Iran in transition.

Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.

No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients.

BACKGROUND: Diffuse malignant mesothelioma (DMM) is increasing in incidence on a worldwide basis and is linked to exposure to asbestos. Simian virus 40 (SV40), a DNA virus, was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963. It has been associated with various types of malignancy in animal experiments. There have been suggestions that SV40 might play a role in the pathogenesis of DMM. OBJECTIVE: To evaluate the association between SV40 and DMM in Iranian patients. METHOD: In a case-control study between the years 2007-2008, isolated DNA from 60 paraffin blocks of patients with DMM and 60 controls was assessed to detect three human polyomaviruses (JCV, BKV, and SV40) using three different sets of primers by multiplex nested PCR analysis. We related the patients with diffuse malignant mesothelioma to possible sites of exposure to asbestos. RESULTS: None of the DMMs nor any patient in the control group had SV40 genome on polymerase chain reaction (PCR). All of the cases were SV40 T antigen negative. CONCLUSION: This study suggests that DMM is independent of SV40 infection in Iran.

Professor Abdulkarim Vessal (1933-2022) and His Role in Promotion of Radiology and Medical Journalism in Iran.

Abdulkarim Vessal, a distinguished professor of the Shiraz School of Medicine, was the founder of the "Archives of Iranian Medicine Journal" and a permanent member of the "Iranian Academy of Medical Sciences", who finally, after five decades of efforts to promote radiology and medical journalism in Iran, passed away on February 18, 2022 in Shiraz. His demise is a great loss for the Iranian medical community, especially in Shiraz. In the present paper, his life and career are briefly reviewed.

Effects of Human Nucleolus Upon Guest Viral-Life, Focusing in COVID-19 Infection: A Mini- Review.

The nucleolus is a subcellular membrane-less structure of eukaryotic cells. In 1965, in a world's southern summer summit in Uruguay, the role of the nucleolus as the site of ribosome synthesis, biogenesis, and processing of tRNA was conclusively established. Today, accumulating evidence confirm the multiple functions of the nucleolus, including tRNA precursor processing, cell stress sensing, as well as being influential in gene silencing, senescence, lifespan, DNA damage response (DDR), and cell cycle regulation. Therefore, nucleolopathy is observed in various human diseases. Modern advances have provided fundamental insights concerning how and why the nucleolus is targeted by different pathogenic organisms. Viruses are major organisms that disrupt the normal function of the nucleus and produce nucleoli proteins for facilitating the replication of viruses causing viral infections. In this review, we focus on the possible role of nucleoli upon coronavirus infections, particularly in coronavirus disease 2019.

Mitochondria determine response to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy: An evidence-based hypothesis.

Immunotherapy based on programmed cell death protein-1 (PD-1) is a promising approach in oncology. However, a significant fraction of patients remain unresponsive. Therefore, it is imperative to clarify the relevant predictive factors. A decrease in cellular adenosine triphosphate (c-ATP) level can predispose to cellular dysfunction. ATP is a prerequisite for proper T cell migration and activation. Therefore, a decrease in the c-ATP level impairs T cell function and promotes cancer progression. This article gives an overview of the potential predictive factors of PD-1 blockade. Besides, it highlights the pivotal role of mitochondria in response to anti-PD-1 therapies.

Targeted Anti-Mitochondrial Therapy: The Future of Oncology.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the dependence on the normal cells. This article illustrates the benefits of new functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells' survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in the metabolism of cancer stem cells (CSCs), the tumor components responsible for cancer recurrence and metastasis. This theory highlights the mitochondria in cancer biology and explains how targeting mitochondria may improve oncological outcomes.

Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus).

BACKGROUND: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. METHODS: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. RESULTS: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. CONCLUSION: Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.

Convergence Science to Transform Biomedicine: A Narrative Review.

