Natural bioactive compounds from marine fungi (2017-2020).

Secondary metabolites generated by marine fungi have relatively small molecular weights and excellent activities and have become an important source for developing drug lead compounds. The review summarizes the structures of novel small-molecule compounds derived from marine fungi in recent years; introduces representative monomers in antimicrobial, antitumor, anti-viral, and anti-neuritis aspects; and discusses their biological activities and molecular mechanisms. This review will act as a guide for further discovering marine-derived drugs with novel chemical structures and specific targeting mechanisms.

Prevalence and risk factors of nocturnal enuresis among children ages 5-12 years in Xi'an, China: a cross-sectional study.

BACKGROUND: Nocturnal enuresis (NE) has a negative impact on children's health and imposes a long-term burden on families. With economic development and cultural improvements, parents and medical professionals pay more attention to NE. The aim of this study was to investigate the prevalence and risk factors of NE among children ages 5-12 years in Xi'an, China. METHODS: A stratified cluster sampling method was used to conduct a cross-sectional study of NE in 10 kindergartens and 20 primary schools in Xi'an. We used univariate analysis to compare the prevalences of characteristics such as gender, duration of disposable diaper (DD) use, toilet training onset time, daily living habits, academic performance, and family history of NE. Logistic regression analysis was used to calculate odds ratio and to determine risk factors of NE. RESULTS: The study included 6568 children ages 5-12 years, of which 262 (3.99%) had NE. The prevalence rates of NE decreased with age, with the highest prevalence at age 5 (9.09% for boys; 6.03% for girls). However, the prevalence increased with duration of DD use. Children experienced more NE if they never accepted toilet training (7.83%) or if they drank sugary beverages during the day (5.36%). Sleep disorders, sweets intake, drinking low amounts of plain water during the day, and family history of NE, were statistically associated with NE. CONCLUSION: NE was closely associated with a family history of NE, being male, long-term use of DD, delayed toilet training, drinking sugary beverages and/or consuming little plain water, and sleep disorders. A supportive parental attitude towards NE and timely medical treatment can improve the quality of life of enuretic children.

Cloning and Characterization of ifitm1 and ifitm3 Expression During Early Zebrafish Development - CORRIGENDUM.

The authors apologise for errors in the corresponding authors details given on page 1 of the article. Below is the correct information of the corresponding author and email address : 1) Wei-Wei Xue, Huan-Nan Wang, Zhi-Meng Wang, Meng-Xi Qiu, Jing Che, Feng-Jiao Deng* and Jiang-Dong Liu* 2) *All correspondence to: Feng-Jiao Deng and Jiang-Dong Liu. e-mail: fish4@whu.edu.cn 3) All authors are from the same one laboratory. The second laboratory was superfluous and should be deleted.

Cloning and characterization of ifitm1 and ifitm3 expression during early zebrafish development.

The family of interferon-inducible transmembrane proteins (IFITMs) plays a crucial role in inhibiting proliferation, promoting homotypic cell adhesion and mediating germ cell development. In the present study, the full-length cDNAs of zebrafish ifitm1 (744 bp) and ifitm3 (702 bp) were obtained by rapid amplification of cDNA ends (RACE). Reverse transcription polymerase chain reaction (RT-PCR) analysis showed that ifitm1 mRNA was expressed in the ovary, testis, brain, muscle, liver and kidney, while ifitm3 mRNA was only detected in the ovary. Based on in situ hybridization, ifitm1 mRNA was found to be strongly expressed in the ooplasm from stage I to stage II and ifitm3 mRNA was also strongly expressed in the ooplasm from stage I to stage II, furthermore ifitm3 expression ultimately localized to the cortex region beneath the plasma membrane of stage IV oocytes. During development, ifitm1 expression was initially detected in the enveloping layer cells and deep layer cells of shield stage embryos. Then, throughout the segmentation phase (10.25-24 hours post-fertilization (hpf)), ifitm1 expression was mainly detected in the head, trunk and tail regions. Unlike ifitm1, ifitm3 expression was initially detected in sphere stage embryos and was then broadly expressed throughout the embryo from the 70% epiboly stage to 24 hpf. Interestingly, ifitm3 was also expressed in primordial germ cells (PGCs) from the bud stage to 24 hpf. This expression analysis indicates that zebrafish ifitm1 may play a critical role in early organogenesis and may perform immune or hematopoietic functions and ifitm3 might be necessary for PGC migration and the formation of female germ cells.

[Structural characterization and spectroscopic analysis of the aloin].

Aloe is widely used in various fields for its rich polysaccharides, proteins, amino acids, vitamins, active enzymes and trace beneficial elements to human body. However, the main active ingredient aloin is also an allergenic ingredient, which even may cause a severe allergic reaction In this study, infrared spectroscopy, Raman spectroscopy applied to the structural characterization of the aloin Density functional theory (DFT) is applied to the theoretical calculations using the B3LYP/6-31G (d) basis set vibration, which was helpful to understand the aloin molecular vibrational frequency. By comparing we choose the optimal experimental condition for water as solvent under alkaline conditions, the detection limit of the Aloin can reach a level of 5 ppm, which can be considered the theoretical basis for rapid detection of aloin content.

Molecular mechanism of angiogenesis for cerebral infarction rats by acupuncture intervention based on sonic hedgehog signaling pathway.

BACKGROUND: To study the factors of the Sonic Hedgehog (Shh) signaling pathway after permanent cerebral ischemic and the effects by acupuncture. METHODS: Male Wistar rats were divided into Electro-acupuncture (EA) group, Model Control (MC) group, and blank control (Control) group. EA and MC were divided into 9 phases, namely 1 h, 3 h, 6 h, 9 h, 12 h, 24 h, 3 d, 7 d, and 12 d after the operation. The neurological deficits and permanent cerebral ischemic volume were observed. The immunofluorescence method was used to examine the angiogenesis. (Polymerase Chain Reaction) PCR and (Immunohistochemistry) IHC were used to test the changes in Shh, Ptch, Smo, and Gli2 mRNA and proteins. RESULTS: The neurological severity scores (NSS) of the Control was 0, the score of the EA group was less than that of the MC. The cerebral permanent ischemic volume of the Control was 0 %, and the EA group's was smaller than that of the MC. The expression of copositive cells in the EA group was higher than the MC's from 12 h to 12 d, and the EA group had more peripheral blood vessels. The rat brain expressions of Shh, Ptch, Smo and Gli2 mRNA and proteins in the MC was higher than that of the Control, the rat brain expression of the EA group was higher than that of the MC. CONCLUSIONS: EA can upregulate the expression of the Shh signaling pathway factors, thereby promoting angiogenesis.

Cytotoxic alkaloids from the fruit pods of Macleaya microcarpa.

19 compounds, including seven previously undescribed alkaloids ((-)-macleayin K (1), (+)-macleayin K (2), macleayin M (3), macleayin N (4), macleayin L (5), macleayin O (6), oxohydrastinine A (7), one new natural product (8), and 11 known compounds, were isolated from the fruit pods of Macleaya microcarpa. Their structures were defined based on NMR, HRESIMS, and electronic circular dichroism (ECD) data. A network pharmacology approach combined with molecular docking and in vitro validation was performed to determine the bioactivity, key targets of the 19 compounds against breast cancer (BC) and cervical cancer (CC). EGFR and PIK3CA could become potential therapeutic targets based a network pharmacology. Moreover, molecular docking suggested that the 19 compounds combined well with EGFR and PIK3CA, respectively. Their cytotoxicity of selected compounds was tested against the MCF-7 and HeLa cells, and the preliminary structure-activity relationship is discussed. Compounds 1 (IC50: 6.00 µM) and 2 (IC50: 6.82 µM) exhibited strong inhibitory activity against the HeLa cells and are worthy of further study.

Identification and characterization of the pumilio-2 expressed in zebrafish embryos and adult tissues.

Pumilio proteins regulate the translation of specific proteins required for germ cell development and morphogenesis. In the present study, we have identified the pumilio-2 in zebrafish and analyze its expression in adult tissues and early embryos. Pumilio-2 codes for the full-length Pumilio-2 protein and contains a PUF-domain. When compared to the mammalian and avian Pumilio-2 proteins, zebrafish Pumilio-2 protein was found to contain an additional sequence of 24 amino acid residues within the PUF-domain. Zebrafish pumilio-2 mRNA is expressed in the ovary, testis, liver, kidney and brain but is absent in the heart and muscle as detected by RT-PCR. The results of in situ hybridization indicate that transcripts of pumilio-2 are distributed in all blastomeres from the 1-cell stage to the sphere stage and accumulate in the head and tail during the 60%-epiboly and 3-somite stages. Transcripts were also detected in the brain and neural tube of the 24 h post-fertilization (hpf) embryos. Western blot analyses indicate that the Pumilio-2 protein is strongly expressed in the ovary, testis and brain but not in other tissues. These data suggest that pumilio-2 plays an important role in the development of the zebrafish germ cells and nervous system.

Inhibitory effects of albuterol and fenoterol on RANTES and IP-10 expression in bronchial epithelial cells.

Short-acting ß2-adrenoreceptor agonist (SABA) is the major asthma reliever as indicated in the GINA guidelines. Regulated on activation, normal T expressed and secreted (RANTES) is a chemokine that attracts eosinophils, mast cells, and basophils toward site of allergic inflammation. Interferon γ-inducible protein (IP)-10 is a Th1-related chemokine that is also important in asthmatic inflammation and also involved in our immune defense against pathogens. Bronchial epithelial cells are first-line barrier against invasive pathogen and also have immunomodulatory function. However, whether albuterol and fenoterol (two SABAs) have modulatory effects on RANTES and IP-10 expression in bronchial epithelial cells is unknown. The human bronchial epithelial cell lines, BEAS-2B cells, were pre-treated with different concentrations of albuterol, fenoterol or dibutyryl-cAMP (a cyclic AMP analog) before polyinosinic-polycytidylic acid (poly I:C) stimulation. In some condition, BEAS-2B cells were pre-treated with ICI-118551, a selective ß2-adrenoreceptor antagonist, 30 min before albuterol or fenoterol treatment. The levels of RANTES and IP-10 were measured by ELISA. Intracellular signaling was investigated using cAMP assay, mitogen-activated protein kinase (MAPK) inhibitor, nuclear factor (NF)-κB inhibitor, and western blot. Albuterol and fenoterol suppressed poly I:C-induced RANTES and IP-10 expression of BEAS-2B cells. ICI-118551 could partly reverse the suppressive effects of albuterol and fenoterol on RANTES and IP-10 expression. Albuterol and fenoterol increased intracellular cAMP levels. Dibutyryl-cAMP conferred the similar effects of albuterol and fenoterol. Western blot revealed that albuterol suppressed p-ERK, p-JNK and pp38, and also their associated kinase expression. Albuterol had no effect on pp65 expression. Albuterol and fenoterol could suppress poly I:C-induced RANTES and IP-10 expression in human bronchial epithelial cells via at least partly the ß2-adrenoreceptor-cAMP and the MAPK pathways, implicating that albuterol and fenoterol could exert anti-inflammatory effect and benefit asthmatic patients by suppressing RANTES and IP-10 expression. However, these suppressive effects of albuterol and fenoterol may inhibit the defense against viral infection.

Cloning and characterization of the SSB-1 and SSB-4 genes expressed in zebrafish gonads.

The protein of the gustavus (gus) gene has a typical SOCS box domain and repeats in the splA and RyR (SPRY) domains. GUS can interact with Vasa and is necessary for the specification of germ cells. We cloned two zebrafish genes, SSB-1 and SSB-4 (SPRY domain SOCS box proteins). Phylogenetic analysis shows that zebrafish SSB-1 and SSB-4 are clustered into clades of SSB-1-like and SSB-4-like genes from other species. RT-PCR analysis of tissues revealed that zebrafish SSB-1 and -4 are expressed in the ovary and testis. We investigated the spatial expression patterns of zebrafish SSB-1 and -4 in embryos from the two-cell stage to 72 h postfertilization (hpf) using whole-mount in situ hybridization. SSB-1 and -4 transcripts were present in all blastomeres during the early embryonic stages, but the genes differ in their expression pattern. SSB-4 mRNA was located in the region of the primordial germ cells in 24 and 72 hpf embryos, but SSB-1 mRNA was not detected at these stages. We hypothesize that SSB-4 plays a role in the early development of germ cells.

Schur convexity of the generalized geometric Bonferroni mean and the relevant inequalities.

In this paper, we discuss the Schur convexity, Schur geometric convexity and Schur harmonic convexity of the generalized geometric Bonferroni mean. Some inequalities related to the generalized geometric Bonferroni mean are established to illustrate the applications of the obtained results.

Majorization involving the cyclic moving average.

We solve an open problem on some majorization inequalities involving the cyclic moving average.

Down-regulation of TGFbeta1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats.

Pretreatment with a low dose of bacterial endotoxin (lipopolysaccharide, LPS) caused the reduction of cytochrome P450 (CYP) enzymes and inflammatory factors which are capable of protecting the liver from a lethal LPS challenge. However, the effects of LPS pretreatment on the expression of transforming growth factor beta1 (TGFbeta1) and leptin in thioacetamide (TAA)-induced liver fibrosis remain unknown. In this study, Sprague-Dawley rats were pretreated intraperitoneally with LPS (5 mg/kg body weight) for 24 h, and subsequently treated with TAA (200 mg/kg body weight/ 3 days) for 1 month to examine the effects of LPS on TAA-injured rats. LPS pretreatment was associated with lower granulation and lower (P < 0.05) GOT/GPT than in TAA-injured rats. The LPS-pretreated group had less collagen (Sirius red histochemical staining). Semiquantitative RT-PCR showed that the levels of collagen 3 and TGFbeta1 mRNAs were lower (P < 0.05) in the liver of LPS-pretreated rats than in TAA-injured rats. TGFbetaRI mRNA in the liver of LPS-pretreated rats exceeded (P < 0.05) that in TAA-injured rats. LPS pretreatment reduced the leptin content (Western blot) below that of TAA-injured rats. These results imply that LPS pretreatment (endotoxin tolerance) alleviates the TAA-induced liver fibrosis of rats by reducing TGFbeta1 and leptin content.

Toona sinensis Roem (Meliaceae) leaf extract alleviates liver fibrosis via reducing TGFbeta1 and collagen.

Toona sinensis Roem (TS) leaf tea as a health food for the improvement of blood sugar and hypertension has been demonstrated. Thioacetamide (TAA), a hepatotoxin, causes the progression of liver fibrosis. In this study, we tested the effects of TS leaf on TAA-induced liver injury. TAA (200mg/kg Bwt/3 days, i.p.) treated rats were orally administrated with TS leaf extract (1g/kg Bwt/10 days) three times. After 30 days treatment, the morphological data showed that TS leaf extract given to TAA-treated rats had less liver fibrosis. The GOT/GPT, collagen 1 and collagen 3 mRNAs of livers in TAA-treated rats were elevated when compared to normal rats. The improvements of GOT/GPT, collagen 1 and collagen 3 mRNAs were shown in the TS leaf extract given to TAA-treated rats. TS leaf extract given to TAA-treated rats showed higher levels of cytochrome P450 (1A1, 2A and reductase) than those of TAA-treated rats. Compared to the TAA-treated group, TGFbeta1 mRNA (RT-PCR) was decreased with an increase of TGFbetaR1 protein (western blot) in the TS leaf extract given to TAA-treated rats. The decreased tendency of FGFR2 was found in the TS leaf extract given to TAA-treated rats. The result implies that TS leaf possesses beneficial effects on liver injury through increments of detoxification and the metabolic pathway.

Schur-convexity, Schur-geometric and Schur-harmonic convexity for a composite function of complete symmetric function.

In this paper, using the properties of Schur-convex function, Schur-geometrically convex function and Schur-harmonically convex function, we provide much simpler proofs of the Schur-convexity, Schur-geometric convexity and Schur-harmonic convexity for a composite function of the complete symmetric function.

Effects of vitamin D3 on the expression of growth-related oncogene-α in THP-1 cells and human primary monocytes.

