Biomolecules

17 pages, 943 KiB

Open AccessReview

Partners in Mischief: Functional Networks of Heat Shock Proteins of Plasmodium falciparum and Their Influence on Parasite Virulence

by Michael O. Daniyan, Jude M. Przyborski and Addmore Shonhai

Biomolecules 2019, 9(7), 295; https://doi.org/10.3390/biom9070295 - 23 Jul 2019

Cited by 32 | Viewed by 7134

Abstract

The survival of the human malaria parasite Plasmodium falciparum under the physiologically distinct environments associated with their development in the cold-blooded invertebrate mosquito vectors and the warm-blooded vertebrate human host requires a genome that caters to adaptability. To this end, a robust stress [...] Read more.

The survival of the human malaria parasite Plasmodium falciparum under the physiologically distinct environments associated with their development in the cold-blooded invertebrate mosquito vectors and the warm-blooded vertebrate human host requires a genome that caters to adaptability. To this end, a robust stress response system coupled to an efficient protein quality control system are essential features of the parasite. Heat shock proteins constitute the main molecular chaperone system of the cell, accounting for approximately two percent of the malaria genome. Some heat shock proteins of parasites constitute a large part (5%) of the ‘exportome’ (parasite proteins that are exported to the infected host erythrocyte) that modify the host cell, promoting its cyto-adherence. In light of their importance in protein folding and refolding, and thus the survival of the parasite, heat shock proteins of P. falciparum have been a major subject of study. Emerging evidence points to their role not only being cyto-protection of the parasite, as they are also implicated in regulating parasite virulence. In undertaking their roles, heat shock proteins operate in networks that involve not only partners of parasite origin, but also potentially functionally associate with human proteins to facilitate parasite survival and pathogenicity. This review seeks to highlight these interplays and their roles in parasite pathogenicity. We further discuss the prospects of targeting the parasite heat shock protein network towards the developments of alternative antimalarial chemotherapies. Full article

(This article belongs to the Special Issue Protein Folding and Quality Control Mechanisms - In Memory of Prof. Oleg B. Ptitsyn (1929-1999))

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17 pages, 2670 KiB

Open AccessArticle

A Simple and Efficient Molecularly Imprinted Electrochemical Sensor for the Selective Determination of Tryptophan

by Yaling Tian, Peihong Deng, Yiyong Wu, Ziyu Ding, Guangli Li, Jun Liu and Quanguo He

Biomolecules 2019, 9(7), 294; https://doi.org/10.3390/biom9070294 - 22 Jul 2019

Cited by 58 | Viewed by 4770

Abstract

In this paper, a tryptophan (Trp) molecularly imprinted chitosan film was prepared on the surface of an acetylene black paste electrode using chitosan as the functional polymer, Trp as the template molecule and sulfuric acid as the crosslinking agent. The surface morphologies of [...] Read more.

In this paper, a tryptophan (Trp) molecularly imprinted chitosan film was prepared on the surface of an acetylene black paste electrode using chitosan as the functional polymer, Trp as the template molecule and sulfuric acid as the crosslinking agent. The surface morphologies of non-imprinted and imprinted electrodes were characterized by scanning electron microscopy (SEM). The formation of hydrogen bonds between the functional polymer and the template molecule was confirmed by infrared spectroscopy. Some factors affecting the performance of the imprinted electrode such as the concentration of chitosan, the mass ratio of chitosan to Trp, the dropping amount of the chitosan-Trp mixture, the solution pH, and the accumulation potential and time were discussed. The experimental results show that the imprinted electrode exhibit good affinity and selectivity for Trp. The dynamic linear ranges of 0.01–4 μM, 4–20 μM and 20–100 μM were obtained by second derivative linear sweep voltammetry, and the detection limit was calculated to be 8.0 nM. The use of the imprinted electrode provides an effective method for eliminating the interference of potentially interfering substances. In addition, the sensor has high sensitivity, reproducibility and stability, and can be used for the determination of Trp in pharmaceutical preparations and human serum samples. Full article

(This article belongs to the Section Cellular Biochemistry)

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19 pages, 4543 KiB

Open AccessArticle

Genome-Wide Identification and Expression Profiling of CBL-CIPK Gene Family in Pineapple (Ananas comosus) and the Role of AcCBL1 in Abiotic and Biotic Stress Response

by Mohammad Aslam, Beenish Fakher, Bello Hassan Jakada, Lihua Zhao, Shijiang Cao, Yan Cheng and Yuan Qin

Biomolecules 2019, 9(7), 293; https://doi.org/10.3390/biom9070293 - 20 Jul 2019

Cited by 55 | Viewed by 6722

Abstract

Ca²⁺ serves as a ubiquitous second messenger regulating several aspects of plant growth and development. A group of unique calcium sensor proteins, calcineurin B-like (CBL), interact with CBL-interacting protein kinases (CIPKs) to decode the Ca²⁺ signature inside the cell. Although CBL-CIPK [...] Read more.

Ca²⁺ serves as a ubiquitous second messenger regulating several aspects of plant growth and development. A group of unique calcium sensor proteins, calcineurin B-like (CBL), interact with CBL-interacting protein kinases (CIPKs) to decode the Ca²⁺ signature inside the cell. Although CBL-CIPK signaling toolkit has been shown to play significant roles in the responses to numerous stresses in different plants, the information about pineapple CBL-CIPK remains obscure. In the present study, a total of eight AcCBL and 21 AcCIPK genes were identified genome-wide in pineapple. The identified genes were renamed on the basis of gene ID in ascending order and phylogenetic analysis divided into five groups. Transcriptomic data analysis showed that AcCBL and AcCIPK genes were expressed differentially in different tissues. Further, the expression analysis of AcCBL1 in different tissues showed significant changes under various abiotic stimuli. Additionally, the ectopic expression of AcCBL1 in Arabidopsis resulted in enhanced tolerance to salinity, osmotic, and fungal stress. The present study revealed the crucial contribution of the CBL-CIPK gene in various biological and physiological processes in pineapple. Full article

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16 pages, 749 KiB

Open AccessArticle

Antihypertensive Indigenous Lebanese Plants: Ethnopharmacology and a Clinical Trial

by Ali A. Samaha, Mirna Fawaz, Ali Salami, Safaa Baydoun and Ali H. Eid

Biomolecules 2019, 9(7), 292; https://doi.org/10.3390/biom9070292 - 20 Jul 2019

Cited by 27 | Viewed by 6582

Abstract

Hypertension is highly prevalent among the Lebanese adult population and is indeed the major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long been practiced. The aim of this study is to document this traditional knowledge and clinically test [...] Read more.

Hypertension is highly prevalent among the Lebanese adult population and is indeed the major cause of mortality in Lebanon. Traditional use of antihypertensive medicinal plants has long been practiced. The aim of this study is to document this traditional knowledge and clinically test the antihypertensive capacity of three of the most commonly used wild plant species Mentha longifolia, Viola odorata and Urtica dioica. Ethno-pharmacological data was collected by personal interviews with herbalists and traditional healers using a semi structured survey questionnaire and assessing relative frequency of citation (RFC). The clinical study was conducted by a randomized, blind, placebo-controlled trial in 29 subjects with mild hypertension distributed in four groups, three plant extract treatments and one placebo. Systolic (SBP) and diastolic blood pressures (DBP) as well as mean arterial blood pressures (MAP) were monitored at weeks 4, 8, 12 and 16 during the treatment with 300 mL/day of plant extract. Results showed that M. longifolia, U. dioica and V. odorata exhibited the highest values of RCF (0.95) followed by Allium ampeloprasum (0.94), Apium graveolens (0.92) and Crataegus azarolus (0.90). The clinical trial revealed dose- and duration-dependent significant reductions in SBP, DBP and MAP of subjects treated with M. longifolia, U. dioica or V. odorata. Our findings indicate that extracts of these plants present an effective, safe and promising potential as a phyto-therapuetical approach for the treatment of mild hypertension. More research on the phytochemistry, pharmacological effects and the underlying mechanisms is necessary. Full article

(This article belongs to the Special Issue Atherosclerosis and Related Diseases: Particular Focus on Molecular Biology)

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13 pages, 3984 KiB

Open AccessArticle

Alginate Gel Reinforcement with Chitin Nanowhiskers Modulates Rheological Properties and Drug Release Profile

by Valentina A. Petrova, Vladimir Y. Elokhovskiy, Sergei V. Raik, Daria N. Poshina, Dmitry P. Romanov and Yury A. Skorik

Biomolecules 2019, 9(7), 291; https://doi.org/10.3390/biom9070291 - 19 Jul 2019

Cited by 54 | Viewed by 6233

Abstract

Hydrogels are promising materials for various applications, including drug delivery, tissue engineering, and wastewater treatment. In this work, we designed an alginate (ALG) hydrogel containing partially deacetylated chitin nanowhiskers (CNW) as a filler. Gelation in the system occurred by both the protonation of [...] Read more.

Hydrogels are promising materials for various applications, including drug delivery, tissue engineering, and wastewater treatment. In this work, we designed an alginate (ALG) hydrogel containing partially deacetylated chitin nanowhiskers (CNW) as a filler. Gelation in the system occurred by both the protonation of alginic acid and the formation of a polyelectrolyte complex with deacetylated CNW surface chains. Morphological changes in the gel manifested as a honeycomb structure in the freeze-dried gel, unlike the layered structure of an ALG gel. Disturbance of the structural orientation of the gels by the introduction of CNW was also expressed as a decrease in the intensity of X-ray diffraction reflexes. All studied systems were non-Newtonian liquids that violated the Cox-Merz rule. An increase in the content of CNW in the ALG-CNW hydrogel resulted in increases in the yield stress, maximum Newtonian viscosity, and relaxation time. Inclusion of CNW prolonged the release of tetracycline due to changes in diffusion. The first phases (0–5 h) of the release profiles were well described by the Higuchi model. ALG-CNW hydrogels may be of interest as soft gels for controlled topical or intestinal drug delivery. Full article

(This article belongs to the Special Issue Carbohydrate Polymers: Science and Applications)

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9 pages, 400 KiB

Open AccessArticle

Analysis of Polymorphism rs1333049 (Located at 9P21.3) in the White Population of Western Siberia and Associations with Clinical and Biochemical Markers

by Elena Shakhtshneider, Pavel Orlov, Sergey Semaev, Dinara Ivanoshchuk, Sofia Malyutina, Valery Gafarov, Yuliya Ragino and Mikhail Voevoda

Biomolecules 2019, 9(7), 290; https://doi.org/10.3390/biom9070290 - 19 Jul 2019

Cited by 8 | Viewed by 3854

Abstract

The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters. The population included [...] Read more.

The 9p21.3 chromosomal region is a marker of the risk of cardiovascular diseases. The aim of this study was to analyze single-nucleotide polymorphism rs1333049 (chr9:22125504) in the population of Western Siberia (Russia) and possible associations with clinical and biochemical parameters. The population included in the analyses was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 participants, >90% white, aged 45–69, males: 50%). In total, 2729 randomly selected patients were included. Plasma lipid levels were determined by standard enzymatic assays. Rs1333049 was analyzed by RT-PCR (BioLabMix, Russia). Frequencies of rs1333049 genotypes C/C (homozygote), C/G (heterozygote), and G/G were 0.22, 0.51, and 0.27 in this population. The Allele G frequency was 0.53. We found an association of allele G with total cholesterol and low-density lipoprotein cholesterol levels among male participants (p = 0.004 and p = 0.002, respectively). Allele C was significantly associated with the risk of myocardial infarction among the male participants (odds ratio 1.96, 95% confidence interval 1.14–3.38, p = 0.017) and the study population (odds ratio 1.83, 95% confidence interval 1.23–2.72, p = 0.004). Thus, rs1333049 is associated with myocardial infarction in the white population of Western Siberia (Russia). Full article

(This article belongs to the Special Issue Atherosclerosis and Related Diseases: Particular Focus on Molecular Biology)

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19 pages, 656 KiB

Open AccessReview

DNA Methylation Status in Cancer Disease: Modulations by Plant-Derived Natural Compounds and Dietary Interventions

by Karin Jasek, Peter Kubatka, Marek Samec, Alena Liskova, Karel Smejkal, Desanka Vybohova, Ondrej Bugos, Kristina Biskupska-Bodova, Tibor Bielik, Pavol Zubor, Jan Danko, Marian Adamkov, Taeg Kyu Kwon and Dietrich Büsselberg

Biomolecules 2019, 9(7), 289; https://doi.org/10.3390/biom9070289 - 18 Jul 2019

Cited by 52 | Viewed by 8790

Abstract

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. [...] Read more.

The modulation of the activity of DNA methyltransferases (DNMTs) represents a crucial epigenetic mechanism affecting gene expressions or DNA repair mechanisms in the cells. Aberrant modifications in the function of DNMTs are a fundamental event and part of the pathogenesis of human cancer. Phytochemicals, which are biosynthesized in plants in the form of secondary metabolites, represent an important source of biomolecules with pleiotropic effects and thus provide a wide range of possible clinical applications. It is well documented that phytochemicals demonstrate significant anticancer properties, and in this regard, rapid development within preclinical research is encouraging. Phytochemicals affect several epigenetic molecular mechanisms, including DNA methylation patterns such as the hypermethylation of tumor-suppressor genes and the global hypomethylation of oncogenes, that are specific cellular signs of cancer development and progression. This review will focus on the latest achievements in using plant-derived compounds and plant-based diets targeting epigenetic regulators and modulators of gene transcription in preclinical and clinical research in order to generate novel anticancer drugs as sensitizers for conventional therapy or compounds suitable for the chemoprevention clinical setting in at-risk individuals. In conclusion, indisputable anticancer activities of dietary phytochemicals linked with proper regulation of DNA methylation status have been described. However, precisely designed and well-controlled clinical studies are needed to confirm their beneficial epigenetic effects after long-term consumption in humans. Full article

(This article belongs to the Special Issue Plant-Derived Natural Compounds in the Management of Cancer: Significance and Challenges)

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10 pages, 1356 KiB

Open AccessArticle

Alleviated Oxidative Damage by Taraxacum officinale through the Induction of Nrf2-MAPK/PI3K Mediated HO-1 Activation in Murine Macrophages RAW 264.7 Cell Line

by Hyun-Seo Yoon and Chung Mu Park

Biomolecules 2019, 9(7), 288; https://doi.org/10.3390/biom9070288 - 18 Jul 2019

Cited by 15 | Viewed by 4136

Abstract

Taraxacum officinale has been consumed as a folk remedy due to its diverse physiological activities. This study aimed to investigate the antioxidative potential of T. officinale water extract (TOWE) and ethanol extract (TOEE) against oxidative stress and compare their molecular mechanism via the [...] Read more.

Taraxacum officinale has been consumed as a folk remedy due to its diverse physiological activities. This study aimed to investigate the antioxidative potential of T. officinale water extract (TOWE) and ethanol extract (TOEE) against oxidative stress and compare their molecular mechanism via the induction of heme oxygenase-1 (HO-1) in RAW 264.7 cells. The antioxidative activity was evaluated through the radical scavenging assay, the cytoprotection assay against oxidative damage, and Western blot analysis. Both extracts dose-dependently induced HO-1 expression without any cytotoxicity in accordance with the activation of a transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOWE induced HO-1 expression through the phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and c-Jun NH₂-terminal kinase (JNK), while TOEE activated HO-1 by PI3K/Akt phosphorylation. In order to identify the antioxidative potential by HO-1 induction, oxidative damage-caused cell death by tert-butyl hydroperoxide (t-BHP) was significantly attenuated by both extracts. Their antioxidative potential was confirmed by HO-1 selective inducer and inhibitor, cobalt protoporphyrin (CoPP), and tin protoporphyrin (SnPP), respectively. These results indicate that TOWE and TOEE potently alleviated oxidative damage via the induction of Nrf2/MAPK/PI3K mediated HO-1 induction in RAW 264.7 cells. Full article

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16 pages, 2195 KiB

Open AccessEditor’s ChoiceArticle

Caveolin-1 Endows Order in Cholesterol-Rich Detergent Resistant Membranes

by Carla Raggi, Marco Diociaiuti, Giulio Caracciolo, Federica Fratini, Luca Fantozzi, Giovanni Piccaro, Katia Fecchi, Elisabetta Pizzi, Giuseppe Marano, Fiorella Ciaffoni, Elena Bravo, Maria L. Fiani and Massimo Sargiacomo

Biomolecules 2019, 9(7), 287; https://doi.org/10.3390/biom9070287 - 17 Jul 2019

Cited by 14 | Viewed by 5169

Abstract

Cholesterol-enriched functional portions of plasma membranes, such as caveolae and rafts, were isolated from lungs of wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mice within detergent resistant membranes (DRMs). To gain insight into their molecular composition we performed proteomic and lipid analysis on [...] Read more.

Cholesterol-enriched functional portions of plasma membranes, such as caveolae and rafts, were isolated from lungs of wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mice within detergent resistant membranes (DRMs). To gain insight into their molecular composition we performed proteomic and lipid analysis on WT and Cav-1 KO-DRMs that showed predicted variations of proteomic profiles and negligible differences in lipid composition, while Langmuir monolayer technique and small and wide-angle X-ray scattering (SAXS-WAXS) were here originally introduced to study DRMs biophysical association state. Langmuir analysis of Cav-1 containing DRMs displayed an isotherm with a clear-cut feature, suggesting the coexistence of the liquid-ordered (L_o) phase typical of the raft structure, namely “cholesterol-rich L_o phase”, with a phase fully missing in Cav-1 KO that we named “caveolin-induced L_o phase”. Furthermore, while the sole lipid component of both WT and KO-DRMs showed qualitatively similar isotherm configuration, the reinsertion of recombinant Cav-1 into WT-DRMs lipids restored the WT-DRM pattern. X-ray diffraction results confirmed that Cav-1 causes the formation of a “caveolin-induced L_o phase”, as suggested by Langmuir experiments, allowing us to speculate about a possible structural model. These results show that the unique molecular link between Cav-1 and cholesterol can spur functional order in a lipid bilayer strictly derived from biological sources. Full article

