The Future of Iran's Population: Balancing Aging Trends and Fertility Rates

en 40453919 The Future of Iran's Population: Balancing Aging Trends and Fertility Rates As current population growth trends persist, Iran's population is projected to reach 42 million by the year 1480, marking a significant transition from a predominantly youthful demographic to an increasingly aging society. While European countries face similar demographic challenges, their population decline is occurring gradually. In contrast, Iran's declining youth population presents a more urgent concern. Presently, there are approximately 5 million couples, representing 10 million individuals of marriageable age, who remain unmarried. It is imperative to provide these individuals with essential resources, including employment opportunities and housing, to facilitate family formation (1). Another critical issue is the prevailing trend of having only one child. As parents age, their children face the difficult choice between establishing their own lives and providing care for their aging parents, a dilemma that poses significant implications for future demographic stability. In approximately 20 years, the rates of birth and death in Iran are expected to equalize, resulting in zero population growth. Subsequently, the number of deaths is projected to exceed births, leading to a decline in the population to below 50 million by the year 1480 (1). Current demographic data indicate that approximately 24% of Iran's population of 85 million consists of children and adolescents under the age of 15. Additionally, 25% are young individuals aged 15 to 29, while 44% are middle-aged, and the remaining population comprises elderly individuals over 65. This demographic structure highlights a predominance of middle-aged individuals. Alarmingly, road traffic accidents claim the lives of approximately 20,000 individuals annually, a significant proportion of whom are productive young people. Urgent preventive measures are necessary to address this issue, including improvements in road conditions, driving culture, and vehicle safety. The car industry, while contributing to road fatalities, also exacerbates environmental pollution through inefficient fuel combustion, positioning it as a potential barrier to population growth. Furthermore, the interval between marriage and the birth of the first child currently spans 4.5 to 5 years, a gap that must be addressed. Delayed marriage and extended intervals between childbirth can diminish the desire for larger families. The average age of marriage among Iranian youth, particularly in provinces where fertility rates have fallen below 1.5, has been on the rise. To counteract these trends, targeted population interventions should be implemented in provinces with fertility rates below 1.5, promoting childbearing through practical measures rather than mere rhetoric. This responsibility extends beyond the Ministry of Health to encompass the entire government. While Level 2 and 3 infertility treatment centers have been established across all provinces, providing essential services to infertile couples, the number of such centers exceeds the number of provincial health facilities. Addressing demographic challenges requires a multifaceted approach that considers economic, social, and cultural factors alongside medical interventions. Over the past 35 years, Iran has made significant strides in infertility treatment, emerging as a regional leader in this field, with health insurance covering nearly 100% of infertility treatment costs. In conclusion, a comprehensive and coordinated policy response is essential to address the demographic challenges facing Iran. By fostering an environment conducive to family formation and addressing the underlying social determinants of fertility, we can work towards a sustainable demographic future. 82 82 https://www.ajmb.org/En/Article.aspx?id=60615 https://www.ajmb.org/PDF/En/FullText/60615.pdf LadanKashaniInfertility Ward, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran92037ShahinAkhondzadeh739

en 40453915 Revolutionary Regeneration Therapy Utilizing Dental Stem Cells and State-of-the-Art Nanotechnology Devices to Heal Injured Teeth and Tissues Regenerative medicine is a field of pharmacy and medicine that focuses on stem cells and other methods such as nanoscience and biotechnology to stimulate the body's natural regenerative processes and repairing damaged tissues and organs to improve function and reduce pain. In this review article, focus is on Dental Stem Cells (DSC) and other cells regeneration in human body. The appropriateness of tissue-engineered therapies relying on the multipotent regenerative abilities of DSC is accompanied by significant challenges, as growth factors and epigenetic components are crucial for preserving their multipotency while being susceptible to a range of natural and environmental factors. Current evidence highlights the positive outcomes associated with select regenerative therapies; nevertheless, to provide further support, additional data must be gathered through standardized therapies and further studies. Organoids (3D cell culture) and nano scaffolds are also being explored as potential tools for regenerative therapies. Understanding the mechanisms that determine the behavior of these cells and how they interact will enable future generation therapies. Demonstrating promise, cell therapy is an alternative approach within regenerative medicine. Developmental factors like extracellular vesicle production are thought to mediate the regenerative response through paracrine effects in cell therapy, which is widely recognized. Cell culture, Immunomodulation, Organoids, Regenerative medicine, Scaffolds, Signal pathways, Stem cell research 83 97 https://www.ajmb.org/En/Article.aspx?id=60606 https://www.ajmb.org/PDF/En/FullText/60606.pdf MohammadBalfaki92325ErfanSalimiTib University of Baku, Baku, Azerbaijan92326

en 40453913 Monocytes and Macrophages as Unique Cellular Compartments Governing Non-Alcoholic Fatty Liver Disease and Inflammation Non-Alcoholic Fatty Liver Disease (NAFLD) is a spectrum of liver diseases from simple steatosis to the most severe form of hepatocellular carcinoma. Liver injuries resulting from various factors, including viral infections, alcohol consumption, and metabolic disorders, trigger the activation of resident immune cells and the recruitment of circulating immune cells to the liver. This chronic inflammatory environment leads to tissue damage and the progression of liver fibrosis. Macrophages are highly versatile immune cells that play a dual role in fibrosis: they contribute to the progression of fibrosis (M1 and Ly6chigh macrophages) and its resolution (M2 and Ly6clow macrophages). M1 macrophages and those with high surface expression of Ly6C exhibit pro-inflammatory characteristics, while M2 macrophages and myeloid cells with low expression of Ly6C mitigate inflammation and inhibit fibrosis progression. Environmental stimuli influence the complex mechanisms hepatic macrophages regulate the fibrosis they encounter. Kupffer cells initiate the inflammatory cascade and recruit monocyte-derived macrophages, which modulate the propagation of fibrosis and promote fibrinolysis. Additionally, hepatic macrophages interact with other cell types through exosomes, facilitating the transfer of cellular components that influence the outcome of liver fibrosis. In this review, the critical role of macrophages in inflammation-induced fibrosis and tissue restoration is discussed. Carcinoma, Exosomes, Fibrinolysis, Hepatocellular, Kupffer cells, Liver cirrhosis, Liver neoplasms, Non-alcoholic fatty liver disease 97 105 https://www.ajmb.org/En/Article.aspx?id=60607 https://www.ajmb.org/PDF/En/FullText/60607.pdf GhazaleHemmatian Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran92327DavoudRostamzadehMedicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran92235KavehBaghaeiGastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran92171MahdiShabani125

en 40453916 Investigation of Anti-Cancerous Effects of L. casei –ATCC-393 and L. rhamnosus-GG on Apoptosis and Cell Cycle of B- CPAP Thyroid Cancer Cell line in Comparison to Fibroblast Cell Line Background: Thyroid cancer is the most common type of cancer affecting the endocrine system. The main treatment approaches consist of surgical procedures and radioiodine therapy. Recently, there has been a heightened interest in investigating alternative treatment options, including probiotics, which could potentially minimize toxicity. Consequently, there is a growing imperative for research aimed at investigating the potential role of probiotics in the management of cancer. Methods: The B-CPAP cell line was maintained in culture and tested with different dilutions of two bacterial strains. Toxicity evaluations were performed using the MTT assay to identify appropriate concentrations. mRNA was extracted and analyzed via real-time PCR to measure the expression levels of the Bcl-2, Bax, and P53 genes. Furthermore, changes in the cell cycle and the induction of apoptosis were examined using flow cytometry. Results: The supernatant derived from Lacticaseibacillus casei (L. casei) – ATCC-393 and Lacticaseibacillus rhamnosus (L. rhamnosus)-GG demonstrated a significant inhibitory effect on the growth of B-CPAP cancer cells. The findings indicated that the combination produced a more pronounced anti-cancer effect by enhancing the expression of pro-apoptotic genes while reducing Bcl-2 gene expression in B-CPAP cells. Conclusion: The findings indicated a notable change in the expression of genes associated with apoptosis and modifications in the cell cycle. This implies that probiotics may enhance the efficacy of chemotherapy in treating thyroid cancer. In particular, L. rhamnosus and L. casei may play a beneficial role in the therapeutic process. Further research is required to investigate the direct impact of probiotics on thyroid function. Apoptosis, bcl-2-associated X protein, Cell cycle, Cell line, Flow cytometry, Gene expression, Iodine radioisotopes, Probiotics, Real time polymerase chain reaction, Thyroid neoplasms 106 113 https://www.ajmb.org/En/Article.aspx?id=60608 https://www.ajmb.org/PDF/En/FullText/60608.pdf MaryamHonardoostCardio-Oncology Research Center, Rajaie Cardiovascular Research Institute, Iran University of Medical Sciences, Tehran, Iran92330FatemehSoleimanifar92331SolatEslami Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran92332SaraCheraghiEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran92333Mohammad EbrahimKhamsehEndocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran92334MaryamDarvishDepartment of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Science, Arak, Iran92335HamedHaddad Kashani Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran92336

en 40453918 Recombinase Polymerase Amplification (RPA)-ELISA as an Isothermal Molecular POCT Method for Bacterial Respiratory Infection Diagnosis Background: Acute Respiratory Infections (ARIs) are a leading cause of childhood mortality worldwide, especially in African and Southeast Asian countries. Point of Care Test (POCT) techniques provide faster diagnoses compared to conventional or real-time PCR methods. Recombinase Polymerase Amplification (RPA) offers rapid on-site detection of these infections. Coupling RPA with Enzyme-Linked Immunosorbent Assay (ELISA) (RPA-ELISA) creates a cost-effective alternative, ideal for clinical applications. This study evaluates RPA-ELISA as a rapid diagnostic tool for bacterial respiratory infections. Methods: From 11 August 2022 to 9 February 2023, respiratory samples were collected and processed using culture methods, biochemical tests, real-time PCR, and RPA assays. The RPA reactions were conducted at 39°C for 30 min, and ELISA was used for detection. Statistical analyses focused on sensitivity, specificity, Positive Predictive Values (PPV), and Negative Predictive Values (NPV). Results: Forty-two respiratory samples, were collected in this period of which 10 samples showed no growth, and 32 tested positive. Among these positive samples, 15 isolates (35.7%) were identified as Klebsiella pneumoniae (K. pneumoniae), 14 isolates (33.3%) as Streptococcus pneumoniae (S. pneumoniae), and 3 isolates (7.1%) as Moraxella catarrhalis (M. catarrhalis). RPA-ELISA demonstrated 100% sensitivity for all pathogens, comparable to or better than RT-PCR, but had slightly lower specificity and PPV. RT-PCR achieved 100% specificity and PPV for all pathogens, indicating higher accuracy; yet, RPA-ELISA's sensitivity points to its effectiveness as a rapid screening tool. Conclusion: RPA-ELISA is significantly faster than real-time PCR and culture methods. Its ease of use makes it suitable for on-site diagnoses in resource-limited environments. Limitations include a small sample size for certain bacteria and the necessity for further validation in varied clinical contexts. Isothermal methods, Point of Care Test (POCT), Respiratory infections, RPA, RPA-ELISA 114 121 https://www.ajmb.org/En/Article.aspx?id=60609 https://www.ajmb.org/PDF/En/FullText/60609.pdf RezaAzizianBiomedical Innovation and Start-up Student Association, Tehran University of Medical Sciences (TUMS), Tehran, Iran92337ErfanehJafariBiomedical Innovation and Start-up Student Association, Tehran University of Medical Sciences (TUMS), Tehran, Iran92338BabakPourakabri92339SetarehMamishiPediatric Infectious Diseases Research Center (PIDRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran92340ReihanehHosseinpour SadeghiPediatric Infectious Diseases Research Center (PIDRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran92341MaryamSotoudeh AnvariDepartment of Pathology, School of Medicine, Children’s Medical Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran92342

en 40453911 Optimization of RfxCas13d Expression in Escherichia coli Host using Response Surface Methodology Background: RfxCas13d, a key member of the Cas13 family, plays a vital role in CRISPR-based diagnostics for RNA sequence detection and gene silencing. This study aimed to enhance RfxCas13d expression by optimizing key parameters using Response Surface Methodology (RSM). Methods: The plasmid pET28b-RfxCas13d-His (Addgene 141322) was introduced into BL21 (DE3) and Rosetta™ (DE3) strains. Initial expression tests were conducted, followed by RSM-guided optimization of factors such as isopropyl β-D-1-thiogalactopyranoside (IPTG) concentration, temperature, cell density at induction, and induction time in BL21 (DE3). Protein expression levels were quantified using ImageJ and AlphaEaseFC software to analyze band intensities. Results: BL21 (DE3) was selected for further optimization based on preliminary results. Analysis of 26 RSM-designed experiments revealed that temperature, induction time, IPTG concentration, and their interactions significantly influenced RfxCas13d expression. Optimal conditions were identified as 0.25 mM IPTG, an OD600 nm of 0.8 at induction, 37°C, and Overnight (ON) of induction. The regression model exhibited high accuracy, with a correlation coefficient of 0.97 and a p-value less than 0.05, confirming a strong linear relationship between predicted and observed values. Conclusion: This study highlights the significant impact of the four optimized factors on RfxCas13d expression. Under optimized conditions, a soluble protein concentration of 3.6 mg/100 ml cell culture was achieved after purification. It represents the first application of RSM for optimizing RfxCas13d expression, providing a foundation for further refinement of expression conditions. Continued use of RSM in future research will enhance the efficiency of RfxCas13d production for diagnostic and therapeutic applications. Base sequence, CRISPR-associated proteins, Escherichia coli, Protein biosynthesis 122 130 https://www.ajmb.org/En/Article.aspx?id=60610 https://www.ajmb.org/PDF/En/FullText/60610.pdf SepidehAbbaszadeh Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran92343ShahinEghbalsaied Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran92344MeysamSoleimaniDepartment of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran92345SadeghKhazalpourDepartment of Analytical Chemistry, Faculty of Chemistry and Petroleum Science, Bu-Ali Sina University, Hamadan, Iran92346SaeidAfshar Cancer Research Center, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran92347

en 40453917 The Pro-Apoptosis Induction of Teucrium persicum Ethyl Acetate Extract on MCF-7 Cells: An In Vitro Study Background: Teucrium persicum (T. persicum) is a well-known Iranian endemic plant that grows in the southern regions of Iran. It is used as a tea to treat abdominal pains, hyperlipidemia, and diabetes in traditional Iranian medicine. It has been previously found that the methanolic extract of T. persicum exerts significant cytotoxicity and inhibitory effects on different cancer cells. This study aimed to investigate the effects of ethyl acetate extract of T. persicum on MCF-7 cells. Methods: The experiments included MTT, DAPI staining, and investigating the expression of BAX and BCL2 genes. The extract had a significant cytotoxic effect on MCF-7 cells, with an IC50 value of 50 µg/ml for 48 hr. Results: DAPI staining assays showed that the extract induced morphological changes, chromatin condensation, and nuclear fragmentation. Additionally, the ethyl acetate extract induced the expression of BAX and down-regulated BCL2 genes. Conclusion: These findings suggest that T. persicum has strong cytotoxic properties and warrants further investigation. Apoptosis, Breast cancer, Cytotoxicity, Gene expression, Teucrium persicum 131 135 https://www.ajmb.org/En/Article.aspx?id=60611 https://www.ajmb.org/PDF/En/FullText/60611.pdf MehdiMoeilDepartment of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran92348MajidTafrihi92107EhsanNazifiDepartment of Biology, Faculty of Science, University of Mazandaran, Babolsar, Iran92350MaryamRadfarDepartment of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran92351

en 40453910 Exploring the Role of hsa_circ_0052112 as a Potential Biomarker in Breast Cancer: Insights from Experimental and In Silico Analyses Background: Circular RNAs (circRNAs) are important in tumorigenesis and cancer progression, highlighting their potential as biomarkers for diagnosis, prognosis, and treatment monitoring. Methods: This study consists of experimental and in silico phases. In the experimental phase, the expression of hsa_circ_0052112 in tumor and blood samples from 40 breast cancer women was analyzed, compared to the control group using Sybr Green real-time RT-PCR followed by total RNA extraction and cDNA synthesis. Statistical analysis was performed using the beta-actin gene as a normalizer, compared to the normal control group as a fold change. In the in silico phase, interactions among circRNA, RNA-Binding Proteins (RBPs), and microRNAs (miRNAs) were investigated using Interactome Database. The miRcancer database was utilized to assess breast cancer-related miRNAs linked to hsa_circ_0052112. Target miRNAs were identified with TargetScan and filtered for relevance through DisGeNET. K-means clustering grouped genes by expression patterns, visualized in Cytoscape to illustrate circRNA-miRNA-mRNA relationships. Hub genes underwent pathway enrichment analysis using Reactome database to determine their functional significance. Results: Data revealed a significant increase in hsa_circ_0052112 expression in both blood and tumour of breast cancer patients. This increase was especially pronounced in patients with estrogen, progesterone, and HER2 receptor positivity, as well as in advanced disease stages with lymph node involvement. Enrichment analysis of hub genes indicates their role in the PI3K/AKT signaling pathway. Conclusion: hsa_circ_0052112 shows promise as a multifaceted biomarker for breast cancer, enhancing diagnosis and prognosis; while supporting personalized treatment strategies. Further clinical validation is necessary to confirm its utility. Breast neoplasms, Circular RNAs, hsa_circ_0052112, MicroRNAs, Prognosis 136 146 https://www.ajmb.org/En/Article.aspx?id=60612 https://www.ajmb.org/PDF/En/FullText/60612.pdf MahdiAlizadehDepartment of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran92352MahdiehSalimi741

en 40453912 Bridging the Skills Gap: Insights and Recommendations for Updating Medical Biotechnology Master's Curriculum in Iran Background: Biotechnology is a rapidly developing field, and Iran aims to enhance its position in biosimilars through improved educational frameworks. Successful nations, such as the U.S., UK, Switzerland, China, and India, exemplify the positive impact of targeted educational programs in producing skilled graduates who advance the biotech sector. Research indicates a significant connection between curriculum relevance and graduate employability, suggesting that comprehensive curriculum assessment and reform can enhance student success and faculty involvement. This study investigated the necessity of revising the Master's curriculum in Medical Biotechnology in Iran to align with industry demands and global advancements. Methods: The current curriculum's effectiveness using the Delphi method was assessed to survey Master's students, professors, and industry stakeholders. Results: Findings revealed that while the current curriculum moderately aligns with educational objectives, significant gaps exist in practical training and resource availability. Many students reported feeling inadequately prepared for employment, particularly in essential skills such as animal cell culture, vaccine and monoclonal antibody design and production, and human skills like effective communication and teamwork. To address these deficiencies, some new courses focusing on practical experience and interdisciplinary approaches were recommended. Recommendations included enhancing laboratory facilities, integrating internships, and adopting team-based learning methods to improve student engagement and skill acquisition. Conclusion: Continuous investment in biotechnology education is crucial for maintaining competitive advantages in a globalized market. Overall, this research highlighted the importance of adapting educational programs to meet the dynamic needs of the biotechnology industry, ensuring graduates possess the necessary skills for successful careers in this field. Curriculum, Internship and residency, Iran, Master of science, Medical biotechnology 147 156 https://www.ajmb.org/En/Article.aspx?id=60613 https://www.ajmb.org/PDF/En/FullText/60613.pdf AmirhosseinAhmadieh-Yazdi Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran92353BehzadImani Department of Operating Room, School of Paramedicine, Hamadan University of Medical Sciences, Hamadan, Iran92354AkramJalaliResearch Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran48FahimehPiryaeiDepartment of Medical Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran92356RaziehDalirfardoueiResearch Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran92357

en 40453914 Toxicity Study of Silver Nanoparticles Synthesized from Suaeda Monoica on Hep-2 Cell Line This is to inform that the authors mentioned below have requested a correction in the published paper as below: Satyavani K, Gurudeeban S, Ramanathan T, Balasubramanian T. "Toxicity Study of Silver Nanoparticles Synthesized from Suaeda Monoica on Hep-2 Cell Line" Avicenna Journal of Medical Biotechnology. 2012 Jan;4(1):35. Revised Figure Legend: Figure 1. Representative AFM image of nanoparticles synthesized from different plant species (Citrullus colocynthis and Suaeda monoica) using callus and leaf extracts. Despite originating from distinct plant sources, the nanoparticles exhibit uniform morphology and an average size of ~31 nm. The consistency in nanoparticle size and shape supports the reproducibility of the synthesis process. 157 157 https://www.ajmb.org/En/Article.aspx?id=60614 https://www.ajmb.org/PDF/En/FullText/60614.pdf