The role and mechanism of action of microRNA-122 in cancer: Focusing on the liver.

microRNA-122 (miR-122) is a highly conserved microRNA that is predominantly expressed in the liver and plays a critical role in the regulation of liver metabolism. Recent studies have shown that miR-122 is involved in the pathogenesis of various types of cancer, particularly liver cancer. In this sense, The current findings highlighted the potential role of miR-122 in regulating many vital processes in cancer pathophysiology, including apoptosis, signaling pathway, cell metabolism, immune system response, migration, and invasion. These results imply that miR-122, which has been extensively studied for its biological functions and potential therapeutic applications, acts as a tumor suppressor or oncogene in cancer development. We first provide an overview and summary of the physiological function and mode of action of miR-122 in liver cancer. We will examine the various signaling pathways and molecular mechanisms through which miR-122 exerts its effects on cancer cells, including the regulation of oncogenic and tumor suppressor genes, the modulation of cell proliferation and apoptosis, and the regulation of metastasis. Most importantly, we will also discuss the potential diagnostic and therapeutic applications of miR-122 in cancer, including the development of miRNA-based biomarkers for cancer diagnosis and prognosis, and the potential use of miR-122 as a therapeutic target for cancer treatment.

Human health risk assessment of heavy metal and pathogenic contamination in surface water of the Punnakayal estuary, South India.

Variation in levels of toxic heavy metals in river system during the COVID-19 pandemic lockdown might potentially assist in development of a public health risk mitigation system associated with the water consumption. The water quality of Punnakayal estuary in the Thamirabarani River system from the south India, a vital source of water for drinking and domestic purposes, industrial usage, and irrigation was assessed here. A comparitive assessment of physico-chemical variables (pH, EC, TDS, DO, BOD, turbidity and NO3), microbiological parameters (total coliform bacteria, fecal coliform bacteria, fecal streptococci and escherichia coli) and toxic metals (As, Cr, Fe, Cu, Zn, Cd, and Pb) suggested a decrease of 20% in the contaminant ratio during the lockdown period in comparison to the pre-lockdown period. The Health risk assessment models (HQ, HI, and TCR) highlighted carcinogenic and non-carcinogenic hazards for both children and adults through the ingestion and dermal adsorption exposures. The HI values for both As and Cr exceeded the acceptable limit (>1) during the lockdown period, but the potential risk for children and adults remained low in compaisio with the pre-lockdown period. Our results suggested that the Thamirabarani River system remained hostile to human health even during the lockdown period, and it requires regular monitoring through a volunteer water quality committee with private and government participations.

Concentration, source apportionment and potential carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) in roadside soils.

PAHs are organic pollutants that have carcinogenic and mutagenic impacts on human health and are a subject of great concern. The soil-bound polycyclic aromatic hydrocarbons (PAHs) in the urban areas can be very lethal to human health. The concentrations, sources, and possible cancer risks of 15 PAHs were analysed by collecting roadside soil samples in Lucknow, India. The range of ∑15PAHs was found to be 478.94 ng/g to 8164.07 ng/g with a mean concentration of 3748.23 ng/g. The highest contribution (32.5%) was found to be from four-ring PAHs, followed by six-ring (24.5%) and five-ring (16.7%) PAHs. The source apportionment through diagnostic ratios ANT/(ANT + PHE) against FL-2/(FL-2+PYR) highlighted the dominance of petroleum, wood, coal, and grass combustion as sources of PAHs in the study area. Source apportionment was also done through positive matrix factorization, confirming the dominance of 'vehicular emissions' (49%), followed by 'coal and biomass combustion' (∼39%), and 'leakages, volatilization and petroleum combustion' (∼12%) as potential sources. The results from lifetime cancer risks (ILCR) varied in the range of 7.5 × 10-4 and 1.3 × 10 × -2 illustrating 'high cancer risk'. The total cancer risk susceptibility of children was found to be 31% more than that of adults. The highest risk associated with toxic equivalent concentration (TEQ) was found at site S8 highlighting the impact of the presence of an international airport, and huge traffic load. The present study will prove to be useful for information related to human exposure to PAHs content in soil in the study area and as baseline study for policy makers, stakeholders, and researchers.

