Isolation and Characterization of Antibacterial Compounds from <i>Aspergillus fumigatus:</i> An Endophytic Fungus from a Mangrove Plant of the Sundarbans.

The Sundarbans, a UNESCO world heritage site, is one of the largest mangrove forests in one stretch. Mangrove plants from this forest are little studied for their endophytic fungi. In this study, we isolated fourteen endophytic fungi from the plants Ceriops decandra and Avicennia officinalis collected from the Sundarbans. Five of them were identified as Aspergillus sp. and one as Penicillium sp. by macroscopic and microscopic observation. Antibacterial activity of the crude extracts obtained from these endophytes was determined against Staphylococcus aureus, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa using resazurin-based microtiter assay. The isolated endophytes showed varying degrees of antibacterial activity with MICs ranging between 5 and 0.078 mg/mL. Molecular identification of the most active endophyte revealed its identity as Aspergillus fumigatus obtained from the leaves of C. decandra. Acute toxicity study of the ethyl acetate extract of A. fumigatus in mice revealed no mortality even at the highest dose of 2000 mg/kg bodyweight, though some opposing results are found in the subacute toxicity study. The extract was subjected to silica gel and Sephadex column chromatography resulting in the isolation of three pure compounds. LC-MS analysis of these pure compounds revealed their identity as fumigaclavine C, azaspirofuran B, and fraxetin. This is the first report of fraxetin from A. fumigatus. All three identified compounds were previously reported for their antibacterial activity against different strains of both Gram-positive and Gram-negative bacteria. Therefore, the observed antibacterial activity of the ethyl acetate (EtOAc) extract of A. fumigatus could be due to the presence of these compounds. These results support the notion of investigating fungal endophytes from the Sundarbans for new antimicrobial compounds

Beta-Catenin Phosphorylated at Threonine 120 Antagonizes Generation of Active Beta-Catenin by Spatial Localization in trans-Golgi Network

The stability and subcellular localization of beta-catenin, a protein that plays a major role in cell adhesion and proliferation, is tightly regulated by multiple signaling pathways. While aberrant activation of beta-catenin signaling has been implicated in cancers, the biochemical identity of transcriptionally active beta-catenin (ABC), commonly known as unphosphorylated serine 37 (S37) and threonine 41 (T41) β-catenin, remains elusive. Our current study demonstrates that ABC transcriptional activity is influenced by phosphorylation of T120 by Protein Kinase D1 (PKD1). Whereas the nuclear β-catenin from PKD1-low prostate cancer cell line C4-2 is unphosphorylated S37/T41/T120 with high transcription activity, the nuclear β-catenin from PKD1-overexpressing C4-2 cells is highly phosphorylated at T120, S37 and T41 with low transcription activity, implying that accumulation of nuclear β-catenin alone cannot be simply used as a read-out for Wnt activation. In human normal prostate tissue, the phosphorylated T120 β-catenin is mainly localized to the trans-Golgi network (TGN, 22/30, 73%), and this pattern is significantly altered in prostate cancer (14/197, 7.1%), which is consistent with known down regulation of PKD1 in prostate cancer. These in vitro and in vivo data unveil a previously unrecognized post-translational modification of ABC through T120 phosphorylation by PKD1, which alters subcellular localization and transcriptional activity of β-catenin. Our results support the view that β-catenin signaling activity is regulated by spatial compartmentation and post-translational modifications and protein level of β-catenin alone is insufficient to count signaling activity

A systematic review on antioxidant and anti-inflammatory activity of Sesame (Sesamum indicum L.) oil and further confirmation of anti-inflammatory activity by chemical profiling and molecular docking

