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2D perovskites with chemical formula A'2 An-1 Bn X3n+1 have recently attracted considerable attention due to their tunable optical and electronic properties, which can be attained by varying the chemical composition. While high color-purity emitting perovskite nanomaterials have been accomplished through changing the halide composition, the preparation of single-phase, specific n-layer 2D perovskite nanomaterials is still pending because of the fast nucleation process of nanoparticles. We demonstrate a facile, rational and efficacious approach to synthesizing single-phase 2D perovskite nanoplates with a designated n number for both lead- and tin-based perovskites through kinetic control. Casting carboxylic acid additives in the reaction medium promotes selective formation of the kinetic product-multilayer 2D perovskite-in preference to the single-layer thermodynamic product. For the n-specific layered 2D perovskites, decreasing the number of octahedral layers per inorganic sheet leads to an increase of photoluminescence energy, radiative decay rate, and a significant boost in photostability.

Persistent chronic liver diseases increase the scar formation and extracellular matrix accumulation that further progress to liver fibrosis and cirrhosis. Nevertheless, there is no antifibrotic therapy to date. The ketogenic diet is composed of high fat, moderate to low-protein, and very low carbohydrate content. It is mainly used in epilepsy and Alzheimer’s disease. However, the effects of the ketogenic diet on liver fibrosis remains unknown. Through ketogenic diet consumption, β-hydroxybutyrate (bHB) and acetoacetate (AcAc) are two ketone bodies that are mainly produced in the liver. It is reported that bHB and AcAc treatment decreases cancer cell proliferation and promotes apoptosis. However, the influence of bHB and AcAc in hepatic stellate cell (HSC) activation and liver fibrosis are still unclear. Therefore, this study aimed to investigate the effect of the ketogenic diet and ketone bodies in affecting liver fibrosis progression. Our study revealed that feeding a high-fat ketogenic diet increased cholesterol accumulation in the liver, which further enhanced the carbon tetrachloride (CCl4)- and thioacetamide (TAA)-induced liver fibrosis. In addition, more severe liver inflammation and the loss of hepatic antioxidant and detoxification ability were also found in ketogenic diet-fed fibrotic mouse groups. However, the treatment with ketone bodies (bHB and AcAc) did not suppress transforming growth factor-β (TGF-β)-induced HSC activation, platelet-derived growth factor (PDGF)-BB-triggered proliferation, and the severity of CCl4-induced liver fibrosis in mice. In conclusion, our study demonstrated that feeding a high-fat ketogenic diet may trigger severe steatohepatitis and thereby promote liver fibrosis progression. Since a different ketogenic diet composition may exert different metabolic effects, more evidence is necessary to clarify the effects of a ketogenic diet on disease treatment.

Tumor suppressor protein p53 plays important roles in initiating cell cycle arrest and promoting tumor cell apoptosis. Previous studies have shown that p53 is either mutated or defective in approximately 50% of human cancers; therefore restoring normal p53 activity in cancer cells might be an effective anticancer therapeutic approach. Herein, we designed a chimeric p53 protein flanked with the MyoD N-terminal transcriptional activation domain (amino acids 1-62, called M3) and a poly-arginine (R12) cell penetrating signal in its N-and C-termini respectively. This chimeric protein, M3-p53-R12, can be expressed in E. coli and purified using immobilized metal ion chromatography followed by serial refolding dialysis. The purified M3-p53-R12 protein retains DNA-binding activity and gains of cell penetrating ability. Using MTT assay, we demonstrated that M3-p53-R12 inhibited the growth of K562, Jurkat as well as HL-60 leukemia cells carrying mutant p53 genes. Results from FACS analysis also demonstrated that transduction of M3-p53-R12 protein induced cell cycle arrest of these leukemia cells. Of special note, M3-p53-R12 has no apoptotic effect on normal mesenchymal stem cells (MSC) and leukocytes, highlighting its differential effects on normal and tumor cells. To sum up, our results reveal that purified recombinant M3-p53-R12 protein has functions of suppressing the leukemia cell lines' proliferation and launching cell apoptosis, suggesting the feasibility of using M3-p53-R12 protein as an anticancer drug. In the future we will test whether this chimeric protein can preferentially trigger the death of malignant cancer cells without affecting normal cells in animals carrying endogenous or xenographic tumors.

Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Sorafenib, a multikinase inhibitor, is the first-line drug approved by the Food and Drug Administration (FDA) for the treatment of patients with advanced HCC. However, most patients who continuously receive sorafenib may acquire resistance to this drug. Therefore, it is important to develop a new compound to treat liver cancer and sorafenib-resistant liver cancer. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic. We previously reported that a novel barbituric acid derivative inhibited carbon tetrachloride-induced liver fibrosis in mice, but its effects on liver cancer remain unknown. Thus, the purpose of this study was to investigate the antitumor effect of barbituric acid derivatives on HCC cells and sorafenib-resistant HCC cells (HCC-SRs). Our findings reveal that one of the barbituric acid derivatives, BA-5, significantly inhibited HCC and HCC-SR cell viability in a dose- and time-dependent manner. Therefore, compound BA-5 was selected for further experiments. Western blot data revealed that BA-5 treatment decreased the phosphorylation of AKT/p70s6k without affecting the MAPK pathway and increased cleaved PARP and cleaved caspase-7 in both HCC and HCC-SR cells. Since epithelial-mesenchymal transition plays a significant role in regulating cancer invasion and migration, we used the wound healing assay to evaluate the antimigratory effect of compound BA-5. The results showed that BA-5 treatment inhibited HCC and HCC-SR cell migration and reduced Vimentin protein expression. These results were confirmed by microarray analysis showing that BA-5 treatment influenced cancer cell motility and growth-related pathways. In the xenograft mouse model experiment, BA-5 administration significantly inhibited HCC cancer cell growth in mice. Furthermore, the combination of BA-5 with a low dose of regorafenib synergistically inhibited HCC-SR cell proliferation. In conclusion, our study showed that the barbituric acid derivative BA-5 is a new candidate for HCC and sorafenib-resistant HCC therapy.

Background Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. Methods Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. Results Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and β-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. Conclusions These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases.

Several studies have examined relatively large body iron stores and the risk of coronary heart disease with conflicting results. No reports of studies that associated body iron stores with stroke were found. To test the hypothesis that relatively high transferrin saturation is associated with increased stroke incidence and mortality in women and men, data from a follow-up study of a national cohort were examined. A total of 5,033 women and men aged 45-74 years from the First National Health and Nutrition Examination Survey Epidemiologic Followup Study who were free of stroke at baseline were followed an average of 12 years. Transferrin saturation (serum iron concentration divided by total iron binding capacity) was used as a measure of the amount of circulating iron available to tissues. In white women aged 45-74, after adjusting for age or for age and other risk variables, the authors observed a significant U-shaped association of transferrin saturation with risk of incident stroke (> 44% vs. 30-36%, relative risk = 1.96, 95% confidence interval 1.15-3.36; < 20% vs. 30-36%, relative risk = 1.80, 95% confidence interval 1.20-2.71). However, no significant associations were found in white men aged 45-74 after adjusting for other risk variables. Similar findings were observed for stroke mortality in whites, but no significant associations were seen in blacks. The significantly increased risk of stroke that was seen at both high and low levels of transferrin saturation in white women should be confirmed in other cohorts of women and men.

It is known that hepatitis D virus (HDV) requires hepatitis B virus (HBV) for supplying envelope proteins (HBsAgs) to produce mature virions, and the HDV large antigen (LDAg) is responsible for interacting with HBsAgs. However, the signal molecules involved in the cross-talk between HBsAgs and LDAg have never been reported. It has been previously demonstrated that the small form of HBsAg can facilitate the translocation of HDV large antigen green fluorescent protein (GFP) fusion protein (GFP–LD) from the nucleus to the cytoplasm. In this study, it was confirmed that the small form of HBsAg can facilitate both GFP–LD and authentic LDAg for nuclear export. It was also shown that the three forms of HBsAgs (large, middle and small) induced various rates (from 35.4 to 57.2 %) of GFP–LD nuclear export. Since HBsAgs are localized inside the endoplasmic reticulum (ER), this suggests that ER stress possibly initiates the signal for inducing LDAg translocation. This supposition is supported by results that show that around 9 % of cells appear with GFP–LD in the cytoplasm after treatment with the ER stress inducers, brefeldin A (BFA) and tunicamycin, in the absence of HBsAg. Western blot and immunofluorescence microscopy results further showed that the activation of NF-κB is linked to the ER stress that induces GFP–LD translocation. Combining this with results showing that tumour necrosis factor alpha (TNF-α) can also induce GFP–LD translocation, it was concluded that LDAg translocation correlates with ER stress and activation of NF-κB. Nevertheless, TNF-α-induced GFP–LD translocation was independent of new protein synthesis, suggesting that a post-translational event occurs to GFP–LD to allow translocation.