Preliminary Biological Data Research Articles

Preliminary biological data of Sahel wetland ecosystems in Burkina Faso: Implications for ecological health assessment

Birds, amphibians, fish, and macroinvertebrates are useful indicators of ecological conditions and ensure considerable conservation value and tools for decision making in management of wetland ecosystems. However, the use of these organisms to monitor wetland ecosystems has rarely been explored in Western Africa. Whereas, we are currently facing to growing multiple anthropogenic pressures and climate warming that impact negatively our wetlands and the biodiversity. Notably, there is an urgent need of cost-effective tools for wetland ecosystems health assessment in Burkina Faso. In this study, we examined the taxonomic composition of birds, amphibians, fish, and macroinvertebrates and explored their potential use for monitoring wetland ecosystems. From our findings, measures of taxa composition and diversity respond to the gradients of anthropogenic alterations. Our results revealed that the highest diversity of fish and macroinvertebrates taxa was recorded in protected sites, whereas the lowest diversity was obtained in degraded sites. Additionally, the findings showed a strong and positive correlation between macroinvertebrates taxa and key water variables, whereas fish taxa were strongly correlated to xylal (deadwood) substrates. Most of bird’s species were recorded in tree-shrubs, and amphibians of protected wetlands were distinguished by identifying indicator taxa through indicator value index. African wetland ecosystems and biodiversity may be sustainably preserved through responsive monitoring programs of wetlands by limnologists.

Synthesis and lipid-lowering effects of phospholipid-polyunsaturated fatty acids (PL-PUFA) in high fat diet induced obese mice

In this study, phospholipid-polyunsaturated fatty acids (PL-PUFA), which was a glycerophosphamide analogue containing DHA/DPA of phospholipid derivative, was synthesized from algae oil in two steps. The compound of P1/P2 in the PL-PUFA was isolated through preparative HPLC with the contained of 70.24%, and 23.86%, respectively. Intragastric administration of 200 mg/kg PL-PUFA can strongly suppress net body weight gain and obesity-related hyperlipidemia. The net body-weight gain of treatment group was decreased 5.18% than that of the normal group. Serum TC levels of treatment group were significantly suppressed, and it was reduced by 55.95%. However, for HDL-C levels, none of the model group and treatment group showed significant differences comparing with the normal group. The preliminary biological data of PL-PUFA in this work strongly supports our belief that the analogue glycerophosphamide structure containing with ω-3 PUFAs is providing a beneficial effect on lowering serum lipids and TGs.

LB952 A phase 1 trial of DSG3-CAART cells in mucosal-dominant pemphigus vulgaris (mPV) patients: Preliminary data

mPV is mediated by anti-desmoglein 3 (DSG3) autoantibodies (Abs) and treated with chronic, broad immunosuppressive therapy. Based on the long-lasting remission of B cell cancers with chimeric antigen receptor T (CART) cells, we genetically modified autologous T cells to express chimeric autoantibody receptors comprising the DSG3 autoantigen (DSG3-CAART) to target only anti-DSG3 B cells. In this ongoing open-label study of adults with active, anti-DSG3 Ab-positive mPV, subjects are assigned to receive 2e7,1e8, 5e8, 2.5e9 and 5-7.5e9 DSG3-CAART after discontinuing immunosuppressives or tapering steroids. The primary endpoint is related adverse events (AEs) within 3 months of infusion. Screening characteristics of the 9 subjects in the first 3 cohorts who have completed 3 months (median (range)): 67% female; age 53y (32-70); disease duration 4.0y (0.3-15.4); PDAI 12 (1-20); anti-DSG3 Ab 104 U/mL (51-169). Prior medications: prednisone (9), rituximab (6) and mycophenolate (6). No dose-limiting toxicities or serious AEs were observed over 3 months. Disease was clear or almost clear (PDAI 0-1) in 0, 1, 2, 5 and 3 of the 9 subjects at screening, baseline and 1, 2 and 3 months after treatment, respectively. Anti-DSG3 Ab levels through month 3 were increased, stable (+/-20%) or decreased in 3, 5 and 1 subjects, respectively. There was a dose-dependent increase in DSG3-CAART persistence (rs=0.85) within 29 days, but at much lower levels than for cancer CART therapy. DSG3-CAART from all subjects exhibited specific in vitro lysis of anti-DSG3-expressing cells. The favorable DSG3-CAART safety profile along with the preliminary clinical and biological data from the first 3 cohorts provide rationale to evaluate higher doses and manufacturing enhancements in future cohorts.

A phase I study of the WT2725 dosing emulsion in patients with advanced malignancies

WT2725 is a Wilms’ tumor gene 1 (WT1)-derived-oligopeptide vaccine designed to induce WT1-specific cytotoxic T-lymphocytes against WT1+ tumors in human leukocyte antigen (HLA)-A*0201+ and/or HLA-A*0206+ patients. Here, we report the results of a phase I study of WT2725. In this phase I, open-label, dose-escalation and expansion two-part study, the WT2725 dosing emulsion was administered as a monotherapy to patients with advanced malignancies known to overexpress WT1, including glioblastoma. In part 1, 44 patients were sequentially allocated to four doses: 0.3 mg (n = 5), 0.9 mg (n = 5), 3 mg (n = 6), and 9 mg (n = 28). In part 2, 18 patients were allocated to two doses: 18 mg (n = 9) and 27 mg (n = 9). No dose-limiting toxicities were observed, so the maximum tolerated dose was not reached. Median progression-free survival was 58 (95% confidence interval [CI] 56–81) days (~ 2 months) across all patients with solid tumors; median overall survival was 394 days (13.0 months) (95% CI 309–648). Overall immune-related response rate in solid tumor patients was 7.5% (95% CI 2.6–19.9); response was most prominent in the glioblastoma subgroup. Overall, 62.3% of patients were considered cytotoxic T-lymphocyte responders; the proportion increased with increasing WT2725 dosing emulsion dose. WT2725 dosing emulsion was well tolerated. Preliminary tumor response and biological marker data suggest that WT2725 dosing emulsion may exert antitumor activity in malignancies known to overexpress the WT1 protein, particularly glioblastoma, and provide a rationale for future clinical development.Trial registration: NCT01621542.

An Integrative Taxonomy of a New Species of Trichogramma Westwood (Hymenoptera: Trichogrammatidae) with High Reproductive Capacity.

A new species of Trichogramma Westwood (Hymenoptera: Trichogrammatidae) is described: Trichogramma foersteri sp. nov. Takahashi from eggs of Anticarsia gemmatalis Hübner, (Lepidoptera: Erebidae) a major soybean defoliating pest. The parasitoid was collected in São José dos Pinhais, Paraná State, Brazil, and molecular and morphological characters were used to confirm the identity of the new species. Preliminary biological data are provided to demonstrate its high capacity of parasitism. The new species is a potential candidate as a biological control agent against some lepidopteran-pests.

JA:2021-19. Developing a Social Marketing Intervention for Heat Safety among Florida Tomato Harvesters: Preliminary Findings of Formative Research

ABSTRACT Purpose: Despite recent improvements in the quality and availability of educational materials to promote heat safety in agriculture, success in addressing the factors that inhibit the adoption of self-protective practices among farmworkers remains limited. Social marketing interventions can address gaps between safety knowledge and implementation by targeting segmented audiences with tailored behavioral products that compete with comfortable yet potentially harmful alternatives. The purpose of this study was to collect preliminary biological and survey data during a 5-day period in the spring of 2019 to identify hydration levels, perceptions, attitudes, knowledge, and behaviors associated with the prevention of heat-related illness (HRI) among 29 tomato harvesters in southwest Florida. Methods: Urine samples were collected before and at the end of each workday. Survey data were collected at baseline and at the end of each workday. Reagent strips were used to assess urine specific gravity, a measurement of hydration status. Descriptive statistics, relative frequency distributions, and bivariate correlation analysis were used to summarize the data. Results/Findings: Results showed that a majority of study participants were slightly or not at all concerned about becoming ill from the heat while working despite the wide prevalence of HRI symptoms. On average, participants were hypohydrated both at the start and end of each workday. Certain cooling practices, such as consumption of electrolyte drinks, tended to be implemented at the onset of HRI symptoms. More than 75% of the harvesters typically avoided taking any rest breaks. Yet all had received some form of heat safety training; knowledge test scores averaged 78%. Findings suggest safety behaviors had more to do with the amelioration of HRI symptoms than with training and knowledge. Practical application: To effectively encourage heat safety among Florida tomato harvesters, social marketing efforts must shift current behaviors from a reactive to a preventive orientation.

Fluorescent Nitric Oxide Photodonors Based on BODIPY and Rhodamine Antennae.

Two novel NO photodonors (NOPDs) based on BODIPY and Rhodamine antennae activatable with the highly biocompatible green light are reported. Both NOPDs exhibit considerable fluorescence emission and release NO with remarkable quantum efficiencies. The combination of the photoreleasing and emissive performance for both compounds is superior to those exhibited by other NOPDs based on similar light-harvesting centres, making them very intriguing for image-guided phototherapeutic applications. Preliminary biological data prove their easy visualization in cell environment due to the intense green and orange-red fluorescence and their photodynamic action on cancer cells due to the NO photo-liberated.

Effects of feed input and planting of submerged aquatic vegetation on methanotrophic communities in the surface sediments of aquaculture ponds

Methanotrophs represent the only biological sink for the greenhouse gas methane, and only few studies have focused on methanotrophic communities in aquaculture ponds. Illumina high-throughput sequencing and real-time quantitative PCR were employed to profile the methanotrophic bacterial community and investigate the pmoA gene abundance in surface sediments from crab, oriental river prawn, perch, and Wuchang fish aquaculture ponds. Results revealed that Gammaproteobacteria (mainly the environmental_samples_norank genera) and Alphaproteobacteria (mainly the Methylocystis genera) were the most and second most abundant methanotrophic bacterial classes, respectively. While the species cultivated in these ponds were significantly different, the planting of submerged vegetation and the feed input were the main factors found to shape the methanotrophic bacterial community. Submerged vegetation potentially influenced methanotrophs in two ways: by increasing the alpha diversity of the methanotrophic community or by increasing methanotrophic abundance through inducing anaerobic root zone conditions, thereby increasing methane oxidation potential. The amount of feed input also influenced the methanotrophic communities in the fishponds (especially Wuchang fishponds), possibly through deposition of nitrogen, phosphorous, and organic matter (especially organic matter). These results provide preliminary biological data for the regulation of methanotrophs in aquaculture ponds in the future.

Phytochemical and Pharmacological Evaluation of Cyperus odoratus Extract

Cyperus odoratus (Family: Cyperaceae) is a 10 to 50 cm long perennial herb used as traditional medicinal plant in Bangladesh to treat various pathological conditions like piles, tumour and wound. The ethanolic extract of C. odoratus (COET) has been evaluated for different bioactivities, for example, antioxidant, analgesic, anthelmintic and cytotoxic activities. Antioxidant activity was investigated by DPPH free radical scavenging assay, analgesic activity was evaluated from ‘acetic acid induced writhing inhibition test’ in mice, anthelmintic activities was tested by ‘time of paralysis and death’ assays and cytotoxic activities was observed from the ‘brine shrimp lethality bioassay’. Total tannin and phenol contents were also measured by using Folin-Ciocalteu reagent. Phytochemical screening indicated that the presence of alkaloids, tannins, flavonoids, glycosides, proteins, gums, steroids and acidic compounds. In DPPH free radical scavenging assay the extract showed IC50 value of 8.05 μg/ml, whereas the standard ascorbic acid showed 31.40 μg/ml. The total tannin and phenolic contents were found to be 3.35 and 1.68 mg GAE/100 g of dried extract, respectively. In acetic acid induced writhing assay, the extract showed 36.23 and 61.32% writhing inhibition at doses of 250 mg/kg and 500 mg/kg body weight, respectively, whereas standard Diclofenac-Na (25 mg/kg) showed 70.03% writhing inhibition. The plant extract showed anthelmintic activity in a dose dependant manner. COET also showed LD50 against brine shrimp nauplii at 11.344 μg/mL. After observing all preliminary biological data, it has been confirmed that the plant has antioxidant, analgesic, cytotoxic and anthelmintic properties.Bangladesh Pharmaceutical Journal 21(2): 150-159, 2018

Heterocycles for Alzheimer Disease: 4- and 5-Substituted Benzothiophenes as Starting Scaffold in the Construction of Potential New Inhibitors of BACE 1

4- and 5-substituted benzothiophenes were synthesized as starting scaffold in the construction of benzothieno[b] pyridines. Such structures were designed as potential new inhibitors of BACE 1. Preliminary promising biological data were reported. These molecules represent a starting point for improved chemicals in Alzheimer’s disease treatment. Obtained preliminary results encourage research advance and further developments.

MBJ-0110, a novel cyclopeptide isolated from the fungus Penicillium sp. f25267.

We have constructed an isolated natural compound library designed to facilitate extensive biological screenings.1 The library consists of over 1000 isolates, including over 140 ‘JBIR compounds’ that were discovered in our laboratory. To enrich this library, we recently initiated a screening program for rare microbial products using the advanced compound-identification system designated as ‘MBJ’s special selection’.2, 3 As a result, our program yielded novel compounds named ‘MBJ compounds’, such as a cytotoxic hydroxamate MBJ-0003 from Micromonospora sp. 29867;4 cytotoxic eremophilane derivatives MBJ-0009 and MBJ-0010 from Nectria sp. f26111;5 MBJ-0011, MBJ-0012 and MBJ-0013 from Apiognomonia sp. f24023;2 cytotoxic chaetoglobosin derivatives MBJ-0038, MBJ-0039 and MBJ-0040 from Chaetomium sp. f24230;3 bicyclic depsipeptides MBJ-0086 and MBJ-0087 from Sphaerisporangium sp. 33226;6 and aziridine-containing peptide MBJ-0035 from Streptosporangium sp. 32552.7 Further screening for novel compounds led to the identification of MBJ-0110 (1) from the culture of Penicillium sp. f25267. Herein we report the fermentation, isolation, structure elucidation and preliminary biological activity data.

Design, Synthesis, Crystallographic Studies, and Preliminary Biological Appraisal of New Substituted Triazolo[4,3-b]pyridazin-8-amine Derivatives as Tankyrase Inhibitors

Searching for selective tankyrases (TNKSs) inhibitors, a new small series of 6,8-disubstituted triazolo[4,3-b]piridazines has been synthesized and characterized biologically. Structure-based optimization of the starting hit compound NNL (3) prompted us to the discovery of 4-(2-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-ylamino)ethyl)phenol (12), a low nanomolar selective TNKSs inhibitor working as NAD isostere as ascertained by crystallographic analysis. Preliminary biological data candidate this new class of derivatives as a powerful pharmacological tools in the unraveling of TNKS implications in physiopathological conditions.

Furanylazaindoles: Potent Anticancer Agents in Vitro and in Vivo

Preliminary biological data on 7-anilino-6-azaindoles (8-11) suggested that hydrophobic substituents at C7 contribute to enhancement of antiproliferative activity. A novel series of 7-aryl-6-azaindole-1-benzenesulfonamides (12-22) were developed and showed improved cytotoxicity compared to ABT751 (5). The conversion of C7 phenyl rings into C7 heterocycles led to a remarkable improvement of antiproliferative activity. Among all the synthetic products, 7-(2-furanyl)-1-(4-methoxybenzenesulfonyl)-6-azaindole (21) exhibited the most potent anticancer activity against KB, HT29, MKN45, and H460 cancer cell lines with IC50 values of 21.1, 32.0, 27.5, and 40.0 nM, respectively. Bioassays indicated that 21 not only inhibits tubulin polymerization by binding to tubulin at the colchicine binding site but also arrests the cell cycle at the G2/M phase with slight arrest at the sub-G1 phase. Compound 21 also functions as a vascular disrupting agent and dose-dependently inhibits tumor growth without significant change of body weight in an HT29 xenograft mouse model. Taken together, compound 21 has potential for further development as a novel class of anticancer agents.

Isolation and genetic characterization of naturally NS-truncated H3N8 equine influenza virus in South Korea

Equine influenza virus (EIV) causes a highly contagious respiratory disease in equids, with confirmed outbreaks in Europe, America, North Africa, and Asia. Although China, Mongolia, and Japan have reported equine influenza outbreaks, Korea has not. Since 2011, we have conducted a routine surveillance programme to detect EIV at domestic stud farms, and isolated H3N8 EIV from horses showing respiratory disease symptoms. Here, we characterized the genetic and biological properties of this novel Korean H3N8 EIV isolate. This H3N8 EIV isolate belongs to the Florida sublineage clade 1 of the American H3N8 EIV lineage, and surprisingly, possessed a non-structural protein (NS) gene segment, where 23 bases of the NS1-encoding region were naturally truncated. Our preliminary biological data indicated that this truncation did not affect virus replication; its effect on biological and immunological properties of the virus will require further study.

Ligand-based and structure-based design of novel histone demethylase inhibitors

The genetic information in eukaryotic cells is organized in a specific structure called chromatin. The basic unit of chromatin is the nucleosome, which consist of four histone proteins and ~147 bp of DNA [1]. The N-terminal tails of these proteins contain sited for post-translational modifications directly linked to gene expression. The modifications include acetylation, methylation, phosphorylation, ubiquitinylation, sumoylation and ribosylation. Specific enzymes mediate each modification. LSD1 (Lysine Specific Demethylase I) is one of the histone demethylases, which removes one methyl group from mono- or di-methylated lysine residue. It has recently been demonstrated that androgen receptor (AR)-LSD1 complex demethylates a repressive histone mark (H3K9) promoting genes activation [2]. Experimental data show, also, that LSD1 is strongly expressed in prostate cancers [3]. For these reasons, specific modulation of LSD1 might be a promising therapeutic strategy in tissues where AR has a key physiological role. LSD1 is a flavin-dependent amine oxidase, which shares sequence identity with other flavin dependent amine oxidases like monoamine oxidase (MAO), and polyamine oxidase (PAO). After we analyzed structural differences and similarities among these enzymes several docking studies were evaluated using the available crystal structures of LSD1 and the related oxidases to discover novel LSD1 inhibitors. For the evaluation studies we selected different ligand data sets containing known inhibitors of MAO and PAO. The docking setup that showed the highest accuracy and enrichment factors was selected for virtual screening of LSD1 inhibitors. Preliminary biological data were obtained and will be discussed in the context of the target structure.

A Total Synthesis of Spirastrellolide A Methyl Ester

A concise total synthesis of spirastrellolide A methyl ester (1 a, R(1) =Me) as the parent compound of a series of highly cytotoxic marine macrolides is disclosed, which exploits and expands the flexibility of a synthesis plan previously developed by our group en route to the sister compound spirastrellolide F methyl ester (6 a, R(1) =Me). Key to success was the masking of the signature Δ(15,16) -bond of 1 a as a C16-carbonyl group until after the stereogenic center at C24 had been properly set by a highly selective hydrogenation of the C24 exo-methylene precursor 66. Conformational control over the macrocyclic frame allowed the proper stereochemical course to be dialed into this reduction process. The elaboration of the C16 ketone to the C15-C16 double bond was accomplished by a chemoselective alkenyl triflate formation followed by a palladium-catalyzed hydride delivery. The role of the ketone at C16 as a strategic design element is also evident up-stream of the key intermediate 66, the assembly of which hinged upon the addition of the polyfunctionalized dithiane 37 to the similarly elaborate aldehyde fragment 46. Other crucial steps of the total synthesis were an alkyl-Suzuki coupling and a Yamaguchi lactonization that allowed the Northern and the Southern sector of the target to be stitched together and the macrocyclic perimeter to be forged. The lateral chain comprising the remote C46 stereocenter was finally attached to the core region by a modified Julia-Kocienski olefination. The preparation of the individual building blocks led to some methodological spin-offs, amongst which the improved procedure for the N-O-bond cleavage of isoxazolines by zero-valent molybdenum and the ozonolysis of a double bond in the presence of other oxidation-prone functionality are most noteworthy. Preliminary biological data suggest that the entire carbon framework, that is the macrocyclic core plus the lateral chain, might be necessary for high cytotoxicity.

A Fibrillar Biodegradable Scaffold for Blood Vessels Tissue Engineering

In recent years there has been a growing interest for the development of tubular scaffolds employed to assist the replacement of small blood vessels. Materials designed for this purpose need to be biodegradable, have good mechanical properties and improve cell adhesion, proliferation and differentiation. To obtain biomaterials with these properties, electrospinning seems to be one of the most useful technique. Several biodegradable synthetic polymers or constituents of the extracellular matrix (ECM) have been electrospun showing optimal mechanical properties and biodegradability. However, such polymers are lacking in versatile chemical structure affordable to immobilize growth factors or chemokines. The glycosaminoglycan heparin is able to bind several growth factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and, when grafted onto the scaffold surface it is able to attract cells thus improving their proliferation and differentiation.Aim of this research was the production and the preliminary in vitro biological characterization of a new biodegradable material, obtained by electrospun a polyaminoacid-graft-polyester copolymer. The electrospun biomaterial has been successfully grafted with heparin exploiting the better chemical reactivity of the polyaminoacid portions of the graft copolymer. Then its morphology has been investigated by scanning electron microscopy (SEM) and the potential biodegradability of the material has been studied until 60 days. Preliminary biological data in vitro, on human endothelial cells, show a good compatibility of the scaffold obtained by electrospinning, with regard to cell adhesion and proliferation. Experiments are in progress to evaluate the effects of heparin on cell differentiation.

Enantioselective synthesis of (10S)- and (10R)-methyl-anandamides

For the development of novel endocannabinoid templates with potential resistance to hydrolytic and oxidative metabolism, we are targeting the bis-allylic carbons of the arachidonoyl skeleton. Toward this end, we recently disclosed the synthesis and preliminary biological data for the (13S)-methyl-anandamide. We report now the total synthesis of the (10S)- and (10R)-methyl-counterparts. Our synthetic approach is stereospecific, efficient, and provides the analogs without the need for resolution. Peptide coupling, P-2 nickel partial hydrogenation, and cis-selective Wittig olefination are the key steps.

Assessment of Pseudomonas aeruginosa N5,N10-Methylenetetrahydrofolate Dehydrogenase - Cyclohydrolase as a Potential Antibacterial Drug Target

The bifunctional enzyme methylenetetrahydrofolate dehydrogenase – cyclohydrolase (FolD) is identified as a potential drug target in Gram-negative bacteria, in particular the troublesome Pseudomonas aeruginosa. In order to provide a comprehensive and realistic assessment of the potential of this target for drug discovery we generated a highly efficient recombinant protein production system and purification protocol, characterized the enzyme, carried out screening of two commercial compound libraries by differential scanning fluorimetry, developed a high-throughput enzyme assay and prosecuted a screening campaign against almost 80,000 compounds. The crystal structure of P. aeruginosa FolD was determined at 2.2 Å resolution and provided a template for an assessment of druggability and for modelling of ligand complexes as well as for comparisons with the human enzyme. New FolD inhibitors were identified and characterized but the weak levels of enzyme inhibition suggest that these compounds are not optimal starting points for future development. Furthermore, the close similarity of the bacterial and human enzyme structures suggest that selective inhibition might be difficult to attain. In conclusion, although the preliminary biological data indicates that FolD represents a valuable target for the development of new antibacterial drugs, indeed spurred us to investigate it, our screening results and structural data suggest that this would be a difficult enzyme to target with respect to developing the appropriate lead molecules required to underpin a serious drug discovery effort.

New record of Tetrastichus howardi (Olliff) as a parasitoid of Diatraea saccharalis (Fabr.) on maize

Diatraea saccharalis (Fabr.) (Lepidoptera: Pyralidae) spends the largest part of its life cycle inside the stalk of the host plant,which provides protection against the action of conventional control methods. Biological control has been considered a viable alternative to control this pest in sugarcane (Saccharum officinarum L.) and corn (Zea mays L.), two pest preferential hosts. This paper reports the occurrence in Brazil of Tetrastichus howardi (Olliff) (Hymenoptera; Chalcidoidea: Eulophidae) parasitizing pupae of D. saccharalis obtained from corn plants. It also includes preliminary biological data about the insect. A single female of T. howardi is able to produce up to 66 offspring using a single pupa of the host D. Saccharalis and apparently does not distinguish between the host pupae of different ages. The life cycle of the parasitoid was around 25.5 days. The presence of the parasitoid in Brazil opens a new perspective on suppression of the sugarcane borer, considering the promising results already obtained in Asian countries. The insect is well adapted to laboratory conditions, can be produced in large scale and may became an additional option for the integrated pest management in those crops where D. saccharalis is a key pest such as the sugarcane, corn and sorghum (Sorghum bicolor (L.) Moench).