Hossein Aazami

Objective

The aim of this study was to evaluate the status of scientific research output of omics in regards to human diseases with more attention shifted toward endocrine and metabolism disorders in Iran, in order to find scientific gaps and also to design future plans for further investigations in this field.

Methods

Extensive search was performed in the electronic databases of Scopus and PubMed, and documents published by Iranian authors up to 27 December 2020 were extracted. Articles related to human diseases were included and categorized based on their types and topics.

Results

A total of 904 publications were found. Followed by checking their titles and abstracts, 327 studies were included. The trend of publication has been increasing during the past years. Regarding this subject, the highest number of publications was in the field of malignant disorders with 82 publications followed by reproductive system diseases and infectious diseases with 33 publications in each subject. Only 12 articles were found in the field of endocrinology and metabolism. The most popular techniques used in those reports were two-dimensional electrophoresis coupled with mass spectrometry (34.4 %) followed by NMR (22.6 %), LC/MS/MS (15 %).

Conclusions

Omics studies in Iran are a relatively new approach and the number of original articles regarding endocrine disorders in humans is limited. Providing appropriate infrastructures including lab facilities with high technology instruments can improve the quality and quantity of basic and clinical researches in this field.

Background and aims

Exosome as a novel biomarker reflecting cell behavior in normal and pathological conditions such as diabetes is being the center of academic attention. Therefore, we aimed to study the research output of exosome in diabetes globally.

Methods

We conducted a bibliometric approach to analyze publications on exosome and diabetes from the beginning to 2021 based on keyword search in the Scopus. Annual publications, citations, contributions, co-authorships, and co-occurrences were analyzed and plotted using VOSviewer and GraphPad Prism.

Results

410 original articles and 149 reviews have published between 2009 and 2021. China and the USA were top countries in research output, sponsorship, and international collaborations. The top journals were Scientific Reports, Stem Cell Research and Therapy and Diabetes. The top institution was the University of Queensland in Australia. The top author was Chopp M. Co-occurrence analysis indicated that researchers focused on 1) extracellular vesicles in insulin resistance induced by metabolic disorders like obesity and diabetes mellitus; 2) diagnostic applicability of exosomal microRNAs as biomarkers for diabetic nephropathy; 3) therapeutic effect of exosome in wound healing and endothelial dysfunction during diabetes mellitus; and 4) The oxidative stress, autophagy, apoptosis, fibrosis, inflammation and angiogenesis mediated by exosomes during diabetes.

Conclusion

The trend in research output has been increased in this field, and advanced countries are involved much more than other countries in terms of research, financial support, and international collaboration. The bibliometric results could be beneficial for further studies in better understanding of novel ideas in exosome and diabetes fields.

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.

Introduction: Prominent prognostic parameters that reflect the severity of coronavirus disease 2019 (COVID-19) to adopt an appropriate therapeutic approach are not fully identified. This systematic review and meta-analysis aimed to explore the association between lymphocyte variation and disease severity in COVID-19 individuals. Methods: We searched Web of Science, Scopus, PubMed, EMBASE and WHO website to retrieve studies investigating lymphocyte subset counts in non-severe and severe cases of COVID-19. The pooled standardized mean difference (SMD) between two groups and the pooled average count of each lymphocyte subset were assessed by employing a random-effect model. Results: Thirty-nine investigations on 5,087 participants, including 3,578 non-severe patients and 1,509 severe patients, were included. The pooled analysis showed that non-severe patients had higher total T lymphocytes (SMD = 1.01; 95% CI: 0.82, 1.20; I 2 = 75.7%), T helper cells (SMD = 1.07; 95% CI: 0.85, 1.28; I 2 = 85.4%), T cytotoxic cells (SMD = 1.07; 95% CI: 0.82, 1.32; I 2 = 87.1%), B cells (SMD = 0.72; 95% CI: 0.45, 0.98; I 2 = 79.7%), and natural killer cells (SMD = 0.65; 95% CI: 0.47, 0.84; I 2 = 63.1%) than severe patients and the average count of the corresponding lymphocyte signatures in non-severe patients/severe patients were 878.88/448.40, 493.12/268.96, 311.91/158.91, 177.09/110.37, and 155.02/103.09 cells/μL, respectively. Conclusion: Lymphopenia may be a dilemma in COVID-19 management because over-activation of lymphocytes may lead to cytokine storm or acute respiratory distress syndrome (ARDS). In contrast, lymphopenia may increase SARS-CoV-2 amplification and COVID-19 severity. Therefore, novel therapies targeting lymphocyte proliferation or contraction may counterbalance lymphocyte counts in these patients.

COVID-19 disease has put life of people in stress worldwide from many aspects. Since the virus has mutated in absolutely short period of time the challenge to find a suitable vaccine has become harder. Infection to COVID-19, especially at severe life threatening states is highly dependent on the strength of the host immune system. This system is partially dependent on the balance between oxidative stress and antioxidant. Besides, this virus still has unknown mechanism of action companied by a probable commune period. From another hand, some reactive oxygen species (ROS) levels can be helpful on the state determination of the disease. Thus it could be possible to use modern bioanalytical techniques for their detection and determination, which could indicate the disease state at the golden time window since they have the potential to show whether specific DNA, RNA, enzymes and proteins are affected. This also could be used as a preclude study or a reliable pathway to define the best optimized time of cure beside effective medical actions. Herein, some ROS and their relation with SARS-CoV-2 virus have been considered. In addition, modern bioelectroanalytical techniques on this approach from quantitative and qualitative points of view have been reviewed.

