Effect of lncRNA KCNQ1OT1 on autophagy and drug resistance of hepatocellular carcinoma cells by targeting miR-338-3p.

The current experiment aimed to investigate the effects of lncRNA KCNQ1OT1 on the proliferation, autophagy and drug resistance of hepatocellular carcinoma cells, as well as the potential molecular mechanism. Hepatocellular carcinoma SK-HEP-1 cells and DDP resistant SK-HEP-1/DDP cells were treated with cisplatin (DDP) of different concentrations (1 nmol/L, 2 nmol/L, 4 nmol/L, 8 nmol/L, 16 nmol/L). The survival rate of SK-HEP-1 and SK-HEP-1/DDP cells was determined by the CCK8 method. QRT-PCR was used to detect the levels of lncRNA KCNQ1OT1 and miR-338-3p in normal hepatocyte HH01, hepatocellular cell SK-HEP-1 and hepatoma cisplatin-resistant cell SK-HEP-1/DDP. Western blot was carried out to detect the expression levels of autophagy-related protein Beclin1 and proliferation-related protein P21 in cells. A dual-luciferase reporter assay system was performed to validate the relationship between KCNQ1OT1 and miR-338-3p. After the treatment of 1 nmol/L, 2 nmol/L, 4nmol/L, 8nmol/L and 16nmol/L cisplatin (DDP), the survival rate of SK-HEP-1/DDP cells is higher than that of SK-HEP-1 cells. The level of lncRNA KCNQ1OT1 was increased successively in HH01, SK-HEP-1 and SK-HEP-1/DDP cells, while miR-338-3p was decreased successively. Silencing lncRNA KCNQ1OT1 or over-expressing miR-338-3p combined with 16nmol/L DDP treatment reduced the survival rate of SK-HEP-1/DDP cells and up-regulate levels of P21 and Beclin1 proteins. LncRNA KCNQ1OT1 targeted and negatively regulated the expression of miR-338-3p. Inhibition of miR-338-3p reversed the effect of silencing lncRNA KCNQ1OT1 on survival, autophagy and cisplatin sensitivity of SK-HEP-1/DDP cell. LncRNA KCNQ1OT1 targets miR-338-3p to regulate the survival rate and autophagy of SK-HEP-1/DDP cells and improve the cisplatin sensitivity of SK-HEP-1/DDP cells.  LncRNA KCNQ1OT1 is a potential molecular target for hepatocellular carcinoma.

Patchouli Oil Attenuates High Fat Diet-induced Non-alcoholic Hepatic Steatosis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Nevertheless, no first-line therapy exists. Hepatic steatosis is the earliest stage of NAFLD, which is characterized by an accumulation of hepatic lipids. Patchouli oil (PO), which is isolated from the well-known Chinese herb named Pogostemon cablin (Blanco) Benth. (Lamiaceae), inhibits hepatic lipid accumulation effectively. However, its potential ability for the treatment of NAFLD had not been reported before. Thus, the objective of this study was to investigate the effectiveness of PO against hepatic steatosis and its underlying mechanisms. We used a high fat diet (HFD)-induced hepatic steatosis model of rats to estimate the effect of PO against NAFLD. Hematoxylin-eosin and oil red O staining were used to analyze the hepatic histopathological changes. ELISA, RT-qPCR, and Western blotting analysis were applied to evaluate the parameters for hepatic steatosis. Our results showed that PO significantly attenuated the lipid profiles and the serum enzymes, evidenced by quantitative and histopathological analyses. It also markedly down-regulated the expression of sterol regulatory element-binding protein 1 (SREPB-1c) with its downstream factors in de novo lipogenesis. And, likewise, in lipid export by very low-density lipoproteins (VLDL), related molecules were dramatically improved. Furthermore, PO observably normalized the aberrant peroxisome proliferator-activated receptor α (PPAR-α) signal in fatty acids oxidation. In conclusion, PO exerted a preventing effect against HFD-induced steatosis and might be due to decrease de novo lipogenesis, promote export of lipids, as well as owing to improve fatty acids oxidation.

Identification of novel ATP7A mutations and prenatal diagnosis in Chinese patients with Menkes disease.