Environmental contamination by heavy metals and associated human health risk assessment: a case study of surface water in Gomti River Basin, India.

The aim of the present study was to assess the status of heavy metal contamination and health risks associated with the use of water from River Gomti by millions of people. The value of the degree of contamination (Cd) was found to be '11.93', signifying 'high' risk levels due to heavy metal contamination in River Gomti across an approximate stretch of 61 km including upstream, midstream, and downstream locations of Lucknow city. The potential sources of heavy metal pollution in River Gomti include both sewage and industrial effluents, being transported by drains which overflow into the river. The heavy metals were found to have low mobility owing to the 'near neutral' pH of river water. The findings from the human health risk assessment revealed that the hazard index associated with non-carcinogenic risks exceeded the permissible limits at all sampling stations. The highest health risk was found at Bharwara sewage treatment plant discharge point, downstream of Lucknow city signifying the elevated levels of heavy metal in the river water post treatment from Bharwara STP. The results of carcinogenic risk assessment suggested that children were more susceptible to health risks, and immediate remedial measures are required to control the elevated levels of heavy metals at all the sampling stations.

Ferumoxytol Is Not Retained in Kidney Allografts in Patients Undergoing Acute Rejection.

PURPOSE: To evaluate whether ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced magnetic resonance imaging (MRI) can detect allograft rejection in pediatric kidney transplant patients. PROCEDURES: The USPIO ferumoxytol has a long blood half-life and is phagocytosed by macrophages. In an IRB-approved single-center prospective clinical trial, 26 pediatric patients and adolescents (age 10-26 years) with acute allograft rejection (n = 5), non-rejecting allografts (n = 13), and normal native kidneys (n = 8) underwent multi-echo T2* fast spoiled gradient-echo (FSPGR) MRI after intravenous injection (p.i.) of 5 mg Fe/kg ferumoxytol. T2* relaxation times at 4 h p.i. (perfusion phase) and more than 20 h p.i. (macrophage phase) were compared with biopsy results. The presence of rejection was assessed using the Banff criteria, and the prevalence of macrophages on CD163 immunostains was determined based on a semi-quantitative scoring system. MRI and histology data were compared among patient groups using t tests, analysis of variance, and regression analyses with a significance threshold of p < 0.05. RESULTS: At 4 h p.i., mean T2* values were 6.6 ± 1.5 ms for native kidneys and 3.9 ms for one allograft undergoing acute immune rejection. Surprisingly, at 20-24 h p.i., one rejecting allograft showed significantly prolonged T2* relaxation times (37.0 ms) compared to native kidneys (6.3 ± 1.7 ms) and non-rejecting allografts (7.6 ± 0.1 ms). Likewise, three additional rejecting allografts showed significantly prolonged T2* relaxation times compared to non-rejecting allografts at later post-contrast time points, 25-97 h p.i. (p = 0.008). Histological analysis revealed edema and compressed microvessels in biopsies of rejecting allografts. Allografts with and without rejection showed insignificant differences in macrophage content on histopathology (p = 0.44). CONCLUSION: After ferumoxytol administration, renal allografts undergoing acute rejection show prolonged T2* values compared to non-rejecting allografts. Since histology revealed no significant differences in macrophage content, the increasing T2* value is likely due to the combined effect of reduced perfusion and increased edema in rejecting allografts.

Mammography Patient Information at Hospital Websites: Most Neither Comprehensible Nor Guideline Supported.

OBJECTIVE: Ongoing controversy regarding screening mammography guidelines has created confusion for many patients. Given recommendations that patient educational material be prepared at or below the 7th grade reading level of average Americans, the purpose of this study was to assess the readability of online mammography information offered by hospitals nationwide. MATERIALS AND METHODS: During 2015, online mammography patient educational materials were identified for all Medicare-recognized hospitals nationwide for which screening mammography metrics were publicly available. Patient educational materials were assessed using six validated readability score algorithms. All references to official screening guidelines were captured. RESULTS: Of 4105 hospitals nationwide, 3252 had websites and confirmable screening mammography services. Of those, 1753 (54%) offered mammography information material online. Only 919 (28%) referenced any professional society guidelines. After excluding information not formatted in HTML and shorter than 100 words (to improve algorithm reliability), 1524 hospital mammography webpages were assessed for grade level scores. Nationally, the mean of each readability score for all hospitals varied between the 10th and 14th grade levels, all higher than the recommended 7th grade level (p < 0.001). At the individual hospital level, only 14 hospitals (0.4%) had mean scores at or below the 7th grade level. CONCLUSION: Of U.S. hospitals that offer screening mammography and have websites, only 54% provide online mammography educational material. Of those, only 0.4% present information at a reading level comprehensible to average Americans, and only 28% offer specific information to help patients reconcile conflicting guidelines. Health systems offering mammography should strive to better meet women's health information and literacy needs.

Quantitative Analyses of Esophageal Cancer Research in Pakistan.

BACKGROUND: Healthcare research is a neglected discipline in Pakistan and research related to esophageal cancer (ranks 9th in Pakistani males and 5th in females) is no exception in this regard. Particularly, there are no data available to delineate the overall status of esophageal cancer epidemiological studies in Pakistan. This study describes the first ever effort to make a systematic quantification, in an attempt to provide a roadmap to all stakeholders for designing appropriate epidemiological, diagnostic and therapeutic strategies. MATERIALS AND METHODS: International (PubMed, ISI Web of Knowledge) and local (PakMedinet) scientific databases as well as Google search engine were searched using specified keywords to extract relevant publication. Well defined inclusion criteria were implemented to select publications for final analyses. All data were recorded by at least 3 authors and consensus data were entered into and analyzed for descriptive statistics (such as frequencies, percentages and annual growth rates) using Microsoft Excel and SPSS software. RESULTS: A total of 79 publications fulfilled the inclusion criteria including 20 publications for which full texts were not available. Of the 79 publications, 59 (74.6%) were original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were research communications, 2 (2.5%) were review articles, 1 was (1.2%) correspondence and 8 (10.1%) were un defined categories. Only 13 <20%) cities of Pakistan contributed towards the 79 publications. On average, only 1.9 relevant publications/year were published from 1976 (year of first publication) to the present. Alarmingly, a decline in the annual growth at 4.1% was recorded in the last six years. CONCLUSIONS: Esophageal cancer research is largely unfathomed in Pakistan. Urgent/dramatic steps are required by all concerned to address this common (and under reported) cancer of Pakistan.

Can Patients Comprehend the Educational Materials that Hospitals Provide about Common IR Procedures?

PURPOSE: To assess the readability of online education materials offered by hospitals describing commonly performed interventional radiology (IR) procedures. MATERIALS AND METHODS: Online patient education materials from 402 hospitals selected from the Medicare Hospital Compare database were assessed. The presence of an IR service was determined by representation in the Society of Interventional Radiology physician finder directory. Patient online education materials about (i) uterine artery embolization for fibroid tumors, (ii) liver cancer embolization, (iii) varicose vein treatment, (iv) central venous access, (v) inferior vena cava (IVC) filter placement, (vi) nephrostomy tube insertion, (vii) gastrostomy tube placement, and (viii) vertebral augmentation were targeted and assessed by using six validated readability scoring systems. RESULTS: Of 402 hospitals sampled, 156 (39%) were presumed to offer IR services. Of these, 119 (76%) offered online patient education material for one or more of the eight service lines. The average readability scores corresponding to grade varied between the ninth- and 12th-grade levels. All were higher than the recommended seventh-grade level (P < .05) except for nephrostomy and gastrostomy tube placement. Average Flesch-Kincaid Reading Ease scores ranged from 42 to 69, corresponding with fairly difficult to difficult readability for all service lines except IVC filter and gastrostomy tube placement, which corresponded with standard readability. CONCLUSIONS: A majority of hospitals offering IR services provide at least some online patient education material. Most, however, are written significantly above the reading comprehension level of most Americans. More attention to health literacy by hospitals and IR physicians is warranted.

Radiation safety knowledge and perceptions among residents: a potential improvement opportunity for graduate medical education in the United States.

RATIONALE AND OBJECTIVES: To investigate residents' knowledge of adverse effects of ionizing radiation, frequency of their education on radiation safety, and their use of radioprotective equipment. MATERIALS AND METHODS: Residents from 15/16 residency programs at Emory University were asked to complete a resident radiation safety survey through SurveyMonkey(®). The associations between the residents' knowledge and use of radioprotective equipment with residents' specialty and year of training were investigated. RESULTS: Response rate was 32.5% (173/532 residents). Thirty-nine percent residents reported radiation safety is discussed in their residency curriculum at least every 6 months. Ninety-five percent believed in a link between radiation exposure and development of cancer. Overall and Radiology residents' knowledge about specific estimated dose effects (correct responses) was limited: radiation dose associated with fetus brain malformation in pregnancy (10% vs. 26%), risk of developing cataract in interventional personnel (27% vs. 47%), lifetime risk of cancer mortality from a single abdominal computed tomography (CT) in children (22% vs. 29%), greater radiosensitivity of children compared to adults (35% vs. 50%), and relative radiation dose from an abdominal CT compared to a chest x-ray (51% vs. 48%). Radiology residents had modestly higher knowledge. There was no significant difference in residents' knowledge across their postgraduate training years. Use of lead thyroid shields was reported by 86% (97% radiology vs. 80% nonradiology; P = .03) and radiation-monitoring badges in 39% (68% radiology vs. 15% nonradiology; P < .001) of the residents. CONCLUSIONS: Although radiology residents scored higher, knowledge of radiation safety for patients and healthcare workers is limited among residents regardless of medical specialty. These findings emphasize the need for educational initiatives.

Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle.

Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes. A wide range of stem cells continues to be investigated for countless applications. This protocol focuses on 3 different stem cell populations: human embryonic kidney 293 (HEK293) cells, human mesenchymal stem cells (hMSC) and induced pluripotent stem (iPS) cells. HEK 293 cells are derived from human embryonic kidney cells grown in culture with sheared adenovirus 5 DNA. These cells are widely used in research because they are easily cultured, grow quickly and are easily transfected. hMSCs are found in adult marrow. These cells can be replicated as undifferentiated cells while maintaining multipotency or the potential to differentiate into a limited number of cell fates. hMSCs can differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, tendon, muscle, and marrow stroma. iPS cells are genetically reprogrammed adult cells that have been modified to express genes and factors similar to defining properties of embryonic stem cells. These cells are pluripotent meaning they have the capacity to differentiate into all cell lineages. Both hMSCs and iPS cells have demonstrated tissue regenerative capacity in-vivo. Magnetic resonance (MR) imaging together with the use of superparamagnetic iron oxide (SPIO) nanoparticle cell labels have proven effective for in vivo tracking of stem cells due to the near microscopic anatomical resolution, a longer blood half-life that permits longitudinal imaging and the high sensitivity for cell detection provided by MR imaging of SPIO nanoparticles. In addition, MR imaging with the use of SPIOs is clinically translatable. SPIOs are composed of an iron oxide core with a dextran, carboxydextran or starch surface coat that serves to contain the bioreactive iron core from plasma components. These agents create local magnetic field inhomogeneities that lead to a decreased signal on T2-weighted MR images. Unfortunately, SPIOs are no longer being manufactured. Second generation, ultrasmall SPIOs (USPIO), however, offer a viable alternative. Ferumoxytol (FerahemeTM) is one USPIO composed of a non-stoichiometric magnetite core surrounded by a polyglucose sorbitol carboxymethylether coat. The colloidal, particle size of ferumoxytol is 17-30 nm as determined by light scattering. The molecular weight is 750 kDa, and the relaxivity constant at 2T MRI field is 58.609 mM(-1) sec(-1) strength. Ferumoxytol was recently FDA-approved as an iron supplement for treatment of iron deficiency in patients with renal failure. Our group has applied this agent in an "off label" use for cell labeling applications. Our technique demonstrates efficient labeling of stem cells with ferumoxytol that leads to significant MR signal effects of labeled cells on MR images. This technique may be applied for non-invasive monitoring of stem cell therapies in pre-clinical and clinical settings.