Background: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM. Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies. Results: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles. Conclusions: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42020196122.

Background
Modifying gut dysbiosis has achieved great success in managing type 2 diabetes mellitus (T2DM) and also T2DM affected the gut microbial composition. Objectives To determine the research trend of scientific publications on the relationship between gut microbiota and T2DM through a bibliometric and descriptive approach.
Method
We included originals and reviews related to both topics of gut microbiota and T2DM through searching in Scopus up to 31 December 2019 and then characterized their bibliometric profiles including the number of publications, citations, institutions, journals, countries, and the collaboration network of authors, countries, terms and keywords. Moreover, we performed a descriptive evaluation of the clinical trials based on their intervention type and its influence on gut dysbiosis.
Results
We achieved 877 articles (436 originals and 441 reviews) according to our inclusion criteria. The annual publications were constantly increased over time and reached 220 publications in 2019. Out of 436 original articles, 231 animal studies and 174 human studies were found. The majority of human studies were clinical trials (n = 77) investigating the influence of drugs (n = 21), regimens (n = 21), pre/pro/symbiotic (n = 19), surgeries (n = 15), or both drug and regimen (n = 1) on gut dysbiosis. Roux-en-Y gastric bypass and metformin were assessed the most in these trials. Obesity side by side T2DM has been assessed in this area of literature based on term and keyword analyses showing their possible similar pathways mediated by gut microbiota.
Conclusion
The exponentially growing documents on gut microbiota and T2DM had been published during the last decade and revealed gut microbiota alteration mediated antidiabetic effect of many interventions. Thus, we suggest other researchers to consider this pathway in efficacy assessment of therapeutic modalities and to find the optimal composition of gut microbiota that guarantees healthy insulin sensitivity.

Aims

Due to the importance of omics approaches in diabetes diagnosis, we were assumed to study the scientific activities on omics and type 2 diabetes worldwide.

Method

Bibliometric approach was utilized to evaluate the documents on proteomics, lipidomics, and metabolomics in patients with type 2 diabetes in the Scopus database from the beginning to 2020. The articles were screened by two reviewers and the number of publications and citations on omics and type 2 diabetes, top-ranked journals, top-cited articles, country co-contributions, co-authorships, author keywords, and terms were analyzed.

Results

The scientific publications in this field consisted of 551 original articles, of which the USA shares the most percent, followed by China and Germany. The frequent keywords showed that the following hotspots were of interest: “Metabolomics, proteomics, and lipidomics as biomarkers for diabetes”, “Omics and diabetic nephropathy”, “The application of omics in obesity, insulin resistance, and type 2 diabetes”.

Conclusion

This study showed an increasing trend in applying omics in type 2 diabetes researches and determined the leading producers in this field. Besides, the research hotspots and the main subjects of documents were provided for future research and policy decision-making.

After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensinconverting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in

Coronavirus disease 2019 (COVID-19) caused a fatal pandemic worldwide. This review aims to discuss laboratory, molecular, and serological methods and their advantages and disadvantages over each other in COVID-19 diagnosis. Moreover, computed tomography (CT) scan, that is used on suspicion of COVID-19 pneumonia and for determining the severity and progression of the disease, is also discussed. Different CT features categorize the patients into low to high-risk groups. Here, we described three kinds of CT classification based on CT patterns within different time courses of the disease. Chest CT imaging should be considered for screening, evaluating, and following up COVID-19 due to its high sensitivity. Approximately, shortly after the onset of symptoms, viral load can be diagnosed by real-time PCR technique through bronchoalveolar lavage, nasopharyngeal and/or oropharyngeal swab sampling. Proper sampling may delineate the result of this test. Although RT-PCR assay is currently considered the gold standard test, false-negative results should be considered. Furthermore, a positive test may indicate the infection with SARS-CoV-2, but not necessarily the disease, and the person may be a carrier or other organs may be involved other than the lungs. In contrast to CT imaging, RT-PCR assay has poor sensitivity, but it helps the decision-making on hospitalization and isolation. The emergence of reliable serological tests has promoted the diagnosis, treatment process, chronic or carrier status of an individual, and epidemiological studies. In addition, an earlier and more accurate diagnosis will be provided for asymptomatic or susceptible individuals.

In early December 2019, the novel coronavirus (COVID-19) causing a cluster of pneumonia of unknown etiology originated from Wuhan, China, and spread rapidly throughout the world. The WHO (World Health Organization) changed the status of COVID-19 outbreak from epidemic into pandemic on March 11, 2020. →What this article adds: Since the emergence of COVID-19, the number of publications on this topic has dramatically grown. About 84% of COVID-19 documents are open-access. The focus of COVID-19 literature in terms of countries, journals, institutions, terms, and keywords which all were discussed in detail sets out the research hotspots and important topics in this field.

