Publications by authors named "Lily Dara"

Article Synopsis
  • The study analyzed clinical features, liver histology, and genetic variants in 57 patients experiencing moderate to severe immune-mediated liver injury from checkpoint inhibitors (ILICI) over a 12-year period.
  • Results showed that ILICI typically occurs within 72 days of treatment initiation, predominantly affecting older non-Hispanic White men, with specific liver injury types noted and high steroid treatment use.
  • Genetic analysis identified variants linked to immune response and drug metabolism that may contribute to ILICI, suggesting future potential for better diagnostics and treatments if these findings are confirmed.
View Article and Find Full Text PDF
Article Synopsis
  • The study examines the roles of PD-L1 expression and tumor mutational burden (TMB) in various metastatic sites of breast cancer, focusing on differences in the tumor microenvironment (TME).
  • Analysis of 3076 patient biopsies revealed that liver metastases (LvMs) have high TMB but lower PD-L1 expression and adaptive immune cell infiltration compared to primary breast tumors (BrTs).
  • The findings suggest that the metastatic site affects immune characteristics and biomarker expression, indicating the need for tailored approaches in immune checkpoint inhibitor treatments based on biopsy locations.
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • * Researchers used single-cell RNA sequencing to analyze NK cells from end-stage cirrhotic livers with different causes: non-alcoholic steatohepatitis (NASH), chronic hepatitis C (HCV), and primary sclerosing cholangitis (PSC).
  • * Findings indicate that while NK cells exhibit similar dysfunctions in cirrhosis, the underlying liver disease affects their variability, suggesting that treatment strategies should consider the specific disease type.
View Article and Find Full Text PDF

There has been a global increase in rates of obesity with a parallel epidemic of non-alcoholic fatty liver disease (NAFLD). Autophagy is an essential mechanism involved in the degradation of cellular material and has an important function in the maintenance of liver homeostasis. Here, we explore the effect of Autophagy-related 5 (Atg5) deficiency in liver CD11c cells in mice fed HFD.

View Article and Find Full Text PDF
Article Synopsis
  • Immune checkpoints CTLA-4 and PD-1/PD-L1 play crucial roles in regulating the immune system, but their inhibitors (ICIs) are transforming cancer treatments while risking immune-related side effects, particularly in the liver.
  • The liver's unique immune tolerance can be disrupted by these inhibitors, leading to immune mediated liver injury from checkpoint inhibitors (ILICI), which can affect up to 20% of treated patients, especially when combining CTLA-4 and PD-1/PD-L1 therapies.
  • The exact mechanisms behind ILICI remain unclear, but factors like CD8 T cells, various CD4 T cell populations, and cytokines may contribute to liver damage, and current research utilizes animal models and clinical
View Article and Find Full Text PDF

Hepatitis A (HAV) has emerged in outbreaks across the United States particularly in at-risk populations such as men who have sex with men, as well as patients with a history of drug use, homelessness, and incarceration. Immunization among these high-risk populations remains underused. In this study, we describe a case of acute HAV and hepatitis B (HBV) coinfection in an MSM patient occurring in the period of these outbreaks.

View Article and Find Full Text PDF

Autoimmune liver diseases are attributed to a complex interplay of biologic, acquired, and environmental factors. Increased prevalence, later stage at presentation, worse response to standard therapy, and transplant-related disparities have all been reported in racial and ethnic minorities such as Black and Latinx patients with autoimmune liver diseases. While biology and inherited genetic predispositions may partly explain these disparities, definitive and universal genetic variations underlying these differences in outcomes have not been defined.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • Regulated cell death (RCD) is essential in determining how severe and damaging liver injuries can be, particularly impacting liver diseases through inflammation and fibrosis.
  • Various cell death processes, such as apoptosis, necrosis, and newer ones like pyroptosis and ferroptosis, have been studied for their roles in liver disease, showing both unique and overlapping traits.
  • The review highlights the signaling pathways involved in each cell death type and discusses findings, controversies, and limitations in research related to liver damage from conditions like alcoholic liver disease and viral hepatitis.
View Article and Find Full Text PDF
Article Synopsis
  • Patients with autoimmune liver diseases can show symptoms of multiple conditions, now known as variant syndromes, with the most common being the overlap between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH).
  • AIH typically shows high levels of serum immunoglobulin G (IgG), while PBC is linked to increased serum immunoglobulin M (IgM), and this distinction is reflected in liver biopsy plasma cell compositions.
  • The study aimed to analyze the immunostaining patterns of IgG and IgM in liver plasma cells specifically among Hispanic patients in Los Angeles who exhibit features of both PBC and AIH, comparing them to patients with only one of the conditions.
View Article and Find Full Text PDF
Article Synopsis
  • Drug-induced liver injury (DILI) is a significant cause of liver toxicity that can lead to severe outcomes like acute liver failure, primarily due to hepatocyte death caused by various drugs.
  • Different types of cell death are involved in DILI, including apoptosis and necrosis, with mitochondrial function being crucial for these processes, while other forms like pyroptosis and ferroptosis have emerged more recently.
  • Most drug-related liver injuries occur in an idiosyncratic manner (IDILI), which is unpredictable and not related to drug dosage, influenced by individual genetic factors and immune responses, and requires further investigation to understand the mechanisms behind these injuries.
View Article and Find Full Text PDF
Article Synopsis
  • RIPK1 and RIPK3 are key proteins that help regulate whether cells live or die, playing crucial roles in processes like necroptosis (a form of regulated cell death) and apoptosis (programmed cell death).
  • These proteins are known for executing necroptosis, which operates independently of caspases, and they first gained attention in relation to liver cells, though their physiological implications are still debated.
  • Recent studies suggest that RIPK1 and RIPK3 may influence liver diseases and inflammation even when not directly causing cell death, indicating the need for more research on their roles beyond necroptosis.
View Article and Find Full Text PDF
Article Synopsis
  • Drug-induced liver injury (DILI) is classified into two types: predictable (like acetaminophen overdose) and unpredictable (idiosyncratic DILI), both leading to liver cell death and inflammation.
  • The mechanisms behind DILI vary by the drug, with predictable DILI causing direct oxidative stress in liver cells, while idiosyncratic DILI involves the immune system triggering cell death.
  • This review covers the pathways of liver cell death from both types of DILI, focusing on acetaminophen toxicity as a case study, and examines the genetic factors and immune responses related to idiosyncratic liver injury.
View Article and Find Full Text PDF
Article Synopsis
  • Acute and chronic liver injuries lead to the death and turnover of liver cells (hepatocytes), which can result in serious conditions like cirrhosis and liver cancer if not controlled.
  • Controlling liver cell death through therapies is crucial to prevent acute liver failure and manage chronic inflammation and fibrosis caused by ongoing cell death.
  • The role of necroptosis, a specific type of regulated cell death, in liver disease is still debated, with recent studies showing mixed results, prompting further research in this area.
View Article and Find Full Text PDF
Article Synopsis
  • * The researchers found that the pseudokinase MLKL is involved in hepatocyte death during ConA-induced liver injury, and this process occurs independently of the RIPK3 protein, which is not present in hepatocytes.
  • * The study suggests MLKL is activated by an unidentified kinase and involves the IFN-γ/STAT1 pathway, highlighting MLKL's potential role in autoimmune hepatitis and its value as a target for new treatments in liver diseases.
View Article and Find Full Text PDF
Article Synopsis
  • RIPK1 is crucial for regulating cell death pathways like apoptosis and necroptosis, impacting immune responses in liver injury.
  • Research on RIPK1 knockdown in mice showed that it worsens liver damage and increases inflammation, linked to heightened apoptotic death of liver cells.
  • Interventions like caspase inhibitors and anti-TNF antibodies provided protection, indicating that RIPK1's role isn't just through its kinase activity but also in preventing apoptosis in liver injuries triggered by immune activation.
View Article and Find Full Text PDF
Article Synopsis
  • The study examined the effectiveness of two different intervals (1 week vs. 2 weeks) for repeat ligation sessions in treating esophageal variceal bleeding, finding that 1-week intervals resulted in faster eradication of varices without increasing complications.
  • Patients on the 1-week schedule showed a higher success rate of variceal eradication at 4 weeks (82% vs. 51%) and achieved this in fewer days on average (18.1 vs. 30.8 days).
  • Overall, while both intervals had similar outcomes regarding complications, rebleeding, and mortality, the findings suggest that the choice of ligation intervals can be personalized based on individual patient needs and practices.
View Article and Find Full Text PDF

In the past decade our understanding of idiosyncratic drug induced liver injury (IDILI) and the contribution of genetic susceptibility and the adaptive immune system to the pathogenesis of this disease process has grown tremendously. One of the characteristics of IDILI is that it occurs rarely and only in a subset of individuals with a presumed susceptibility to the drug. Despite a clear association between single nucleotide polymorphisms in human leukocyte antigen (HLA) genes and certain drugs that cause IDILI, not all individuals with susceptible HLA genotypes develop clinically significant liver injury when exposed to drugs.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the mechanisms of cell death induced by acetaminophen (APAP), focusing on the roles of RIPK1 and RIPK3 in necrosis and necroptosis.
  • Researchers confirmed that RIPK1 is actively involved in necrosis regulation while finding no evidence of RIPK3's contribution to APAP-induced damage, as it is only expressed in nonparenchymal cells.
  • The findings suggest that RIPK1 operates independently of RIPK3 and MLKL, acting upstream of JNK activation to mediate necrosis from acetaminophen toxicity.
View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionfqgm7lbacfqq0oaajbphd0c4u9pvktmj): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once