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Hesperidin and Hesperetin: EpigeneticStemness Crosstalk, Antitumor Mechanisms, Preclinical Data and Translation Barriers

Hesperidin is a natural flavonoid derived from citrus plants, which can be hydrolyzed into hesperetin in vivo. Both compounds have anti-inflammatory, antioxidant and antitumor activities. At present, there is a lack of reviews focusing on the epigenetic regulation of cancer stem cells (CSCs) mediated by hesperidin and hesperetin. This review summarizes the molecular crosstalk between hesperidin/hesperetin and CSCs mediated via three major epigenetic pathways, including direct regulatory effects, indirect modulatory actions, and mechanistic relationships proposed based on scientific hypotheses. We elaborate their effects on inhibiting the self-renewal, invasion and metastasis of CSCs as well as reversing chemoresistance, and analyze the crosstalk between epigenetic networks and classical signaling pathways of CSCs.

The Application of Newcastle Disease Virus (NDV): Vaccine Vectors and Tumor Therapy

Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research has highlighted the potential of NDV as a vector for vaccine development and gene therapy, owing to its transcriptional modularity, low recombination rate, and lack of a DNA phase during replication. Furthermore, NDV exhibits oncolytic capabilities, efficiently eliciting antitumor immune responses, thereby positioning it as a promising therapeutic agent for cancer treatment.

Neuropsychological Profile and Cognitive Trajectories of Patients With Biomarker Evidence of Alzheimer Disease or Dementia With Lewy bodies

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FGF21 synergizes with leptin to counteract obesityrelated metabolic comorbidities by reversing hepatic leptin resistance

Obesity-induced leptin resistance is a major challenge for clinical management and drug development. This study finds that FGF21 synergizes with leptin in counteracting obesity-related metabolic multimorbidity by enhancing leptin sensitivity in hepatocytes via adiponectin-induced expression of leptin receptors.

Blocking a mitochondrial transporter may curb inflammation from ‘zombie’ cells without killing them

Researchers have uncovered a previously unknown mechanism that helps aging cells drive the chronic inflammation linked to many age-related diseases. The findings reveal how dysfunctional mitochondria—the cell’s energy-producing structures—work with the cell’s epigenetic machinery to switch on inflammatory genes, opening the door to a new therapeutic approach for promoting healthier aging.

The study, published in Nature, builds on years of research showing that senescent, or “zombie,” cells accumulate with age. While these cells no longer divide, they remain metabolically active and release a cocktail of inflammatory molecules known as the senescence-associated secretory phenotype, or SASP.

This persistent inflammation is thought to contribute to frailty, cardiovascular disease, cancer, neurodegeneration and other disorders of aging.

The oceans near Australia may be the best places to fertilize for removing carbon dioxide

Deploying ocean iron fertilization—a strategy for carbon dioxide capture—in higher latitudes rather than near the equator could reduce environmental impacts while still achieving removal of carbon dioxide from the atmosphere, according to a modeling study published in Nature. The findings offer insight into best practices for maximizing carbon dioxide removal while reducing potential ecological trade-offs typically associated with iron fertilization.

Current carbon emissions are projected to surpass the Paris Climate Agreement’s limit of 2°C above preindustrial levels. Ocean iron fertilization—in which iron is added to surface water to stimulate phytoplankton growth for carbon dioxide removal—is a potential solution. However, the ecological impacts of this strategy, such as creating runaway algal blooms and depleting nutrients in the water, have been a limitation.

Jun Yu, Adam Martiny and colleagues used an ocean iron fertilization model to assess the climate benefits and ecological trade-offs of the approach. By analyzing more than six decades of fertilization data, they found that net carbon dioxide removal was up to 5.3 parts per million, which corresponds to a removal rate of 0.70 gigatons of carbon dioxide per year.

NRF2mediated inhibition of alveolar macrophage MHC II expression during Mycobacterium tuberculosis infection

Pham et al. show that, during Mycobacterium tuberculosis infection, NRF2 activation in alveolar macrophages inhibits MHC II but not MHC I, leading to dampening of antigen presentation and CD4+ T cell activation. Although NRF2 promotes a cell-protective program, it unexpectedly impairs innate-adaptive crosstalk and host immunity in the lung.

Antihistamines likely offer no meaningful benefit for eczema and may increase harms

Adding oral antihistamines to existing eczema treatments is unlikely to lead to clinically important reductions in eczema and itch severity and may not reduce sleep disturbance or flare-ups, finds a review of the latest trial evidence published by The BMJ today.

Some antihistamines may also increase side effects such as drowsiness and the risk of patients stopping treatment.

The researchers say this review addresses longstanding uncertainty surrounding the role of antihistamines in treating eczema, and the results do not support their use in routine eczema management.

Pathophysiology of irritable bowel syndrome

Despite the continued absence of a definitive biomarker for irritable bowel syndrome (IBS), research over the last three decades has identified a wide range of underlying pathophysiological abnormalities. Peripheral mechanisms include gastrointestinal infection, changes in the gut microbiome, visceral hypersensitivity, increased intestinal permeability, low-grade mucosal inflammation and altered immune function, abnormal gastrointestinal motility, and the role of serotonin, bile acid metabolism, and carbohydrate metabolism.

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