Background: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-β was significantly elevated in the sinonasal tissue of patients with CRSsNP. Conclusions: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.

Epigenetics regulate gene function without any alteration in the DNA sequence. The epigenetics represent one of the most important regulators in different cellular processes and have initially been developed in microorganisms as a protective strategy. The evaluation of the epigenetic mechanisms is also important in achieving an efficient control strategy in tuberculosis (TB). TB is one of the most significant epidemiological concerns in human history. Despite several in vivo and in vitro studies that have evaluated different epigenetic modifications in TB, many aspects of the association between epigenetics and TB are not fully understood. The current paper is aimed at reviewing our knowledge on histone modifications and DNA methylation modifications, as well as miRNAs regulation in TB.

The scientometric analysis of science has been widely employed to explore the scientific production of countries, academic institutions, universities, journals, and individual researchers. →What this article adds: Analysis of the Medical Journal of the Islamic Republic of Iran illustrated several trends in publishing a scientific journal in field of health, some of which including: dominance of multiauthorship vs single-authorship and publishing more at each volume annually. These may be related to either/both economic interests of publishers or/and exponentially accelerating development of science.

Although IgE levels increase in the sera of patients with nasal polyps, and most studies have examined its rate and role in these patients, IgA has not been studied as the most abundant antibody after IgG in sera of patients with CRS. →What this article adds: There is no significant difference in total IgA, IgA1, and IgA2 levels in serum of patients with CRS in comparison to healthy controls. Therefore, serum IgA is not a good marker for diagnosis and prognosis of CRS, consequently local investigation of these biomarkers may result in better interpretation.

Background: Chronic Rhinosinusitis (CRS) is a persistent inflammatory disease affecting paranasal sinuses. CRS is categorized into two distinct subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Although several immune cells are involved in the CRS pathogenesis, the role of T cells is not fully understood. The objective of the present study was to evaluate the frequency of CD4 + and CD8 + T cells and macrophages in the sinonasal mucosa of CRS patients, as well as to investigate the specific transcription factors for Th1, Th2, Th17, and Treg cells.

Methods: In this study, 15 healthy controls, 12 CRSsNP, and 23 CRSwNP patients participated. CD4 + , CD8 + , and CD68 + cells were investigated in the sinonasal tissues using immunohistochemistry. The expression of transcription factors related to Th subsets (T-bet, GATA3, Ror-γt, and FoxP3) was evaluated using real-time PCR. Furthermore, CRSwNP patients were defined as eosinophilic when eosinophils consisted of more than 10% of total inflammatory cells. The Kruskal-Wallis, Mann-Whitney, and Spearman tests were used in statistical analyses.

Results: The median (range) age of the studied groups was: 32 (14-67) for CRSwNP, 28 (10-43) for CRSsNP, and 27 (17-44) for controls. The number of eosinophils in CRSwNP patients was higher than two other groups, whereas neu-trophils were elevated in both CRSwNP and CRSsNP groups in comparison to controls. The frequency of CD4 + and CD8 + T cells, macrophages, and total inflammatory cells were significantly increased in CRSwNP and CRSsNP patients compared with controls. The mRNA expression of GATA3 was increased in CRSwNP patients while mRNA expression of Ror-γt was elevated in CRSsNP patients. No significant difference was observed in T-bet mRNA expression among three groups. Both CRSwNP and CRSsNP patients showed decreased FoxP3 mRNA expression in comparison to controls.

Conclusion: The frequency of CD4 + and CD8 + T cells was elevated in CRS patients. In addition, we demonstrated Th2 dominance in CRSwNP patients and Th17 dominance in CRSsNP patients, implicating different mechanisms may underlie the disease. Better CRS classification and targeted therapeutic strategies may be achievable by determining the pattern of infiltrating inflammatory cells. Therefore, further experimental investigations on T cells are needed.

Background. Microsurgery is a surgical procedure requiring a high degree of precision and is commonly facilitated through the use of an intraoperative microscope. When operating the microscope system, the long-term posture leads to musculoskeletal disorders in surgeons, and seats are commonly employed to diminish these problems. The present study was conducted to evaluate musculoskeletal discomfort during work with a saddle seat in comparison with conventional seats for microscopic work.

Methods. Two types of seats, a saddle and a conventional one, were evaluated for 73 microsurgical surgeons in terms of musculoskeletal discomfort. Corlett and Bishop's body part discomfort scale was used to assess musculoskeletal discomfort before and after working with the seats.

Results. The highest amount of discomfort that microsurgical surgeons acquire in the workplace was focused on their neck, shoulders, arms and back. During work with a saddle seat, a significant reduction was found for discomfort values in the neck, shoulder, arm, back, elbow and forearm, as well as the whole body (p < 0.05).

Conclusion. This study showed that the use of saddle seats provides a more appropriate physical posture at work, and can decrease musculoskeletal discomfort in different parts of the body of microsurgical surgeons.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.