Menkes disease (MD) is a fatal X-linked multisystem disease caused by mutations in ATP7A. In this study, clinical and genetic analysis was performed in 24 male MD patients. Development delay, seizures, kinky coarse hair, and dystonia were found in 24, 22, 24, and 24 patients, respectively. Serum ceruloplasmin/copper tested in 19 patients was low. Abnormal classic features of MD presented in the MRI/MRA of 19 patients. Seventeen mutations of ATP7A were identified in 22 patients. Twelve were novel mutations including three small deletion/insertion, one missense mutation, two nonsense mutations, three splicing-site mutations, and three gross deletions. Twenty-two patients were genetically diagnosed; neither point mutation nor deletion/duplication was found in two of them. c.2179G > A found in five patients might be a hot-spot mutation. Prenatal molecular diagnosis was performed for five unrelated fetuses (1 female and 4 male), which found four fetuses to be wild type and one male carried the same mutation as the proband. This study of the largest sample of Chinese MD patients examined to date discovered the unique phenotype and genotype spectrum in Chinese patients with 12 novel mutations of ATP7A, and that c.2179G > A might be a hot-spot mutation in MD patients. Five successful prenatal diagnosis contributed important information for MD families.

[Clinical and ATP7A gene analysis of three infants with Menkes disease and prenatal diagnosis for a fetus at risk].

Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development confirmed the prenatal diagnosis.

[Epidemiological study on developmental delay of 18-month-old children from four districts/counties in Beijing].

OBJECTIVE: To investigate epidemiological characteristics of prevalence, impact factors and etiology on developmental delay of 18-month-old children from four districts/counties in Beijing. METHODS: An epidemiological study on developmental delay was designed to investigate all the 18-month-old children enrolled from Shunyi,Daxing,Miyun and Yanqing districts/counties in Beijing from May to September, 2011. Combining the tertiary network of child health with hospital clinical study was used. Child developmental questionnaires were completed by doctors in communities of the first network of child health. Gesell Developmental Schedules for children with Denver developmental screening test (DDST) screening positive results were assessed by doctors in districts/counties hospitals of the second network of child health. The children diagnosed as developmental delay were transferred to the tertiary hospitals of the third network of child health for further etiological diagnosis, follow-up and developmental evaluation. The case-control study compared between children with/without developmental delay were performed in accordance with the 1:4 ratios by gender and residence community matched. SPSS 16.0 was adopted for data analysis of the case-control study. RESULTS: A total of 3 182 children were screened among the 4 037 children fitting the criteria,and the coverage rate was 78.8% (3 182/4 037). Of the 3 182 screened children, 22 children were diagnosed as developmental delay. The prevalence rate was 6.91 ‰ (22/3 182). Out of the 22 children with developmental delay, 15 were boys and 7 were girls. The sex ratio was 2.1:1. The prevalence rates of the children with developmental delay in Shunyi, Daxing, Miyun and Yanqing were 3.45 ‰ (4/1 160), 4.50 ‰(5/1 111), 15.87 ‰(7/441) and 12.77 ‰ (6/479), respectively. The results from one-way ANOVA analysis showed the main risk factors in children with developmental delay included low-income families, mothers' low educational level, small size for gestational age infant, multiple fetuses, serious diseases after birth, congenital malformations and physical retardation (P<0.05). CONCLUSION: The screening coverage rate of this study is 78.8%. The prevalence rate of children with developmental delay is 6.91 ‰, which is significantly different in sex ratio and districts of the subjects. The etiology of developmental delay might be associated with social-economic and biological factors.

Association of Apolipoprotein E Gene Polymorphism with Type 2 Diabetic Nephropathy in the Southern Chinese Population.

Background: Common polymorphisms within the apolipoprotein E (APOE) gene are rs429358 and rs7412, which result in three major alleles (ɛ2, ɛ3, and ɛ4) and six genotypes (E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4). Although APOE gene polymorphisms have been suggested to be associated with the development of diabetic nephropathy (DN), their potential association remains unclear in different regions. This study aims to unveil the genetic effects of APOE gene polymorphisms on DN susceptibility and serum lipid profiles in southern Chinese population. Methods: A total of 306 DN patients and 483 type 2 diabetic patients as controls were included in the study. The APOE gene polymorphisms were analyzed by polymerase chain reaction (PCR) microarray gene chip. Relevant medical records and information of these participants were collected. Results: There were statistically significant differences (p < 0.05) in gender, SBP, hypertension, hyperuricemia, UTP, TG and HDL-C between DN patients and controls. DN patients exhibited a higher frequency of the ε2 allele and E2/E3 genotype than controls (p < 0.001). Logistic regression analysis indicated that the ε2 allele and E2/E3 genotype were independent risk factors (adjusted OR: 3.237, 95% CI: 1.789-5.854, p < 0.001; adjusted OR: 3.453, 95% CI: 1.873-6.368, p < 0.001), while the ε3 allele or E3/E3 genotype might serve as protective role (adjusted OR: 0.395, 95% CI: 0.255-0.612, p < 0.001) for development of DN. Conclusion: Our study indicates a correlation between APOE polymorphisms and DN in the southern Chinese Hakka population. Specifically, individuals carrying the APOE ε2 allele and E2/E3 genotype are at a higher risk of developing DN. Conversely, those with the APOE ε3 allele and E3/E3 genotype have a lower risk of DN in southern Chinese population.

Brusatol suppresses the tumor growth and metastasis of colorectal cancer via upregulating ARRDC4 expression through modulating PI3K/YAP1/TAZ Pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high metastasis and lethality. Arrestin domain-containing 4 (ARRDC4) is involved in inhibiting cancer glycolytic phenotypes. Brusatol (BR), extracted from Bruceae Fructus, exerts good anti-cancer effects against a number of cancers. PURPOSE: In the present study, we aimed to explore the efficacy of BR on inhibiting CRC metastasis and elucidate the underlying mechanisms involving the upregulation of the ARRDC4 expression. METHODS: Cell viability, colony formation, wound healing and transwell assay were used to detect the anti-proliferative and anti-metastatic effects of BR against CRC in vitro. Microarray analysis was performed to find out differential genes in CRC cells after treatment with BR. Analysis of the CRC patients tumor samples and GEPIA database were first conducted to identify the expression of ARRDC4 on CRC. Stable overexpression and knockdown of ARRDC4 CRC cells were established by lentiviral transfection. The role of ARRDC4 in mediating the anti-metastatic effects of BR on CRC was measured using qRT-PCR, western blotting, immunohistochemical and immunofluorescence analysis. Orthotopic xenograft and pulmonary metastasis mouse models of CRC were established to determine the anti-cancer and anti-metastatic effects of ARRDC4 and BR. RESULTS: BR markedly suppressed the cell proliferation, migration, invasion and inhibited tumor growth and tumor metastasis. Microarray analysis demonstrated that BR treatment markedly increased the gene expression of ARRDC4 in CRC cells. ARRDC4 was significantly repressed in CRC in the clinical samples and GEPIA analysis. ARRDC4 overexpression plus BR produced better inhibitory effects on CRC metastasis than BR treatment alone, while ARRDC4 knockdown could partially eliminate the inhibitory effects of BR against CRC metastasis. BR exerted anti-metastatic effects against CRC via upregulating ARRDC4 and inhibiting epithelial-mesenchymal transition (EMT) processing through modulating PI3K/Hippo pathway. CONCLUSION: This study reported for the first time that BR is a potent ARRDC4 agonist, and is worthy of further development into a new therapeutic strategy for CRC.

NIPA2 located in 15q11.2 is mutated in patients with childhood absence epilepsy.

While pathogenic copy number variations (CNVs) in 15q11.2 were recently identified in Caucasian patients with idiopathic generalized epilepsies (IGEs), the epilepsy-associated gene(s) in this region is/are still unknown. Our study investigated whether the CNVs in 15q11.2 are associated with childhood absence epilepsy (CAE) in Chinese patients and whether the selective magnesium transporter NIPA2 gene affected by 15q11.2 microdeletions is a susceptive gene for CAE. We assessed IGE-related CNVs by Affymetrix SNP 5.0 microarrays in 198 patients with CAE and 198 controls from northern China, and verified the identified CNVs by high-density oligonucleotide-based CGH microarrays. The coding region and exon-intron boundaries of NIPA2 were sequenced in all 380 patients with CAE and 400 controls. 15q11.2 microdeletions were detected in 3 of 198 (1.5%) patients and in no controls. Furthermore, we identified point mutations or indel in a heterozygous state of the NIPA2 gene in 3 out of 380 patients, whereas they were absent in 700 controls (P = 0.043). These mutations included two novel missense mutations (c.532A>T, p.I178F; c.731A>G, p.N244S) and one small novel insertion (c.1002_1003insGAT, p.N334_335EinsD). No NIPA2 mutation was found in 400 normal controls. We first identified that NIPA2, encoding a selective magnesium transporter, is a susceptible gene of CAE, and 15q11.2 microdeletions are important pathogenic CNVs for CAE with higher frequency in Chinese populations than that previously reported in Caucasians. The haploinsufficiency of NIPA2 may be a mechanism underlying the neurological phenotypes of 15q11.2 microdeletions.

Major Constituents From Brucea javanica and Their Pharmacological Actions.

Brucea javanica (Ya-dan-zi in Chinese) is a well-known Chinese herbal medicine, which is traditionally used in Chinese medicine for the treatment of intestinal inflammation, diarrhea, malaria, and cancer. The formulation of the oil (Brucea javanica oil) has been widely used to treat various types of cancer. It has also been found that B. javanica is rich in chemical constituents, including quassinoids, triterpenes, alkaloids and flavonoids. Pharmacological studies have revealed that chemical compounds derived from B. javanica exhibit multiple bioactivities, such as anti-cancer, anti-bacterial, anti-diabetic, and others. This review provides a comprehensive summary on the pharmacological properties of the main chemical constituents presented in B. javanica and their underlying molecular mechanisms. Moreover, the review will also provide scientific references for further research and development of B. javanica and its chemical constituents into novel pharmaceutical products for disease management.

Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: experiments in a rat model of brachial plexus avulsion.

BACKGROUND: Brachial plexus avulsion (BPA) physically involves the detachment of spinal nerve roots themselves and the associated spinal cord segment, leading to permanent paralysis of motor function of the upper limb. Root avulsion induces severe pathological changes, including inflammatory reaction, oxidative damage, and finally massive motoneuron apoptosis. Quercetin (QCN), a polyphenolic flavonoid found in abundance in fruit and vegetables, has been reported to possess anti-oxidative, anti-inflammatory, and neuroprotective effects in many experimental models of both central nervous system (CNS) and peripheral nervous system (PNS) disorders. The purpose of this study was to investigate whether QCN could improve motor function recovery after C5-7 ventral root avulsion and C6 reimplantation in a rat model of BPA. METHODS: The right fifth cervical (C5) to C7 ventral roots were avulsed followed by re-implantation of only C6 to establish the spinal root avulsion plus re-implantation model in rats. After surgery, rats were treated with QCN (25, 50, and 100 mg/kg) by gavage for 2 or 8 consecutive weeks. The effects of QCN were assessed using behavior test (Terzis grooming test, TGT) and histological evaluation. The molecular mechanisms were determined by immunohistochemistry analysis and western blotting. RESULTS: Our results demonstrated that QCN significantly expedited motor function recovery in the forelimb as shown by the increased Terzis grooming test score, and accelerated motor axon regeneration as evidenced by the ascending number of Fluoro-Ruby-labeled and P75-positive regenerative motoneurons. The raised ChAT-immunopositive and cresyl violet-stained neurons indicated the enhanced survival of motoneurons by QCN administration. Furthermore, QCN treatment markedly alleviated muscle atrophy, restored functional motor endplates in biceps and inhibited the microglial and astroglia activation via modulating Nrf2/HO-1 and neurotrophin/Akt/MAPK signaling pathway. CONCLUSIONS: Taken together, these findings have for the first time unequivocally indicated that QCN has promising potential for further development into a novel therapeutic in conjunction with reimplantation surgery for the treatment of BPA. .

Brucein D augments the chemosensitivity of gemcitabine in pancreatic cancer via inhibiting the Nrf2 pathway.

