Impact of Doxorubicin and Docetaxel on Immune Checkpoint Expression in Colorectal Cancer: Insights into Chemotherapy Resistance Mechanisms.

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin. After treatment, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze PD-L1, CTLA-4, and VISTA gene expression in the SW-1116 cell line. The upregulation of VISTA expression showed a significant increase (p < 0.0001) in response to both chemotherapy agents. Moreover, the expression of CTLA-4 exhibited a remarkable level of significance (p < 0.0001), and PD-L1 expression also displayed notable significance (p < 0.0001). Chemotherapeutic agents heighten immune checkpoint gene expression, highlighting potential immune response pathway modulation.

Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.

Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.

Cerebral protection in acute type A aortic dissection surgery: a systematic review and meta-analysis.

Background: Acute type A aortic dissection (ATAAD) still challenges physicians and warrants emergent surgical management. Two main methods to reduce cerebrovascular events in ATAAD surgeries are antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). We conducted a systematic review and meta-analysis to compare the outcomes of ACP and RCP methods during the ATAAD surgery. Methods: In this study, we searched the databases until March 29th, 2023. Studies that reported the data for comparison of different types of brain perfusion protection during aortic surgery in patients with ATAAD were included. Results: Twenty-six studies met the eligibility criteria. All studies had a low risk of bias as they were evaluated by the Joanna Briggs Institute (JBI) critical appraisal tool. Eventually, we included 26 studies in the current meta-analysis, and a total of 13,039 patients were evaluated. The calculated risk ratio (RR) for permanent neurologic dysfunction (PND) in ACP and RCP comparison was RR =1.23, 95% confidence interval (CI): (0.84, 1.80) (P value =0.2662), and in unilateral ACP (uACP) and bilateral ACP (bACP) was RR =1.2786, 95% CI: (0.7931, 2.0615) (P value =0.3132). When comparing the ACP-RCP and uACP-bACP groups, significant differences were found between ACP-RCP the groups in terms of circulatory arrest time (P value =0.0017 and P value =0.1995, respectively), cardiopulmonary bypass time (P value =0.5312 and P value =0.7460, respectively), intensive care unit (ICU)-stay time (P value =0.2654 and P value =0.0099), crossclamp time (P value =0.6228 and P value =0.2625), and operative mortality (P value =0.9368 and P value =0.2398, respectively), and when comparing the u-ACP and b-ACP groups for transient neurologic deficit (TND), an RR of 1.32, 95% CI: (1.05, 1.67) (P value =0.0199). The results showed high heterogeneity and no publication bias. Conclusions: This study demonstrated that the ACP and RCP are both safe and acceptable techniques to use in emergent settings. The uACP technique is equivalent to bACP in terms of PND and mortality, however, uACP is preferred over bACP in terms of TND.

New immunotherapy approaches for colorectal cancer: focusing on CAR-T cell, BiTE, and oncolytic viruses.

Colorectal cancer is one of the most common causes of mortality worldwide. There are several potential risk factors responsible for the initiation and progression of colorectal cancer, including age, family history, a history of inflammatory bowel disease, and lifestyle factors such as physical activity and diet. For decades, there has been a vast amount of study on treatment approaches for colorectal cancer, which has led to conventional therapies such as chemotherapy, surgery, etc. Considering the high prevalence and incidence rate, scholars believe there is an urgent need for an alternative, more efficacious treatment with fewer adverse effects than the abovementioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and has become one of the fastest-evolving therapeutic methods. Immunotherapy works by activating or enhancing the immune system's power to identify and attack cancerous cells. This review summarizes the most crucial new immunotherapy methods under investigation for colorectal cancer treatment, including Immune checkpoint inhibitors, CAR-T cell therapy, BiTEs, Tumor-infiltrating lymphocytes, and Oncolytic virus therapy. Furthermore, this study discusses the application of combination therapy, precision medicine, biomarker discovery, overcoming resistance, and immune-related adverse effects. Video Abstract.

Could admission level of uric acid predict total diuretic dose in acute heart failure?

BACKGROUND: Recent studies have shown that increases in serum UA levels are associated with adverse clinical outcomes in patients with chronic heart failure (CHF); the aim of this study was to determine the relationship between serum uric acid and total diuretic dose received during hospitalization in hospitalized patients with acute exacerbation of heart failure. The main purpose of this study is to determine the role of uric acid as a biomarker that can be a substitute for pro-BNP in clinical evaluation and the need for diuretics in hospitalized patients with acute heart failure. METHODS: After approving the plan in the Research Council of the Heart Department and obtaining an ethical code from the Regional Committee on Research Ethics (Human Subjects Studies), the researcher referred to the archives of our center, the case of 100 patients diagnosed with acute heart failure. Cardiac patients were selected, and the information required for the study was collected using a pre-prepared data collection form, and the information was entered into SPSS software after categorization and appropriate analysis and statistical tests were performed on it. Were performed and in all statistical tests the statistical significance level was considered 0.05: RESULTS: 100 patients with acute heart failure were included in this study with a mean age of 63.43 ± 14.78 years. 66% of them were men. The mean dose of furosemide in these patients was 680.92 ± 377.47 mg and the mean serum uric acid level in these patients was 8.55 ± 2.50 mg / dL. In the study of the relationship between the variables, there was a significant relationship between the dose of furosemide received with the serum level of serum uric acid (P = 0.017, r = 0.248 and P = 0.009, r = -0.267, respectively). There is also a significant relationship between serum uric acid level and patient mortality (P = 0.013, r = 0.247). However this relationship lost its significance after multivariate analysis. CONCLUSION: There is a significant relationship between serum uric acid level and diuretic use. However, in-hospital mortality is not related to uric acid levels at admission.

Potential diagnostic application of a novel deep learning- based approach for COVID-19.

COVID-19 is a highly communicable respiratory illness caused by the novel coronavirus SARS-CoV-2, which has had a significant impact on global public health and the economy. Detecting COVID-19 patients during a pandemic with limited medical facilities can be challenging, resulting in errors and further complications. Therefore, this study aims to develop deep learning models to facilitate automated diagnosis of COVID-19 from CT scan records of patients. The study also introduced COVID-MAH-CT, a new dataset that contains 4442 CT scan images from 133 COVID-19 patients, as well as 133 CT scan 3D volumes. We proposed and evaluated six different transfer learning models for slide-level analysis that are responsible for detecting COVID-19 in multi-slice spiral CT. Additionally, multi-head attention squeeze and excitation residual (MASERes) neural network, a novel 3D deep model was developed for patient-level analysis, which analyzes all the CT slides of a given patient as a whole and can accurately diagnose COVID-19. The codes and dataset developed in this study are available at https://github.com/alrzsdgh/COVID . The proposed transfer learning models for slide-level analysis were able to detect COVID-19 CT slides with an accuracy of more than 99%, while MASERes was able to detect COVID-19 patients from 3D CT volumes with an accuracy of 100%. These achievements demonstrate that the proposed models in this study can be useful for automatically detecting COVID-19 in both slide-level and patient-level from patients' CT scan records, and can be applied for real-world utilization, particularly in diagnosing COVID-19 cases in areas with limited medical facilities.

Empagliflozin and colchicine in patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction: a randomized, double-blinded, three-arm parallel-group, controlled trial.

PURPOSE: There is accumulating evidence regarding the potential benefits of empagliflozin in individuals with acute myocardial infarction (MI). Based on the literature, colchicine could also reduce the risk of MI and death in individuals with cardiovascular disease (CVD). However, trials investigating the effects of the combination of empagliflozin with colchicine and high-dose empagliflozin monotherapy in this setting are lacking. METHODS: In this trial, 106 non-diabetic participants with reduced left ventricular ejection fraction (LVEF) following recent ST-elevation MI were randomly assigned to empagliflozin 10 mg/day, empagliflozin 10 mg/day plus colchicine 0.5 mg twice daily, or empagliflozin 25 mg/day groups within 72 h after primary percutaneous coronary intervention (PCI). The study's primary outcomes were the changes in New York Heart Association (NYHA) functional class and high-sensitivity C-reactive protein (hs-CRP) over 12 weeks. RESULTS: The baseline characteristics of individuals were statistically similar between the study groups. Changes in NYHA functional class over 12 weeks were not significantly different between the study groups. hs-CRP was significantly reduced in all groups (all P < 0.001); however, there was no significant change between the groups over the study period. Changes in tumor necrosis factor-alpha (TNF-α), LVEF, and left ventricular end-diastolic dimension (LVEDD) during the research period did not differ significantly between groups. CONCLUSION: This study showed that neither the combination treatment of empagliflozin 10 mg/day with colchicine nor the monotherapy of empagliflozin 25 mg/day was superior to empagliflozin 10 mg/day in terms of changes in clinical, inflammatory, and echocardiographic outcome parameters in patients with recent MI with reduced LVEF over 3 months. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022. https://www.irct.ir/trial/66216.

