Fangchinoline inhibits growth and biofilm of Candida albicans by inducing ROS overproduction.

Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis-benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 µg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH-DA staining suggested its anti-Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N-acetyl-cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti-Candida therapies.

RbPbI3 Seed Embedding in PbI2 Substrate Tailors the Facet Orientation and Crystallization Kinetics of Perovskites.

High power conversion efficiencies (PCEs) in perovskite solar cells (PSCs) have always been awe-inspiring, but perovskite films scalability is an exacting precondition for PSCs commercial deployment, generally unachievable through the antisolvent technique. On the contrary, in the two-step sequential method, the perovskite's uncontrolled crystallization and unnecessary PbI2 residue impede the device's performance. These two issues motivated to empower the PbI2 substrate with orthorhombic RbPbI3 crystal seeds, which act as grown nuclei and develop orientated perovskites lattice stacks, improving the perovskite films morphologically and reducing the PbI2 content in eventual perovskite films. Thence, achieving a PCE of 24.17% with suppressed voltage losses and an impressive life span of 1140 h in the open air.

Antifungal and anti-biofilm activities of patchouli alcohol against Candida albicans.

The opportunistic fungal pathogen Candida albicans could cause severe clinical outcomes which could be exacerbated by the scarcity of antifungals. The capacity of C. albicans to form biofilms on medical devices that are hard to eradicate, further deepen the need to develop antifungal agents. In this study, we, for the first time, showed that patchouli alcohol (PA) can inhibit the growth of multiple C. albicans strains, as well as four other Candida species, with MICs of 64 µg/mL and MFCs from 64 to 128 µg/mL. The biofilm formation and development, adhesion, yeast-to-hyphal transition and extracellular polysaccharide of C. albicans can be inhibited by PA in a concentration-dependent manner. Confocal microscopy analyses of cells treated with PA showed that PA can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. In C. elegans, PA did not influence the survival below 64 µg/mL. In this study PA demonstrated antifungal and antibiofilm activity against C. albicans and our results showed the potential of developing PA to fight Candida infections.

A Functional Biological Molecule Restores the PbI2 Residue-Induced Defects in Two-Step Fabricated Perovskites.

Coating the perovskite layer via a two-step method is an adaptable solution for industries compared to the anti-solvent process. But what about the impact of unreacted PbI2? Usually, it is generated during perovskite conversion in a two-step method and considered beneficial within the grain boundaries, while also being accused of enhancing the interface defects and nonradiative recombination. Several additives are mixed in PbI2 precursors for the purpose of improving the perovskite crystallinity and hindering the Pb2+ defects. Herein, in lieu of adding additives to the PbI2, the effects of the PbI2 residue via the electron transport layer/perovskite interface modification are explored. Consequently, by introducing artemisinin decorated with hydrophobic alkyl units and a ketone group, it reduces the residual PbI2 and improves the perovskites' crystallinity by coordinating with Pb2+. In addition, artemisinin-deposited perovskite enhances both the stability and efficiency of perovskite solar cells by suppressing nonradiative recombination.

A lymph node metastasis-related protein-coding genes combining with long noncoding RNA signature for breast cancer survival prediction.

Integrating protein-coding gene (PCG) with long noncoding RNA (lncRNA) expression profiles, our aim is to identify a multidimensional transcriptome model that can predict individual prognosis of patients with breast cancer (BRCA). After diverse bioinformatics and statistical analyses, we obtained gene expression profiles of 1,016 BRCA samples from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, and constructed a prognostic signature, which is composed of four PCGs (TFCP2, LRRC75B, PROSER2, and STOML1) and one lncRNA (AL355592.1). In the training set, the multidimensional transcriptome signature could part patients with BRCA into two groups with different survival, defined as high- and low-risk group by Kaplan-Meier (KM) analysis (p < 0.001). In the other five validation datasets, the PCG-lncRNA signature showed a similar predictive performance in BRCA by KM (p < 0.05). The prognostic independence for the PCG-lncRNA model was verified by the multivariable Cox regression analysis. Because Chi-squared test showed the signature was associated with lymph node metastasis status, stratification analysis found that it could further subdivide lymph node metastasis status more precisely in BRCA. The function analysis suggested that the genes from the signature were associated with immunity-related pathways. In summary, we constructed a PCG-lncRNA signature, which could accurately predict survival in patients with BRCA.

Characterization of Lactobacillus plantarum Lp27 isolated from Tibetan kefir grains: a potential probiotic bacterium with cholesterol-lowering effects.

Lactobacillus plantarum Lp27 was isolated from Tibetan kefir grains. The Lp27 isolate survived a 3-h incubation at pH 2.0 and grew normally in 0.3% oxgall. In addition, the Lp27 isolate exhibited an adhesion ratio of 9.5 ± 2.5% with Caco-2 cells. Antibiotic susceptibility tests indicated that the Lp27 isolate was sensitive to gentamicin, tetracycline, erythromycin, and chloramphenicol, and was resistant to vancomycin with a minimum inhibitory value of 23µg/mL. The Lp27 isolate inhibited cholesterol absorption through downregulation of Niemann-Pick C1-like 1 (NPC1L1) expression in Caco-2 cells. The Lp27 isolate was fed to hypercholesterolemic rats at a dose of 10(9) cfu/d for 4wk. The Lp27 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides concentrations, but no change was observed in the serum high-density lipoprotein cholesterol concentrations. In addition, liver total cholesterol and triglycerides were decreased in the Lp27-fed group. The expression of NPC1L1 in the duodenum and jejunum was significantly decreased following Lp27 feeding. These results indicate that Lp27 might be an effective cholesterol-lowering probiotic and a possible mechanism for the cholesterol-reducing effects of probiotics.

Lactobacillus plantarum strains as potential probiotic cultures with cholesterol-lowering activity.

Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. The search for mediators that fine-tune cholesterol homeostasis has revealed lactic acid bacteria (LAB) to be potentially beneficial. The aim of the present study was to identify and characterize probiotic strains with bile salt hydrolase activity from kefir grains and evaluate their potential use as cholesterol-reducing probiotics in rats. Two isolates, Lp09 and Lp45, obtained from kefir grains were identified as Lactobacillus plantarum via molecular typing methods. Lactobacillus plantarum Lp09 and Lp45 exhibited excellent tolerance to low pH levels and high bile salt concentrations and showed potential bile salt hydrolase activity, bile salt deconjugation activity, and cholesterol coprecipitation ability. Additionally, the potential effect of Lb. plantarum Lp09 and Lp45 on plasma cholesterol levels was evaluated in Sprague-Dawley rats. Rats in 3 treatment groups were fed different experimental diets: a high-cholesterol diet, a high-cholesterol diet plus Lb. plantarum Lp09, or a high-cholesterol diet plus Lb. plantarum Lp45 for 4 wk. Total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels in serum as well as cholesterol and triglyceride levels in liver were significantly decreased in the LAB-treated rats compared with rats fed a high-cholesterol diet without LAB supplementation. Also, both fecal cholesterol and bile acid levels were significantly increased after LAB administration. No significant changes were detected in high-density lipoprotein cholesterol levels. These results suggest that the Lb. plantarum Lp09 and Lp45 strains present the potential to be explored as probiotic agents for the management of hypercholesterolemia.

Potentiation of mutant CFTR Cl- channel currents by the naturally occurring stilbene compound resveratrol.

Previously, we found that the naturally occurring stilbene compound resveratrol (RES) could potentiate cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. Because some wild-type CFTR activators also potentiate its mutant forms, we investigated effect of RES on the two most common forms of CF-related mutation (deltaF508 and G551D-CFTR). Cell-based fluorescence studies indicated that RES dose-dependently potentiated both deltaF508 and G551D mutant CFTR Cl- channel activities. Transepithelial Cl- currents were stimulated by RES in deltaF508 and G551D mutant CFTR-expressing FRT cells. Further excised inside-out patch-clamp measurements revealed that RES significantly induced the chloride current of deltaF508 and G551D mutant CFTRs by increasing the open time of the channels. In ex vivo studies, RES stimulated fluid secretion in mouse trachea by optical measurement of single gland secretion. These data suggested that RES is a potent deltaF508 and G551D mutant CFTR potentiator, and RES may present a novel class of therapeutic lead compounds in treating cystic fibrosis.

CFTR chloride channel is a molecular target of the natural cancer preventive agent resveratrol.

The naturally occurring polyphenol compound resveratrol (RES) has been receiving wide attention because of its variety of health benefits and favourable biological activities. Previous studies have shown that RES could induce intestinal chloride secretion in mouse jejunum and stimulate cAMP-dependent Cl- secretion in T84, primary cultured murine nasal septal and human sinonasal epithelial cells, but the precise molecular target is not clear. We therefore tested the hypothesis that RES may stimulate the activity of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Using cell-based fluorescent assays, transepithelial short-circuit current measurements and excised inside-out patch-clamp analysis; we found that RES dose-dependently potentiate CFTR Cl- channel activities, which was reversed by CFTR inhibitors CFTR(inh)-172 and GlyH101. Transepithelial Cl- secretion by CFTR-expressing FRT cells was stimulated by RES with half maximal concentration -80 microM. Intracellular cAMP content was not elevated by RES in FRT cells. Excised inside-out patch-clamp analysis indicated that RES significantly increased the chloride currents of CFTR. In ex vivo studies, RES stimulated the transmucosal chloride current of rat colon by short-circuit current assay. These data suggested that CFTR is a molecular target of RES. Our findings add a new molecular target to RES, and RES may represent a novel class of therapeutic lead compounds in treating CFTR-related diseases including CF and habitual constipation.

Elderly Chinese and their family caregivers' perceptions of good care: a qualitative study in Shandong, China.

This study aims to understand what older Chinese people with chronic illness and their family caregivers perceive to be good care, and to compare perspectives of those living in rural and urban areas. We conducted semistructured interviews with 24 care recipients and 23 caregivers in Shandong, China. Two major themes were identified: (a) filial piety as the standard, and (b) modifying cultural ideals to meet reality. There was overall consistency in perceptions of study participants. Variations between rural and urban elders' perceptions appear to reflect differences in socioeconomic development and institutional structures.

Effects of N-methyl-D-aspartate receptor knockdown and hypoxia/reoxygenation injury on the neuronal proteome and transcriptome.

Introduction: Brain tissue is extremely sensitive to hypoxia/reoxygenation (H/R) injury, which can easily cause irreversible damage to neurons. H/R injury can induce neuronal apoptosis through glutamate-mediated excitotoxicity. N-methyl-d-aspartate receptor (NMDAR) is one of the main receptors of excitatory glutamate, and blocking NMDAR protects brain tissue from ischemic and hypoxic injury. However, NMDAR hypofunction can also cause psychotic symptoms or cognitive impairment. There is still a lack of systematic research on the changes in the proteome and transcriptome in neuronal cells under conditions of NMDAR hypofunction and H/R injury. Methods: We compared the changes in the proteome, transcriptome and lncRNA expression levels in neurons after NMDAR knockdown and H/R by isobaric tags for relative and absolute quantitation (iTRAQ) and RNA sequencing (RNA-Seq). Results: The results showed that the proteins Rps9, Rpl18 and Rpl15 and the lncRNAs XLOC_161072 and XLOC_065271 were significantly downregulated after NMDAR knockdown but upregulated after H/R; in contrast, the mRNAs Bank1 and Pcp4l1 and the lncRNAs XLOC_159404 and XLOC_031922 were significantly upregulated after NMDAR knockdown but downregulated after H/R. Discussion: In this study, we demonstrated the characterization of protein, mRNA, and lncRNA expression profiles in neurons following NMDAR knockdown and H/R injury. These molecules are involved in multiple biological functions and signaling pathways, and their roles in neurons lacking NMDAR and subjected to H/R injury deserve further study. Additionally, we found that lncRNAs respond fastest to hypoxic stimulation and that Gapdh is not suitable as a reference protein for NMDAR-reduced neuron-related experiments.

Antifungal effects of alantolactone on Candida albicans: An in vitro study.

The human fungal pathogen Candida albicans can cause many kinds of infections, including biofilm infections on medical devices, while the available antifungal drugs are limited to only a few. In this study, alantolactone (Ala) demonstrated antifungal activities against C. albicans, as well as other Candida species, with a MIC of 72 µg/mL. Ala could also inhibit the adhesion, yeast-to-hyphal transition, biofilm formation and development of C. albicans. The exopolysaccharide of biofilm matrix and extracellular phospholipase production could also be reduced by Ala treatment. Ala could increase permeability of C. albicans cell membrane and ROS contribute to the anti-biofilm activity of Ala. Overall, the present study suggests that Ala may provide a promising candidate for developing antifungal drugs against C. albicans infections.

Carnosol inhibits the growth and biofilm of Candida albicans.

OBJECTIVE: This study was to explore the inhibitory effects of carnosol on the growth and biofilm of Candida albicans. RESULTS: Our results showed that carnosol inhibited the planktonic growth of C. albicans with a MIC of 100 µg/mL. Carnosol can also inhibit the biofilm formation and development of C. albicans. 25-100 µg/mL of carnosol can obviously inhibit the yeast-to-hyphal transition in four kinds of hyphal-inducing media and the adhesion of C. albicans to polystyrene surfaces. Results from PI staining indicated that carnosol may disrupt cell membrane of C. albicans. CONCLUSION: Carnosol can inhibit the planktonic growth and virulence factors of C. albicans, such as biofilm formation, adhesion and hyphal growth. The antifungal mechanism may involve the increase in cell membrane permeability.

Bombyxin II Regulates Glucose Absorption and Glycogen Synthesis through the PI3K Signaling Pathway in HepG2 Cells.

Bombyxin, as an insulin-like insect hormone, was discovered in the silkmoth Bombyx mori. It can regulate the metabolism of trehalose and glycogen in Bombyx mori, but whether it has glucose absorption and glycogen synthesis effect on mammalian cells was not clear. BombyxinII (BbxII) and mutant BbxII (mBbxII) genes were cloned into pcDNA3.1(+) vector, respectively; then, gene vectors were transfected into 293FT cells using Lipofectamine 2000. Levels of mRNA and protein expression of BbxII and mBbxII were detected by PCR and Western blot in 293FT cells, respectively. Glucose consumption and glycogenesis were determined by glucose oxidase-peroxidase (GOD-POD) and periodic acid-Schiff (PAS) staining in HepG2 cells; the PI3K signaling pathway was inhibited with wortmannin S1952 in HepG2 cells. Result showed that BbxII and mBbxII genes were being successfully expressed in 293FT cells, respectively. The expression protein of BbxII gene is 10kd pre-bombyxinII, and yet, the expression protein of mBbxII gene is 4kd mature bombyxinII. Only the 4kd bombyxinII showed increased glucose uptake and glycogenesis in HepG2 cells, and the ability of increasing glucose uptake was equal to the human insulin (10 nM). PI3K-wortmannin S1952 inhibitor can decrease the glycogen synthesis induced by bombyxin II protein in HepG2 cells. In conclusion, mature bombyxin II may adjust glucose absorption and glycogen synthesis in HepG2 cells through the PI3K signaling pathway.

Alantolactone: A sesquiterpene lactone with diverse pharmacological effects.

Alantolactone (Ala) is a sesquiterpene lactone that can be isolated from many herbal plants belonging to Asteraceae. Besides the antimicrobial activities against bacteria, fungi and viruses, Ala has also demonstrated significant anti-inflammatory effects in various models by inhibiting NF-κB and MAPKs to decrease the pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α. The antitumor effects of Ala have been demonstrated in vitro and in vivo via inducing intrinsic apoptosis, oxidative stress, ER stress, cell cycle arrest and inhibiting autophagy and STAT3 phosphorylation, which are also involved in its combination or synergy with other antitumor drugs. Ala also has neuroprotective activity through attenuating oxidative stress and inflammation, besides its modulation of glucose and lipid metabolism. This review summarizes the recent advances of the pharmacological effects of Ala, including anti-inflammatory, antitumor, antimicrobial, neuroprotective activities, as well as the underlying mechanisms. Ala might be employed as a potential lead to develop drugs for multiple diseases.

Sodium houttuyfonate: A review of its antimicrobial, anti-inflammatory and cardiovascular protective effects.

There is an almost unlimited interest in searching and developing new drugs, especially when we are in an era that are witnessing more and more emerging pathogens. Natural products from traditional medicines represent a large library for searching lead compounds with novel bioactivities. Sodium houttuyfonate is such one bioactive compound derived from Houttuynia cordata Thunb which has been employed in traditional medicine for treating infectious and inflammatory diseases. Sodium houttuyfonate has demonstrated multiple kinds of pharmacological effects, including antifungal, antibacterial, anti-inflammatory, and cardiovascular protective activities, which are discussed here to provide insights into our understanding of the pharmacological effects of SH and the underlying mechanisms.

Corrigendum to "Lycorine Hydrochloride Inhibits the Virulence Traits of Candida albicans".

[This corrects the article DOI: 10.1155/2019/1851740.].

Expression of TMEM16A in Colorectal Cancer and Its Correlation With Clinical and Pathological Parameters.

TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. TMEM16A protein expression was performed by immunohistochemistry in 80 CRC tissues. The correlation between TMEM16A expression and clinicopathological parameters, and known genes and proteins involved in CRC was analyzed. The results showed that TMEM16A mRNA expression was frequently detected in 51 CRC tissues (76%), whereas TMEM16A protein expression was determined at a relatively lower frequency (26%). TMEM16A mRNA expression in tumor tissues was higher than its expression in normal para-carcinoma tissues (P < 0.05). TMEM16A mRNA expression was significantly correlated with TNM stage (p = 0.039) and status of lymph node metastasis (p = 0.047). In addition, there was a strong positive correlation between TMEM16A mRNA expression and MSH2 protein. More importantly, TMEM16A protein expression was positively associated with KRAS mutation, and negatively correlated with mutant p53 protein. Logistic regression analysis demonstrated that TMEM16A mRNA expression was an important independent predictive factor of lymph node metastasis (OR = 16.38, CI: 1.91-140.27, p = 0.01). TMEM16A mRNA and protein expression was not significantly related with patient survival. Our findings provide original evidence demonstrating TMEM16A mRNA expression can be a novel predictive marker of lymph node metastasis and TMEM16A protein expression may be an important regulator of tumor proliferation and metastasis in CRC.

Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4.

PURPOSE: A long noncoding RNA called small nucleolar RNA host gene 7 (SNHG7) is known to be a key regulator of biological processes in multiple human cancer types. In this study, our aims were to determine the expression status of SNHG7 in cervical cancer, to figure out the detailed roles of SNHG7 in cervical cancer cells, and to identify the mechanism underlying the activity of SNHG7 in cervical cancer. METHODS: Reverse-transcription quantitative PCR was performed to measure SNHG7 expression in cervical cancer. A Cell Counting Kit-8 assay, flow-cytometric analysis, cell migration and invasion assays, and a tumor xenograft experiment were conducted to respectively determine the effects of SNHG7 on cervical cancer cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. RESULTS: SNHG7 was found to be markedly upregulated in cervical cancer tissues and cell lines. Higher SNHG7 expression significantly correlated with FIGO stage, lymph node metastasis, the depth of cervical invasion, and shorter overall survival in patients with cervical cancer. Functional experiments indicated that a SNHG7 knockdown attenuated proliferation, migration, and invasiveness and promoted apoptosis of cervical cancer cells in vitro. The SNHG7 knockdown also slowed tumor growth in vivo. Further investigation showed that SNHG7 acts as a competing endogenous RNA for microRNA-485 (miR-485) in cervical cancer cells, and the inhibitory actions of the SNHG7 knockdown on the malignant phenotype were reversed by miR-485 inhibition. P21-activated kinase 4 (PAK4) was identified as a direct target gene of miR-485 in cervical cancer, and PAK4 expression was promoted by SNHG7. CONCLUSION: SNHG7 functions as an oncogenic RNA in cervical cancer, competitively binds to miR-485, and thereby upregulates PAK4. This SNHG7-miR-485-PAK4 regulatory network may provide insights into the pathogenesis of cervical cancer, and can help in the identification of novel diagnostic and therapeutic approaches for cervical cancer.

[Investigation in vivo of effect of ultrasound-mediated microbubble destruction on entrance of feridex into the aortal wall].

OBJECTIVE: To explore feasibility for entrance of the contrast agent Sonovue and Feridex into the aortal wall. METHODS: 17 male Japanese giant ears rabbits (common grade), including 11 atherosclerosis (AS) animal models fed with food containing high-content lipid and normal animals fed with common food as control. Respectively, 10 animals in the AS group and 6 animals in the normal group were selected in a random way to undergo ultrasound-mediated microbubble destruction (UMMD) and no ultrasound-mediated microbubble destruction (-UMMD) half and half. One animal was administrated with double doses of Feridex. After general anesthesia, MR plain scan and intravenous injection of Feridex 100 micromol Fe/kg, immediately ultrasound focused on the front wall of the aortic arch, which underwent UMMD at the pressure of 3.5 Mpa with MI1.2 while 10 ml solution (Sonovue + normal saline)was injected intravenously at the speed of 0.5 ml/min FOR 20 min. 3T magnetic resonance (MR) was performed with a moderately T2* weighted gradient sequence. Enhanced scan were performed for 1 h, 24 h, 48 h, 72 h and after killing the animal. then the specimen were delivered to conduct optical and electronic microscope examination. Variance test for the re-measured data was adopted to verify the data obtained in every group. RESULTS: The effect of UMMD group on SPIO particles entrance into the aortal wall is of marked significance (P = 0.0004) statistically. The effect of UMMD on distribution in the vessel wall is of statistical significance (P = 0.01), more particles in the dventitia. Gas or microbubbles were found to enter into the intima, media of the aorta, and verified by Oil Red O staining. After staining the findings of iron particle in the cell and out of the cell are different. CONCLUSIONS: UMMD may facilitate entrance of those SPIO particles with a bigger diameter and microbubbles into the aortal wall. This discovery may provide a new solution for penetration of complex macromolecule probes and gene-carried drug through the tunica intima of the aorta.