A combined strategy to mitigate the accumulation of arsenic and cadmium in rice (Oryza sativa L.).

Arsenic and cadmium in rice grain are of growing concern in the global food supply chain. Paradoxically, the two elements have contrasting behaviors in soils, making it difficult to develop a strategy that can concurrently reduce their uptake and accumulation by rice plant. This study examined the combined impacts of watering (irrigation) schemes, different fertilizers and microbial populations on the bioaccumulation of arsenic and cadmium by rice as well as on rice grain yield. Compared to drain-flood and flood-drain treatments, continuously flooded condition significantly reduced the accumulation of cadmium in rice plant but the level of arsenic in rice grain remained above 0.2 mg/kg, which exceeded the China national food safety standard. Application of different fertilizers under continuously flooded condition showed that compared to inorganic fertilizer and biochar, manure addition effectively reduced the accumulation of arsenic over three to four times in rice grain and both elements were below the food safety standard (0.2 mg/kg) while significantly increasing the rice yield. Soil Eh was the critical factor in the bioavailability of cadmium, while the behavior of arsenic in rhizosphere was associated with the iron cycle. The results of the multi-parametric experiments can be used as a roadmap for low-cost and in-situ approach for producing safe rice without compromising the yield.

Rapid phosphorylation of glucose-6-phosphate dehydrogenase by casein kinase 2 sustains redox homeostasis under ionizing radiation.

Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, casein kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.

Mesenchymal stem cells-derived IL-6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK-STAT3 signalling.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin-6 (IL-6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL-6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs-derived IL-6 on tumour invasion and metastasis. SUBJECTS AND METHODS: The effects of MSC-derived IL-6 and tocilizumab on the proliferation, mobility, and epithelial-mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo. RESULTS: The results showed that the expression of MSCs and EMT-related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL-6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3. CONCLUSIONS: The results indicated that MSCs-derived IL-6-promoted tumour invasion and metastasis via JAK-STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.

FGF8 induces epithelial-mesenchymal transition and promotes metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and with 354 864 new cases each year. Cancer metastasis, recurrence, and drug resistance are the main causes to cripples and deaths of OSCC patients. As potent growth factors, fibroblast growth factors (FGFs) are frequently susceptible to being hijacked by cancer cells. In this study, we show that FGF8 is upregulated in OSCC tissues and high FGF8 expression is related with a set of clinicopathologic parameters, including age, drinking, and survival time. FGF8 treatment enhances the invasive capability of OSCC cells. Lentivirus-based FGF8 expression promotes OSCC metastasis in a mouse lung metastasis model. Further, mechanistic study demonstrates that FGF8 induces epithelial-mesenchymal transition (EMT) in OSCC cells. These results highlight a pro-metastatic function of FGF8, and underscore the role of FGF8 in OSCC development.

TRIM28 and TRIM27 are required for expressions of PDGFRß and contractile phenotypic genes by vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.

NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.

BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .

Role of miR-155 in immune regulation and its relevance in oral lichen planus.

Oral lichen planus (OLP) is a chronic mucosal inflammatory disease. The World Health Organization has described it as a potentially malignant condition. The pathogenesis of OLP remains to be fully elucidated, but extensive evidence suggests that immunologic and inflammatory factors have important roles. MicroRNAs (miRs), which are small non-coding RNAs, have been reported to be involved in OLP. In particular, miR-155 is significantly upregulated in patients with OLP. miR-155 has numerous functions and is closely linked to inflammation and immune system regulation. However, in-depth studies of the mechanisms via which miR-155 is involved in OLP are currently insufficient. Considering the close association between miR-155 and immune regulation as well as the importance of immune factors in OLP, the role of miR-155 in the immune system was herein summarized with a focus on OLP. The present review provides a basis for further study of the molecular mechanisms underlying the development and progression of OLP.

Roles of FGF8 subfamily in embryogenesis and oral­maxillofacial diseases (Review).

Fibroblast growth factors (FGFs) are diffusible polypeptides released by a variety of cell types. FGF8 subfamily members regulate embryonic development processes through controlling progenitor cell growth and differentiation, and are also functional in adults in tissue repair to maintain tissue homeostasis. FGF8 family members exhibit unique binding affinities with FGF receptors and tissue distribution patterns. Increasing evidence suggests that, by regulating multiple cellular signaling pathways, alterations in the FGF8 subfamily are involved in craniofacial development, odontogenesis, tongue development and salivary gland branching morphogenesis. Aberrant FGF signaling transduction, caused by mutations as well as abnormal expression or isoform splicing, plays an important role in the development of oral diseases. Targeting FGF8 subfamily members provides a new promising strategy for the treatment of oral diseases. The aim of this review was to summarize the aberrant regulations of FGF8 subfamily members and their potential implications in oral­maxillofacial diseases.

