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.

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.

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.

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.

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.

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.].

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.

Lycorine Hydrochloride Inhibits the Virulence Traits of Candida albicans.

The human opportunistic fungal pathogen Candida albicans causes a severe health burden while the biofilms formed by C. albicans present a kind of infections that are hard to cure, highlighting the pressing need for new antifungal drugs against C. albicans. This study was to explore the antifungal activities of lycorine hydrochloride (LH) against C. albicans. The minimal inhibitory concentration (MIC) of LH against C. albicans SC5314 was 64 µM. Below its MIC, LH demonstrated antivirulence property by suppressing adhesion, filamentation, biofilm formation, and development, as well as the production of extracellular phospholipase and exopolymeric substances (EPS). The cytotoxicity of LH against mammalian cells was low, with half maximal inhibitory concentrations (IC50) above 256 µM. Moreover, LH showed a synergistic effect with AmB, although its interaction with fluconazole, as well as caspofungin, was indifferent. Thus, our study reports the potential use of LH, alone or in combination with current antifungal drugs, to fight C. albicans infections.

Fisher linear discriminant analysis for classification and prediction of genomic susceptibility to stomach and colorectal cancers based on six STR loci in a northern Chinese Han population.

OBJECTIVE: Gastrointestinal cancer is the leading cause of cancer-related death worldwide. The aim of this study was to verify whether the genotype of six short tandem repeat (STR) loci including AR, Bat-25, D5S346, ER1, ER2, and FGA is associated with the risk of gastric cancer (GC) and colorectal cancer (CRC) and to develop a model that allows early diagnosis and prediction of inherited genomic susceptibility to GC and CRC. METHODS: Alleles of six STR loci were determined using the peripheral blood of six colon cancer patients, five rectal cancer patients, eight GC patients, and 30 healthy controls. Fisher linear discriminant analysis (FDA) was used to establish the discriminant formula to distinguish GC and CRC patients from healthy controls. Leave-one-out cross validation and receiver operating characteristic (ROC) curves were used to validate the accuracy of the formula. The relationship between the STR status and immunohistochemical (IHC) and tumor markers was analyzed using multiple correspondence analysis. RESULTS: D5S346 was confirmed as a GC- and CRC-related STR locus. For the first time, we established a discriminant formula on the basis of the six STR loci, which was used to estimate the risk coefficient of suffering from GC and CRC. The model was statistically significant (Wilks' lambda = 0.471, χ2 = 30.488, df = 13, and p = 0.004). The results of leave-one-out cross validation showed that the sensitivity of the formula was 73.7% and the specificity was 76.7%. The area under the ROC curve (AUC) was 0.926, with a sensitivity of 73.7% and a specificity of 93.3%. The STR status was shown to have a certain relationship with the expression of some IHC markers and the level of some tumor markers. CONCLUSIONS: The results of this study complement clinical diagnostic criteria and present markers for early prediction of GC and CRC. This approach will aid in improving risk awareness of susceptible individuals and contribute to reducing the incidence of GC and CRC by prevention and early detection.

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.

Mutation Status and Immunohistochemical Correlation of KRAS, NRAS, and BRAF in 260 Chinese Colorectal and Gastric Cancers.

KRAS, NRAS and BRAF are kinases involved in the RAS-RAF-MAPK signaling pathway and also potential tumor-driven genes. Patients with KRAS/NRAS/BRAF mutations are resistant to anti-EGFR monoclonal antibody therapy. The main purpose of this study is to investigate the mutation status and distribution of KRAS/NRAS/BRAF in Chinese colorectal and gastric cancers, and to explore the histopathological changes and related immunohistochemical marker changes caused by these mutations. The mutation status of KRAS (exons 2, codon 12/13), NRAS (exons 2/3/4, codon 12/13/59/61/117/146) and BRAF (exons 15, codon 600) were detected by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 86 colon cancer, 140 rectal cancer and 34 gastric cancer tissues. Then, the frequencies and distribution of KRAS/NRAS/BRAF mutations were described in detail. Furthermore, the relationship between KRAS/NRAS/BRAF mutations and the features of histopathological and related immunohistochemical markers were analyzed. The results showed that KRAS/NRAS/BRAF mutation rates in colon cancer were 44.2, 1.2, and 3.5%; in rectal cancer were 37.1, 4.3, and 0.7%; in gastric cancer were none, none and 2.9%. The mutation rate of KRAS in female (48.8%) is significantly higher than that of male (27.8%), and the mutation rate increased with the higher degree of differentiation. Additionally, the mutation rate of BRAF detected by ARMS-PCR (1.77%) was significantly lower than that by immunohistochemistry (4.11%). It also showed that the KRAS/NRAS/BRAF mutation status had a certain relationship with the expression of some immunohistochemical markers. This study provides more data support for clinical research on KRAS/NRAS/BRAF mutation in CRCs or gastric cancers.

Dioscin Inhibits Virulence Factors of Candida albicans.

Candida albicans infections present a heavy burden upon public health, with only a few drugs available, while biofilms formed by C. albicans worsen this situation. Dioscin has antitumor, anti-inflammatory, and hepatoprotective effects, and this study was conducted to evaluate the effects of dioscin on the biofilm formation and development, as well as other virulence factors of C. albicans such as morphological transition, adhesion, and extracellular secreted phospholipase. Our results showed dioscin inhibits these virulence factors and has low cytotoxicity against mammalian cells. Considering protective effects of dioscin against damage on liver and kidney, dioscin may be used as a potential candidate for antifungal development.

Association of SREBP2 gene polymorphisms with the risk of osteonecrosis of the femoral head relates to gene expression and lipid metabolism disorders.

Although lipid metabolism disorders have been recognized as a primary factor of osteonecrosis of the femoral head (ONFH), the molecular pathogenesis remains unclear. Sterol regulatory element­binding protein 2 (SREBP2) specifically regulates cholesterol and fatty acid metabolism to maintain lipid homeostasis. To explore the roles of the SREBP2 gene in the development of ONFH, the authors analyzed the gene polymorphism and gene expression of three tag single nucleotide polymorphisms of the SREBP2 gene, the serum lipids levels, and their associations with ONFH development in 182 ONFH patients and 179 healthy controls. The results demonstrated that the stage IV proportions of ONFH patients carrying the rs2267439CT or CC genotype were significantly higher and lower than the stage III proportions of ONFH patients (P=0.039), respectively. The serum triglyceride, low­density lipoprotein (LDL)­c levels, and LDL­C/high­density lipoprotein (HDL)­C ratio in the ONFH group were significantly increased compared to those in the control group (P=0.01, P=0.005, P=0.0001) while the HDL­C level of ONFH group was remarkably lower than that of the control group (P=0.0001). Association analysis further revealed that the LDL­c levels of the rs226744 GG and AG genotype carriers were statistically higher than that of the AA genotype carriers (P=0.039, P=0.05). These results demonstrated that the gene polymorphism of SREBP2 not only significantly associated with the clinical phenotypes of ONFH but also closely related to lipid metabolism disorder. The results indicated that SREBP2 gene polymorphism and function may play key roles in the development of ONFH.

Associations of IGFBP3 Gene Polymorphism and Gene Expression with the Risk of Osteonecrosis of the Femoral Head in a Han Population in Northern China.

The critical roles of IGFBP3 in regulating the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells strongly indicate its potential effects on the pathogenesis of osteonecrosis of the femoral head (ONFH). In this study, we investigated the association of IGFBP3 gene polymorphism and its protein expression with the development of ONFH to further explore its molecular pathogenesis. Ligase detection reactions and enzyme-linked immunosorbent assay were used to detect the polymorphisms of rs2453839[C/T] and rs3110697[A/G] and the serum protein expression of IGFBP3 gene in 182 cases and 179 controls, respectively. The serum lipids level was also measured by automatic biochemistry analyzer. The results revealed that the recessive model of rs3110697 and the dominant model of rs2453839 were significantly associated with the increased risk of ONFH (p = 0.048, p = 0.047, respectively). The genotypes of rs2453839 were also significantly related to the clinical stages of ONFH (p = 0.017). More importantly, the serum protein expression of IGFBP3 and insulin-like growth factor 1 (IGF1) in the ONFH group were statistically increased compared with the control group (p = 0.044, p = 0.007). The serum triglyceride and low-density lipoprotein cholesterol level in the ONFH group were significantly higher than the control group (p = 0.01, p = 0.005, respectively), but the serum high-density lipoprotein cholesterol level of the ONFH group was dramatically lower than the control group (p = 0.0001). Our results showed that both the gene polymorphisms of IGFBP3 and the abnormal protein expression of serum IGFBP3 and IGF1 closely associated with the development of ONFH.