Recently convergence science was proposed and promoted in a large report from US National Science Foundation and Department of Commerce (NSF/DOC). The report was entitled "converging technologies for improving human performance. "It was dealing with converging of four technologies as: Nanotechnology, Biotechnology, Information technology and Cognitive science (NBIC). The report has gained tremendous popularity throughout the academia and scientific world. On Dec 2015 in a monthly meeting of the department of basic science of Iran Academy of Medical Science, the report of NSF/DOC on NBIC has been discussed. A working group has been established for more discussion and application in Iran. Several seminars in this regard have been performed, and presently this technology has been started as pilot in some technical universities in Iran. After US National Research Council (NCR) in the year 2014 and Massachusetts Institute of Technology (MIT) on convergence in biomedicine, the concept opened a new gate to approach solving medical and health care problems; the convergence technology in biomedical sciences has become interested and gained great popularity among the working group of convergence science in academy of medical science. This technology can lead to advances in fighting chronic diseases such as cancer, dementia, psychiatric disorders, disease of aging and others. The following is summary of proposed discussions in several gathered groups of scientists in this field.

Antinociceptive effect of chronic lithium on visceral hypersensitivity in a rat model of diarrhea-predominant irritable bowel syndrome: The role of nitric oxide pathway.

BACKGROUND AND AIM: Lithium, a widely used drug in bipolar-affective disorders, plays gastro-protective roles. The effects of lithium on several tissues are mediated through nitric oxide (NO), which regulates gastrointestinal motility and mucosal integrity. The aim of this study was to investigate the protective effect of chronic lithium administration on visceral hypersensitivity and to investigate the role of NO as a potential mechanism of lithium in a rat model of irritable bowel syndrome. METHODS: Colitis was induced by the intracolonic administration of acetic acid. After subsidence of inflammation on the seventh experimental day, nociception and defecation parameters were measured. A subgroup of animals had been pretreated with lithium carbonate (600 mg/L) for 35 days. Thereafter, either a non-selective NO synthase (NOS) inhibitor (N-nitro-L-arginine methyl ester [L-NAME], 10 mg/kg), a selective NOS inhibitor (aminoguanidine, 100 mg/kg), or saline were administered intraperitoneally 1 h before measurements. RESULTS: Chronic lithium attenuated the visceral hypersensitivity, increased the nociceptive threshold, and decreased stool frequency. L-NAME and aminoguanidine decreased the nociceptive threshold and reduced the protective effects of lithium on visceral hypersensitivity. Stool frequency was increased in both the lithium-treated and water-treated groups by L-NAME administration, but not aminoguanidine. The form of defecation in the lithium-treated rats shifted toward hard stools rather than being soft and formless, but NOS inhibitors did not change the stool consistency pattern. CONCLUSION: The results indicate the antinociceptive property of chronic lithium on visceral hypersensitivity. As this effect was lowered by NOS inhibitors, NO might play a role in the protective effect of lithium to some extent.

In commemoration of Haj Mohammad Nemazee (1895-1972): the founder of Nemazee Hospital in Shiraz.

Nemazee Hospital in Shiraz, Fars Province, in southern Iran is a well-equipped modern hospital, which was founded in 1955. It is one of the greatest memorials of a Shirazi beneficent merchant, the late Haj Mohammad Nemazee (1895-1972), who dedicated much of his wealth to charitable affairs in his birthplace. This paper briefly explores the history of the establishment of Nemazee Hospital in Shiraz.

New Insights into Connection of Nucleolar Functions and Cancer.

The nucleolus is an intranuclear membrane-less organelle. It is involved in ribosome biogenesis and protein synthesis. When the demand for protein synthesis increases in cell growth and proliferation (e.g., tumors), the cell upregulates ribosome biogenesis. Changes in nucleolar size and number have been recognized as known features of many tumor types. Recent evidence suggests that overproduction of ribosome, decreased ribosome biogenesis, and quantitative and qualitative changes in the nucleolus function, may result in oncogenesis. Today, it is clear that the nucleolus is involved in processes other than ribosome biogenesis. Other functions of the nucleolus include detecting and responding to endogenous and exogenous stress, maintaining genome stability, and regulating cell cycle progression, telomere function, cellular senescence, gene expression, and chromatin structure. Alterations in many of these fundamental nucleolar processes may contribute to the formation of cancer cell phenotypes. This phenomenon suggests that normal nucleolar functions are a safeguard against the development of malignancies and have potential therapeutic effects, as reported in non-small-cell lung carcinoma and other malignancies.

Cell Energy: A New Hypothesis in Decoding Cancer Evolution.

The present study deviates from previous approaches as it focuses on the concept of energy to illuminate cancer-related issues. Energy is a prerequisite for any function; cellular function is no exception, and thus, reduced energy in human cells can impair their performance. This hypothesis provides a novel view of cancer formation. It shows that a normal cell transforms into its cancerous counterpart in response to cellular adenosine triphosphate (ATP) depletion. Moreover, it presents a new definition for the origin of cancer stem cells and how they can regenerate cancer. This article regards a distinct aspect of cancer that helps to differentiate various phases of its progression and shed light on some of the uncharted zones of its pathway for the first time that needs further confirmation by empirical studies.

An international collaborative pathologic study of surgical lung biopsies from mustard gas-exposed patients.

BACKGROUND: Recent studies have shown strong evidence that bronchiolitis obliterans is the major long-term sequelae of exposure to sulfur mustard (SM). This study is the first to examine the histopathologic spectrum of changes in a large number of surgical lung biopsies from patients exposed to SM. METHOD: Fifteen patients with chronic respiratory disease from mustard gas exposure were divided into severe (6 cases) and mild exposure (9 cases). All had surgical (open or thoracoscopic) lung biopsy, pulmonary function tests (PFTs) and chest high-resolution computed tomography scan (HRCT). RESULT: The mean age of the cases was 43.8+/-9.6 (range 33-65). All patients had dyspnea and cough as the two main complaints. Only one patient was a smoker. Thirteen patients had normal PFTs, while one had obstruction and one had mild restriction. Six (66.6%) patients in the mild exposure and 3 (50%) in the severe exposure group showed evidence of more than 25% air trapping on chest HRCT. Among the mild group, 3 had features of constrictive bronchiolitis and another had features suggestive of this (bronchiolectasis and mucus stasis). The next most common finding was a mild-to-moderate chronic cellular bronchiolitis (3 patients). Two among the 6 in the severe group showed constrictive bronchiolitis and one showed features suggestive of constrictive bronchiolitis. CONCLUSION: We conclude that about half of patients had diagnostic constrictive bronchiolitis, or bronchiolectasis and mucus stasis consistent with more proximal luminal compromise. The fact that there were no differences between the low- and high-dose groups suggests that effects of SM are not solely dependent on the severity of exposure. The results also indicate that the diagnosis of chronic lung disease due to SM may be difficult. Surgical lung biopsy may be helpful in difficult cases, as constrictive (obliterative) bronchiolitis can be present in symptomatic patients with normal PFTs and chest HRCT.

New Advances in RNAs.

Since the discovery of the first microRNA gene, lin-4, in Caenorhabditis elegans in 1993, many of this small regulatory genes have been reported in plants, viruses, and various kinds of animals. This announced a new world of RNA molecules, which subverted our traditional thinking about RNA. In this review, I summarized the main findings from researchers at different laboratories on microRNAs importance, functionality, production, and different aspects of their biologic activities.A narrative literature overview of relevant papers known to the author and that were retrieved from PubMed is presented.MicroRNA, a nonprotein-coding small RNA with almost 21 - 23 nucleotides in length, is an essential regulatory apparatus in the cells and their environment. They are crucial molecules for development, evolution, cellular differentiation, proliferation, embryogenesis, and cell death. Two classes of microRNAs exist: small temporal RNA--stRNA (miRNAs) and small interfering RNA--siRNAs (RNAi). The latter is a useful tool for the diagnosis, treatment, and prevention of diseases particularly cancer and viral diseases.There have been tremendous research regarding various aspects of these genes silencing and regulatory molecules which are preserved in all kinds of creatures. Currently, about 1% of the known human genes encode microRNAs.

A Brief History of Oral and Maxillofacial Pathology in Iran.

This is a brief look at the establishment and development of oral and maxillofacial pathology in Iran. The program of the oral and maxillofacial pathology at first was integrated into the curriculum of the Dental School of Tehran University in 1960. The Iranian Society of Oral and Maxillofacial Pathologists was officially founded in 1999.

Recent Advances on Nucleolar Functions in Health and Disease.

The nucleolus is an internuclear organelle without a visible membrane via the light microscope inside the cell nucleus. It is the main site for synthesis of ribosome as a complex machine for coordinating protein production. It forms around a specific chromosomal feature called the nucleolar organizing region (NOR) which possesses numerous ribosomal DNA (rDNA). Although the nucleolus is best known as coordinator of ribosomal biogenesis and protein synthesis, recently, there is exciting awareness both on better understanding of ribosome biogenesis and non-ribosomal nucleolar functions. A great amount of research has clearly indicated that the nucleolus has functional activities in both ribosomal and non-ribosomal conditions such as development, aging, cell cycle, gene stability, lifespan regulation, and progeria. Through recent sophisticated and advanced technologies such as genomics, proteomics, metabolomics, advances of knowledge in RNA species and new approaches in microscopic analysis methods, researchers have shown that perturbation in the nucleolar structure and function (nucleolar stress) have been associated with human diseases including cancer, viral infection, cardiovascular and neurodegenerative diseases. In this review, we discuss the impact of current research providing new information regarding nucleolar roles and functions in some human diseases and aging.

The first medical journal of Tehran University.

The School of Medicine of Tehran University was officially established in 1934. Then, in December 1939, Professor Charles Oberling (1895-1960), the famous French pathologist was appointed as the Dean of Medical, Pharmacy, and Dentistry Schools and a new era of medical education was ushered in. He suggested to the Ministry of Culture's authorities to publish a medical journal; subsequently, the first Persian academic medical journal in Iran was founded and published in 1943. Herein, we present a brief account of this medical journal's foundation as well as biographies of its founders and editorial board.

Religious and cultural traits in HIV/AIDS epidemics in sub-Saharan Africa.

BACKGROUND: The pandemic of HIV/AIDS in sub-Saharan Africa and the rise of epidemics in Asia to the previously unforeseen level are likely to have global social, economic, and political impacts. In this emergency, it is vital to reappraise the weight of powerful religious and cultural factors in spreading the disease. The role of Islam in shaping values, norms, and public policies in North African states is to be appreciated for the lowest HIV prevalence in their populations. Yet, the place of religion in prevention of the disease diffusion is not fully understood nor worldwide acknowledged by the primary decision makers. Another topic, which has received little attention to date, despite the abundance of literature concerning the unfortunate Africa's anti-AIDS campaign, is an issue of colonial past. METHODS: To better comprehend the share of both traits in diverse spread of HIV in sub-Saharan Africa, we studied the correlation between Muslim and Christian proportions in the state's population and HIV rate. RESULTS: By this method, Muslim percentage came out as a potential predictor of HIV prevalence in a given state. In another approach, most subcontinental countries were clustered by colocalization and similarity in their leading religion, colonial past, and HIV seroprevalence starting from barely noticeable (0.6 - 1.2%, for Mauritania, Senegal, Somalia, and Niger) and low levels (1.9 - 4.8%, for Mali, Eritrea, Djibouti, Guinea, Guinea-Bissau, Burkina-Faso, and Chad) for Muslim populated past possessions of France and Italy, in the northern part of the subcontinent. Former territories of France, Belgium, Portugal, and the UK formed two other groups of the countries nearing the equator with Catholic prevailing (Democratic Republic of Congo, Republic of Congo, Rwanda, Gabon, and Burundi) or mixed populations comprising Christian, Muslim, and indigenous believers (Benin, Ghana, Uganda, Togo, Angola, Nigeria, Liberia, Kenya, Cameroon, Côte d'Ivoire, and Sierra-Leone), which covered the HIV prevalence range from 1.9% to 7%. Albeit being traced by origin to the central part of the continent, HIV has reached the highest rates in the South, particularly Malawi (14.2%), Zambia (16.5%), South Africa (21.5%), Zimbabwe (24.6%), Lesotho (28.9%), Botswana (37.3%), and Swaziland (38.8%)-all former British colonies with dominating Christian population. CONCLUSION: In the group ranking list, a distinct North to South oriented incline in HIV rates related to prevailing religion and previous colonial history of the country was found, endorsing the preventive role of the Islam against rising HIV and the increased vulnerability to menace in states with particular colonial record.

In commemoration of Dr. Mostafa Habibi-Golpayegani (1904 - 1948): pioneer of modern pathology in Iran.

In the first decade of the twentieth century, a child was born who subsequently became an influential figure in the Iranian contemporary medicine. He was the late Dr. Mostafa Habibi-Golpayegani (1904 - 1948), pioneering professor of the modern pathology in Iran. Herein, a brief account of his life and career is presented.