The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
WHO’s classification of hepatitis D virus as carcinogenic raises urgent questions for vaccination, screening, and treatment strategies worldwide.
The human gut renews itself faster than any other tissue: every few days, new cells are created from specialized stem cells. However, as we get older, epigenetic changes build up in these stem cells. These are chemical markers on the DNA that act like switches, determining which genes remain active.
The study, recently published in Nature Aging, was conducted by an international team led by Prof. Francesco Neri from the University of Turin, Italy, and shows that changes in the gut do not occur randomly. Rather, a specific pattern develops over the course of aging, which the researchers refer to as ACCA (Aging-and Colon Cancer-Associated) drift. “We observe an epigenetic pattern that becomes increasingly apparent with age,” explains Prof. Neri, former group leader at the Leibniz Institute on Aging—Fritz Lipmann Institute in Jena.
Genes that maintain the balance in healthy tissue are particularly affected, including those that control the renewal of the intestinal epithelium via the Wnt signaling pathway. The changes described as “drifting” can be detected not only in the aging gut, but also in almost all colon cancer samples examined. This suggests that the aging of stem cells creates an environment that promotes the development of cancer.
Deep within your bone marrow, a specialized set of stem cells is busy pumping out new blood cells to sustain your body. As we age, these hematopoietic stem cells (or HSCs) become less productive, affecting our immune system and increasing our risk of conditions like anemia and cancer.
Now, scientists have found a way to rewind the clock in aging HSCs, which could potentially help to treat age-related blood and immune deficiencies.
Like most of our cells, HSCs contain tiny compartments known as lysosomes. These are the cells’ recycling centers, where complex molecules like proteins and lipids are sent to be broken down into smaller, reusable parts.
Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases.
Mitochondrial ATP production by oxidative phosphorylation (OXPHOS) is essential for cellular functions, such that mitochondria are known as the powerhouses of the cell (Verschueren et al., 2019). The mitochondrial ETC consists of five enzyme complexes in the inner membrane of the mitochondria. ETC generates a charge across the inner mitochondrial membrane, which drives ATP synthase (complex V) to synthesize ATP from ADP and inorganic phosphate.
Several studies have shown impairments of all five complexes in multiple areas of the AD brain (Kim et al., 2000, 2001; Liang et al., 2008). Mitochondrial dysfunction in AD is apparent from a decrease in neuronal ATP levels, which is associated with the overproduction of ROS, and indicates that mitochondria may fail to maintain cellular energy. A substantial amount of ATP is consumed in the brain due to the high energy requirements of neurons and glia. Since an energy reserve (such as fat or glucose) is not available in the central nervous system (CNS), brain cells must continuously generate ATP to sustain neuronal function (Khatri and Man, 2013). Mitochondria are the primary source of cellular energy production, but aged or damaged mitochondria produce excess free radicals, which can reduce the supply of ATP and contribute to energy loss and mitochondrial dysfunction in AD. Importantly, oxidative damage of the promoter of the gene encoding subunit of the mitochondrial ATP synthase results in reduced levels of the corresponding protein, leading to decreased ATP production, nuclear DNA damage to susceptible genes, and loss of function (Lu et al., 2004; Reed et al., 2008).
In advanced stages of AD, substantial nitration of ATP synthase subunits can take place, leading to the irregular function of the respiratory chain (Castegna et al., 2003; Sultana et al., 2006; Reed et al., 2009). Likewise, ATP-synthase lipoxidation occurs in the hippocampus and parietal cortex of patients with mild cognitive impairment (Reed et al., 2008). Compromised OXPHOS contributes to a characteristic mitochondrial dysfunction in AD brains, leading to decreased ATP production, elevated oxidative stress, and ultimately cell death (Reddy, 2006; Reddy and Beal, 2008; Du et al., 2012). The specific mechanisms of OXPHOS deficiency in AD remain a long-standing scientific question, but the role of mitochondrial F1Fo ATP synthase dysfunction in AD-related mitochondrial OXPHOS failure is emphasized by emerging evidence (Beck et al., 2016; Gauba et al., 2019).
The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system.
An injection that blocks the activity of a protein involved in aging reverses naturally occurring cartilage loss in the knee joints of old mice, a Stanford Medicine-led study has found. The treatment also prevented the development of arthritis after knee injuries mirroring the ACL tears often experienced by athletes or recreational exercisers. An oral version of the treatment is already in clinical trials with the goal of treating age-related muscle weakness.
Samples of human tissue from knee replacement surgeries—which include both the extracellular scaffolding, or matrix, in the joint as well as cartilage-generating chondrocyte cells—also responded to the treatment by making new, functional cartilage.
The study results suggest it may be possible to regenerate cartilage lost to aging or arthritis with an oral drug or local injection, rendering knee and hip replacement unnecessary.
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms.
Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The discovery indicates that the two may interact in the body in ways that could lead to harmful effects when these processes become unregulated.
Understanding Microclots
