Cordycepin, a 3-deoxyadenosine, is the predominant functional component of the fungus Cordyceps militaris, a traditional Chinese medicine. Previous studies investigating the inhibition of cancer cells by cordycepin identified that it not only promotes cell apoptosis, but also controls cell proliferation. Furthermore, studies have elucidated the molecular mechanisms of inhibiting cell proliferation by cordycepin binding the A3 adenosine receptor, activating G protein, inhibiting cAMP formation, decreasing glycogen synthase kinase-3β/β-catenin activation and suppressing cyclin D1 and c-myc expression. The most significant signaling pathway in which cell apoptosis is induced by cordycepin is the caspase pathway. Cordycepin induces cell apoptosis via binding the DR3 receptor and consequently activating caspase-8/-3. Taken together, these studies demonstrate that cordycepin may be used as a natural medicine, as it can not only control tumor cell proliferation, but also induce cancer cell apoptosis.

Metal ion homeostasis and heavy metal detoxification systems are regulated by certain genes associated with metal ion transport. Metallothionein (MT) and metal response element binding transcription factor 1 (MTF‑1) are important regulatory proteins involved in the mediation of intracellular metal ion balance. Differences in the zinc‑binding affinities of the zinc fingers of MTF‑1 and the α‑ and β‑domains of MT facilitate their regulation of Zn2+ concentration. Alterations in the intracellular concentration of Zn2+ influence the MTF‑1 zinc finger number, and MTF‑1 containing certain zinc finger numbers regulates the expression of corresponding target genes. The present review evaluates the association between zinc finger number in MTF‑1 protein, MTF‑1 target genes and the mechanism underlying MT regulation of the zinc finger number in MTF‑1.

Aging is a systemic process marked by progressive multi-organ dysfunction, metabolic dysregulation, and chronic low-grade inflammation ("inflammaging"), which collectively drive neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Emerging evidence underscores the brain–muscle–liver axis as a central hub for maintaining energy homeostasis and neuroimmune crosstalk during aging. Here, we elucidate how exercise orchestrates inter-organ communication to counteract age-related decline through metabolic reprogramming, immunomodulation, and neuroprotection. Mechanistically, exercise enhances mitochondrial biogenesis and oxidative capacity in skeletal muscle via AMPK/PGC-1α signaling, restoring fatty acid oxidation and glucose metabolism while producing myokines (e.g., BDNF and IL-6) that promote neuronal survival and synaptic plasticity. Concurrently, hepatic SIRT1 activation promotes lipid metabolism, mitigates insulin resistance, and reduces systemic inflammation, hence preserving brain energy supply. In the aging brain, exercise stimulates neurogenesis, suppresses neuroinflammation via NF-κB inhibition, and elevates BDNF levels, which synergistically enhance cognitive resilience. vitally, exercise modulates the neuro-immunometabolic axis by balancing pro- and anti-inflammatory cytokines (e.g., IL-6’s hormetic role), optimizing immune cell function, and enhancing autophagy-mediated clearance of toxic aggregates (Aβ, α-synuclein). These adaptations are further amplified by epigenetic reprogramming, including but not limited to Nrf2-driven antioxidant responses and circadian rhythm synchronization. Our synthesis highlights exercise as a pleiotropic intervention that transcends single-organ influences, instead leveraging multi-tissue networks to delay aging and neurodegeneration. Unresolved challenges—personalized exercise regimens, molecular biomarkers for efficacy prediction, and combinatorial therapies with pharmacologic agents—underscore the need for translational studies integrating omics technologies and circadian biology. By bridging mechanistic insights with clinical applications, this review positions exercise as a cornerstone of precision medicine for aging populations.

Background: RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results: Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions: High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

Guinian Wang, M.D., Longzi Wang, M.D., Sijing Sun, M.S., Juan Wu, B.S., and Qinglu Wang, Ph.D.. Ann Lab Med 2015;35:226-32. https://doi.org/10.3343/alm.2015.35.2.226

Ferroptosis requires not only the accumulation of iron ions, but also changes in many ferroptosis-related regulators, including a decrease in GPX4 and inhibition of SLC7A11 for classical ferroptosis, a deletion of FSP1 or GCH1. Surprisingly, adipose tissue (AT) in the obesity conditions is also accompanied by iron buildup, decreased GSH, and increased ROS. On the neurological side, the pro-inflammatory factor released by AT may have first caused ferroptosis in the vagus nerve by inhibiting of the NRF2-GPX4 pathway, resulting in disorders of the autonomic nervous system. On the immune side, obesity may cause M2 macrophages ferroptosis due to damage to iron-rich ATMs (MFe^hi) and antioxidant ATMs (Mox), and lead to Treg cells ferroptosis through reductions in NRF2, GPX4, and GCH1 levels. At the same time, the reduction in GPX4 may also trigger the ferroptosis of B1 cells. In addition, some studies have also found the role of GPX4 in neutrophil autophagy, which is also worth pondering whether there is a connection with ferroptosis. In conclusion, this review summarizes the associations between neuroimmune regulation associated with obesity and ferroptosis, and on the basis of this, highlights their potential molecular mechanisms, proposing that ferroptosis in one or more cells in a multicellular tissue changes the fate of that tissue.