Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.

Skin cancer is caused by abnormal proliferation, gene regulation and mutation of epidermis cells. Compound C is commonly used as an inhibitor of AMP‑activated protein kinase (AMPK), which serves as an energy sensor in cells. Recently, compound C has been reported to induce apoptotic and autophagic death in various skin cancer cell lines via an AMPK‑independent pathway. However, the signaling pathways activated in compound C‑treated cancer cells remain unclear. The present oligodeoxynucleotide‑based microarray screening assay showed that the mRNA expression of the zinc‑finger transcription factor early growth response‑1 (EGR‑1), which helps regulate cell cycle progression and cell survival, was significantly upregulated in compound C‑treated skin cancer cells. Compound C was demonstrated to induce EGR‑1 mRNA and protein expression in a time and dose‑dependent manner. Confocal imaging showed that compound C‑induced EGR‑1 protein expression was localized in the nucleus. Compound C was demonstrated to activate extracellular signal‑regulated kinase (ERK) phosphorylation. Inhibition of this compound C‑induced ERK phosphorylation downregulated the mRNA and protein expression of EGR‑1. In addition, removal of compound C‑induced reactive oxygen species (ROS) not only decreased ERK phosphorylation, but also inhibited compound C‑induced EGR‑1 expression. A functional assay showed that knock down of EGR‑1 expression in cancer cells decreased the survival rate while also increasing caspase‑3 activity and apoptotic marker expression after compound C treatment. However, no difference in autophagy marker light chain 3‑II protein expression was observed between compound C‑treated control cells and EGR‑1‑knockdown cells. Thus, it was concluded that that EGR‑1 may antagonize compound C‑induced apoptosis but not compound C‑induced autophagy through the ROS‑mediated ERK activation pathway.

Mitochondria, vital organelles that generate ATP, determine cell fate. Dysfunctional and damaged mitochondria are fragmented and removed through mitophagy, a mitochondrial quality control mechanism. The FDA-approved drug IMQ, a synthetic agonist of Toll-like receptor 7, exhibits antitumor activity against various skin malignancies. We previously reported that IMQ promptly reduced the level of the antiapoptotic Mcl-1 protein and that Mcl-1 overexpression attenuated IMQ-triggered apoptosis in skin cancer cells. Furthermore, IMQ profoundly disrupted mitochondrial function, promoted mitochondrial fragmentation, induced mitophagy, and caused cell death by generating high levels of ROS. However, whether Mcl-1 protects mitochondria from IMQ treatment is still unknown. In this study, we demonstrated that Mcl-1 overexpression induced resistance to IMQ-induced apoptosis and reduced both IMQ-induced ROS generation and oxidative stress in cancer cells. Mcl-1 overexpression maintained mitochondrial function and integrity and prevented mitophagy in IMQ-treated cancer cells. Furthermore, IL-6 protected against IMQ-induced apoptosis by increasing Mcl-1 expression and attenuating IMQ-induced mitochondrial fragmentation. Mcl-1 overexpression ameliorates IMQ-induced ROS generation and mitochondrial fragmentation, thereby increasing mitochondrial stability and ultimately attenuating IMQ-induced cell death. Investigating the roles of Mcl-1 in mitochondria is a potential strategy for cancer therapy development.

Air pollution, particularly particulate matter (PM), poses a significant health risk worldwide, with rhinitis emerging as a prevalent respiratory condition. This review explores the association between air pollution and rhinitis, focusing on PM-induced inflammation and the potential preventive role of nutritional supplements. A comprehensive literature search was conducted using the PubMed and Scopus databases, covering studies from inception to 2024 that investigated air pollution, rhinitis, and nutritional interventions. This review synthesizes evidence linking PM exposure to increased prevalence and exacerbation of rhinitis through various inflammatory mechanisms. We further examine the potential of nutritional supplements, including kefir peptides, lactoferrin, vitamin D, polyunsaturated fatty acids, and probiotics, in mitigating PM-induced inflammation and rhinitis symptoms. However, the evidence regarding the role of these supplements in modulating immune responses and reducing inflammation related to PM-induced rhinitis is limited. This review highlights the potential efficacy of nutritional interventions in preventing and managing air pollution-associated rhinitis, offering a complementary approach to environmental regulations in addressing this public health challenge.