Pyrogallol from Spirogyra neglecta Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3ß/ß-catenin Signaling Pathway.

Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. The high proliferation and metastasis rates have made CRPC one of the most challenging types of cancer for medical practitioners and researchers. In this study, the anti-cancer properties and inhibition of CRPC progression by S. neglecta extract and its active constituents were determined using two CRPC cell lines, DU145 and PC3. The ethyl acetate fraction of S. neglecta (SnEA) was obtained using a solvent-partitioned extraction technique. The active constituents of SnEA were then determined using the HPLC technique, which showed that SnEA mainly contained syringic acid, pyrogallol, and p-coumaric acid phenolic compounds. After the determination of cytotoxic properties using the SRB assay, it was found that pyrogallol, but not the other two major compounds of SnEA, displayed promising anti-cancer properties in both CRPC cell lines. SnEA and pyrogallol were then further investigated for their anti-proliferation and apoptotic induction properties using propidium iodide and Annexin V staining. The results showed that SnEA and pyrogallol inhibited both DU145 and PC3 cell proliferation by inducing cell cycle arrest in the G0/G1 phase and significantly decreased the expression of cell cycle regulator proteins (cyclin D1, cyclin E1, CDK-2, and CDK-4, p < 0.001). SnEA and pyrogallol treatments also promoted apoptosis in both types of CRPC cells through significantly downregulating anti-apoptotic proteins (survivin, Bcl-2, and Bcl-xl, p < 0.001) and upregulating apoptotic proteins (cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP-1, p < 0.001). Mechanistic study demonstrated that SnEA and pyrogallol inactivated the Akt signaling pathway leading to enhancement of the active form of GSK-3ß in CRPC cell lines. Therefore, the phosphorylation of ß-catenin was increased, which caused degradation of the protein, resulting in a downregulation of ß-catenin (unphosphorylated form) transcriptional factor activity. The current results reflect the potential impact of S. neglecta extract and pyrogallol on the management of castration-resistant prostate cancer.

Sequencing of Camelina neglecta, a diploid progenitor of the hexaploid oilseed Camelina sativa.

Camelina neglecta is a diploid species from the genus Camelina, which includes the versatile oilseed Camelina sativa. These species are closely related to Arabidopsis thaliana and the economically important Brassica crop species, making this genus a useful platform to dissect traits of agronomic importance while providing a tool to study the evolution of polyploids. A highly contiguous chromosome-level genome sequence of C. neglecta with an N50 size of 29.1 Mb was generated utilizing Pacific Biosciences (PacBio, Menlo Park, CA) long-read sequencing followed by chromosome conformation phasing. Comparison of the genome with that of C. sativa shows remarkable coincidence with subgenome 1 of the hexaploid, with only one major chromosomal rearrangement separating the two. Synonymous substitution rate analysis of the predicted 34 061 genes suggested subgenome 1 of C. sativa directly descended from C. neglecta around 1.2 mya. Higher functional divergence of genes in the hexaploid as evidenced by the greater number of unique orthogroups, and differential composition of resistant gene analogs, might suggest an immediate adaptation strategy after genome merger. The absence of genome bias in gene fractionation among the subgenomes of C. sativa in comparison with C. neglecta, and the complete lack of fractionation of meiosis-specific genes attests to the neopolyploid status of C. sativa. The assembled genome will provide a tool to further study genome evolution processes in the Camelina genus and potentially allow for the identification and exploitation of novel variation for Camelina crop improvement.

Marine Bioprospecting: Enzymes and Stress Proteins from the Sea Anemones Anthopleura dowii and Lebrunia neglecta.

The bioprospecting of sea anemone tissues and secretions has revealed that they are natural libraries of polypeptides with diverse biological activities that can be utilized to develop of biotechnological tools with potential medical and industrial applications. This study conducted a proteomic analysis of crude venom extracts from Anthopleura dowii Verrill, 1869, and Lebrunia neglecta Duchassaing & Michelotti, 1860. The obtained data allowed us to identify 201 polypeptides, of which 39% were present in both extracts. Among the obtained sequences, hydrolase-type enzymes, oxidoreductases, transferases, heat shock proteins, adhesion proteins, and protease inhibitors, among others, were identified. Interaction analysis and functional annotation indicated that these proteins are primarily involved in endoplasmic reticulum metabolic processes such as carbon metabolism and protein processing. In addition, several proteins related to oxidative stress were identified, including superoxide dismutase, peroxiredoxins, thioredoxin, and glutathione oxidase. Our results provide novel information on the polypeptide composition of the crude venom extract from sea anemones, which can be utilized to develop molecules for therapeutic tools and industrial applications.

The Phytochemical Profile and Biological Activity of Malva neglecta Wallr. in Surgically Induced Endometriosis Model in Rats.

Leaves and aerial parts of Malva neglecta Wallr. have been traditionally used in Anatolia for the treatment of pain, inflammation, hemorrhoids, renal stones, constipation, and infertility. This study investigated the effects of M. neglecta leaves in a rat endometriosis model. The dried plant material was extracted with n-hexane, ethyl acetate, and methanol, successively. Experimental endometriosis was surgically induced in six-week-old female, non-pregnant, Wistar albino rats by autotransplant of endometrial tissue to the abdominal wall. After twenty-eight days, rats were evaluated for a second laparotomy. Endometrial foci areas were assessed, and intraabdominal adhesions were scored. Rats were divided into five groups as control, n-hexane, ethyl acetate, methanol, and aqueous extracts, as well as reference. At the end of the treatment, all rats were sacrificed and endometriotic foci areas and intraabdominal adhesions were re-evaluated and compared with the previous findings. Moreover, peritoneal fluid was collected to detect tumor necrosis factor- α (TNF-α), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels, and cDNA synthesis, and a quantitative real-time polymerase chain reaction (PCR) test was done. The phytochemical content of the most active extract was determined using High-Performance Liquid Chromatography (HPLC). Both endometrial volume and adhesion score decreased significantly in the group treated with methanol extract. In addition, significant decreases were observed in TNF-α, VEGF, and IL-6 levels in animals administered methanol extract. HPLC results showed that the activity caused by the methanol extract of M. neglecta was due to the polyphenols. Taken together, these novel findings indicate that M. neglecta may be a promising alternative for the treatment of endometriosis.

Ameliorating Effect of Malva neglecta Wallr on Obesity and Diabetes in Wistar Rats: A Mechanistic Study.

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 - 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 - 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds.

Dermatosis neglecta.

Dermatosis neglecta (DN) is a frequently underdiagnosed and under-reported dermatological entity, which occurs due to unconscious neglect of self-cleaning in individuals with some underlying physical or mental pathology. The lack of cleaning leads to accumulation of scales, dirt, sweat and sebum compacted together in the skin. Owing to its asymptomatic nature, diverse background and deceptive clinical presentation, DN is often missed or misdiagnosed by physicians. Awareness and recognition of this condition is essential to avoid unnecessary diagnostic and treatment procedures. The focus of this review article is to provide insights into this condition. We also intend to develop an algorithm for practical approach to a clinical diagnosis of dirt-like dermatoses with reasonable accuracy. A few interesting cases of DN encountered in our institution are included in this article.

Trophic niche of Australian cownose rays (Rhinoptera neglecta) and whitespotted eagle rays (Aetobatus ocellatus) along the east coast of Australia.

Australian cownose rays (Rhinoptera neglecta) and whitespotted eagle rays (Aetobatus ocellatus) are large myliobatiform rays that co-occur off temperate eastern Australia. Here, we performed stable-isotope analyses (δ13 C, δ15 N and δ34 S) on fin clips of both species to gain insights into their trophic interactions and isotopic niches, and assess the effect of preservation (ethanol-stored versus frozen) on isotopic values of fin-clip tissue of R. neglecta. Linear mixed models identified species as the main factor contributing to variation among δ15 N and δ34 S values, and disc width for δ13 C. Bayesian ecological niche modelling indicated a 57.4% to 74.5% overlap of trophic niches, with the niche of R. neglecta being smaller and more constrained. Because values of δ13 C were similar between species, variation in isotopic niches were due to differences in δ15 N and δ34 S values. Linear mixed models failed to detect differences in isotopic values of ethanol-stored and frozen fin tissue of R. neglecta. This study provides the first examination of the trophic ecology of R. neglecta and the comparison of isotopic niche with A. ocellatus, which will facilitate future research into the trophic interactions of these species and aid better resource management.

A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus.

Four new chromene derivatives, pestalotiochromenoic acids A - D (1, 2, 4, and 5), and two new chromone derivatives, pestalotiochromones A and B (6 and 7), were obtained from the marine alga-derived fungus Pestalotiopsis neglecta SCSIO41403, as well as a reported derivate named piperochromenoic acid (3) with its configuration determined for the first time. Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic analyses, while the absolute configurations were established by theoretical NMR and electronic circular dichroism (ECD) calculation, including Mo2(OAc)4-induced ECD experiments. Those chromene and chromone derivatives displayed weak cytotoxicity, but showed obvious liver X receptors (LXRs) modulatory activities, by in vitro tests on the expression of LXRα, LXRß and theirtarget gene ABCA1, as well as in silico docking analysis. Moreover, the high binding affinities between pestalotiochromone A (6) and LXRα, revealed by surface plasmon resonance (SPR) with the dissociation equilibrium constant (KD) value of 6.2 µM, demonstrated 6 could act as a new potential LXR agonist.

New pestallic acids and diphenylketone derivatives from the marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403.

Three new carboxylic acid derivatives, pestallic acids F and G (1 and 2), pestalotiopyrone N (3), and a new diphenylketone derivative named neopestalone (5) were obtained from the liquid cultures of marine alga-derived endophytic fungus Pestalotiopsis neglecta SCSIO41403, along with six known compounds (4, 6-10). The structures of those new compounds were elucidated mainly by analysis of their NMR and MS data. The isolated compounds were evaluated for their anti-Dengue virus and COX-2 inhibitory activities, and two diphenylketone derivatives (5 and 6) exhibited obvious COX-2 inhibitory activities, with the IC50 values being 5.8 and 3.4 µM, respectively.

Ene-yne Hydroquinones from a Marine-derived Strain of the Fungus Pestalotiopsis neglecta with Effects on Liver X Receptor Alpha.

Seven unusual new ene-yne hydroquinones (1-3, 5-8), including three rare glycosylated derivatives named pestalotioquinosides A-C (6-8), were obtained from the marine-derived strain SCSIO41403 of the fungus Pestalotiopsis neglecta. Their structures including absolute configurations were elucidated by spectroscopic analysis and induced electronic circular dichroism experiments. In silico molecular docking and in vitro surface plasmon resonance studies showed that pestalotioquinoside C (8) could act as a liver X receptor alpha (LXRα) modulator. Further study showed that LXR target gene ABCA1 was significantly upregulated by 8, which revealed 8 as a potential LXRα agonist.