Chromium has two main valence states: hexavalent chromium (Cr[VI]) and trivalent chromium (Cr[III]). Cr(VI), a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V]), tetravalent chromium (Cr[IV]) or Cr(III) via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III) complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI) and/or Cr(III) compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI) and Cr(III) and chemoprevention with different antioxidants.

Background and Aim Helicobacter pylori (H. pylori) infection rates have been changing with different populations and geographic areas. We systematically evaluated the longitudinal trends in H. pylori prevalence in China over the past decades. Methods We performed a systematic review of literature reporting the prevalence of H. pylori infection in mainland China from 1990 to 2019 in the PubMed and China National Knowledge Infrastructure databases. We conducted a meta‐analysis of qualified studies using a random effects model to estimate the pooled prevalence with a 95% confidence interval (95%CI). Results A total of 412 eligible studies with 1 377 349 subjects were included. The pooled H. pylori prevalence was 44.2% (95%CI: 43.0–45.5%) in mainland China, with an estimated 589 million individuals infected with H. pylori. The prevalence was relatively high in the Northwest (51.8%, 95%CI: 47.5–56.1%), East (47.7%, 95%CI: 45.4–50.0%), and Southwest China (46.6%, 95%CI: 42.1–51.1%). The prevalence significantly decreased from 58.3% (95%CI: 50.7–65.5%) in the period 1983–1994 to 40.0% (95%CI: 38.2–41.8%) in the period 2015–2019. The prevalence increased with age, ranging from 28.0% (95%CI: 23.9–32.5%) in children and adolescents to 46.1% (95%CI: 44.5–47.6%) in adults. Conclusion Although the burden of H. pylori infections is still huge in China, the infection rate has been decreasing over the past decades. Targeted H. pylori eradication strategies may be considered in areas or populations with a high incidence of gastric cancer.

With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research.

Nickel nanoparticles (Ni NPs) have been applied in various fields along with the rapid development of nanotechnology. However, the potential adverse health effects of the Ni NPs are unclear. To investigate the cyto- and genotoxicity and compare the differences between the Ni NPs and the nickel fine particles (Ni FPs), Sprague-Dawley (SD) rats and A549 cells were treated with different doses of Ni NPs or FPs. Intra-tracheal instillation of Ni NPs and FPs caused acute toxicity in the lungs, liver and kidneys of the SD rats. Even though the histology of the lungs showed hyperplastic changes and the protein expression of HO-1 and Nrf2 detected by western blot showed lung burden overload, no significant increase was observed to the expression level of oncoprotein C-myc. The results from cell titer-Glo assay and comet assay indicated that Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs. In addition, Ni NPs increased the expression of C-myc in vitro, but these increases may not have been due to oxidative stress since no significant dose-dependent changes were seen in HO-1 and Nrf2 expressions. Although Ni NPs have the potential to cause DNA damage in A549 cells in vitro, the molecular mechanisms that led to these changes and their tumorigenic potential is still debatable. In short, Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs, and intra-tracheal instillation of Ni NPs and FPs caused toxicity in organs of the SD rats, while it showed similar to the effects for both particle types. These results suggested that both Ni NPs and FPs have the potential to be harmful to human health, and Ni NPs may have higher cyto- and genotoxic effects than Ni FPs under the same treatment dose.

Forkhead box M1 (FoxM1) is an oncogenic transcription factor involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. It is overexpressed in many human cancers, especially in breast cancers. Posttranslational modifications are known to play an important role in regulating the expression and transcriptional activity of FoxM1. In this review, we characterize the posttranslational modifications of FoxM1, summarize modifications of FoxM1 by different kinases, explore the relationship between the different sites of modifications and comprehensively describe how posttranslational modifications to regulate the function of FoxM1 by changing protein stability, nucleus localization and transcriptional activity. Additionally, we systematically summarize the roles of FoxM1 in breast cancer occurrence, therapy and drug resistance. The purpose of this paper tries to give a better understanding of the regulatory mechanisms of FoxM1 in cell regulation and highlights potential of a new method for breast cancer therapy by targeting FoxM1.

The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However, its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study, by combining in silico analysis and sgRNA library based drug resistance screening assay, we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient's samples. Furthermore, down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis, whereas, overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated IκBα that resulted in the activation of NF-κB. Taken together, we report that silencing of SENP2 and consequent activation of NF-κB through the modulation of IκBα sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma. Multiple myeloma (MM) is a malignant plasma cell tumor that account for 12% of blood malignant tumors, which is the second most commonly diagnosed hematologic malignancy 1. Despite applying multiple therapeutic drugs such as, proteasome inhibitor bortezomib 2 and immunomodulator thalidomide 3 , the median MM patient survival was only slightly improved from 3-5 years to 5-7 years 4. Moreover, MM is still featured as a recurrence and insensitive to treatment due to drug resistance development 5. The bortezomib is the first class of proteasome inhibitor approved for the treatment of MM. Bortezomib is a dipeptidyl boronic acid that reversibly binds to chymotrypsin-like catalytic subunit of 20 S proteasome and inhibits its activity 6. Proteasome plays a critical role in cellular homeostasis by degrading unwanted cellular proteins 7. The imbalance between synthesis and degradation of proteins arises due to proteasome inhibition results in the accumulation of regulatory proteins causing endoplasmic reticulum stress and activation of the unfolded protein response leading to induction of apoptosis in malignant cells via multiple mechanisms 8,9 .

With rapid industrialization, China is now facing great challenges in heavy metal contamination in the environment. Human exposure to heavy metals through air, water and food commonly involves a mixture consisting of multiple heavy metals. In this study, eight common heavy metals (Pb, Cd, Hg, Cu, Zn, Mn, Cr, Ni) that cause environmental contamination were selected to investigate the combined toxicity of different heavy metal mixtures in HL7702 cells. Toxicity (24 h LC50 ) of each individual metal on the cells ranked Hg > Cr = Cd > Cu > Zn > Ni > Mn > Pb; toxicity of the different mixtures ranked: M5 > M3PbHgCd > M5+Mn > M5+Cu > M2CdNi > M4A > M8-Mn > M8 > M5+Zn > M4B > M8-Cr > M8-Zn > M8-Cu > M8-Pb > M8-Cd > M8-Hg > M8-Ni > M3PbHgNi > M3CuZnMn. The cytotoxicity data of individual metals were successfully used to build the additive models of two- to eight-component metal mixtures. The comparison between additive model and combination model or partly additive model was useful to evaluate the combined effects in mixture. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures. These results suggest that the combined effects should be considered in the risk assessment of heavy metal co-exposure, and more comprehensive investigations on the combined effects of different heavy metal mixtures are needed in the future. Copyright © 2016 John Wiley & Sons, Ltd.

To explore the health effects of multi-heavy metal exposure, Sprague Dawley (SD) rats were orally given one dose of heavy metal mixtures (HMMs). The eight most common detectable heavy metals in Ningbo area are zinc (Zn), copper (Cu), manganese (Mn), chromium (Cr), nickel (Ni), cadmium (Cd), lead (Pb) and mercury (Hg). In this study, mixtures of these eight heavy metals were prepared using the compounds zinc sulfate heptahydrate, cupric sulfate, manganese dichloride, potassium dichromate, nickel dichloride, cadmium dichloride, lead acetate, and methyl mercury chloride with ion mass proportions of 1070.0, 312.6, 173.1, 82.6, 30.0, 13.3, 6.6, and 1.0, respectively. The rats were randomly divided into four groups. Beside the control group, each rat received a corresponding dose of HMMs 215, 464 or 1000 mg per kg body weight (bwt), respectively. The rats were observed for 4 weeks. During the last week of observation, the Morris water maze test was used to investigate spatial learning and memory in the treated rats. The rats were exsanguinated under complete chloral hydrate anesthesia and organ coefficients were measured. Biochemical tests of blood and serum samples were carried out. The results showed abnormalities in the hematological system, decreased renal function, hepatic injury and disturbances in the electrolyte balance of the rats treated with a high dose of HMMs. Death of some rats was also observed. This paper analyzed how a one-time high dose oral administration of HMMs induced systemic toxicity.