protein kinase STK11 (LKB1)-dependent manner. AMPK activation is associated with inhibition of the serine/threonine-protein kinase mTOR (mTOR), leading to favorable phenotypic outcomes in cancer cells, such as reduced protein synthesis and proliferation rates, activation of autophagy, and inhibition of inflammatory responses.

The advantage of using Metformin compared to other medications:

The research articles underscore the potential of metformin as a viable chemotherapeutic agent for the prevention of colorectal cancer (CRC), highlighting its safety profile, high patient adherence, cost-effectiveness, and well-defined mechanism of action. In contrast, non-steroidal anti-inflammatory drugs (NSAIDs), particularly COX-2 inhibitors, have demonstrated a significant reduction in CRC risk; however, they are associated with an elevated risk of major cardiovascular events. Metformin, a medication that has been utilized for several decades in the management of diabetes and other health conditions, was evaluated in a clinical trial. This trial revealed that low doses administered over one year resulted in minimal and mild adverse effects, thereby affirming its safety for prolonged use. The results indicate that metformin represents an economical and appropriate option for patients in need of long-term chemopreventive therapy.

Conclusion:

Collectively, both preclinical and clinical research indicates that metformin may play a significant role in the prevention and treatment of colorectal cancer (CRC), particularly in individuals at elevated risk, such as those with acromegaly or inflammatory bowel disease (IBD). Metformin has been shown to enhance the efficacy of various chemotherapeutic agents and to aid in overcoming chemoresistance associated with CRC. Furthermore, studies have demonstrated that metformin can substantially impede the development of new colorectal polyps and adenomas in non-diabetic individuals. Notably, even low doses of metformin (250 mg daily) have been associated with a decreased risk of colorectal polyps and adenomas.

References:

۱. Salovska B, Gao E, Müller-Dott S, Li W, Cordon CC, Wang S, Dugourd A, Rosenberger G, Saez-Rodriguez J, Liu Y. Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates the mechanism of action and potential therapeutic opportunities. Clin Transl Med. 2023 Feb;13(2):e1179. Doi: 10.1002/ctm2.1179. PMID: 36781298; PMCID: PMC9925373.

۲. Ala M. The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for the Management of Colorectal Cancer. Curr Diabetes Rev. 2022;18(8):e051121197762. doi: 10.2174/1573399818666211105125129. PMID: 34749618.

زینب میرنژاد

Zeynab Mirnezhad

Department of Medical Laboratory Sciences. Varastegan Institute for Medical Sciences, Mashhad, Iran

مهدیه حسینی نژاد

Mahdieh Sadat Hosseini Nezhad

Department of Medical Laboratory Sciences. Varastegan Institute for Medical Sciences, Mashhad, Iran

part 2

Hematology

-Gene therapy for Hemophilia B with etranacogene dezaparvovec

Hematology

Antibacterial Capacity of chitosan in wound healing

The skin is a complex organ that plays a vital role in protecting the body from external environmental factors, regulating body temperature, and providing a physical barrier against water loss. It is the largest organ of the human body, representing approximately 15% of body weight [1]. The skin is composed of three main layers: the epidermis, dermis, and hypodermis, each with unique structures and functions. The outermost layer is the epidermis, which is primarily composed of keratinocytes and serves as the primary barrier against external environmental factors, such as UV radiation, chemicals, and microorganisms. The epidermis also plays a critical role in vitamin D synthesis [2-4]. The dermis is the second layer of the skin, which is composed of a fibroblast cell population. Fibroblasts are responsible for producing and secreting key extracellular matrix components, including collagen and elastin, which provide mechanical and elastic strength to the skin [6]. The dermis also contains other cell types, such as immune cells and sensory receptors, which play important roles in immune defense and sensory perception. The deepest layer of the skin is the hypodermis, which is composed of adipose tissue and connective tissue. The hypodermis plays a key role in thermal insulation by providing a layer of subcutaneous fat, which helps to regulate body temperature, and also acts as a mechanical barrier, protecting underlying tissues from damage [7,8].

Figure 1. Layers of the skin
Figure 1. Layers of the skin

Wounds can be caused by physical injury, genetic disorders, or trauma [9,10,11]. Wound healing is a set of multifactorial and dynamic physiological processes. Different tissue repair processes consist of four stages coagulation and homeostasis, inflammation, proliferation, and regeneration. These four stages are time-dependent [12,13]. Local and systemic factors can influence the recovery process [14-17].

Wound healing results from interactions between cytokines, growth factors, blood, and extracellular network. Cytokines promote wound healing in various ways, such as stimulating the production of membrane components, preventing body dehydration, increasing inflammation, and creating granular tissue. This wound-healing process depends on various local and systemic factors. Some local factors include hypothermia (abnormally low body temperature), pain, infection, complete blood supply, and tissue oxygenation, which directly affect wound characteristics. And among systemic factors, we can mention stress, age, sex hormones, diseases such as diabetes, obesity, cancer, AIDS, smoking, and surgical technique [9,11]. Wound dressings are covers placed on the wound to protect the cells around the wound from environmental factors. In addition, wound dressings provide a suitable substrate for the growth and proliferation of cells. Wound dressings can partially fulfill the functions of damaged skin. Creating a barrier to prevent the penetration of bacteria and other factors that cause infection, keeping the wound environment moist, and allowing the penetration of gas molecules (permeability) are the most important features of a suitable wound dressing. The appropriate choice of a wound dressing depends on the characteristics of the wound, the information obtained from the wound, and the type of wound dressings available [12-15].

Biologically active natural materials have been used as potential materials in restoration due to their special properties. Due to their physical and chemical similarity, they can mimic the structure of human tissue. Natural polymers are more biocompatible than most synthetic polymers. Chitosan has been studied as one of the biopolymers, due to its unique properties, as a potential bioactive material. Chitosan is a derivative of chitin found in the exoskeleton of crustaceans, algae, and the bacterial cell wall [18,19].

Chitosan is distinguished from other biomaterials due to its unique properties: abundance, biodegradability, biocompatibility, hydrophilicity, non-toxic, antibacterial, antifungal, and wound healing effects [20]. It also has excellent elasticity, flexibility, and low inflammatory response [21]. The human body fully absorbs the products of the breakdown of chitosan (harmless amino sugars) [22-23]. These desirable properties accelerate the healing of various tissues and facilitate wound healing [24]. These unique properties have led to its use in some commercial products such as ChitoSamTM [25], ChitoGauze XR pro [26], ChitoFlex [27], and Axiostat® [۲۸]. However, the high molecular weight and high viscosity of chitosan and insolubility in most organic solvents and acid-free aqueous media limit it [29].

In this review, we will first evaluate chitosan's physicochemical and biological properties. Then we will examine the wound healing process and the use of chitosan in wound dressing based on research and patents made in recent years.

Chitosan

Rouget first boiled some chitin in potassium hydroxide in an experiment in 1859, which led to the discovery of chitosan [30]. Chitosan is a polymer in the family of linear polymers consisting of glucosamine and N-acetyl-D-glucosamine monomers. [31,32]. Also, the deacetylation reaction doesn’t cause the breakdown of chitosan chains [33]. Molecular weight and degree of deacetylation affect the product's pH, viscosity, turbidity, and temperature-sensitive properties [34]. The N-acetylated form of this polymer is called chitin. Chitin has a polysaccharide framework modified and amplified by a protein matrix [35]. Chitosan is a semi-acetyl (alkaline) form of chitin. In nature, the second biopolymer after cellulose is chitin [36].

Chitosan has a higher solubility than chitin. This difference in solubility causes the polysaccharide to be converted to a polyelectrolyte in an acidic environment [37]. Hydrophilicity and solubility of chitosan due to its free amino group, this material has a greater potential for chemical changes than chitin. Chitosan has three nucleophilic functional groups, including the C-2 NH2 group, the secondary C-3 OH group, and the primary C-6 OH group, present in each repeating chitosan molecule [38]. These functional groups in chitosan play a vital role in some physicochemical properties. Chitosan has derivatives consisting of hydrophilic and hydrophobic components. These derivatives result from modifications in the amino group or the hydroxyl groups. Chitosan has many special properties, including accelerating wound healing, antimicrobial, anticoagulant, antibacterial, antifungal, antitumor, anti-thrombogenic, film forming, hydrating agent, renewable, adsorbent, non-toxic and hemostatic [ 39-41]. It also can trap positive metal ions such as Ni2+, Zn2+, Co2+, Fe2+, Mg2+, and Cu2+. Of course, this capacity appears only in acidic conditions [42]. Today, chitosan has been considered by scientists and researchers and has been widely used in industries and biomedical products (fig.2). In the following, we will examine some unique properties of chitosan.

Figure 2. Schematic representation of applications of chitosan-based bioactive materials
Figure 2. Schematic representation of applications of chitosan-based bioactive materials

Sources & Extraction

In 1811, chitin or poly (β-(۱ → ۴) -N-acetyl-D-glucosamine) was discovered by Henri Braconnot [43]. Chitin is a type of biopolymer (polysaccharide) found in abundance in nature [44]. Chitin is present in many living organisms, such as insects (cuticles), crustaceans, and skeletal species [45-49]. Among the mentioned sources, shrimp and crabs are the most common sources as raw materials for preparing chitosan due to their low price and high chitin content. However, other sources, such as oysters, are also used [50- 53]. Different organisms contain different amounts (by weight) of chitin. For example, crustaceans have about 30 to 50 percent of calcium carbonate and 20 to 30 percent of weight of chitin. Still, Nephrop, which is a type of lobster in its shell, has about It weighs 60 to 75 percent by weight of chitin, which is the highest of all chitin-containing organisms [52, 54, 55]. Found in raw materials. Alkaline methods, including degreasing, degreasing, demineralization, and decolorization, are used to extract chitin [56].

The main derivative of chitin is chitosan (β- (l-4) -2-amino-2-deoxy-D-glucopyranose), which is a yellow linear polysaccharide containing the units N-acetyl-glucosamine and N-glucosamine [57]. The number of units of N-glucosamine is known as the degree of deacetylation (DDA) and plays an important role in chitosan. These units directly affect chitosan's physicochemical, biodegradable, and immunological properties [58]. The degree of chitosan deacetylation is measured by near-infrared spectroscopy, nuclear magnetic resonance spectroscopy, infrared spectroscopy, first derivative ultraviolet spectroscopy, etc [59].

Extraction of chitosan from chitin with different degrees of acetylation is done in two ways:

  1. Heterogeneous deacetylation
  2. Homogeneous deacetylation [60].

Both methods require concentrated alkaline solutions and a long processing time for acetylation. The processing time for the acetylation reaction may vary from 1 to 80 hours. Alternative processing methods, such as a set of thermal-mechanical processes using a low-alkaline cascade reactor [61], saturated steam flash operation [62], and the use of microwave dielectric heating [63]; And intermittent rinsing of water [64], have been created to reduce the processing time and a large amount of alkali. The most common processes available for the preparation of chitosan are mentioned.

As an alternative method