Cadmium (Cd) is a ubiquitous environmental pollutant, which mainly input to the aquatic environment through discharge of industrial and agricultural waste, can be a threat to human and animal health. Selenium (Se) possesses a beneficial role in protecting animals and ameliorating the toxic effects of Cd. However, the comparative antagonistic effects of different Se sources such as inorganic, organic Se and nano-form Se on Cd toxicity are still under-investigated. Hence, the purpose of this study was to evaluate the comparative of Se sources antagonism on Cd-induced nephrotoxicity via oxidative stress and selenoproteome transcription. In the present study, Cd-diet disturbed in the system balance of 5 trace elements (Zinc (Zn), copper (Cu), Iron (Fe), Se, Cd) and impaired renal function. Se sources, including nano- Se (NS), Se- yeast (SY), sodium selenite (SS) and mixed selenium (MS) significantly recovered the balance of 4 trace elements (Zn, Cu, Cd, Se) and renal impaired indexes (blood urea nitrogen (BUN) and creatinine (CREA)). Histological appearance of Cd-treated kidney indicated renal tubular epithelial vacuoles, particle degeneration and enlarged capsular space. Ultrastructure observation results illustrated that Cd-induced mitochondrial cristae reduction, membrane disappearance, and nuclear deformation. Treatment with Se sources, NS appeared a better impact on improving kidney tissues against the pathological alterations resulting from Cd administration. Meanwhile, NS reflected a significant impact on relieving Cd-induced kidney oxidative damage, and significantly restored the antioxidant defense system of the body. Our findings also showed NS ameliorated the Cd-induced downtrends expression of selenoproteome and selenoprotein synthesis related transcription factors. Overall, NS was the most effective Se source in avoiding of Cd cumulative toxicity, improving antioxidant capacity and regulating of selenoproteome transcriptome and selenoprotein synthesis related transcription factors expression, which contributes to ameliorate Cd-induced nephrotoxicity in chickens. These results demonstrated diet supplement with NS may prove to be an effective approach for alleviating Cd toxicity and minimizing Cd -induced health risk.

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.

Fluoroquinolones (FQs) are synthetic broad-spectrum antimicrobial agents that have been recently repurposed to anticancer candidates. Designing new derivatives of FQs with different moieties to target DNA topoisomerases could improve their anticancer efficacy. The present study aimed to synthesize a novel ciprofloxacin derivative, examine its anticancer activity against HepG2 and A549 cancer cells, and investigate the possible molecular mechanism underlying this activity by examining its ability to inhibit the topo I/II activity and to induce the apoptotic and necro-apoptotic pathways. Molecular docking, cell viability, cell migration, colony formation, cell cycle, Annexin V, lactate dehydrogenase (LDH) release, ELISA, and western blotting assays were utilized. Molecular docking results showed that this novel ciprofloxacin derivative exerted dual topo I and topo II binding and inhibition. It significantly inhibited the proliferation of A549 and HepG2 cancer cells and decreased their cell migration and colony formation abilities. In addition, it significantly increased the % of apoptotic cells, caused cell cycle arrest at G2/M phase, and elevated the LDH release levels in both cancer cells. Furthermore, it increased the expression of cleaved caspase 3, RIPK1, RIPK3, and MLKL proteins. This novel ciprofloxacin derivative exerted substantial dual inhibition of topo I/II enzyme activities, showed antiproliferative activity, suppressed the cell migration and colony formation abilities for A549 and HepG2 cancer cells and activated the apoptotic pathway. In addition, it initiated another backup deadly pathway, necro-apoptosis, through the activation of the RIPK1/RIPK3/MLKL pathway.

This study aims to evaluate the tolerance of endophytic fungi isolated from the fibrous roots of Polygonatum kingianum to arsenic (As) and cadmium (Cd) and their physiological response mechanisms. Five isolated strains were obtained with EC ₅₀ values for As(V) ranging from 421 to 1281 mg/L, while the other three strains tolerated Cd(II) with an EC ₅₀ range of 407–1112 mg/L. Morphological and molecular identification indicated that these eight strains were Cladosporium spp. belonging to dark septate endophytes (DSEs) . The contents of metal ions in mycelium sharply increased, reaching 38.87 mg/kg for strain MZ‐11 under As(V) stress and 0.33 mg/kg for fungus PR‐2 under Cd(II). The physiological response revealed that the biomass decreased with increasing concentrations of As(V) or Cd(II), and the activity of superoxide dismutase significantly improved under the corresponding EC ₅₀ ‐concentration As/Cd of the strains, as well as the contents of antioxidant substances, including metallothionein, glutathione, malondialdehyde, melanin, and proline. Taken together, the filamentous fungi of Cladosporium spp. accounted for a high proportion of fungi isolated from the fibrous roots of P. kingianum and had a strong capacity to tolerate As(V) or Cd(II) stress by improving antioxidase activities and the content of antioxidant substances, and immobilization of metal ions in hyphae.

Colorectal cancer (CRC) is one of the leading causes of mortality among men and women. Chemo‑resistance, adverse effects and disease recurrence are major challenges in the development of effective cancer therapeutics. Substantial literature on this subject highlights that populations consuming diets rich in fibers, fruits and vegetables have a significantly reduced incidence rate of CRC. This chemo‑preventive effect is primarily associated with the presence of phytochemicals in the dietary components. Plant‑derived chemical agents act as a prominent source of novel compounds for drug discovery. Phytochemicals have been the focus of an increasing number of studies due to their ability to modulate carcinogenic processes through the alteration of multiple cancer cell survival pathways. Despite promising results from experimental studies, only a limited number of phytochemicals have entered into clinical trials. The purpose of the current review is to compile previously published pre‑clinical and clinical evidence of phytochemicals in cases of CRC. A PubMed, Google Scholar and Science Direct search was performed for relevant articles published between 2008‑2018 using the following key terms: ‘Phytochemicals with colorectal cancers’, ‘apoptosis’, ‘cell cycle’, ‘reactive oxygen species’ and ‘clinical anticancer activities’. The present review may aid in identifying the most investigated phytochemicals in CRC cells, and due to the limited number of studies that make it from the laboratory bench to clinical trial stage, may provide a novel foundation for future research.