Local-field engineering in slot waveguide for fabricating on-chip Bragg grating filters with high reflectivity across a flat broadband.

On-chip Bragg gratings with high reflectivities have been found to have widespread applications in filters, resonators, and semiconductor lasers. However, achieving strong Bragg reflections with flat response across a broad bandwidth on the popular 220 nm silicon-on-insulator (SOI) platform still remains a challenge. In this paper, such a high performance device is proposed and fabricated, which is based on a slot waveguide with gratings etched on the inner sidewalls of the slot. By manipulating the local field in the slot region using a chirped and tapered grating-based mode transition, the device achieves a flat response with ultra-high reflection and low transmission for the TE mode across a broad operating bandwidth. Leveraging the ultra-high birefringence of the SOI waveguide, the device functions both as a TE slot waveguide reflector and a TM pass polarizer. Simulation results demonstrate that the device exhibits an ultra-high rejection of more than 50 dB and a reflectivity exceeding 0.99 for the TE mode across a 91 nm wavelength range, while maintaining a high transmittance of larger than 0.98 for the TM mode. Experimental results validate that the device performance is consistent with the simulation results. A fabricated device based on such a gratings exhibits a low insertion loss (<0.8 dB) and high polarization extinction ratio (>30 dB) over 100 nm bandwidth (1484 nm-1584 nm), demonstrating that the performance of the present design is competitive with that of the state-of-the-art SOI Bragg gratings.

CHOP Regulates Endoplasmic Reticulum Stress-Mediated Hepatoxicity Induced by Monocrotaline.

Monocrotaline (MCT), a pyrrolizidine alkaloid, is the major toxin in Crotalaria, which causes cell apoptosis in humans and animals. It has been reported that the liver is a vulnerable target of MCT. However, the exact molecular mechanism of the interaction between endoplasmic reticulum (ER) stress and liver injury induced by MCT is still unclear. In this study, the cytotoxicity of MCT on primary rat hepatocytes was analyzed by a CCK-8 assay and Annexin V-FITC/PI assay. Protein expression was detected by western blotting and immunofluorescence staining. As a result, MCT significantly decreased the cell viability and mediated the apoptosis of primary rat hepatocytes. Meanwhile, MCT could also induce ER stress in hepatocytes, indicated by the expression of ER stress-related proteins, including GRP78, p-IRE1α, ATF6, p-eIF2α, ATF4, and CHOP. Pretreatment with 4-PBA, an inhibitor of ER stress, or knockdown of CHOP by siRNA could partly enhance cell viability and relieve the apoptosis. Our findings indicate that ER stress is involved in the hepatotoxicity induced by MCT, and CHOP plays an important role in this process.

Swainsonine promotes apoptosis by impairing lysosomal function and inhibiting autophagic degradation in rat primary renal tubular epithelial cells.

Swainsonine (SW), an indolizidine alkaloid, is the primary toxin in locoweeds that causes toxicity syndrome in livestock. Current research shows that SW can induce both apoptosis and autophagy. However, the relationship between, and regulatory mechanism of, autophagy and apoptosis in SW-mediated cytotoxicity remain unclear. In this study, we investigated the role of autophagy and apoptosis in SW-induced cytotoxicity in rat primary renal tubular epithelial cells (RTECs). We examined the effect of SW on lysosomal function using western blotting, transmission electron microscopy, fluorescent microscopy, and flow cytometry. The results showed that SW induced both autophagy and apoptosis, and autophagy protected RTECs from cellular damage. Activating autophagy using rapamycin (Rapa) inhibited apoptosis, while suppressing autophagy using bafilomycin A1 (Baf A1) greatly enhanced SW-induced apoptosis. SW treatment suppressed the expression of lysosomal-related proteins, and co-incubation with SW and aloxistatin (E64d) further promoted apoptosis and LC3-II accumulation in RTECs. These results suggest that SW causes toxicity by disrupting lysosomal dysfunction, inhibiting autophagic degradation, and promoting apoptosis.

Cytochrome P450s regulates aloperine-induced pathological changes in mouse liver and kidney.

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.

Diosmetin Induces Apoptosis by Downregulating AKT Phosphorylation via P53 Activation in Human Renal Carcinoma ACHN Cells.

BACKGROUND: Diosmetin (DIOS) is the aglycone of the flavonoid glycoside, diosmin, derived naturally from the leaves of the legume, Olea europaea, and Acacia farnesiana. It has potent anticancer activity against multiple forms of cancers. However, the role of DIOS in renal carcinoma and its mechanism of action remain unclear. OBJECTIVE: The purpose of this study is to investigate the effect of DIOS on cell viability and apoptosis in renal carcinoma cells and explore the possible mechanism of action. METHODS: Cell viability, cytotoxicity, caspase activity, apoptosis, and expression of apoptotic related proteins were analyzed in renal carcinoma ACHN cells. RESULTS: The results showed that DIOS inhibited the cell viability, and induced cytotoxicity and apoptosis in ACHN cells. Furthermore, DIOS increased expression of p53 mRNA and proteins, and downregulated phosphorylation of the phosphoinositide 3-kinase and protein B kinase (PI3K/AKT). In addition, it was observed that the anticancer effect of DIOS was significantly enhanced by the p53 activator, but inhibited by the p53 inhibitor. CONCLUSION: Our data suggested that DIOS induced apoptosis in renal carcinoma ACHN cells by reducing AKT phosphorylation through p53 upregulation.

The PERK/eIF2α/ATF4/CHOP pathway plays a role in regulating monocrotaline-induced endoplasmic reticulum stress in rat liver.

Monocrotaline (MCT) belongs to the category of Pyrrolizdine Alkaloids (PAs), which is one of important hepatotoxic alkaloid in Crotalaria Lin. Apoptosis is one mechanism of toxic responses induced by MCT. However, the underlying mechanism of liver apoptosis caused by MCT through Endoplasmic reticulum (ER) stress continues to be incompletely understood. In this study, we describe the role of ER stress in MCT induced hepatotoxicity in rats. 24 male rats were randomly divided into 3 groups: normal saline group, 45 mg/kg MCT group and 90 mg/kg MCT group. After 48 h of saline/MCT administration, the livers were collected for analysis of ER stress-related proteins by Western blotting. The expression of GRP78, p-IRE1α, ATF6 and caspase-12 showed a dose-dependent increase. PERK/eIF2α/ATF4/CHOP pathway is one of the major ER stress pathways which is required for cell survival. Therefore, through analyzing the effects of MCT on this pathway, we found the protein levels of p-PERK, p-eIF2α, ATF4 and CHOP were increase obviously. All these results indicate that MCT induces ER stress in rat liver. The PERK/eIF2α/ATF4/CHOP pathway is involved in the regulation of MCT-induced ER stress in the liver of rat.

Aloperine Induces Apoptosis by a Reactive Oxygen Species Activation Mechanism in Human Ovarian Cancer Cells.

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer. OBJECTIVE: The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism. METHODS: Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed. RESULTS: Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells. CONCLUSION: Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.