BACKGROUND: Gemcitabine (GEM) is the first-line chemotherapeutic drug used to treat pancreatic ductal adenocarcinoma carcinoma (PDAC), but chemoresistance is often encountered clinically. Nrf2, an oxidative stress responsive transcription factor, is an important contributor to chemoresistance and poor prognosis of PDAC. Brucein D (BD), a naturally occurring quassinoid, has been reported to exert anti-tumor effect in several cancers including PDAC. In this study, we aimed to investigate the efficacy of BD and the role of Nrf2 axes on the chemosensitivity of GEM and elucidate the underlying molecular mechanisms. METHODS: Analyses of clinical samples of PDAC and GEPIA database were first conducted to identify the expression of Nrf2 in PDAC. We then established cell lines with stable deletion of Nrf2 through transfecting lentivirus into PDAC cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to determine the expression of Nrf2 in these cell lines. The effects of BD and Nrf2 axes on PDAC cell proliferation, colony-formation, tumor growth and chemosensitivity were determined both in vitro and in vivo. Orthotopic xenograft and genetically engineered KPC mouse models of PDAC were used to evaluate the anti-pancreatic cancer effects of BD and GEM. RESULTS: Nrf2 was highly expressed in PDAC in the clinical samples and GEPIA analysis. Gain- and lost-function study demonstrated that Nrf2 affected the chemosensitivity of GEM on PDAC cells both in vitro and in vivo. We further found that BD effectively inhibited PDAC cell proliferation and enhanced the chemosensitivity of GEM. Mechanistic studies revealed that BD sensitized GEM in PDAC cells through the ubiquitin-proteasome-dependent degradation of Nrf2, and downregulating the Nrf2 pathway. Silencing of Nrf2 plus BD treatment resulted in more potent inhibitory effects of GEM. In contrast, Nrf2 activation attenuated the chemosensitivity of GEM, indicating that the action of BD was Nrf2 dependent. Finally, the efficacy of BD alone and in combination with GEM on PDAC was validated on both orthotopic xenograft and genetically engineered KPC mouse models. CONCLUSIONS: BD was able to enhance the chemosensitivity of GEM in PDAC through inhibition of the Nrf2 pathway. Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC.

Patchouli alcohol ameliorates acute liver injury via inhibiting oxidative stress and gut-origin LPS leakage in rats.

Alcoholism represents a predisposing factor for liver-related morbidity and mortality worldwide. Pogostemon cablin has been widely used in China for the treatment of digestive system diseases. Patchouli oil, the major active fraction of Pogostemon cablin, can ameliorate alcohol-induced acute liver injury (ALI). However, patchouli alcohol (PA),a principal bioactive ingredient of PO, exerts a protection against ALI remains elusive. Thepresentwork focused on the hepatoprotection of PA against acute ethanol-induced hepatotoxicity in rats. In this study, male Wistar rats orally received PA (10, 20, or 40 mg/kg), PO (400 mg/kg) and silymarin (200 mg/kg) for ten days. On the 8th day, the rats orally received 65% ethanol (10 mL/kg, 6.5 g/kg) every 12 h for 3 days. Results showed that PA wasfound to reduce alcohol-induced ALI, as evidenced bysignificantly alleviated histopathologicalalterations, decreased the elevation ofALT and AST levels, and enhancedthe alcoholdehydrogenase(ADH) andaldehyde dehydrogenase (ALDH) activities. Additionally, PA markedly suppressed ROS levels and increased antioxidant enzyme activities via the CYP2E1/ROS/Nrf2/HO-1 pathway. PA regulated lipid accumulation by markedly inhibiting the expression of lipogenesis-related genes and stimulating that of lipolysis-relatedgenes, which were associated with the activation of theAMPKpathway. What's more, PA pretreatment also restored acute alcohol-inducedalterationsin gut barrier function, colonic histopathology, and gut microbiota richness and evenness. PA pretreatment alleviated gut-origin LPS-inducedinflammation by inhibiting the MyD88/TLR4/NF-κB signal pathway. In general, PA ameliorates ethanol-induced ALI via restoration of CYP2E1/ROS/Nrf2/HO-1-mediatedoxidativestressand AMPK-mediated fat accumulation, as well as alleviation of gut-LPS-leakage-induced inflammation regulated by the MyD88/TLR4/NF-κB signaling pathway.

