Investigating the mortality trend of gastrointestinal cancers in Babol, North Iran (2013-2021).

BACKGROUND AND AIM: This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people's lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates. METHOD: This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated. RESULTS: Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period. CONCLUSION: The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.

Interaction of RIPK1 and A20 modulates MAPK signaling in murine acetaminophen toxicity.

Acetaminophen (APAP)-induced liver necrosis is a form of regulated cell death (RCD) in which APAP activates the mitogen-activated protein kinases (MAPKs) and specifically the c-Jun-N-terminal kinase (JNK) pathway, leading to necrotic cell death. Previously, we have shown that receptor interacting protein kinase-1 (RIPK1) knockdown is also protective against APAP RCD upstream of JNK. However, whether the kinase or platform function of RIPK1 is involved in APAP RCD is not known. To answer this question, we used genetic mouse models of targeted hepatocyte RIPK1 knockout (RIPK1HepCKO) or kinase dead knock-in (RIPK1D138N) and adult hepatocyte specific knockout of the cytoprotective protein A20 (A20HepCKO), known to interact with RIPK1, to study its potential involvement in MAPK signaling. We observed no difference in injury between WT and RIPK1D138N mice post APAP. However, RIPK1HepCKO was protective. We found that RIPK1HepCKO mice had attenuated pJNK activation, while A20 was simultaneously upregulated. Conversely, A20HepCKO markedly worsened liver injury from APAP. Mechanistically, we observed a significant upregulation of apoptosis signal-regulating kinase 1 (ASK1) and increased JNK activation in A20HepCKO mice compared with littermate controls. We also demonstrated that A20 coimmunoprecipitated (co-IP) with both RIPK1 and ASK1, and that in the presence of RIPK1, there was less A20-ASK1 association than in its absence. We conclude that the kinase-independent platform function of RIPK1 is involved in APAP toxicity. Adult RIPK1HepCKO mice are protected against APAP by upregulating A20 and attenuating JNK signaling through ASK1, conversely, A20HepCKO worsens injury from APAP.

The survival rate of liver transplantation in children: a systematic review and meta-analysis.

Liver transplantation is a life-saving treatment for children who are in liver failure. The survival rate index is used to assess the success rate of liver transplantation. The study aimed to assess the survival rate of liver transplantation in children. We searched 5 international databases in this study, including Medline/PubMed, ProQuest, Scopus, Web of Knowledge, and Google Scholar, for published articles by the end of 2020. Also, meta-regression analysis was performed based on the year of the study, and subgroup analysis was performed according to continents. A total of 425 titles were reviewed. Based on the results, 96 articles were entered in the meta-analysis. Established on the random-effect model, the survival rates of 1, 3, 5, and 10 years of transplantation were 86.62%, 77.74%, 73.95%, and 68.60%, respectively. Also, based on the meta-regression results, there was a relationship between the year of the study and the survival rate, as the study year gets more recent, the survival rate is increased. This study can provide documented and comprehensive evidence which can be the basis of many policies and decisions in various sectors of health development, including evaluating treatment options and health interventions in transplantation.

Cardiovascular diseases burden in COVID-19: Systematic review and meta-analysis.

BACKGROUND: High rate of cardiovascular disease (CVD) have been reported among patients with novel coronavirus disease (COVID-19). Meanwhile there were controversies among different studies about CVD burden in COVID-19 patients. Hence, we aimed to study CVD burden among COVID-19 patients, using a systematic review and meta-analysis. METHODS: We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs. We have also performed a descriptive meta-analysis on different CVDs. RESULTS: Fifty-six studies entered into meta-analysis for ICU admission and mortality outcome and 198 papers for descriptive outcomes, including 159,698 COVID-19 patients. Results of meta-analysis indicated that acute cardiac injury, (OR: 13.29, 95% CI 7.35-24.03), hypertension (OR: 2.60, 95% CI 2.11-3.19), heart Failure (OR: 6.72, 95% CI 3.34-13.52), arrhythmia (OR: 2.75, 95% CI 1.43-5.25), coronary artery disease (OR: 3.78, 95% CI 2.42-5.90), and cardiovascular disease (OR: 2.61, 95% CI 1.89-3.62) were significantly associated with mortality. Arrhythmia (OR: 7.03, 95% CI 2.79-17.69), acute cardiac injury (OR: 15.58, 95% CI 5.15-47.12), coronary heart disease (OR: 2.61, 95% CI 1.09-6.26), cardiovascular disease (OR: 3.11, 95% CI 1.59-6.09), and hypertension (OR: 1.95, 95% CI 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients. CONCLUSION: Findings of this study revealed a high burden of CVDs among COVID-19 patients, which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.

Characterization Methods of Acellularized Tissue and Organs.

The extracellular matrix (ECM) of mammalian organs and tissues has been applied as a substitute scaffold to simplify the restoration and reconstruction of several tissues. Such scaffolds are prepared in various arrangements including sheets, powders, and hydrogels. One of the more applicable processes is using natural scaffolds, for this purpose discarded tissues or organs are naturally derived by processes that comprised decellularization of following tissues or organs. Protection of the complex structure and 3D (three dimensional) ultrastructure of the ECM is extremely necessary but it is predictable that all protocols of decellularization end in disruption of the architecture and potential loss of surface organization and configuration. Tissue decellularization with conservation of ECM bioactivity and integrity can be improved by providing well-designed protocols regarding the agents and decellularization techniques operated during processing. An overview of the characterization of decellularized scaffolds and the role of reagnets can validate the applied methods' efficacy.

Fetal Lung Tissue Engineering.

Lung transplantation may be considered as a final treatment option for diseases such as chronic lung disease, pulmonary hypertension, bronchopulmonary dysplasia, pulmonary fibrosis, and end-stage lung disease. The five-year survival rate of lung transplants is nearly 50%. Unfortunately, many patients will die before a suitable lung donor can be found. Importantly, the shortage of donor organs has been a significant problem in lung transplantation. The tissue engineering approach uses de- and recellularization of lung tissue to create functional lung substitutes to overcome donor lung limitations. Decellularization is hope for generating an intact ECM in the development of the engineered lung. The goal of decellularization is to prepare a suitable scaffold of lung tissue that contains an appropriate framework for the functionality of regenerated lung tissue. In this chapter, we aim to describe the decellularization protocols for lung tissue regenerative purposes.

Survival Rate of Colorectal Cancer in Eastern Mediterranean Region Countries: A Systematic Review and Meta-Analysis.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. Survival rates are among the most important factors in quality control and assessment of treatment protocols. This study was aimed to assess the survival rate of colorectal cancer in Eastern Mediterranean Region Countries. In the present study we comprehensively searched 6 international databases including PubMed/Medline, ProQuest, Scopus, Embase, Web of Knowledge and Google Scholar for published articles until November 2018. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was applied to evaluate the quality of included studies. The heterogeneity of papers was assessed with the Cochran Test and I-Square statistics. Meta-regression test was performed based on publication year, sample size and Human Development Index (HDI) of each study. Among the total of 1023 titles found in the systematic search, 43 studies were eligible to be included in the present meta-analysis. According to the results, the 1-year, 3-year and 5-year survival rate of patients with Colorectal Cancer was 88.07% (95% CI, 83.22-92.92), 70.67% (95% CI, 66.40-74.93) and, 57.26% (95% CI, 50.43-64.10); respectively. Furthermore, Meta-regressions did not show significant correlations between survival rate and year, sample size or Human Development Index. Survival rates, especially the 5-year survival rate in the EMRO were less than European countries and the USA. Documented and comprehensive evidence-based findings of the present meta-analysis can be used to enhance policies and outcomes of different medical areas including prophylaxis, treatment and health related objectives in colorectal cancer.

Cell Death in Liver Diseases: A Review.

Regulated cell death (RCD) is pivotal in directing the severity and outcome of liver injury. Hepatocyte cell death is a critical event in the progression of liver disease due to resultant inflammation leading to fibrosis. Apoptosis, necrosis, necroptosis, autophagy, and recently, pyroptosis and ferroptosis, have all been investigated in the pathogenesis of various liver diseases. These cell death subroutines display distinct features, while sharing many similar characteristics with considerable overlap and crosstalk. Multiple types of cell death modes can likely coexist, and the death of different liver cell populations may contribute to liver injury in each type of disease. This review addresses the known signaling cascades in each cell death pathway and its implications in liver disease. In this review, we describe the common findings in each disease model, as well as the controversies and the limitations of current data with a particular focus on cell death-related research in humans and in rodent models of alcoholic liver disease, non-alcoholic fatty liver disease and steatohepatitis (NASH/NAFLD), acetaminophen (APAP)-induced hepatotoxicity, autoimmune hepatitis, cholestatic liver disease, and viral hepatitis.

Effective factors of severity of traffic accident traumas based on the Haddon matrix: a systematic review and meta-analysis.

Objective: This study aims to investigate the factors affecting the severity of trauma caused by traffic accidents based on martrix Haddon; a systematic review and meta-analysis. Methods: In this study searched five international databases in this study, including Medline/PubMed, ProQuest, Scopus, Web of Knowledge, and Google Scholar, for published articles by the end of 2022. Data were entered into the statistical program and analyses were performed using STATA 17.0 software. Odds ratio (OR) values were computed for severity accidents. Results: Results of study showed that among the risk factors related to the host, not using helmet increased the risk of injury severity by 3.44 times compared to people who have used helmets (OR Not using helmet/Using helmet = 3.44, 95% CI: 2.27-5.00, P=0.001, I2=0.00%). Also, crossing over a centre divider has a protective role for the risk of injury severity compared to undertaking (OR crossing over a centre divider/undertaking=0.39, 95% CI: 0.20-0.75, P=0.01, I2=25.79%). in terms of the type of accident, accident of car-car reduces the risk of injury severity by 23% compared to accident of car-pedestrian (OR accident of car-car/accident of car-pedestrian=0.77, 95% CI: 0.61-0.96, P=0.02, I2=0.00%). Conclusions: It is necessary to pay attention to the intersection of human, vehicle and environmental risks and their contribution and how they interact. Based on the Haddon matrix approach, special strategies can be designed to prevent road damage. Safety standards for vehicles should also be addressed through stricter legal requirements and inspections.

Burden of upper gastrointestinal cancers in the east of Golestan province (Golestan cohort study).

BACKGROUND: Cancers, especially Upper Gastrointestinal Cancers (UGCs), pose a substantial burden on society, particularly in developing nations. Golestan province, Iran, is known for its high UGC rates globally. AIMS: This study delves into the disease burden of UGCs in the eastern part of Golestan province. METHODS AND RESULTS: This study was conducted using the results of the Golestan cohort study. 2711 patients participating in this cohort, who visited Atrak Clinic during 2001-2020, participated in this study. After excluding patients with incomplete records, 2481 patients were included in the study. To compute the metrics of years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life years (DALY), we utilized the World Health Organization's standard life table, stratified by age and gender. The majority of UGC patients in our study were married (81.8%), had limited formal education (82.6%), and were predominantly male (61.1%). A substantial proportion resided in suburban areas (85.8%), and over half of the patients (52%) reported a history of drug addiction. The mean age at diagnosis for men was 65.76 years with a standard deviation of 11.34, while for women, it was 64.38 years with a standard deviation of 11.66. Regarding disease impact, YLL, YLD, and DALY for men were 21 240, 1956, and 23 196 (307.8 per 100 000), respectively. For women, these figures were 15 609 for YLL, 1367 for YLD, and 16 976 (223.1 per 100 000) for DALY. CONCLUSION: After the increasing trend of the burden of UGCs in Golestan province in the early years of the study, this rate has been decreasing in recent years. Effective strategies necessitate collaborative efforts across various sectors to alleviate this burden, focusing on preventive measures, timely diagnosis, and well-coordinated therapeutic interventions.

Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors.

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI). Learning how to uncouple ILICI from ICI anti-tumor activity is of paramount clinical importance. We developed a murine model to recapitulate human ILICI using CTLA4+/- mice treated with either combined anti-CTLA4 + anti-PDL1 or IgG1 + IgG2. We tested two forms of antisense oligonucleotides to knockdown caspase-3 in a total liver (parenchymal and non-parenchymal cells) or in a hepatocyte-specific manner. We also employed imaging mass cytometry (IMC), a powerful multiplex modality for immunophenotyping and cell interaction analysis in our model. ICI-treated mice had significant evidence of liver injury. We detected cleaved caspase-3 (cC3), indicating apoptosis was occurring, as well as Nod-like receptor protein 3 (NLRP3) inflammasome activation, but no necroptosis. Total liver knockdown of caspase-3 worsened liver injury, and induced further inflammasome activation, and Gasdermin-D-mediated pyroptosis. Hepatocyte-specific knockdown of caspase-3 reduced liver injury and NLRP3 inflammasome activation. IMC-generated single-cell data for 77,692 cells was used to identify 22 unique phenotypic clusters. Spatial analysis revealed that cC3+ hepatocytes had significantly closer interactions with macrophages, Kupffer cells, and NLRP3hi myeloid cells than other cell types. We also observed zones of three-way interaction between cC3+ hepatocytes, CD8 + T-cells, and macrophages. Our work is the first to identify hepatocyte apoptosis and NLRP3 inflammasome activation as drivers of ILICI. Furthermore, we report that the interplay between adaptive and innate immune cells is critical to hepatocyte apoptosis and ILICI.

Detection of FLAD1 mutations and lipid storage myopathy in a 5-year-old boy: a case report study.

Lipid storage myopathy due to flavin adenine dinucleotide synthetase 1 (FLAD1) deficiency is an autosomal recessive error of metabolism that causes variable mitochondrial dysfunction. Case presentation: At the age of 3, the patient was found to have movement problems, such as difficulty rising from a chair (Gower's sign) and climbing stairs, which led to hospital admission and diagnosis. At the age of 4, carrier detection for spinal muscular atrophy was normal; however, at the age of 5, whole-exome sequencing revealed a pathogenic variant of Chr1: 154960762: A>T c.A554T:p.D185V in exon-2 of FLAD1 gene was identified as homozygous. Clinical discussion: In general, it is expected that the treatment of type 2 FLAD1 gene mutation with riboflavin has a better prognosis, but these interventions may not be sufficient for the survival of the patient. Treatment with riboflavin has increased various functions, including skeletal-muscular, and cardiovascular function. As a result, like the patient in our study, the mutation in exon-2 is more severe and less responsive to riboflavin treatment. Conclusion: Checking the FLAD1 gene is recommended in all people with multiple acyl-CoA dehydrogenase deficiency.

Physical activity and metabolic syndrome: A population base study (forest and tree model algorithms).

BACKGROUND & AIM: Lifestyle changes, prominently low mobility in recent years, have increased the prevalence of metabolic syndrome (MetS), and cardiovascular disease risk. This study aimed to determine the relationship between physical activity and MetS using modern statistical methods in a population-based study. METHODS: The target population included 10,663 people aged 40-70 years in phase 1 of the Persian Kharameh cohort study conducted in 2017. The data used in this study had questions about physical activity, demographic, anthropometrics, blood pressure, and biochemical data. RESULTS: Participants who their activity was within the fourth quarter were 36% less likely to develop MetS than the participants in the first quarter. In the decision-Tree algorithm with all variables, physical activity was significant after gender and comorbidity. With a lack of comorbidities and physical activity less than 2338 Metabolic Equivalent of Task (MET) and age greater than 53 years, the probability was 26.7% for the male population. For the female population, if associated with comorbidities, a history of diabetes in first-degree relatives, or both, the chance of developing MetS was estimated to be 70.4%. In the decision-tree algorithm, 56.0% of the predictions for MetS were due to gender. After gender, the presence of comorbidities, age, occupation, family history of diabetes, place of residence, and physical activity was discovered as the essential variables in predicting and identifying factors associated with MetS, respectively. CONCLUSION: Modern statistical methods can be used in similar research due to better presentation of results in applied clinical laws. An essential approach for treating the syndrome and preventing its complications is a lifestyle change, including educating about physical activity and promoting it.

The Relationship between Air Pollution and Brain Cancer: A Systematic Review and Meta-Analysis.

Background: There is very little epidemiological evidence on the effects of ambient air pollution on brain tumor risk. The purpose of this study was to determine the relationship between exposure to air pollution and the incidence of brain tumors. Methods: A comprehensive literature search in five international databases, including PubMed/Medline, ProQuest, Scopus, Embase, and ISI/WOS on April 15, 2019, was conducted. The methodology of the present study was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of the selected papers. Results: Five studies that measured adult brain tumors as well as their long-term exposure to at least one of the pollutants criteria for air pollution, PM2.5 absorbance, and proximity to traffic (Trafnear) were reviewed. The results showed that the pooled relative risk (RR) for incidence of brain tumor and long term exposure to Trafnear, PM2.5, PM2.5 absorbance, O3 and NOx were RR = 1.07, (95% CI 0.99-1.16), P = 0.079, for Trafnear; RR = 0.90, (95% CI 0.80-1.00), P = 0.064 for PM2.5; RR = 1.63, (95% CI 1.04-2.55), P = 0.031 for PM2.5 absorbance; RR = 1.3, (95% CI 1.03-1.6), P = 0.023 for O3; and RR = 1.16, (95% CI 0.93-1.45), P = 0.173 for NOx. Exposure to other air pollutants had no statistically significant association with brain tumor incidence. Conclusion: The results showed that exposure to air pollutants, such as O3 and PM2.5 absorbance, had the highest correlation with brain tumor incidence. They also showed an absence of correlation between exposure to certain pollutants (SO2, CO, NO2, PM10, PM2.5) and brain tumor incidence.

Gender Differences in Psychological Distress in Patients with Colorectal Cancer and Its Correlates in the Northeast of Iran.

PURPOSE: Colorectal cancer has a significant impact on patients' physical, psychological, and social aspects. This study aimed to examine the gender difference in anxiety and depression and its relationship with some of the characteristics of the disease and demographic in the northeast of Iran. METHODS: In this cross-sectional study, patients with colorectal cancer aged over 18 years who were admitted to hospitals, without considering the disease stage and type of treatment, were enrolled during 2014-2016. The Hospital Anxiety and Depression Scale (HADS) Questionnaire was completed via interview. RESULTS: A total of 303 survivors of colorectal cancer were included in the current analysis, of whom 55.1% (167) were male. The overall frequency of depression was 44.9%, and it was 38.3% and 32.9% for men and women, respectively. The overall frequency of anxiety was 53.4% (50.3% and 57.4% for men and women, respectively). The results showed that compared to men, women (52%) were more likely to report depression (OR = 0.48, 95% CI = 0.22-1.04, P = 0.065); in contrast, men (12%) were less likely than women to report anxiety (OR = 0.88, 95% CI = 0.38-2.03, P = 0.779), which was less than 12% in men. Among other variables, education and employment were identified as independent and strong predictive variables for depression and anxiety. CONCLUSIONS: The frequency of anxiety and depression is high among colorectal cancer survivors, especially in women. Therefore, screening for psychological distress is recommended in clinical settings and there is a need to pay attention to women.

Dysregulated expression and functions of microRNA-330 in cancers: A potential therapeutic target.

As small non-coding RNAs, MicroRNAs (miRNAs) bind to the 3' untranslated region (3'-UTR) of mRNA targets to control gene transcription and translation. The gene of miR-330 has two miRNA products, including miR-330-3p and miR-330-5p, which exhibit anti-tumorigenesis and/or pro-tumorigenesis effects in many kinds of malignancies. In cancers, miR-330-3p and miR-330-5p aberrant expression can influence many malignancy-related processes such as cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition, as well as angiogenesis and responsiveness to treatment. In many cancer types (such as lung, prostate, gastric, breast, bladder, ovarian, colorectal, and pancreatic cancer, and osteosarcoma), miR-330-5p acts as an anti-tumor agent. These cancers have low levels of miR-330-5p that leads to the upregulation of the tumor promotor target genes leading to tumor progression. Here, overexpression of miR-330-5p using miRNA inducers can prevent tumor development. Dual roles of miR-330-5p have been also indicated in the thyroid, liver and cervical cancers. Moreover, miR-330-3p exhibits pro-tumorigenesis effects in lung cancer, pancreatic cancer, osteosarcoma, bladder cancer, and cervical cancer. Here, downregulation of miR-330-3p using miRNA inhibitors can prevent tumor development. Demonstrated in breast and liver cancers, miR-330-3p also has dual roles. Importantly, the activities of miR-330-3p and/or miR-330-5p are regulated by upstream regulators long non-coding RNAs (lncRNAs), including circular and linear lncRNAs. This review comprehensively explained miR-330-3p and miR-330-5p role in development of cancers, while highlighting their downstream target genes and upstream regulators as well as possible therapeutic strategies.

Survival Rate of Liver Transplantation in Asia: A Systematic Review and Meta-Analysis.

Background: Liver transplantation is one of the most effective treatments for acute liver failure, chronic liver cirrhosis, and hepatocellular carcinoma. This study was implemented to evaluate the survival rate of liver transplant in Asia. Methods: Studies that investigated the survival rate of liver transplant were selected using a systematic search strategy in the following databases: Medline, Embase, Scopus, ProQuest, ISI Web of Science, and Cochrane to Nov 30th, 2020. Pooled survival rate and 95% confidence intervals were calculated using Der-Simonian and Laird method. Stata 16.0 (Stata Corp, College Station, TX, USA) was used for analysis. Results: One, 2, 3, 5, and 10-year survival rates of liver transplant were estimated to be 85%, 80%, 75%, 73%, and 71%, respectively. The results of the univariate meta-regression for defining the sources of heterogeneity for one-Year survival rate (SR) showed significant effects of bias (ß high risk/moderate risk =0.059, 95% CI: 0.002, 0.115, P-Value=0.04) and follow up time (ß= -0.0002, 95% CI: -0.0003, -0.00, P-Value=0.02) on heterogeneity. Conclusion: The survival rate of liver transplant in Asia is comparable with the corresponding rate reported in the United States and Europe. This study provides a better view of the efficiency of medical cares, regarding liver transplantation. Medical care be enhanced to increase the survival of liver transplant patients.

Streptococcal bacterial components in cancer therapy.

The incidence rate of cancer is steadily increasing all around the world, and there is an urgent need to develop novel and more effective treatment strategies. Recently, bacterial therapy has been investigated as a new approach to target cancer, and is becoming a serious option. Streptococcus strains are among the most common and well-studied virulent bacteria that cause a variety of human infections. Everyone has experienced a sore throat during their lifetime, or has been asymptomatically colonized by streptococci. The ability of Streptococcus bacteria to fight cancer was discovered more than 100 years ago, and over the years has undergone clinical trials, but the mechanism is not yet completely understood. Recently, several animal models and human clinical trials have been reported. Streptococcal strains can have an intrinsic anti-tumor activity, or can activate the host immune system to fight the tumor. Bacteria can selectively accumulate and proliferate in the hypoxic regions of solid tumors. Moreover, the bacteria can be genetically engineered to secrete toxins or enzymes that can specifically attack the tumors.

Association between iron deposition in splenic,hepatic and myocardial tissues assessed by T2* relaxometry technique.

BACKGROUND: Decreasing signal intensity of the spleen assessed by T2* MRI is a frequent finding in patients with beta-thalassemia due to iron deposition within the reticuloendothelial cells in this organ. This parameter can also be applied to determine the candidates for blood cell transfusion. However, the association between splenic siderosis and iron overload in other vital organs such as heart and liver remains unclear. The present study aimed to assess the correlation between iron deposition in splenic, hepatic and myocardial tissues by T2* relaxometry technique. METHODS: This cross-sectional study included 39 consecutive patients with a definitive diagnosis of beta-thalassemia major who underwent spleen, liver and heart MRI examinations for iron deposition and cardiac function. RESULTS: No significant correlation was found between the heart and splenic T2* relaxation time (R=0.206, P=0.357). We revealed a strong correlation between the splenic T2* relaxation time and hepatic calculated T2*s (R=0.515, P=0.014). The liver T2* values can be predicted from the splenic T2*s by a new linear equation. According to the ROC curve analysis, the splenic T2* could significantly, but moderately predict moderate to severe from mild liver iron excess (AUC=0.667). CONCLUSION: Our study demonstrated a significant linear correlation between the splenic and hepatic T2* relaxation time, probably indicative of the same iron deposition mechanism, and made us available to write a linear model that would predict the deposited iron density in the spleen with the use of the magnetic resonance T2* values.

Mechanisms of immune checkpoint inhibitor-mediated liver injury.

The immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1/ligand-1 (PD-1/PD-L1) are vital contributors to immune regulation and tolerance. Recently immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, they come with the cost of immune related adverse events involving multiple organs such as the liver. Due to its constant exposure to foreign antigens, the liver has evolved a high capacity for immune tolerance, therefore, blockade of the immune checkpoints can result in aberrant immune activation affecting the liver in up to 20% of patients depending on the agent(s) used and underlying factors. This type of hepatotoxicity is termed immune mediated liver injury from checkpoint inhibitors (ILICI) and is more common when CTLA4 and PD-1/PD-L1 are used in combination. The underlying mechanisms of this unique type of hepatotoxicity are not fully understood; however, the contribution of CD8+ cytotoxic T lymphocytes, various CD4+ T cells populations, cytokines, and the secondary activation of the innate immune system leading to liver injury have all been suggested. This review summarizes our current understanding of the underlying mechanisms of liver injury in immunotherapy using animal models of ILICI and available patient data from clinical studies.