Therapeutic applications of melatonin in disorders related to the gastrointestinal tract and control of appetite.

Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time.

The association of subacute thyroiditis with viral diseases: a comprehensive review of literature

Introduction: Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight. Objective: Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases. Method: Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023. Result: According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text. Conclusions: According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness.

Harmaline exerts potentially anti-cancer effects on U-87 human malignant glioblastoma cells in vitro.

BACKGROUND: Harmaline is a ß-carboline alkaloid that can be extracted from the seeds of Peganum harmala. Harmaline has been shown to exhibit a potent cytotoxic effect against tumor cells. In this study, the anti-glioblastoma activity of harmaline was investigated in vitro. METHODS AND RESULTS: Cell viability, apoptosis, and cell cycle arrest were assessed in U-87 cells treated with harmaline at different doses. Reactive oxygen species (ROS) generation and the mRNA expression of apoptosis-associated genes were assessed. The anti-metastatic effect of harmaline on U-87 cells was evaluated by gelatin zymography assay where matrix metalloproteinase [MMP]-2/-9 enzymatic activity was measured, and the scratch assay was used to assess migratory responses. Flow cytometry demonstrated that harmaline could suppress the proliferation and induce sub-G1 cell cycle arrest and apoptotic cell death in glioblastoma cells. Harmaline treatment was also associated with an upregulation of the cell cycle-related genes, p21 and p53, and pro-apoptotic Bax, as well as the induction of ROS. The zymography assay indicated that the essential steps of metastasis were potently suppressed by harmaline through inhibiting the expression of MMP-2 and - 9. In addition, the migration of U-87 cells was significantly reduced after harmaline treatment. CONCLUSION: Our data suggest a basis for further research of harmaline which has potential cytotoxic activities in glioblastoma cells; inducing cell cycle arrest and apoptosis, repression of migration, possibly invasion, and metastasis.

Diagnostic Accuracy of Ultrasonography for Detection of Intussusception in Children; a Systematic Review and Meta-Analysis.

Introduction: The diagnosis of intussusception can be challenging in children due to the fact that the findings of clinical evaluations are nonspecific and most of the patients present with unclear history. Therefore, in this systematic review and meta-analysis, we aimed to investigate the diagnostic accuracy of ultrasonography for detection of intussusception and also compare the efficacy of point-of-care ultrasound (POCUS) with radiologist-performed ultrasound (RADUS). Methods: Two independent reviewers systematically searched different online electronic databases including MEDLINE, Scopus, Web of Science, Google Scholar, Embase, and Cochrane from inception to December 1, 2022 to identify published papers reporting accuracy of ultrasonography for diagnosis of intussusception. The quality assessment of the included studies was investigated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Results: A total of 1446 records were retrieved in the initial search of databases. After screening the titles, a total of 344 studies were retrieved for the detailed assessment of full-text. Finally, 37 studies were included in qualitative and quantitative analysis. The pooled sensitivity and specificity of ultrasonography for diagnosis of intussusception were 0.96 (95% CI: 0.95-0.97) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 24.57 (95% CI: 8.26-73.03) and 0.05 (95% CI: 0.04-0.08), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.989. Mete-regression showed that there is no significant difference between diagnostic performance of POCUS and RADUS (p = 0.06 and rDOR (diagnostic odds ratio) = 4.38 (95% CI: 0.92-20.89)). Conclusion: This meta-analysis shows that ultrasonography has excellent sensitivity, specificity, and accuracy for diagnosis of intussusception in pediatric patients. Moreover, we found that diagnostic performance of POCUS is similar to that of RADUS for diagnosis of intussusception.

The role of hypoxia-inducible factors in breast cancer stem cell specification.

Breast tumor is heterogeneous cancer with high morbidity and mortality rates, particularly in developing countries. Despite new efforts to reduce the breast cancer implications, the number of newly diagnosed cases is increasing worldwide. It is believed that cancer stem cells (CSCs) are responsible for the implication of cancers including breast cancer. Although CSCs compose a small population in tumor bulks, they play a crucial role in tumor initiation, progression, metastasis, and chemotherapeutic resistance. These events are mediated by the hypoxia-inducible factor (HIF) pathway which regulates the transcription of genes involved in CSC maintenance and tumorigenesis. In this review, we discussed the mechanisms by which hypoxia- or chemotherapy-induced HIFs promote breast CSC specification.

Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19.

The emerging COVID-19 pandemic led to a dramatic increase in global mortality and morbidity rates. As in most infections, fatal complications of coronavirus affliction are triggered by an untrammeled host inflammatory response. Cytokine storms created by high levels of interleukin and other cytokines elucidate the pathology of severe COVID-19. In this respect, repurposing drugs that are already available and might exhibit anti-inflammatory effects have received significant attention. With the in vitro and clinical investigation of several studies on the effect of antidepressants on COVID-19 prognosis, previous data suggest that selective serotonin reuptake inhibitors (SSRIs) might be the new hope for the early treatment of severely afflicted patients. SSRIs' low cost and availability make them potentially eligible for COVID-19 repurposing. This review summarizes current achievements and literature about the connection between SSRIs administration and COVID-19 prognosis.

Immunologic aspects of migraine: A review of literature.

Migraine headaches are highly prevalent, affecting 15% of the population. However, despite many studies to determine this disease's mechanism and efficient management, its pathophysiology has not been fully elucidated. There are suggested hypotheses about the possible mediating role of mast cells, immunoglobulin E, histamine, and cytokines in this disease. A higher incidence of this disease in allergic and asthma patients, reported by several studies, indicates the possible role of brain mast cells located around the brain vessels in this disease. The mast cells are more specifically within the dura and can affect the trigeminal nerve and cervical or sphenopalatine ganglion, triggering the secretion of substances that cause migraine. Neuropeptides such as calcitonin gene-related peptide (CGRP), neurokinin-A, neurotensin (NT), pituitary adenylate-cyclase-activating peptide (PACAP), and substance P (SP) trigger mast cells, and in response, they secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) as a selective result of corticotropin-releasing hormone (CRH) secretion. This stress hormone contributes to migraine or intensifies it. Blocking these pathways using immunologic agents such as CGRP antibody, anti-CGRP receptor antibody, and interleukin-1 beta (IL-1ß)/interleukin 1 receptor type 1 (IL-1R1) axis-related agents may be promising as potential prophylactic migraine treatments. This review is going to summarize the immunological aspects of migraine.

MicroRNA let-7 and viral infections: focus on mechanisms of action.

MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.