Asthma and many autoimmune diseases, such as systemic lupus erythematosus, have been reported to associate with vitamin D deficiency recently. Growth-related oncogene-α (GRO-α)/CXCL1, a neutrophil-related chemokine, have an important influence on the chronic inflammation of these diseases. It is unknown whether vitamin D has regulatory effects on GRO-α expression in human monocytes. To this end, the human monocytic leukemia cell line, THP-1, and human primary monocytes were pretreated with 1α, 25-(OH)(2)D(3), and was stimulated with lipopolysaccharide (LPS). Supernatants were collected to determine GRO-α level by ELISA. The intracellular signaling was investigated by nuclear factor (NF)-κB inhibitor, the mitogen-activated protein kinase (MAPK) inhibitors, and Western blot. In our studies, LPS-induced GRO-α was significantly enhanced in THP-1 cells, but suppressed in human primary monocytes by 1α, 25-(OH)(2)D(3). Western blotting revealed that 1α, 25-(OH)(2)D(3) increased LPS-stimulated pp38 expression in THP-1 cells, but suppressed LPS-stimulated pMEK1/2-pERK and pJNK in human primary monocytes. In conclusion, the opposite effects of 1α, 25-(OH)(2)D(3) on GRO-α expression in THP-1 cells and human primary monocytes indicated that the data from THP-1 cells should be further confirmed by human primary monocytes. Moreover, vitamin D3 may have potentiality in treating GRO-α-related chronic inflammatory diseases, like asthma and autoimmune diseases.

Suppressive effects of imidapril on Th1- and Th2-related chemokines in monocytes.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are used to control hypertension and are superior to other antihypertensive agents in protecting the progressive deterioration of autoimmune-related nephritis. An imbalance of T helper 1 (Th1)/Th2 is thought to contribute to the pathogenesis of autoimmune diseases and their related glomerulonephritis. I-309 is a Th2-related chemokine involved in the recruitment of Th2 cells toward Th2-related inflammation. Tumor necrosis factor α (TNF-α) and Th1-related chemokines, interferon-inducible protein 10 (IP-10)/CXCL10 are also involved in autoimmune glomerulonephritis. However, the modulatory effects and the mechanisms of ACEIs on TNF-α and Th1- and Th2-related chemokines in monocytes remain poorly defined. OBJECTIVE: We investigated the effects of imidapril and perindopril, 2 ACEIs, on the expression of IP-10, I-309, and TNF-α in human monocytes and also the associated intracellular mechanism. RESULTS: Imidapril and perindopril significantly downregulated lipopolysaccharide (LPS)-induced TNF-α, I-309, and IP-10 in THP-1 cells and human primary monocytes. All 3 mitogen-activated protein kinase inhibitors suppressed LPS-induced TNF-α and I-309 expression in human primary monocytes. Only extracellular signal-regulated kinases and c-Jun N-terminal kinases (JNK) mitogen-activated protein kinase inhibitors suppressed LPS-induced IP-10 expression. Lipopolysaccharide-induced mitogen-activated protein kinase kinase 4 (MKK4), p-JNK, and c-Jun expression in human primary monocytes was suppressed by imidapril. CONCLUSIONS: These data demonstrate that ACEI is effective in downregulating LPS-induced TNF-α, I-309, and IP-10, which play important roles in the pathogenesis of inflammation. Its suppressive effect on TNF-α, I-309, and IP-10 may, at least in part, involve the down-regulation of LPS-induced MKK4-JNK-c-Jun expression.

Effects of PGI2 analogues on Th1- and Th2-related chemokines in monocytes via epigenetic regulation.