Malignant transformation of oral leukoplakia treated with carbon dioxide laser: a meta-analysis.

A series of studies are dedicated to research the clinical outcomes of oral leukoplakia (OLK) treated with carbon dioxide laser (CO2 laser); however, the results vary from studies especially related to recurrence and malignant transformation. Hence, we performed this meta-analysis to precisely evaluate the malignant transformation of OLK dealt with CO2 laser and investigate the association between its malignant transformation and kinds of related risk factors, such as gender, clinical classification, long duration of leukoplakia, and degree of epithelial dysplasia and lesion regions. We performed a systematic search of the Cochrane Library, EMBASE, Pubmed, Web of Science, and SCOPUS. Single-arm rate of the overall risk of malignant transformation in OLK treated with CO2 laser was calculated using the Der-Simonian Liard method. We applied subgroup analysis to compare the risk of malignant transformation according to the degree of epithelial dysplasia, clinical type, and region of OLK. Moreover, a pooled odds ratio (OR) is calculated, along with its 95% confidence interval (CI), to compare the risk of malignant transformation according to patients' gender, tobacco, and alcohol consumption. We used the meta package of R software for quantitative data synthesis and analysis. The rate of malignant transformation of OLK treated with carbon dioxide laser ranged from 0 to 15.38% in included studies. The overall rate of malignant transformation of OLK treated with CO2 laser is 4.50% under the random effect model [95% CI 0.0305-0.0659]. A systematic review of observational studies of OLK reported that the estimated overall (mean) malignant transformation rate was 3.5%, with a wide range between 0.13 and 34.0%. Interestingly, our result revealed that it was the male, homogeneous type, no tobacco consumption, and without alcohol-use who had a higher tendency of malignancy after laser surgery. However, this result lack statistically significant data. Generally speaking, whether oral leukoplakia patients underwent laser surgical treatment or not, it may have little effect on malignant transformation. In addition, we strongly advise that it had better not to perform CO2 laser intervention on OLK patients with the following clinical characteristics: homogeneous type, male, no tobacco consumption, and without alcohol-use. Evidence is still lacking in terms of relationship between malignant transformation and risk factors among OLK patients managed with CO2 laser. Thus, these associations should be further investigated.

Role of fibroblast growth factor receptor 4 in cancer.

Fibroblast growth factor receptors (FGFR) play a significant role in both embryonic development and in adults. Upon binding with ligands, FGFR signaling is activated and triggers various downstream signal cascades that are implicated in diverse biological processes. Aberrant regulations of FGFR signaling are detected in numerous cancers. Although FGFR4 was discovered later than other FGFR, information on the involvement of FGFR4 in cancers has significantly increased in recent years. In this review, the recent findings in FGFR4 structure, signaling transduction, physiological function, aberrant regulations, and effects in cancers as well as its potential applications as an anticancer therapeutic target are summarized.

Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Nanometer-precision linear sorting with synchronized optofluidic dual barriers.

The past two decades have witnessed the revolutionary development of optical trapping of nanoparticles, most of which deal with trapping stiffness larger than 10-8 N/m. In this conventional regime, however, it remains a formidable challenge to sort out sub-50-nm nanoparticles with single-nanometer precision, isolating us from a rich flatland with advanced applications of micromanipulation. With an insightfully established roadmap of damping, the synchronization between optical force and flow drag force can be coordinated to attempt the loosely overdamped realm (stiffness, 10-10 to 10-8 N/m), which has been challenging. This paper intuitively demonstrates the remarkable functionality to sort out single gold nanoparticles with radii ranging from 30 to 50 nm, as well as 100- and 150-nm polystyrene nanoparticles, with single nanometer precision. The quasi-Bessel optical profile and the loosely overdamped potential wells in the microchannel enable those aforementioned nanoparticles to be separated, positioned, and microscopically oscillated. This work reveals an unprecedentedly meaningful damping scenario that enriches our fundamental understanding of particle kinetics in intriguing optical systems, and offers new opportunities for tumor targeting, intracellular imaging, and sorting small particles such as viruses and DNA.

Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy.

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies.