Environmental and occupational exposure to cadmium has been shown to induce kidney damage, liver injury, neurodegenerative disease, and osteoporosis. However, the mechanism by which cadmium induces autophagy in these diseases remains unclear. Studies have shown that cadmium is an effective inducer of oxidative stress, DNA damage, ER stress, and autophagy, which are thought to be adaptive stress responses that allow cells exposed to cadmium to survive in an adverse environment. However, excessive stress will cause tissue damage by inducing apoptosis, pyroptosis, and ferroptosis. Evidently, oxidative stress-induced autophagy plays different roles in low- or high-dose cadmium exposure-induced cell damage, either causing apoptosis, pyroptosis, and ferroptosis or inducing cell survival. Meanwhile, different cell types have different sensitivities to cadmium, which ultimately determines the fate of the cell. In this review, we provided a detailed survey of the current literature on autophagy in cadmium-induced tissue damage. A better understanding of the complex regulation of cell death by autophagy might contribute to the development of novel preventive and therapeutic strategies to treat acute and chronic cadmium toxicity.

Apicomplexan protozoans of the genus Eimeria cause coccidiosis, one of the most economically relevant parasitic diseases in chickens. The lack of a complete understanding of molecular mechanisms in the host-parasite interaction limits the development of effective control measures. In the present study, RNA sequencing (RNA-Seq) was applied to investigate the host mRNA profiles of the cecal mucosa collected at day 5 post-infection with Eimeria maxima (EM). Total RNA from cecal samples of the uninfected naïve control and the EM groups was used to make libraries, generating 354,924,372 and 356,229,250 usable reads, respectively, which were assembled into a total of 386,088 high-quality unigenes (transcripts) in Trinity software. RNA-Seq analysis of cecal samples in the two groups revealed 332 upregulated and 363 downregulated genes with significant differences (P ≤ 0.05), including several significant immune-related gene families, such as the major histocompatibility complex (MHC) class I alpha chain, granzyme A and immunoglobulin subtype genes among upregulated differentially expressed genes. In addition, a total of 60 clusters of differentiation (CD) molecular genes and 570 novel genes were found. The completeness of the assembled transcriptome was further assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene ontology (GO), eggNOG and CAZy for gene annotation. The broad gene categories represented by the highly differentiated host genes suggested enrichment in immune responses, and downregulation in the metabolic pathway, MARK signaling pathway, vascular smooth muscle contraction, and proteins processing in endoplasmic reticulum after EM infection. Eimeria maxima induced statistically significant differences in the cecal mucosal gene expression of infected chickens. These findings provide new insights into the host-parasite interaction and enhance our understanding of the molecular mechanism of avian coccidiosis.

Osteoprotegerin (OPG) is a new member of the tumor necrosis factor (TNF) receptor superfamily, which can inhibit the differentiation and activity of osteoclasts by binding to nuclear factor kappa B receptor activator (RANK) competitively with nuclear factor kappa B receptor activator ligand (RANKL). The previous experiments found that OPG can induce apoptosis of mature osteoclasts in vitro, which can inhibit the activity of mature osteoclasts, thereby exerting its role in protecting bone tissue. In addition, pyroptosis is a new type of cell death that is different from apoptosis. It is unclear whether OPG can induce mature osteoclast pyroptosis and thereby play its role in protecting bone tissue. In this study, the results showed that compared with the control group, the survival rate of osteoclasts in the OPG group was significantly reduced, and the contents of IL-1β, IL-18, and LDH in the supernatant both increased. Many osteoclast plasma membranes were observed to rupture in bright fields, and OPG induced loss of their morphology. Flow cytometry was used to analyze the pyroptosis rate; OPG significantly increased the osteoclast pyroptosis rate. To further reveal the mechanism of OPG-induced osteoclast pyroptosis, we examined the expression level of pyroptosis-related genes and proteins, and the results found that OPG increased the expression of NLRP3, ASC, caspase-1, and GSDMD-N compared with the control group. In summary, OPG can induce osteoclast pyroptosis, and its mechanism is related to the expression levels of ASC, NLRP3, caspase 1 and GSDMD, which were included in the classical pathway of pyroptosis.

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl₂, 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.

Cadmium (Cd) is a widespread environmental contaminant related to renal immunosuppression and metabolic dysfunction. Lycium barbarum polysaccharides (LBPs) are active extracts of wolfberry and possess a variety of excellent properties. However, the specific mechanism of action for Cd and LBP remain unclear. In the present study, Shaoxing ducks were used to establish an in vivo model to elucidate the effects of combined Cd and LBP exposure on the kidneys and the underlying mechanisms. The ducks were exposed to CdCl ₂ (50 mg/kg) and/or LBP (50 mg/kg) for 30 days. We observed that Cd exposure increased the kidney index and the levels of the renal function indicators CREA and UA. Further research revealed that Cd exposure caused histopathological damage and ultrastructural alterations. In addition, Cd accumulation induced oxidative stress by disrupting ionic homeostasis and inhibiting the Nrf2-mediated antioxidant defense pathway. Finally, we found that Cd promoted lipid accumulation, disrupted lipid metabolism, and thereby induced renal immunosuppression. Notably, LBP effectively alleviated Cd-induced renal injury, suggesting beneficial effects against Cd-triggered nephrotoxicity.

Hydrogen sulfide (H ₂ S) is a pervasive environmental toxicant with well-established immunotoxic effects. However, its action on lymphoid organs—particularly whether it triggers splenic pyroptosis—remains elusive. This study explored the effect of acute H ₂ S exposure on rat spleen and the therapeutic potential of Xuebijing (XBJ), a traditional Chinese medicine for sepsis. Rats were exposed to 300 ppm H ₂ S for 3 h, with or without 7-day XBJ pretreatment (4 mg/kg, i.p.). Splenic injury was evaluated by histopathology, ultrastructure, oxidative stress parameters, immunofluorescence, and immunoblotting. H ₂ S exposure alone caused marked splenic damage, evidenced by increased organ coefficient, disrupted tissue architecture, mitochondrial swelling, and redox imbalance [depleted glutathione (GSH), superoxide dismutase (SOD), catalase (CAT); elevated malondialdehyde (MDA)]. Mechanistically, H ₂ S activated the NF-κB/NLRP3/caspase-1 axis, upregulating NLRP3, ASC, cleaved caspase-1, and GSDMD-N, along with elevated interleukin-1β (IL-1β) and interleukin-18 (IL-18). XBJ pretreatment reversed these alterations, suppressing NF-κB phosphorylation, inflammasome assembly, and pyroptotic cell death. These findings demonstrate that H ₂ S induces splenic pyroptosis via the NF-κB/NLRP3/caspase-1 pathway, and that XBJ confers protection by interrupting this cascade, offering a mechanism-based candidate for the treatment of acute H ₂ S poisoning.