Chemokines play important roles in asthma. Prostaglandin I(2) (PGI(2)) analogue is recently suggested as a candidate for treating asthma. However, the effects of PGI(2) analogues on the expression of Th1- and Th2-related chemokines are unknown. To this end, we investigated the in vitro effects of PGI(2) analogues on the expression of Th1-related chemokine interferon-γ-inducible protein-10 (IP-10/CXCL10) and Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) in human monocytes. The human monocytes were pretreated with iloprost and treprostinil before lipopolysaccharide (LPS) stimulation. IP-10 and MDC were measured by ELISA. Intracellular signaling was investigated by cyclic adenosine monophosphate (cAMP) assay, western blot and chromatin immunoprecipitation. PGI(2) analogues enhanced MDC, but suppressed IP-10 expression in LPS-stimulated monocytes. These effects were reversed by the I prostanoid (IP) receptor antagonist (CAY10449), peroxisomal proliferators-activated receptor (PPAR)-α antagonist (GW6741) and PPAR-γ antagonist (GW9662). PGI(2) analogues increased intracellular cAMP levels. Forskolin, an adenyl cyclase activator, conferred similar effects. PGI(2) analogue-enhanced MDC expression was reduced by nuclear factor (NF) κB inhibitor (BAY 117085) and mitogen-activated protein kinase (MAPK)-p38 inhibitor (SB203580). PGI(2) analogues up-regulated phospho-p65 and phospho-p38 but down-regulated phospho-ERK expression. Iloprost enhanced H3 acetylation in MDC promoter area and suppressed H3 acetylation, H3K4, and H3K36 trimethylation in IP-10 promoter area. PGI(2) analogues enhanced MDC expression via the I prostanoid-receptor-cAMP, PPAR-α and PPAR-γ, NFκB-p65, MAPK-p38-ATF2 pathways and increasing histone acetylation, and suppressed IP-10 expression via the IP-receptor-cAMP, PPAR-γ, MAPK-ERK-ELK1 pathways and inhibiting histone acetylation and trimethylation in LPS-stimulated monocytes. PGI(2) analogues may therefore increase Th2 recruitment and inflammation.

Natural flavone kaempferol suppresses chemokines expression in human monocyte THP-1 cells through MAPK pathways.

There is increasing evidence that daily intake of flavonoids reduced severity and prevalence of allergic diseases. However, the mechanism of its antiinflammatory effects in allergic diseases remains uncertain. Kaempferol, which belongs to the flavone group, is a strong antioxidant among natural flavonoids and is the essential component of many beverages and vegetables. Because chemokine is one of the key mediators in allergic inflammatory process, we investigated the effect of kaempferol on chemokines expression in monocytes. Our data demonstrated that kaempferol significantly inhibited the lipopolysaccharide (LPS)-induced production of monocyte-derived chemokine (MDC), interferon gamma-induced protein 10 (IP-10), and interleukin-8 (IL-8) in THP-1 cells. Growth-related oncogene-α (GRO-α) was also suppressed at a higher concentration. We also found that kaempferol was able to suppress LPS-induced mitogen-activated protein kinase (MAPK) pathways, as well as the phosphorylation of upstream c-raf and MEK1/2. In brief, kaempferol suppressed LPS-induced T helper 1 (Th1), T helper 2 (Th2), and neutrophil-related chemokines production in monocytes might be via the MAPK pathways.

The natural flavonoid apigenin suppresses Th1- and Th2-related chemokine production by human monocyte THP-1 cells through mitogen-activated protein kinase pathways.

Dietary flavonoids have various biological functions, and there is increasing evidence that reduced prevalence and severity of allergic reactions are associated with the intake of flavonoids. Among natural flavonoids, apigenin is a potent anti-inflammatory agent. However, the mechanisms of apigenin's effect remain uncertain. Monocyte-derived chemokine (MDC) plays a pivotal role in recruiting T-helper (Th) 2 cells in the allergic inflammation process. In the late phase of allergic inflammation, the Th1 chemokine interferon-inducible protein 10 (IP-10) has also been found in elevated levels in the bronchial alveolar fluid of asthmatic children. We used human THP-1 monocyte cells, pretreated with or without apigenin, prior to lipopolysaccharide stimulation. By means of enzyme-linked immunosorbent assay, we found that apigenin inhibited production of both MDC and IP-10 by THP-1 cells and that the suppressive effect of apigenin was not reversed by the estrogen receptor antagonist ICI182780. The p65 phosphorylation of nuclear factor kappaB remained unaffected, but the phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase mitogen-activated protein kinase pathways were all blocked. We found that inhibition of c-raf phosphorylation might be the target of apigenin's anti-inflammation property.