Digital Commons Network^™

Trichophycins B–F, Chlorovinylidene-Containing Polyketides Isolated From A Cyanobacterial Bloom, Matthew Bertin, Josep Sauri, Yizhou Liu, Christopher W. Via, Alexandre F. Roduit, R. Thomas Williamson

Biomedical and Pharmaceutical Sciences Faculty Publications

NMR-guided isolation (based on 1D ¹H and ¹³C NMR resonances consistent with a chlorovinylidene moiety) resulted in the characterization of five new highly functionalized polyketides, trichophycins B-F (1-5) and one non-chlorinated metabolite tricholactone (6) from a collection of Trichodesmium bloom material from the Gulf of Mexico. The planar structures of 1-6 were determined using 1D and 2D NMR spectroscopy, mass spectrometry and complementary spectroscopic procedures. Absolute configuration analysis of 1 and 2 were carried out by ¹H NMR analysis of diastereomeric Mosher esters in addition to ECD spectroscopy, J-based configuration analysis and …

Augmentation Of Vaccine-Induced Humoral And Cellular Immunity By A Physical Radiofrequency Adjuvant, Yan Cao, Xiaoyue Zhu, Md Nazir Hossen, Prateek Kakar, Yiwen Zhao, Xinyuan Chen

Biomedical and Pharmaceutical Sciences Faculty Publications

Protein/subunit vaccines often require external adjuvants to induce protective immunity. Due to the safety concern of chemical adjuvants, physical adjuvants were recently explored to boost vaccination. Physical adjuvants use physical energies rather than chemicals to stimulate tissue stress and endogenous danger signal release to boost vaccination. Here we present the safety and potency of non-invasive radiofrequency treatment to boost intradermal vaccination in murine models. We show non-invasive radiofrequency can increase protein antigen-induced humoral and cellular immune responses with adjuvant effects comparable to widely used chemical adjuvants. Radiofrequency adjuvant can also safely boost pandemic 2009 H1N1 influenza vaccination with adjuvant effects …

Levodopa-Reduced Mucuna Pruriens Seed Extract Shows Neuroprotective Effects Against Parkinson’S Disease In Murine Microglia And Human Neuroblastoma Cells, Caenorhabditis Elegans, And Drosophila Melanogaster, Shelby L. Johnson, Hyun Y. Park, Nicholas A. Dasilva, Dhiraj A. Vattem, Hang Ma, Navindra P. Seeram

Biomedical and Pharmaceutical Sciences Faculty Publications

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including ‘kampavata’ (tremors) or Parkinson’s disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (Caenorhabditis elegans, and Drosophila melanogaster models. In BV-2 cells, MPE (12.5–50 μg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7−18.6%), decreased reactive oxygen species production (29.1−61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9–60%. MPE (12.5−50 μg/mL) mitigated SH-SY5Y cell apoptosis by 6.9−40.0% in a non-contact co-culture assay with …

Albisporachelin, A New Hydroxamate Type Siderophore From The Deep Ocean Sediment-Derived Actinomycete Amycolatopsis Albispora Wp1t, Qihao Wu, Robert W. Deering, Gaiyun Zhang, Bixia Wang, Xin Li, Jiadong Sun, Jianwei Chen, Huawei Zhang, David C. Rowley, Hong Wang

Biomedical and Pharmaceutical Sciences Faculty Publications

Marine actinobacteria continue to be a rich source for the discovery of structurally diverse secondary metabolites. Here we present a new hydroxymate siderophore produced by Amycolatopsis albispora, a recently described species of this less explored actinomycete genus. Strain WP1^T was isolated from sediments collected at −2945 m in the Indian Ocean. The new siderophore, designated albisporachelin, was isolated from iron depleted culture broths and the structure was established by 1D and 2D NMR and MS/MS experiments, and application of a modified Marfey’s method. Albisporachelin is composed of one N-methylated-formylated/hydroxylated l-ornithine (N-Me-fh-l-Orn), one l-serine (l-Ser), one formylated/hydroxylated l-ornithine (fh-l-Orn) and …

The Effects Of Volume Versus Intensity Of Long-Term Voluntary Exercise On Physiology And Behavior In C57/Bl6 Mice, Lisa S. Robison, Dominique L. Popescu, Maria E. Anderson, Steven I. Beigelman, Shannon M. Fitzgerald, Antonina E. Kuzmina, David A. Lituma, Sarima Subzwari, Michalis Michaelos, Brenda J. Anderson, William E. Van Nostrand, John K. Robinson

Biomedical and Pharmaceutical Sciences Faculty Publications

Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group – usually unlimited running wheel access – resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a …

Beyond The Biomarker: Understanding The Diverse Roles Of Human Epididymis Protein 4 In The Pathogenesis Of Epithelial Ovarian Cancer, Nicole E. James, Clinton Chichester, Jennifer R. Ribeiro

Biomedical and Pharmaceutical Sciences Faculty Publications

Human epididymis protein 4 (HE4) is an important clinical biomarker used for the detection of epithelial ovarian cancer (EOC). While much is known about the predictive power of HE4 clinically, less has been reported regarding its molecular role in the progression of EOC. A deeper understanding of HE4’s mechanistic functions may help contribute to the development of novel targeted therapies. Thus far, it has been difficult to recommend HE4 as a therapeutic target owing to the fact that its role in the progression of EOC has not been extensively evaluated. This review summarizes what is collectively known about HE4 signaling …

Evaluation Of Polyphenol Anthocyanin-Enriched Extracts Of Blackberry, Black Raspberry, Blueberry, Cranberry, Red Raspberry, And Strawberry For Free Radical Scavenging, Reactive Carbonyl Species Trapping, Anti-Glycation, Anti-Β-Amyloid Aggregation, And Microglial Neuroprotective Effect, Hang Ma, Shelby L. Johnson, Weixi Lu, Nicholas A. Dasilva, Susan Meschwitz, Joel A. Dain, Navindra P. Seeram

Biomedical and Pharmaceutical Sciences Faculty Publications

Glycation is associated with several neurodegenerative disorders, including Alzheimer’s disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude …

A Novel Transgenic Rat Model Of Robust Cerebral Microvascular Amyloid With Prominent Vasculopathy, Judianne Davis, Feng Xu, Joshua Hatfield, Hedok Lee, Michael D. Hoos, Dominique Popescu, Elliot Crooks, Regina Kim, Steven O. Smith, John K. Robinson, Helene Benveniste, William Van Nostrand

Biomedical and Pharmaceutical Sciences Faculty Publications

Accumulation of fibrillar amyloid β protein in blood vessels of the brain, a condition known as cerebral amyloid angiopathy (CAA), is a common pathology of elderly individuals, a prominent comorbidity of Alzheimer disease, and a driver of vascular cognitive impairment and dementia. Although several transgenic mouse strains have been generated that develop varying levels of CAA, consistent models of associated cerebral microhemorrhage and vasculopathy observed clinically have been lacking. Reliable preclinical animal models of CAA and microhemorrhage are needed to investigate the molecular pathogenesis of this condition. Herein, we describe the generation and characterization of a novel transgenic rat (rTg-DI) …

Dna Base Sequence Effects On Bulky Lesion-Induced Conformational Heterogeneity During Dna Replication, Ang Cai, Katie A. Wilson, Satyakam Patnaik, Stacey D. Wetmore, Bongsup P. Cho

Biomedical and Pharmaceutical Sciences Faculty Publications

4-Aminobiphenyl (ABP) and its structure analog 2-aminofluorene (AF) are well-known carcinogens. In the present work, an unusual sequence effect in the 5′-CTTCTG₁G₂TCCTCATTC-3′ DNA duplex is reported for ABP- and AF-modified G. Specifically, the ABP modification at G₁ resulted in a mixture of 67% major groove B-type (B) and 33% stacked (S) conformers, while at the ABP modification at G₂ exclusively resulted in the B-conformer. The AF modification at G₁ and G₂ lead to 25%:75% and 83%:17% B:S population ratios, respectively. These differences in preferred conformation are due to an interplay between stabilizing …

Oral Microbiota Of Periodontal Health And Disease And Their Changes After Nonsurgical Periodontal Therapy, Casey Chen, Christopher L. Hemme, Joan Beleno, Zhou Jason Shi, Daliang Ning, Yujia Qin, Qichao Tu, Michael Jorgensen, Zhili He, Liyou Wu

Biomedical and Pharmaceutical Sciences Faculty Publications

This study examined the microbial diversity and community assembly of oral microbiota in periodontal health and disease and after nonsurgical periodontal treatment. The V4 region of 16S rRNA gene from DNA of 238 saliva and subgingival samples of 21 healthy and 48 diseased subjects was amplified and sequenced. Among 1979 OTUs identified, 28 were overabundant in diseased plaque. Six of these taxa were also overabundant in diseased saliva. Twelve OTUs were overabundant in healthy plaque. There was a trend for disease-associated taxa to decrease and health-associated taxa to increase after treatment with notable variations among individual sites. Network analysis revealed …

Mir-155, A Potential Serum Marker Of Extramammary Paget's Disease, Hao Guo, Rui-Qun Qi, Jie Sheng, Chang Liu, Hang Ma, He-Xiao Wang, Jiu-Hong Li, Xing-Hua Gao, Yin-Sheng Wan, Hong-Duo Chen

Biomedical and Pharmaceutical Sciences Faculty Publications

Background: Extramammary Paget’s disease (EMPD), a rare skin malignancy with non-specific manifestations, is often misdiagnosed as eczema of scrotum or tinea cruris. Although the diagnosis of EMPD could be confirmed by biopsy, it can be delayed as patients are reluctant to receive invasive operations. Herein, we investigated the serum miRNA expressions of EMPD patients and compared to that of the eczema of scrotum or tinea cruris patients as well as health volunteers for potential diagnostic markers for EMPD.

Methods: Altogether 45 subjects including 16 patients diagnosed with EMPD, 12 patients diagnosed with eczema of scrotum or tinea cruris and 17 …

The Combined Therapeutic Effects Of 131Iodine-Labeled Multifunctional Copper Sulfide-Loaded Microspheres In Treating Breast Cancer, Qiufang Liu, Yuyi Qian, Panli Li, Sihang Zhang, Zerong Wang, Jianjun Liu, Xiaoguang Sun, Michel Fulham, Dagan Feng, Zhigang Chen, Shaoli Song, Wei Li, Gang Huang

Biomedical and Pharmaceutical Sciences Faculty Publications

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading ¹³¹I-labeled hollow copper sulfide nanoparticles and paclitaxel (¹³¹I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. ¹⁸F-fluordeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P<0.05) following intra-tumoral (i.t.) injection with ¹³¹I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by …

Nanoparticle Anchoring Targets Immune Agonists To Tumors Enabling Anti-Cancer Immunity Without Systemic Toxicity, Yuan Zhang, Na Li, Heikyung Suh, Darrel J. Irvine

Biomedical and Pharmaceutical Sciences Faculty Publications

Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)−2 generate effective anti-tumor immunity but also elicit serious toxicities, hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity, but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity, we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models, immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes …