The Role of microRNAs in Hepatocellular Cancer: A Narrative Review Focused on Tumor Microenvironment and Drug Resistance.

Globally, hepatic cancer ranks fourth in terms of cancer-related mortality and is the sixth most frequent kind of cancer. Around 80% of liver cancers are hepatocellular carcinomas (HCC), which are the leading cause of cancer death. It is well known that HCC may develop resistance to the available chemotherapy treatments very fast. One of the biggest obstacles in providing cancer patients with appropriate care is drug resistance. According to reports, more than 90% of cancer-specific fatalities are caused by treatment resistance. By binding to the 3'-untranslated region of target messenger RNAs (mRNAs), microRNAs (miRNAs), a group of noncoding RNAs which are around 17 to 25 nucleotides long, regulate target gene expression. Moreover, they play role in the control of signaling pathways, cell proliferation, and cell death. As a result, miRNAs play an important role in the microenvironment of HCC by changing immune phenotypes, hypoxic conditions, and acidification, as well as angiogenesis and extracellular matrix components. Moreover, changes in miRNA levels in HCC can effectively resist cancer cells to chemotherapy by affecting various cellular processes such as autophagy, apoptosis, and membrane transporter activity. In the current work, we narratively reviewed the role of miRNAs in HCC, with a special focus on tumor microenvironment and drug resistance.

Comorbidities affecting re-admission and survival in COVID-19: Application of joint frailty model.

BACKGROUND: One of the common concerns of healthcare systems is the potential for re-admission of COVID-19 patients. In addition to adding costs to the healthcare system, re-admissions also endanger patient safety. Recognizing the factors that influence re-admission, can help provide appropriate and optimal health care. The aim of this study was to assess comorbidities that affect re-admission and survival in COVID-19 patients using a joint frailty model. METHODS: This historical cohort study was done using data of patients with COVID-19 who were re-hospitalized more than twice in a referral hospital in North of Iran. We used the joint frailty model to investigate prognostic factors of survival and recurrence, simultaneously using R version 3.5.1 (library "frailtypack"). P-values less than 0.05 were considered as statistically significant. RESULTS: A total of 112 patients with mean (SD) age of 63.76 (14.58) years old were recruited into the study. Forty-eight (42.9%) patients died in which 53.83% of them were re-admitted for a second time. Using adjusted joint model, the hazard of re-admission increased with cancer (Hazard ratio (HR) = 1.92) and hyperlipidemia (HR = 1.22). Furthermore, the hazard of death increased with hyperlipidemia (HR = 4.05) followed by age (HR = 1.76) and cancer (HR = 1.64). It Also decreased with lung disease (HR = 0.11), hypothyroidism (HR = 0.32), and hypertension (HR = 0.97). CONCLUSION: Considering the correlation between re-admission and mortality in the joint frailty model, malignancy and hyperlipidemia increased the risk of both re-admission and mortality. Moreover, lung disease probably due to the use of corticosteroids, was a protective factor against both mortality and re-admission.

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.

B-cell acute lymphoblastic leukemia associated with hypereosinophilia: a case report and brief literature review.

Few cases of B-cell acute lymphoblastic leukemia (B-ALL)-eosinophilia (ALL-eo) association have been reported. The lack or absence of blasts in the peripheral blood smear (PBS) along with urticarial rash, fever, arthralgia, myalgia, sweating, and dyspnea are common features of this condition. Herein, we report a 16-year-old male patient admitted to the emergency department with urticaria and generalized itching. PBS was examined, and eosinophils (90%) were seen in different fields. However, blast cells were not seen in PBS. In a bone marrow examination, terminal deoxynucleotidyl transferase-positive and CD20-positive lymphoid blasts were reported along with eosinophilia. Eventually, the B-ALL diagnosis was confirmed for the patient, and he was started on the Berlin-Frankfurt-Münster chemotherapy regimen. The association of B-ALL with hypereosinophilia is a rare condition. We hope this case report and literature review can help clinicians to manage this rare condition properly.

5-Flourouracil-induced toxicity in both male and female reproductive systems: A narrative review.

The chemotherapeutic drug 5-flourouracil (5FU) is frequently used to treat a wide range of solid malignant tumors, such as colorectal, pancreatic, gastric, breast, and head and neck cancers. Its antitumoral effects are achieved by interfering with the synthesis of RNA and DNA and by inhibiting thymidylate synthase in both malignant and non-malignant cells. Therefore, it can be responsible for severe toxicities in crucial body organs, including heart, liver, kidney, and reproductive system. Given the fact that 5FU-induced reproductive toxicity may limit the clinical application of this drug, in this study, we aimed to discuss the main locations and mechanisms of the 5FU-induced reproductive toxicity. Initially, we discussed the impact of 5FU on the male reproductive system, which leads to damage of the seminiferous epithelial cells and the development of vacuoles in Sertoli cells. Although no noticeable changes occur at the histopathological level, there is a decrease in the weight of the prostate. Additionally, 5FU causes significant abnormalities in spermatogenesis, including germ cell shedding, spermatid halo formation, polynucleated giant cells, and decreased sperm count. Finally, in females, 5FU-induced reproductive toxicity is characterized by the presence of atretic secondary and antral follicles with reduced numbers of growing follicles, ovarian weight, and maturity impairment.

Toxic mechanisms of cadmium and exposure as a risk factor for oral and gastrointestinal carcinomas.

Incidence and mortality rates of gastrointestinal (GI) and oral cancers are among the highest in the world, compared to other cancers. GI cancers include esophageal, gastric, colon, rectal, liver, and pancreatic cancers, with colorectal cancer being the most common. Oral cancer, which is included in the head and neck cancers category, is one of the most important causes of death in India. Cadmium (Cd) is a toxic element affecting humans and the environment, which has both natural and anthropogenic sources. Generally, water, soil, air, and food supplies are reported as some sources of Cd. It accumulates in organs, particularly in the kidneys and liver. Exposure to cadmium is associated with different types of health risks such as kidney dysfunction, cardiovascular disease, reproductive dysfunction, diabetes, cerebral infarction, and neurotoxic effects (Parkinson's disease (PD) and Alzheimer's disease (AD)). Exposure to Cd is also associated with various cancers, including lung, kidney, liver, stomach, hematopoietic system, gynecologic and breast cancer. In the present study, we have provided and summarized the association of Cd exposure with oral and GI cancers.

miRNAs and Multiple Myeloma: Focus on the Pathogenesis, Prognosis, and Drug Resistance.

Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients' bone marrow (BM). Around 1% of all cancers and 13% of hematological malignancies are caused by MM, making it one of the most common types of cancer. Diagnostic and therapeutic methods for managing MM are currently undergoing extensive research. MicroRNAs (miRNAs) are short noncoding RNAs that reduce or inhibit the translation of their target mRNA after transcription. Because miRNAs play an influential role in how myeloma develops, resources, and becomes resistant to drugs, miRNA signatures may be used to diagnose, do prognosis, and treat the myeloma response. Consequently, researchers have investigated the levels of miRNA in plasma cells from MM patients and developed tools to test whether they directly impacted tumor growth. This review discusses the latest discoveries in miRNA science and their role in the development of MM. We also emphasize the potential applications of miRNAs to diagnose, prognosticate, and treat MM in the future.

The study of trends in mortality of respiratory system cancers in Babol, North of Iran (2013-2021).

Background: In Iran, cancers are known as the second leading cause of death, among which respiratory system cancers are particularly important because lung cancer is the second most common cause of death in this country. This study aimed to estimate the crude and age-standardized mortality and its trends during 9 years in the Northern city of Iran, Babol. Methods: In this cross-sectional study, all the recorded deaths due to respiratory system cancers in Babol during the years 2013-2021 on the Classification of Causes of Deaths and Death Registration System of Babol University of Medical Sciences were taken into consideration, and the population estimate was based on the latest census. Finally, the crude and age-standardized rates of mortality and trends of cancer incidents were calculated. Results: In general, 393 deaths with an overall mean age of 67.8±3.9 years have happened due to respiratory system cancers. The crude and standardized rates of respiratory system cancers increased from 6.5 and 5.5 per hundred thousand people in 2013 to 9.1 and 7.8 per hundred thousand people in 2021, respectively. With each decade in age, their trends increased significantly in men (p=0.024) and remained constant in women (p=0.262). In examining the trend of respiratory system cancers, we found an increasing trend for lung cancer and a constant trend for larynx and oropharynx cancers. There was also a decreasing trend for hypopharyngeal cancer. Conclusions: The age-standardized rate and trend of respiratory system cancers are increasing. Therefore, it is important to prevent their prevalence by reducing the risk factors and increasing the general awareness of risks and timely diagnosis.

Transport of barium in fractured dolomite and sandstone saline aquifers.

To understand the advective-dispersive transport of Ba in fractured dolomite and sandstone saline aquifers, we conducted core-flooding experiments and reactive transport simulations. We used intact and synthetic fractured dolomite and sandstone cores collected from formations where hydraulic fracturing (HF) wastewater is disposed in Oklahoma, USA. The core-flooding experiments were conducted using saline water containing typical concentrations of NaCl (90 g/L), Ca (5 g/L), Mg (1 g/L), and Ba (100 mg/L) in HF wastewaters. At typical concentrations of NaCl, Ca, and Mg in HF wastewater, our experimental results show similar Ba transport rates in both intact and fractured dolomites but faster Ba transport rates in intact than in fractured sandstones. We found a match between measured and simulated breakthrough curves of Ba in intact and fractured sandstones. This supports the hypothesis that the inhibitory effect of salinity on Ba sorption increases Ba transport through matrix pores bordering the fracture while reducing its transport through the fracture. This is reflected by a reduction of the overall rate of Ba transport through fractured dolomites and sandstones. We found that the effect of salinity in retarding Ba transport through fractured dolomites and sandstones increases with increased matrix porosity and/or fracture aperture size. We implemented the multiple interacting continua (MINC) method developed for modeling fluid flow in fractured porous media to successfully capture the effect of salinity, matrix porosity and fracture aperture size on Ba transport in fractured sandstones. The measured and simulated results have significant implications on efforts of field-scale simulations of Ba transport in dolomite and sandstone saline aquifers where HF wastewater is disposed.

Petroleum produced water disposal: Mobility and transport of barium in sandstone and dolomite rocks.

To assess the risk of underground sources of drinking water contamination by barium (Ba) present in petroleum produced water disposed into deep saline aquifers, we examined the effect of salinity (NaCl), competition of cations (Ca, Mg), temperature (22 and 60°C), and organic fracturing additives (guar gum) on the sorption and transport of Ba in dolomites and sandstones. We found that at typical concentration levels of NaCl, Ca, and Mg in petroleum produced water, Ba sorption in both dolomites and sandstones is inhibited by the formation of Ba(Cl)+ complexes in solution and/or the competition of cations for binding sites of minerals. The inhibition of Ba sorption by both mechanisms is greater in dolomites than in sandstones. This is reflected by a larger decrease in the breakthrough times of Ba through dolomites than through sandstones. We found that the presence of guar gum has little influence on the sorption and thus the transport of Ba in both dolomites and sandstones. Contrary to most heavy metals, Ba sorption in both dolomites and sandstones decreases with increasing temperature, however the reducing effect of temperature on Ba sorption is relevant only at low salinity conditions. Higher inhibition of Ba sorption in dolomites than in sandstones is due to the greater reactivity of dolomite over sandstone. The results of this study which includes the formulation of a reactive transport model and estimation of partition coefficients of Ba in dolomites and sandstones have significant implications in understanding and predicting the mobility and transport of Ba in deep dolomite and sandstone saline aquifers.

Effect of brine salinity and guar gum on the transport of barium through dolomite rocks: Implications for unconventional oil and gas wastewater disposal.

This research aimed to elucidate the effect of brine salinity and guar gum on the sorption and transport of Ba in dolomite rocks collected from the Arbuckle formation in Oklahoma, USA. Guar gum represents the most important organic additive used in viscosified fracturing fluids, and Ba constitutes the most common and abundant heavy metal found in unconventional oil and gas (UOG) wastewater. Batch experiments conducted using powdered dolomite rocks (500-600 µm particle size) revealed that at brine salinities of UOG wastewater, chloro-complexation reactions between Ba and Cl ions and pH changes that results from dolomite dissolution are the controlling factors of Ba sorption on dolomite. Competition of Ba with common cations (Ca and Mg) for hydration sites of dolomite, plays a secondary role. Core-flooding experiments conducted to analyze the transport of Ba through natural and synthetic dolomite core plugs are in agreement with the batch sorption experimental results. The transport of Ba through dolomite rocks, increases with increasing brine salinity (0-180,000 mg-NaCl/L). The presence guar gum (50-500 mg/L) does not affect the transport of Ba through dolomite rocks of high flow properties (25-29.6% porosity, 9.6-13.7 mD permeability). However, core-flooding experiments conducted using tight dolomite rocks (6.5-8.6% porosity, 0.06-0.3 mD permeability), revealed that guar gum can retard the transport of Ba by clogging high permeability/porosity regions of tight dolomite rocks. The mechanism of Ba sorption on dolomite can be represented by a sorption model that accounts for both surface complexation reactions on three distinct hydration sites (>CaOHo, >MgOHo, and >CO3Ho), and the kinetic dissolution of dolomite. These results are important in understanding and predicting the fate of Ba present in UOG wastewater disposed into deep dolomite saline aquifers.