Patchouli oil ameliorates 5-fluorouracil-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported. AIM OF THE STUDY: To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects. RESULTS: The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea. CONCLUSIONS: P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.

Disinfection efficacy of green synthesized gold nanoparticles for medical disinfection applications.

BACKGROUND: In recent times, biosyntheses of metal nanoparticles were used for several life rescue applications. In this study, Dillenia indica leaf aqueous extract was utilized for the synthesis of gold nanoparticles. OBJECTIVE: To test anti-microbial properties of biologically fabricated gold nanoparticles. METHODS: Gold nanoparticles were efficiently prepared by making use of aqueous leaf extract of Dillenia indica. The excitation of formed AuNPs was confirmed using UV-Vis spectrophotometer. In particular, absorption spectra of AuNPs exhibited a well-defined SPR band centered at around 530 nm. RESULTS: The high-resolution Scanning Electron Microscope (SEM) results of the obtained AuNPs confirmed the formation of particles with a size range of 5-50 nm. The ultra-high resolution TEM (UHRTEM) images displayed clear lattice fringes on the particle surfaces. Single crystalline nature of the biosynthesized AuNPs was represented by means of selected-area electron diffraction pattern. CONCLUSION: The antibacterial activity of AuNPs revealed significant activity towards both gram negative and gram positive bacteria signifying their potential disinfection related applications in medicine and biology.

Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

Antioxidative and Anti-Inflammatory Effects of Water Extract of Acrostichum aureum Linn. against Ethanol-Induced Gastric Ulcer in Rats.

Acrostichum aureum Linn., a medicinal pteridophyte growing in mangrove forests and coastal regions of tropical and subtropical areas worldwide, has been proved to possess various biological effects. However, the protective effect of Acrostichum aureum Linn. against gastric ulcer still remains unidentified. Therefore, the gastroprotective effect of the water extract of Acrostichum aureum Linn. (WEAC) was investigated in ethanol-induced gastric injury model. According to our results, pretreatment with WEAC (100, 200, and 400 mg/kg) could dramatically decrease the ulcer areas and ameliorate the pathological damage induced by alcohol in rat's gastric tissues. In addition, WEAC administration prevented the stomach from oxidative damage via markedly increasing the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and decreasing the malondialdehyde (MDA). Besides, WEAC pretreatment alleviated inflammatory infiltration by reducing the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) as well as decreasing the protein expressions of phosphorylation of IκBα and p65. Taken together, WEAC exerted potential therapeutic efficacy for gastric ulceration, and this may be involved in the suppression of oxidative stress and inflammatory response.

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.

Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway.

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2-Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate-cysteine ligase catalytic (GCLC) subunit, glutamate-cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2-Keap1 signaling pathway.

Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation.

Excessive alcohol consumption can cause serious hepatic injury which is associated with oxidative stress and fatty metabolic disturbance. Patchouli oil (PO) is a sort of food supplement with high medicinal value in hepatoprotection, but its ability against ethanol-induced liver failure has not been demonstrated. Thus, this study aimed to investigate the potential hepatoprotection of PO through an ethanol-induced hepatotoxicity rat model. Our results showed that PO pretreatment could dramatically decrease the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum, paralleled by an improvement of histopathology alterations. Additionally, PO could markedly suppress the content of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), free fatty acid (FFA), and triglyceride (TG), while enhancing the activities of glutathione (GSH), glutathione reductase (GR), and superoxide dismutase (SOD) as well as the ratio of glutathione to oxidized glutathione (GSH/GSSG) in liver. The protective effect of PO against oxidative stress was interrelated with restraining the mRNA and protein expression of hepatic microsomal enzyme cytochrome P450 2E1 (CYP2E1). What's more, PO pretreatment could also accelerate lipometabolism via up-regulating expressions of adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor α (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) and down-regulating expressions of nuclear factor-kappaB (NF-κB) p65, sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1). To conclude, PO showed potent effect against ethanol-induced hepatotoxicity by relieving oxidative stress and preventing lipid accumulation.

Correction: Patchouli oil isolated from the leaves of Pogostemon cablin ameliorates ethanol-induced acute liver injury in rats via inhibition of oxidative stress and lipid accumulation.

[This corrects the article DOI: 10.1039/C8RA02422G.].