The Biological Clock of Liver Metabolism in Metabolic Dysfunction-Associated Steatohepatitis Progression to Hepatocellular Carcinoma.

Circadian rhythms are endogenous behavioral or physiological cycles that are driven by a daily biological clock that persists in the absence of geophysical or environmental temporal cues. Circadian rhythm-related genes code for clock proteins that rise and fall in rhythmic patterns driving biochemical signals of biological processes from metabolism to physiology and behavior. Clock proteins have a pivotal role in liver metabolism and homeostasis, and their disturbances are implicated in various liver disease processes.

Normalization of the ATP1A1 Signalosome Rescinds Epigenetic Modifications and Induces Cell Autophagy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In metabolic dysfunction-associated steatohepatitis (MASH)-related HCC, cellular redox imbalance from metabolic disturbances leads to dysregulation of the α1-subunit of the Na/K-ATPase (ATP1A1) signalosome. We have recently reported that the normalization of this pathway exhibited tumor suppressor activity in MASH-HCC.

The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions.

Metabolic dysfunction-associated steatohepatitis (MASH) is one of the major risk factors for chronic liver disease and hepatocellular carcinoma (HCC). The incidence of MASH in Western countries continues to rise, driving HCC as the third cause of cancer-related death worldwide. HCC has become a major global health challenge, partly from the obesity epidemic promoting metabolic cellular disturbances but also from the paucity of biomarkers for its early detection.

A systematic evidence map for the evaluation of noncancer health effects and exposures to polychlorinated biphenyl mixtures.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches.

Cell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma.

Autophagy, a cellular self-digestion process, involves the degradation of targeted cell components such as damaged organelles, unfolded proteins, and intracellular pathogens by lysosomes. It is a major quality control system of the cell and plays an important role in cell differentiation, survival, development, and homeostasis. Alterations in the cell autophagic machinery have been implicated in several disease conditions, including neurodegeneration, autoimmunity, cancer, infection, inflammatory diseases, and aging.

Tumor-Suppressor Role of the α1-Na/K-ATPase Signalosome in NASH Related Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, with an estimate of 0.84 million cases every year. In Western countries, because of the obesity epidemic, non-alcoholic steatohepatitis (NASH) has become the major cause of HCC.

Risk of bias in non-randomized observational studies assessing the relationship between proton-pump inhibitors and adverse kidney outcomes: a systematic review.

Background: Proton-pump inhibitors (PPIs) are widely prescribed as acid-suppression therapy. Some observational studies suggest that long-term use of PPIs is potentially associated with certain adverse kidney outcomes. We conducted a systematic literature review to assess potential bias in non-randomized studies reporting on putative associations between PPIs and adverse kidney outcomes (acute kidney injury, acute interstitial nephritis, chronic interstitial nephritis, acute tubular necrosis, chronic kidney disease, and end-stage renal disease).

Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients.

Objective: Prescription opioid use and deaths related to serious toxicity, including overdose, have increased dramatically in the United States since 1999. However, factors associated with serious opioid-related respiratory or central nervous system (CNS) depression or overdose in medical users are not well characterized. The objective of this study was to examine the factors associated with serious toxicity in medical users of prescription opioids.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

Objective: To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations.

Study Design: Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates.

Interaction of the delta-aminolevulinic acid dehydratase polymorphism and lead burden on cognitive function: the VA normative aging study.

Objective: We evaluated the modifying influence of a delta-aminolevulinic acid dehydratase (ALAD) polymorphism on the relation between lead burden and cognition among older men.

Methods: Information on ALAD genotype, lead measurements, potential confounders, and cognitive testing was collected from 982 participants. For each cognitive test and lead biomarker, we fit separate multiple linear regression models, which included an interaction term for ALAD genotype and the lead biomarker and adjusted for potential confounders.

Lead burden and psychiatric symptoms and the modifying influence of the delta-aminolevulinic acid dehydratase (ALAD) polymorphism: the VA Normative Aging Study.

The authors evaluated the association between lead burden and psychiatric symptoms and its potential modification by a delta-aminolevulinic acid dehydratase (ALAD) polymorphism. Lead measurements in blood or bone and self-reported ratings on the Brief Symptom Inventory from 1991 to 2002 were available for 1,075 US men participating in the Department of Veterans Affairs (VA) Normative Aging Study. The authors estimated the prevalence odds ratio for the association between interquartile-range lead and abnormal symptom score, adjusting for potential confounders.

A pilot study of blood lead levels and neurobehavioral function in children living in Chennai, India.

The relationship between blood lead level and neurodevelopment was assessed in a pilot cross-sectional study of 74 4-14-year-old children in Chennai, India. Mean blood lead level was 11.1 microg/dL (2.