Gastric cancer (GC), second most leading cause of cancer-associated mortality globally, is the cancer of gastrointestinal tract in which malignant cells form in lining of the stomach, resulting in indigestion, pain, and stomach discomfort. Autophagy is an intracellular system in which misfolded, aggregated, and damaged proteins, as well as organelles, are degraded by the lysosomal pathway, and avoiding abnormal accumulation of huge quantities of harmful cellular constituents. However, the exact molecular mechanism of autophagy-mediated GC management has not been clearly elucidated. Here, we emphasized the role of autophagy in the modulation and development of GC transformation in addition to underlying the molecular mechanisms of autophagy-mediated regulation of GC. Accumulating evidences have revealed that targeting autophagy by small molecule activators or inhibitors has become one of the greatest auspicious approaches for GC managements. Particularly, it has been verified that phytochemicals play an important role in treatment as well as prevention of GC. However, use of combination therapies of autophagy modulators in order to overcome the drug resistance through GC treatment will provide novel opportunities to develop promising GC therapeutic approaches. In addition, investigations of the pathophysiological mechanism of GC with potential challenges are urgently needed, as well as limitations of the modulation of autophagy-mediated therapeutic strategies. Therefore, in this review, we would like to deliver an existing standard molecular treatment strategy focusing on the relationship between chemotherapeutic drugs and autophagy, which will help to improve the current treatments of GC patients.

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Potential Therapeutic Action of Autophagy in Gastric Cancer Managements: Novel Treatment Strategies and Pharmacological Interventions

The microRNA (miRNA) has a unique physiological regulation function in tissues, thus its expression level can reflect the development of various diseases. Nevertheless, due to the low-abundance and high-homologous similarity of miRNA, the precise detection of miRNA remained a challenge. Herein, a CRISPR/Cas12a-assisted multi-amplification strategy-mediated programmable miRNA (Cas-Master) biosensor was constructed based on photoelectrochemistry (PEC) and colorimetry (CM). Initially, by employing the rolling circle amplification (RCA), the miRNA was transformed into the long single-stranded DNA with a large repetitive sequence region, which specifically triggered the Cas12a’s trans-cleavage performance. Afterwards, the activated-Cas12a randomly cleaved the trigger strands of hybridization chain reaction (HCR). Thus, Cas12a was used as the medium of RCA and HCR reaction to form the multi-amplification circuit. Then, the glucose oxidase (GOx) was combined with β-CD@AuNPs and NH 2 -MIL-88B (Fe) nanozyme to form dual-cascade system for PEC and CM response, respectively. Both the PEC and CM signal showed linear relationship with the logarithm of the miRNA concentrations from 1 fM to 100 nM with the limit of detection of 0.3 fM (PEC) and 0.5 fM (CM). Furthermore, through the programmed design of the RCA reaction, the Cas-Master can be applied to recognize different types of miRNAs. Besides, a portable device was constructed based on Cas-Master, providing a new solution to expand the Cas12a-based platform into areas of point-of-care test (POCT) and early disease diagnosis. • Cas12a was used as the medium of RCA and HCR to form the multi-amplification circuit. • Glucose oxidase induced dual-cascade system to realize PEC and colorimetry detection. • The programmed design of the RCA reaction can recognize different types of miRNAs. • A portable device was constructed for the POCT of miRNAs with high specificity. 

Programmable readout sensor for microRNA: CRISPR/Cas12a-assisted multi-amplification strategy activated photoelectrochemistry-colorimetry detection

Hormone therapy is one of the most effective breast cancer treatments, however, its application is limited by the progression of hormonal resistance, both primary or acquired. The development of hormonal resistance is caused either by an irreversible block of hormonal signalling (suppression of the activity or synthesis of hormone receptors), or by activation of oestrogen-independent signalling pathways. Recently the effect of exosome-mediated intercellular transfer of hormonal resistance was revealed, however, the molecular mechanism of this effect is still unknown. Here, the role of exosomal miRNAs (microRNAs) in the transferring of hormonal resistance in breast cancer cells has been studied. The methods used in the work include extraction, purification and RNAseq of miRNAs, transfection of miRNA mimetics, immunoblotting, reporter analysis and the MTT test. Using MCF7 breast cancer cells and MCF7/T tamoxifen-resistant sub-line, we have found that some miRNAs, suppressors of oestrogen receptor signalling, are overexpressed in the exosomes of the resistant breast cancer cells. The multiple (but not single) transfection of one of the identified miRNA, miR-181a-2, into oestrogen-dependent MCF7 cells induced the irreversible tamoxifen resistance associated with the continuous block of the oestrogen receptor signalling and the activation of PI3K/Akt pathway. We suppose that the miRNAs-ERα suppressors may act as trigger agents inducing the block of oestrogen receptor signalling and breast cancer cell transition to an aggressive oestrogen-independent state.

Towards Unravelling the Role of ERα-Targeting miRNAs in the Exosome-Mediated Transferring of the Hormone Resistance.

Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. At the same time, they can regulate various biological functions and therefore play an essential role as oncogenes or tumor suppressors in human cancers. MAFG-AS1 is an antisense RNA of MAF BZIP Transcription Factor G (MAFG) located at chromosome 17q25.3 head-to-head with the MAFG encoding gene containing a transcript size of 1895 bp. Accumulating evidence shows that MAFG-AS1 is overexpressed in many cancers, functions as an oncogene, and is significantly associated with poor clinical characteristics and prognosis. In this review, we first discuss the recent literature regarding the role of MAFG-AS1 in different cancers as well as its diagnostic and prognostic values. Then we will provide insights into its biological functions, such as its role in cancer progression, competing endogenous RNA (ceRNA) activity, regulation of EMT, glycolysis, energy metabolism, transcription factors, proteasomal degradation, and signaling pathways. 

A review on the roles and molecular mechanisms of MAFG-AS1 in oncogenesis.

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Gold Nanoparticle-Based Enzyme-Assisted Cyclic Amplification for the Highly-Sensitive Detection of miRNA-21

Targeting miRNAs with anesthetics in cancer: Current understanding and future perspectives

In recent years Artificial intelligence (AI) techniques are rapidly evolving into clinical practices such as diagnosis and prognosis processes, assess treatment effectiveness, and monitoring of diseases. The previous studies showed interesting results regarding the diagnostic efficiency of AI methods in differentiating Multiple sclerosis (MS) patients from healthy controls or other demyelinating diseases. There is a great lack of a comprehensive systematic review study on the role of AI in the diagnosis of MS. We aimed to perform a systematic review to document the performance of AI in MS diagnosis.A systematic search was performed using four databases including PubMed, Scopus, Web of Science, and IEEE on August 2021. All original studies which focused on deep learning or AI to analyze any modalities with the purpose of diagnosing MS were included in our study.Finally, 38 studies were included in our systematic review after the abstract and full-text screening. A total of 5433 individuals were included, including 2924 cases of MS and 2509 healthy controls. Sensitivity and specificity were reported in 29 studies which ranged from 76.92 to 100 for sensitivity and 74 to 100 for specificity. Furthermore, 34 studies reported accuracy ranged 81 to 100. Among included studies, Magnetic Resonance Imaging (MRI) (20 studies), OCT (six studies), serum and cerebrospinal fluid markers (six studies), movement function (three studies), and other modalities such as breathing and evoked potential was used for detecting MS via AI.In conclusion, diagnosis of MS based on new markers and AI is a growing field of research with MRI images, followed by images obtained from OCT, serum and CSF biomarkers, and motor associated markers. All of these results show that with advances made in AI, the way we monitor and diagnose our MS patients can change drastically. 

Artificial intelligence in the diagnosis of multiple sclerosis: A systematic review.

Autologous hematopoietic stem cell transplantation in neuromyelitis optica spectrum disorder: A systematic review and meta-analysis

We aimed to assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes (T2DM) during an 18-year follow-up.The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: (1) normal FPG (NFG) to NFG (reference category); (2) NFG to impaired fasting glucose (IFG) (i.e., 126 > FPG ≥ 100 mg/dl); (3) NFG to T2DM; (4) IFG to NFG; (5) IFG to IFG; (6) IFG to T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia was used to estimate hazard ratios (HRs (95% CI)) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated.During follow-up, 2,362 all-cause mortality events were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95%CI 1.24 (0.98-1.57), p = 0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM group were at increased risk for CV mortality (2.21 (1.42-3.44)). We also found that women in NFG-IFG (1.52 (1.20-1.91)), NFG-T2DM (2.90 (1.52-5.51)), and IFG-IFG (1.30 (1.02-1.66)) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 (1.15-2.74)) and IFG-T2DM (1.34 (1.04-1.72)). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts (RHR; 1.24 (1.01-1.54)). After further adjustment for physical activity, results were in line with the main findings, excluding T2DM up to six years after the measurement period and early mortality events.In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality. 

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Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis

Glioma is one of the most common malignancies of the central nervous system. Due to inadequate response to the current treatments available, glioma has been at the center of recent cancer studies searching for novel treatment strategies. This has prompted an intensive search using linkage studies and preliminary evidence to gain efficient insight into the mechanisms involved in the alleviation of the pathogenesis of glioma mediated by miRNAs, a group of noncoding RNAs that affect gene expression posttranscriptionally. Dysregulated expression of miRNAs can exacerbate the malignant features of tumor cells in glioma and other cancers. Natural products can exert anticancer effects on glioma cells by stimulating the expression levels of tumor suppressor miRNAs and repressing the expression levels of oncogenic miRNAs. In this review, we aimed to collect and analyze the literature addressing the roles of natural products in the treatment of glioma, with an emphasis on their involvement in the regulation of miRNAs.

Soroush Masrouri

Papers

Targeting miRNAs with anesthetics in cancer: Current understanding and future perspectives

Artificial intelligence in the diagnosis of multiple sclerosis: A systematic review.

Autologous hematopoietic stem cell transplantation in neuromyelitis optica spectrum disorder: A systematic review and meta-analysis

Changes in Fasting plasma glucose status and risk of mortality events in individuals without diabetes over two decades of Follow-up: a pooled cohort analysis

Natural products in suppressing glioma progression: A focus on the role of microRNAs