Heme oxygenase‑1 (HO‑1) is an inducible cytoprotective enzyme that degrades heme into free iron, carbon monoxide and biliverdin, which is then rapidly converted into bilirubin. These degradation products serve an important role in the regulation of inflammation, oxidative stress and apoptosis. While the expression level of HO‑1 is typically low in most cells, it may be highly expressed when induced by a variety of stimulating factors, a process that contributes to the regulation of cell homeostasis. In the 5'‑non‑coding region of the HO‑1 gene, there are two polymorphic sites, namely the (GT)n dinucleotide and T(‑413)A single nucleotide polymorphism sites, which regulate the transcriptional activity of HO‑1. These polymorphisms have been shown to be closely associated with the occurrence and progression of numerous diseases, including cardiovascular, pulmonary, liver and kidney, various types of cancer and viral diseases. The present article reviews the progress that has been made in research on the association between the two types of polymorphisms and these diseases, which is expected to provide novel strategies for the diagnosis, treatment and prognosis of various diseases.

Cadmium (Cd) is a widespread heavy metal with osteotoxicity, and bone mineral density (BMD) is often used as an early sensitive biomarker of bone damage. This study retrieved worldwide epidemiological studies to conduct a systematic meta-analysis to explore the association between Cd exposure and bone damage. A random effect model was used to establish the relationship between urinary Cd (U-Cd) and BMD and explore the influence of covariate factors. The benchmark dose method was used to calculate the safety threshold of U-Cd when the BMD decrease within an acceptable range. Toxicokinetic (TK) model was used to estimate the health-based guidance value (HBGV) of dietary Cd exposure based on the U-Cd threshold. The 95% lower confidence interval of benchmark dose of U-Cd derived in this study was 1.71 μg/g Cr, and the HBGV of dietary Cd exposure was determined to be 0.64 μg/kg bw/day. Gender had the greatest influence on BMD, followed by body mass index (BMI), age, and race. This study conducted a comprehensive systematic analysis of global research and was the first exploration to quantify the decreased BMD caused by Cd exposure in a large-scale population. The results provided reference for the risk assessment of Cd exposure and the formulation of dietary exposure standards.

Mercury (Hg) is a widespread heavy metal causing various damages to health, while insufficient studies assessed its exposure risk across China. This study explored concentrations in food items and dietary exposure risks across China by comprehensively analyzing the researches on total Hg (THg) in eight food items and methylmercury (MeHg) in aquatic foods published between 1980 and 2021. According to the included 695 studies, the average THg concentration in all food items was 0.033 mg/kg (ranging from 0.004 to 0.185 mg/kg), with the highest concentration in edible fungi. The average daily dietary THg exposure from all foods was 12.9 μg/day. Plant-based foods accounted for 62.7% of the dietary THg exposure. Cereals and vegetables were the primary source of THg exposure. The MeHg concentration in aquatic foods was 0.08 mg/kg, and the average dietary exposure was 3.8 μg/day. Monte Carlo simulations of the dietary exposure risk assessment of THg and MeHg showed that approximately 6.4 and 7.0% of residents exceeded the health-based guidance value set by the European Food Safety Authority, with higher exposure risk in Southwest and South China. The nationwide target hazard quotient index of THg was greater than 1, suggesting that the non-carcinogenic risk of dietary exposure to THg needed further concern. In summary, this study has a comprehensive understanding of dietary Hg exposure risks across China, which provide a data basis for Hg exposure risk assessment and policy formulation.

Background: Gastric cancer represents a highly lethal malignancy with an elevated mortality rate among cancer patients, coupled with a suboptimal postoperative survival prognosis. Nectin-4, an overexpressed oncological target for various cancers, has been exploited to create antibody-drug conjugates (ADCs) to treat solid tumors. However, there is limited research on Nectin-4 ADCs specifically for gastric cancer, and conventional immunoglobulin G (IgG)-based ADCs frequently encounter binding site barriers. Based on the excellent tumor penetration capabilities inherent in nanobodies (Nbs), we developed Nectin-4-targeting Nb drug conjugates (NDCs) for the treatment of gastric cancer. Results: An immunized phage display library was established and employed for the selection of Nectin-4-specific Nbs using phage display technology. Subsequently, these Nbs were engineered into homodimers to enhance Nb affinity. To prolong in vivo half-life and reduce immunogenicity, we fused an Nb targeting human serum albumin (HSA), resulting in the development of trivalent humanized Nbs. Further, we site-specifically conjugated a monomethyl auristatin E (MMAE) at the C-terminus of the trivalent Nbs, creating Nectin-4 NDC (huNb26/Nb26-Nbh-MMAE) with a drug-to-antibody ratio (DAR) of 1. Nectin-4 NDC demonstrated excellent in vitro cell-binding activities and cytotoxic efficacy against cells with high Nectin-4 expression. Subsequent administration of Nectin-4 NDC to mice bearing NCI-N87 human gastric cancer xenografts demonstrated rapid tissue penetration and high tumor uptake through in vivo imaging. Moreover, Nectin-4 NDC exhibited noteworthy dose-dependent anti-tumor efficacy in in vivo studies. Conclusion: We have engineered a Nectin-4 NDC with elevated affinity and effective tumor uptake, further establishing its potential as a therapeutic agent for gastric cancer. Graphical