armin mokhtariye†

Autophagy is a fundamental process in eukaryotic cells, essential for maintaining cellular homeostasis and promoting survival. This process involves the formation of a structure known as the autophagosome, which sequesters damaged cellular components such as misfolded proteins and dysfunctional organelles. These components are subsequently transported to lysosomes for degradation. Autophagy allows cells to withstand various stress conditions, including nutrient deprivation, hypoxia, and microbial infections. There are three primary types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, each characterized by distinct mechanisms and features. The autophagy process is tightly regulated by autophagy-related genes (ATG) and consists of several stages: induction, autophagosome formation, fusion with lysosomes, and cargo degradation. Dysfunctional autophagy has been implicated in the development of various diseases, including cancer, neurodegenerative disorders, metabolic diseases, and bacterial or viral infections. Recent studies have highlighted the dual role of autophagy in cancer: while it can act as a tumor suppressor in early stages, it may also support tumor cell survival in advanced stages. In the nervous system, autophagy helps prevent the accumulation of harmful proteins and supports neuronal function. Additionally, autophagy plays a significant role in combating invasive pathogens, serving as a defensive mechanism against bacteria and viruses. Research indicates that autophagy is a promising target for developing new therapeutic strategies for a wide range of diseases. In-depth investigations into the molecular pathways regulating autophagy, particularly the mTOR and AMPK pathways, offer potential avenues for innovative treatments. This review provides a comprehensive analysis of the mechanisms and functions of autophagy, exploring its association with various human diseases. It presents a novel perspective on the potential clinical applications of autophagy, highlighting its role in the development of therapeutic strategies and deepening our understanding of this essential cellular process.

Pompe Disease is a type of lysosomal storage disease that is caused by a deficiency of the lysosomal alpha glucosidase. Pompe disease, as a multi-systemic disorder has a broad spectrum of clinical symptoms. The objective of this research was to validate and standardize the fluorometric method to detect alpha glucosidase activity, which can be used to identify patients with Pompe disease. This study was performed on 45 Pompe patients and 50 healthy control subjects. Dried blot spots were collected and subjected to an alpha glucosidase activity assay using the fluorometric method. The obtained fluorometric outcomes were then compared to those of the validated MS-MS method. The control group showed a greater level of lysosomal alpha glucosidase activity compared to patients with Pompe disease (P value <0.001). A strong correlation was observed between fluorometric and MS-MS methods, as indicated by the high correlation coefficient (R2=0.955). Accurate and reliable detection of Pompe disease is based on laboratory diagnosis. Alpha glucosidase activity assays are used for initial diagnosis because of they are cost-effective and simple. However, the current research shows that the fluorometric method is also a reliable, cost-effective, and simple alternative to identify Pompe disease.

Hyperthyroidism and hypothyroidism are common thyroid disorders. Thyroid hormones have a great role in regulating mucosal cells and the growth of the gastrointestinal tract. In this study, we investigated the presence of Helicobacter pylori (H. pylori) infection in various types of thyroid disorders.

Our study included 297 patients whose thyroid status was identified by evaluation of thyroid hormones; triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) using Roche Electrochemiluminescence (ECL). H. pylori antibodies and antigen were evaluated by enzyme-linked immunosorbent assay (ELISA) kits in all cases.

Hypothyroidism had a significant correlation with H. pylori infection (p < 0.001). Hyperthyroidism was not related to H. pylori infection (p = 0.171). Also, in hypothyroidism, female sex more than male sex had a significant correlation with H. pylori infection (p = 0.004).

Decreasing thyroid hormones can result in dysregulation of gastric mucosal cells, therefore hypothyroidism can lead to more chance of having H. pylori infection.

Lysosomal storage disorders (LSD) are a class of metabolic disturbance in which manifested by the accumulation of large molecules (complex lipids, glycoproteins, glycosaminoglycans, etc.) in lysosomes. LSDs have a wide range of clinical symptoms that may contain organ dysfunction, neurological and skeletal disorders. The first stage of diagnosis is clinically suspected by a physician. Next stage is enzyme activity assays including Fluorometry and MS/MS methods. These methods usually placed in newborn program screening. The second laboratory diagnostic stage is molecular examination (RFLP-PCR and ARMS-PCR, Mutations Scanning Methods, DNA sequencing, MLPA and NGS methods) that is confirmation of the enzyme assays. In this article, routine diagnostic methods for LSDs were discussed. The gold standard for enzyme activity assay and molecular diagnosis is TMS and NGS, respectively.

Quantitative metabolite profiling in biological samples has the potential to reflect physiological status and to identify disease associated disorders in metabolic pathways. This approach is hindered by a wide range of pre-analytical variables. Pre-analytical variables account for 32-75% of laboratory errors, which includes the time from when the test is ordered by the physician until the sample is ready for analysis. The aims of this study was to evaluate the pre-analytical errors in diagnostic methods of inherited metabolic disorders. In this study, 35 articles with the key words Pre-analytical Errors, Metabolic disorders, Samples, Mass Spectrometry, and Gas Chromatography were searched in PubMed, Google Scholar, and Scopus databases from the year 1987 to 2018. There are some less controllable sources of pre-analytical errors that can strongly influence the reliability of test results in inborn errors of metabolism. These primarily include specimen collection, handling samples and physiological variables such as the effect of lifestyle, diet, stress, age, gender, positional effects, and endogenous variables such as drugs and circulating antibodies. As pre-analytical sources of variation can produce unpredictable and unfavorable impacts on the wellbeing of patients, a reduction in laboratory testing errors play a significant role in assessing and quality improvements. In this respect, good quality specimens, resulting from proper training and knowledge about effective factors on laboratory results, are essential for minimizing errors and optimizing resource utilization and whole patient management process to assure accurate diagnosis.