Traditionally sesame oil has been used as a popular food and medicine. The review aims to summarize the antioxidant and anti-inflammatory effects of sesame oil (SO) and its identified compounds as well as further fatty acid profiling and molecular docking study to correlate the interaction of its identified constituents with COX-2. For this, a literature study was made using Google Scholar, Pubmed and SciFinder databases. Literature study demonstrated that SO has potential antioxidant and anti-inflammatory effects in various test systems, including humans, animals and cultured cells through various pathways such as inhibition of COX, non-enzymatic defense mechanism, inhibition of pro-inflammatory cytokines, NF-kB or MAPK signaling and prostaglandin synthesis pathway. Fatty acidanalysis of SO using gas chromatography identified known 9 fatty acids.In-silico study revealed thatsesamin, sesaminol, sesamolin, stigmasterol, Δ5-avenasterol, and Δ7-avenasterol(-9.6 to -10.7 kcal/mol) were the most efficient ligand for interaction and binding with COX-2. The known fatty acid were also showed binding efficiency with COX-2 to some extent (-6.0 to -8.4 kcal/mol).In summary, it is evident that sesame oil may be one of promising traditional medicine that we could use in the prevention and management of diseases associated with oxidative stress and inflammation

A systematic review on anti-diabetic and cardioprotective effects of gallic acid: A widespread dietary phytoconstituent

Gallic acid (GA) is a bioactive phytoconstituent that has been reported to prevent a number of diseases. However, there is no systematic review to-date on its anti-diabetic and cardioprotective potential including molecular mechanisms for such activities. This review aims to summarize the anti-diabetic and cardioprotective effects of GA and further propose a molecular mechanism of its anti-diabetic effects. Accumulation of associated literature was conducted through the use of databases including Google Scholar, PubMed, Web of Science, Science Direct and Scopus databases. Articles published until December 2018 were extracted and all the retracted articles were sorted based on the inclusion and exclusion criteria and relevant articles were further consulted for necessary information. We have found substantial investigations in animals and cultured cells that supports anti-diabetic and cardioprotective effects of GA with several underlying mechanisms including antioxidant enzyme systems and non-enzymatic defense mechanisms. The reported antioxidant activity of GA as well as the modulation of some key proteins linked to diabetes could be a part of the mechanisms by which GA showed anti-diabetic effect. In summary, it is evident that GA is one of the promising dietary phytochemicals that could be beneficial for the treatment and management of diabetes and associated myocardial damage

Healthcare Facilities as Potential Reservoirs of Antimicrobial Resistant Klebsiella pneumoniae: An Emerging Concern to Public Health in Bangladesh.

The emergence of virulent extended spectrum β-lactamase producing Klebsiella pneumoniae (ESBL-KP) including carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired infections has resulted in significant morbidity and mortality worldwide. We investigated the antibiotic resistance and virulence factors associated with ESBL-KP and CRKP in tertiary care hospitals in Bangladesh and explored their ability to form biofilm. A total of 67 ESBL-KP were isolated from 285 Klebsiella pneumoniae isolates from environmental and patient samples from January 2019 to April 2019. For ESBL-KP isolates, molecular typing was carried out using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), antibiotic susceptibility testing, PCR for virulence and drug-resistant genes, and biofilm assays were also performed. All 67 isolates were multidrug-resistant (MDR) to different antibiotics at high levels and 42 isolates were also carbapenem-resistant. The most common β-lactam resistance gene was blaCTX-M-1 (91%), followed by blaTEM (76.1%), blaSHV (68.7%), blaOXA-1 (29.9%), blaGES (14.9%), blaCTX-M-9 (11.9%), and blaCTX-M-2 (4.5%). The carbapenemase genes blaKPC (55.2%), blaIMP (28.4%), blaVIM (14.9%), blaNDM-1 (13.4%), and blaOXA-48 (10.4%) and virulence-associated genes such as fimH (71.6%), ugeF (58.2%), wabG (56.7%), ureA (47.8%) and kfuBC (28.4%) were also detected. About 96.2% of the environmental and 100% of the patient isolates were able to form biofilms. ERIC-PCR-based genotyping and hierarchical clustering of K. pneumoniae isolates revealed an association between environmental and patient samples, indicating clonal association with possible transmission of antimicrobial resistance genes. Our findings can help in improving patient care and infection control, and the development of public health policies related to hospital-acquired infections

Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL

Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease