Background: Glyoxal (GO), and methylglyoxal (MGO) are among the most toxic compounds emitted by electronic cigarette (E-cig) and regular tobacco cigarette smoke. Airway diseases presented mucus over production as their major pathophysiologic feature. However, the effects of GO and MGO on pro-inflammatory cytokines and mucin expression in human nasal epithelial cells, as well as the underlying signaling pathway, have not yet been studied. Objective: This study is to determine whether GO and MGO induce pro-inflammatory cytokines, and MUC5AC/5B expression via mitogen-activated protein kinase (MAPK)s and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. Methods: The effect of GO, and MGO on pro-inflammatory cytokines, mucins expression and the signalling pathway of GO and MGO were investigated using water-soluble tetrazolium salt-1, enzyme immunoassays, and immunoblot analysis with specific inhibitors and small interfering RNA. Results: GO and MGO did not affect cell viability up to 2 mM in human nasal epithelial cells. GO and MGO increased production of pro-inflammatory such as interleukin (IL)-1β and IL-6) and MUC5AC/5B. Additionally, GO and MGO significantly activated extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and NF-κB. Whether ERK1/2, p38 MAPK, and NF-κB signaling pathway were involved in GO and MGO-induced production of pro-inflammatory cytokines (IL-1β and IL-6) and MUC5AC/5B, we used specific inhibitors and siRNA transfection. These significantly repressed GO- and MGO-induced expression of pro-inflammatory cytokines (IL-1β and IL-6) and MUC5AC/5B. Conclusions: GO and MGO induced pro-inflammatory cytokines and MUC5AC/5B expression via ERK1/2, p38 MAPK, and NF-κB in human nasal epithelial cells. These results suggested that GO and MGO may be involved in mucus hypersecretion-related airway diseases.

Objectives. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial.Methods. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA.Results. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells.Conclusion. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which amyloid β accumulation, tau pathology, chronic neuroinflammation, and metabolic stress converge to drive synaptic dysfunction and neuronal loss. Rather than resulting from a single mechanism, increasing evidence indicates that neurodegeneration in AD is mediated by the coordinated activation of multiple regulated cell death pathways. These pathways include apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, each characterized by distinct molecular mediators and execution programs. Evidence from human brain tissues, animal models, and in vitro systems demonstrates that core pathological drivers such as amyloid β and tau pathology, oxidative stress, and sustained neuroinflammation engage these death pathways in a spatially, temporally, and cell-type-dependent manner across neurons and glial populations. In this review, we synthesize the current knowledge on regulated cell death mechanisms in AD, emphasizing their molecular signatures, cellular specificity, and stage-dependent involvement, together with recent advances in immunohistochemical, imaging, and biofluid-based approaches for detecting neuronal death. By integrating evidence across molecular, cellular, and system levels, this review positions regulated cell death as a unifying framework for understanding neurodegeneration and developing pathway-specific biomarkers and combinatorial neuroprotective strategies.

Mucus plays an important role in protecting the respiratory tract from irritants. However, mucus hypersecretion is a major indicator of airway diseases. 1,2-Benzisothiazolin-3-one (BIT), as a microbicide, induces asthmatic inflammation. Therefore, we focused on the effects of BIT-related mucin secretion in airway epithelial cells. Our in vivo study showed increased mucus and MUC5AC expressions in the bronchioles of mice that inhaled BIT. For investigating the signaling pathways, we performed experiments in human airway epithelial cells. BIT induced the MUC5AC expression and significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The specific inhibitors of ERK1/2, p38, and NF-κB blocked the BIT-induced MUC5AC expression. Therefore, these results suggest that BIT induces the MUC5AC expression via the ERK1/2, p38, and NF-κB pathways in human airway epithelial cells, which may be involved in mucus hypersecretion associated with airway inflammatory diseases.

Alzheimer’s disease (AD) is a neurodegenerative disorder defined not only by amyloid-β plaques and tau pathology but also by several interacting processes that drive disease progression. These include neuroinflammation, neuronal cell death, synaptic dysfunction, blood–brain barrier (BBB) breakdown, and myelin and axonal damage. Together, they lead to neuronal loss and cognitive decline. In this review, we present a cell-centered framework linking these processes with key molecular markers. Neuroinflammation is driven by activated microglia and astrocytes and is associated with markers such as Iba1, CD68, GFAP, and C3, along with cytokines including IL-1β and TNF-α. Neuronal cell death occurs through apoptosis, ferroptosis, pyroptosis, and necroptosis, with markers such as caspase-3, GPX4, GSDMD, and MLKL. Synaptic dysfunction is reflected by reduced synaptic proteins, including synaptophysin and PSD-95. BBB breakdown increases permeability and reduces clearance of toxic molecules. Myelin and axonal damage, associated with MBP and NfL, disrupt neural connectivity. These processes are dynamically interconnected and may contribute differently across disease stages. This integrated cell-centered and systems-level framework provides insight into AD progression while highlighting potential biomarkers and therapeutic targets for diagnosis, disease monitoring, and therapeutic intervention.