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.

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.

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.

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.

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.

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.

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.

An Overview of Epidemic Typhus in the World and Iran during the 19th and 20th Centuries.

The present article provides a concise historical review on classical epidemic typhus (exanthemata typhus) in the world as well its outbreaks in Iran mainly during the 19th and 20th centuries. Typhus is still a potential public health threat under certain conditions, despite the fact that nowadays, efficient antibiotics are accessible and sanitary conditions which lead to typhus outbreaks have improved significantly.

History of Medical Parasitology and Parasitic Infections in Iran.

Parasites and parasitic diseases have been prevalent in Iran according to Iranian ancient scholars and physicians' inscriptions dating back to 865-1496. Some protozoan diseases such as malaria and cutaneous leishmaniasis have been introduced by clinical manifestations and helminthic infections by size and morphology of the worms. Scientific studies of Parasitology started in Iran from 1833, first by foreign physicians and continued from 1909 by Iranian researchers. The pioneer medical parasitologists of Iran were Dr N. Ansari and Dr. Sh. Mofidi who established the Department of Medical Parasitology in the School of Medicine, University of Tehran, 1939. Afterward, a considerable number of researchers and professors of parasitology have been active in training and research works in the fields of medical parasitology throughout the entire nation. At present, some significant parasitic diseases such as bilharsiasis and dracunculiasis are more or less eradicated and malaria is in the elimination phase. The prevalence of most helminthic infections has considerably decreased. Most of the departments of medical Parasitology in Iran are active in training MD, MSPH and PhD students. The Iranian Society of Parasitology established in 1994 is active with many eligible members and its creditable publication, the Iranian Journal of Parasitology, published seasonally since 2006. From 1833, when the scientific studies of Parasitology have started in Iran up to 2013, many researchers have been done on various fields of medical Parasitology and parasitic diseases in Iran and 2517 papers in English and 1890 papers in Persian have been published in national and international scientific journals. In addition, more than 420 books related in the field of medical parasitology field have been published in Persian language.

A History of Leishmaniasis in Iran from 19th Century Onward.

The history of leishmaniasis dates back to the distant past; however, its etiologic agent was unidentified until the mid-19th century. Here is an overview of some historical aspects of leishmaniasis in Iran mainly focused on the cutaneous form, from the mid-19th century onwards. In addition, short biographies of several contemporary researchers and experts of leishmaniasis and their achievements in the past decades are presented.

Immunohistochemical findings of the granulomatous reaction associated with tuberculosis.

OBJECTIVE/BACKGROUND: The histological diagnosis of Mycobacterium tuberculosis (MTB) has long been a diagnostic challenge in the anatomical pathology field despite availability of different laboratory methods. Immunohistochemistry (IHC) could not only confirm granulomatous tissue involvement but also demonstrate MTB antigen immunolocalization. This study tries to clarify the details of IHC staining for MTB with pAbBCG. METHODS: A total of 50 patients undergoing simultaneous biopsy and tissue culture with positive tissue culture for MTB during 2005-2009 were selected from the MRC Department at Masih Daneshvari Hospital, Tehran, Iran. Using the archives of the Pathology Department of this hospital, which is a referral center for pathological lung lesions, hematoxylin and eosin slides of the selected patients were evaluated. Twenty-three confirmed TB granulomatous tissue samples with adequate tissue and number of granulomas were chosen and studied by Ziehl-Neelsen and IHC staining with pAbBCG. RESULTS: A total of 23 cases were evaluated, of which 17 (73.9%) were males. The types of tissue obtained from study cases were as follows: pleura (9 cases, 39.1%), lymph node (cervical, axillary, and thoracic [9 cases, 39.1%]), and lung tissues (5 cases, 21.7%). IHC staining was positive in all samples, whereas Ziehl-Neelsen staining was positive in nine cases of 23 (39.1%). IHC showed positive coarse granular cytoplasmic and round, fragmented bacillary staining. In this study, epithelioid cells clearly showed more positive staining at the periphery rather than at the center of granuloma. There is also positive staining in endothelial cells, fibroblasts, plasma cells, macrophages, and lymphocytes outside the granuloma. CONCLUSION: Detection of TB in tissue slides is still based on the histological pattern of the granuloma, which has several differential diagnoses with different treatments. Presence of mycobacterial antigens and tissue morphology can be evaluated using the IHC technique. Considering the criteria of positive IHC staining of TB granulomatous reactions, this stain not only highlights the presence of mycobacterial antigens for tissue diagnosis, but also could morphologically localize their distribution in different cells. Pathologists must be familiar with adequate staining pattern, elimination of background staining, and type of selected antibody. This method is especially important for application in countries with high prevalence of TB as a technique with early diagnostic value in tissue specimens. Early diagnosis using this technique can reduce related morbidity and mortality and decrease the rate of complications due to misdiagnosis and mistreatment of TB.