Empagliflozin and colchicine in patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: a study protocol for a randomized, double-blinded, three-arm parallel-group, controlled trial.

BACKGROUND: Patients with acute myocardial infarction are at greater risk for chronic heart failure and mortality. Currently, there is limited evidence supporting the beneficial effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in non-diabetic patients with reduced left ventricular ejection fraction following acute myocardial infarction. Furthermore, the clinical effects of the combination of standard-dose sodium-glucose cotransporter-2 inhibitors with colchicine and high-dose sodium-glucose cotransporter-2 inhibitors in this setting have not been evaluated yet. METHODS: A prospective, double-blinded, parallel-group, placebo control randomized trial will be carried out at Shahid Madani Heart Center, the largest teaching referral hospital for cardiovascular diseases, affiliated with Tabriz University of Medical Sciences. A total of 105 patients with reduced left ventricular ejection fraction (≤ 40%) following the first episode of ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention with stent insertion will be randomized 1:1:1 to receive empagliflozin 10 mg daily, a combination of empagliflozin 10 mg daily and colchicine 0.5 mg twice daily, or empagliflozin 25 mg daily for 12 weeks. The primary outcomes are changes in the New York Heart Association functional classification and high-sensitivity C-reactive protein from the randomization through week 4 and week 12. DISCUSSION: The present study will be the first trial to evaluate the efficacy and safety of early treatment with the combination of standard-dose empagliflozin and colchicine as well as high-dose empagliflozin in non-diabetic patients with reduced left ventricular ejection fraction following ST-elevation myocardial infarction. The results of this research will represent a significant step forward in the treatment of patients with acute myocardial infarction. TRIAL REGISTRATION: Clinical trial ID: IRCT20111206008307N39. Registration date: 27 October 2022.

Cancer immunotherapy focusing on the role of interleukins: A comprehensive and updated study.

Cytokines bind to specific receptors on target cells to activate intracellular signaling pathways that control diverse cellular functions, such as proliferation, differentiation, migration, and death. They are essential for the growth, activation, and operation of immune cells and the control of immunological reactions to pathogens, cancer cells, and other dangers. Based on their structural and functional properties, cytokines can be roughly categorized into different families, such as the tumor necrosis factor (TNF) family, interleukins, interferons, and chemokines. Leukocytes produce interleukins, a class of cytokines that have essential functions in coordinating and communicating with immune cells. Cancer, inflammation, and autoimmunity are immune-related disorders brought on by dysregulation of cytokine production or signaling. Understanding cytokines' biology to create novel diagnostic, prognostic, and therapeutic methods for various immune-related illnesses is crucial. Different immune cells, including T cells, B cells, macrophages, and dendritic cells, and other cells in the body, including epithelial cells and fibroblasts, generate and secrete interleukins. The present study's main aim is to fully understand interleukins' roles in cancer development and identify new therapeutic targets and strategies for cancer treatment.

Molecular characterization of PMQR carrying bacteriophages in effluent discharge samples of Azerbaijan hospitals.

Quinolones are one of the most widely used drugs in medicine. Resistance to this agent has been increased significantly among the nosocomial isolates. The objective of this research was to study generalized transduction, as a potential mechanism for plasmid-mediated quinolone resistance (PMQR) genes acquisition among hospital effluent isolates. Discharge samples from hospital effluent were taken from four medical centers in Azerbaijan. Resident phages were enriched against resident enterobacterial hosts using standard phage enrichment protocols. Polymerase chain reaction (PCR) was used to examine phage stocks and bacterial isolates for the presence of PMQR determinants. All positive bacterial isolates for target genes were subjected to transduction assays. Restriction fragment length polymorphism (RFLP) profiles were determined for cluster analysis. A total of 55 pure phage stocks were prepared from 42 effluents. A total of 95 non-duplicated Gram-negative bacteria were isolated. Thirty-two EcoRV-RFLP profiles were determined for the 40 Escherichia coli phage stocks. Twenty-six of 40 (65%) E. coli phages were positive for qnrB (n = 15), qnrD (n = 7), qnrA (n = 3), and qnrC (n = 2) genes. A total of 34 (35.7%) bacterial isolates were recognized to have any PMQR genes including qnrB (n = 23), qnrD (n = 8), qnrA (n = 5), and qnrC (n = 3) genes. Present research provided a strong evidence for potential role of generalized transduction in persistence and circulation of PMQR genes in health care settings of Azerbaijan.

Worsening renal function in hospitalized patients with systolic heart failure: prevalence and risk factors.

AIMS: Heart failure (HF) is usually associated with complications of other organs. Renal impairment is seen in a significant proportion of HF patients and is characterized by worsening renal function (WRF). WRF can be used for predicting symptom exacerbation in systolic HF. This study aimed to determine the prevalence and risk factors of WRF among hospitalized patients with systolic HF. METHODS AND RESULTS: In this cross-sectional study, data from medical records of 347 hospitalized patients diagnosed with HFrEF from 2019 to 2020, admitted to Tabriz Shahid Madani Heart Hospital, who met the predefined inclusion criteria, were retrieved. Patients were divided into two groups based on the in-hospital occurrence of WRF. Laboratory tests and para-clinical findings were collected and analysed using SPSS Version 20.0. Statistical significance was accepted at a P value of <0.05. In this study, 347 hospitalized patients with HFrEF were included. The mean (standard deviation) age was 62.34 (±18.87) years. The mean (SD) length of stay was 6.34 (±4) days. According to our findings, 117 patients (33.71%) had WRF. Following multivariate analysis of potential predictors of WRF occurrence, hyponatremia, haemoglobin concentration, white blood cell count and prior diuretic use were found to be independent predictors for WRF occurrence in patients with systolic heart failure. CONCLUSIONS: This study revealed that in patients with WRF, mortality rate and length of stay were significantly greater than those of patients without WRF. Initial clinical characteristics of HF patients who developed WRF can help physicians identify patients with a higher risk of WRF.

Deep Multirepresentation Learning for Data Clustering.

Deep clustering incorporates embedding into clustering in order to find a lower-dimensional space suitable for clustering tasks. Conventional deep clustering methods aim to obtain a single global embedding subspace (aka latent space) for all the data clusters. In contrast, in this article, we propose a deep multirepresentation learning (DML) framework for data clustering whereby each difficult-to-cluster data group is associated with its own distinct optimized latent space and all the easy-to-cluster data groups are associated with a general common latent space. Autoencoders (AEs) are employed for generating cluster-specific and general latent spaces. To specialize each AE in its associated data cluster(s), we propose a novel and effective loss function which consists of weighted reconstruction and clustering losses of the data points, where higher weights are assigned to the samples more probable to belong to the corresponding cluster(s). Experimental results on benchmark datasets demonstrate that the proposed DML framework and loss function outperform state-of-the-art clustering approaches. In addition, the results show that the DML method significantly outperforms the SOTA on imbalanced datasets as a result of assigning an individual latent space to the difficult clusters.

Effects of Triamterene in Hospitalized Patients with Heart Failure and Diuretic Resistance: A Randomized Clinical Trial.

Due to the potential benefits of triamterene in diuretic resistance, this study was performed to assess whether triamterene add-on to the standard treatment of heart failure (HF)-related diuretic resistance improves outcomes. A randomized clinical trial was performed on 45 hospitalized patients with HF with reduced ejection fraction who had diuretic resistance. Patients were randomized to receive either triamterene 50 mg plus hydrochlorothiazide 25 mg (n = 23) or hydrochlorothiazide 50 mg alone (n = 22) until hospital discharge. The primary outcomes were changes in weight and fluid input-to-output ratio. Secondary outcomes were respiratory rate, hospitalization duration, serum sodium and potassium, estimated glomerular filtration rate, creatinine, and blood urea nitrogen levels during the study period. The mean (standard deviation) of weight changes was not significantly different in the intervention and the control groups (-6.3 [4.8] vs -4.8 [2.4] kg, respectively; P = .1). No significant differences were shown in input-to-output changes between the 2 groups (208.0 [243.4] in the intervention and 600.2 [250.3] in the control group; P = .4). Although the respiratory rate of triamterene-treated patients decreased, the difference did not reach statistical significance (P = .2). Other secondary outcomes were also similar in both groups. This study did not support the use of triamterene as an add-on therapy for patients with HF-related diuretic resistance.

Miniature Integrated 2.4 GHz Rectennas Using Novel Tunnel Diodes.

This work presents the design, fabrication, and measured results of a fully integrated miniature rectenna using a novel tunnel diode known as the Asymmetrical Spacer Layer Tunnel (ASPAT). The term rectenna is an abbreviation for a rectifying antenna, a device with a rectifier and antenna coexisting as a single design. The ASPAT is the centrepiece of the rectifier used for its strong temperature independence, zero bias, and high dynamic range. The antenna is designed to be impedance matched with the rectifier, eliminating the need for a matching network and saving valuable real estate on the gallium arsenide (GaAs) substrate. The antenna is fully integrated with the rectifier on a single chip, thus enabling antenna miniaturisation due to the high dielectric constant of GaAs and spiral design. This miniaturisation enables the design to be fabricated economically on a GaAs substrate whilst being comparable in size to a 15-gauge needle, thus unlocking applications in medical implants. The design presented here has a total die size of 4 × 1.2 mm2, with a maximum measured output voltage of 0.97 V and a 20 dBm single-tone 2.35 GHz signal transmitted 5 cm away from the rectenna.

New immunotherapeutic approaches for cancer treatment.

Neoplasms are a worldwide recognized non-contagious disease which has the most mortality rate after cardiovascular diseases. For decades, there has been a vast amount of study on treatment methods of cancer which has led to conventional therapies such as chemotherapy, radiation therapy, surgery and so on. Clinicians and researchers believed that there is an urgent need, considering the high rate of incidence and prevalence, for an alternative treatment option which is more efficacious and has less adverse effects than the above-mentioned treatments. Immunotherapy has emerged as a potential treatment alternative in a few years and became one of the fastest developing therapeutic approaches. Different kinds of immunotherapies are FDA approved and available for treatment of various cancer types. In this review, we have summarized the major immunotherapy methods including checkpoint inhibitors, CAR T cell therapies and cancer vaccines. Furthermore, application of combination therapy, precision medicine, biomarker discovery, overcoming resistance and reduction of adverse effects are discussed in this study.

SGLT2 Inhibitors' Cardiovascular Benefits in Individuals Without Diabetes, Heart Failure, and/or Chronic Kidney Disease: A Systematic Review.

Despite the growing body of evidence regarding the beneficial cardiovascular effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors, clinical data in individuals without diabetes, heart failure (HF), and/or chronic kidney disease (CKD) is limited. A systematic review of the literature was conducted in PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar, from database inception until May 4, 2023, to explore new evidence of SGLT2 inhibitors' cardiovascular benefits in individuals without diabetes, HF, and/or CKD. A total of 1156 individuals from 14 studies (13 randomized controlled trials and 1 nonrandomized study) were included. The results showed the benefits of SGLT2 inhibitors on blood pressure, weight, and body mass index in this population with an acceptable safety profile. The current evidence supports the potential role of SGLT2 inhibitors as primary prevention in individuals without diabetes, HF, and/or CKD. This review may shed light on the use of SGLT2 inhibitors in conditions such as stage A HF and metabolic syndrome. The literature trend is going toward uncovering SGLT2 inhibitors' role in stage B HF, different types of myocardial infarction, and cardiac arrhythmias.

Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles.

Introduction: Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). Methods: Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy. Results: Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. Conclusion: Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Revisiting Inhibition Effects of miR-28 as a Metastasis Suppressor in Gastrointestinal Cancers.

MicroRNAs are critical epigenetic regulators that can be used as diagnostic, prognostic, and therapeutic biomarkers for the treatment of various diseases, including gastrointestinal cancers, among a variety of cellular and molecular biomarkers. MiRNAs have also shown oncogenic or tumor suppressor roles in tumor tissue and other cell types. Studies showed that the dysregulation of miR-28 is involved in cell growth and metastasis of gastrointestinal cancers. MiR-28 plays a key role in controlling the physiological processes of cancer cells including growth and proliferation, migration, invasion, apoptosis, and metastasis. Therefore, miR-28 expression patterns can be used to distinguish patient subgroups. Based on the previous studies, miR-28 expression can be a suitable biomarker to detect tumor size and predict histological grade metastasis. In this review, we summarize the inhibitory effects of miR-28 as a metastasis suppressor in gastrointestinal cancers. miR-28 plays a role as a tumor suppressor in gastrointestinal cancers by regulating cancer cell growth, cell differentiation, angiogenesis, and metastasis. As a result, using it as a prognostic, diagnostic, and therapeutic biomarker in the treatment of gastrointestinal cancers can be a way to solve the problems in this field.