(This article belongs to the Special Issue Beyond Lipid Rafts and Caveolae: From Caveolae Compartmentalization of Signal Transduction to Medicine)

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23 pages, 2809 KiB

Open AccessReview

The Role of Protein Tyrosine Phosphatase (PTP)-1B in Cardiovascular Disease and Its Interplay with Insulin Resistance

by Shahenda S. Abdelsalam, Hesham M. Korashy, Asad Zeidan and Abdelali Agouni

Biomolecules 2019, 9(7), 286; https://doi.org/10.3390/biom9070286 - 17 Jul 2019

Cited by 96 | Viewed by 11580

Abstract

Endothelial dysfunction is a key feature of cardiovascular disorders associated with obesity and diabetes. Several studies identified protein tyrosine phosphatase (PTP)-1B, a member of the PTP superfamily, as a major negative regulator for insulin receptor signaling and a novel molecular player in endothelial [...] Read more.

Endothelial dysfunction is a key feature of cardiovascular disorders associated with obesity and diabetes. Several studies identified protein tyrosine phosphatase (PTP)-1B, a member of the PTP superfamily, as a major negative regulator for insulin receptor signaling and a novel molecular player in endothelial dysfunction and cardiovascular disease. Unlike other anti-diabetic approaches, genetic deletion or pharmacological inhibition of PTP1B was found to improve glucose homeostasis and insulin signaling without causing lipid buildup in the liver, which represents an advantage over existing therapies. Furthermore, PTP1B was reported to contribute to cardiovascular disturbances, at various molecular levels, which places this enzyme as a unique single therapeutic target for both diabetes and cardiovascular disorders. Synthesizing selective small molecule inhibitors for PTP1B is faced with multiple challenges linked to its similarity of sequence with other PTPs; however, overcoming these challenges would pave the way for novel approaches to treat diabetes and its concurrent cardiovascular complications. In this review article, we summarized the major roles of PTP1B in cardiovascular disease with special emphasis on endothelial dysfunction and its interplay with insulin resistance. Furthermore, we discussed some of the major challenges hindering the synthesis of selective inhibitors for PTP1B. Full article

(This article belongs to the Special Issue Atherosclerosis and Related Diseases: Particular Focus on Molecular Biology)

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36 pages, 1792 KiB

Open AccessReview

Phytohormones Regulate Accumulation of Osmolytes Under Abiotic Stress

by Anket Sharma, Babar Shahzad, Vinod Kumar, Sukhmeen Kaur Kohli, Gagan Preet Singh Sidhu, Aditi Shreeya Bali, Neha Handa, Dhriti Kapoor, Renu Bhardwaj and Bingsong Zheng

Biomolecules 2019, 9(7), 285; https://doi.org/10.3390/biom9070285 - 17 Jul 2019

Cited by 591 | Viewed by 20585

Abstract

Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. [...] Read more.

Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. The most common osmolytes that play crucial role in osmoregulation are proline, glycine-betaine, polyamines, and sugars. These compounds stabilize the osmotic differences between surroundings of cell and the cytosol. Besides, they also protect the plant cells from oxidative stress by inhibiting the production of harmful ROS like hydroxyl ions, superoxide ions, hydrogen peroxide, and other free radicals. The accumulation of osmolytes is further modulated by phytohormones like abscisic acid, brassinosteroids, cytokinins, ethylene, jasmonates, and salicylic acid. It is thus important to understand the mechanisms regulating the phytohormone-mediated accumulation of osmolytes in plants during abiotic stresses. In this review, we have discussed the underlying mechanisms of phytohormone-regulated osmolyte accumulation along with their various functions in plants under stress conditions. Full article

(This article belongs to the Special Issue Phytohormones)

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20 pages, 2422 KiB

Open AccessArticle

CoCUN, a Novel Ubiquitin Binding Domain Identified in N4BP1

by Ridvan Nepravishta, Federica Ferrentino, Walter Mandaliti, Anna Mattioni, Janine Weber, Simona Polo, Luisa Castagnoli, Gianni Cesareni, Maurizio Paci and Elena Santonico

Biomolecules 2019, 9(7), 284; https://doi.org/10.3390/biom9070284 - 17 Jul 2019

Cited by 13 | Viewed by 5481

Abstract

Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors and amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize the hydrophobic path centered on Ile44, including residues Leu8, Ile44, His68, and Val70. A variety [...] Read more.

Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors and amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize the hydrophobic path centered on Ile44, including residues Leu8, Ile44, His68, and Val70. A variety of different orientations, which can be attributed to specific contacts between each UBD and surface residues surrounding the hydrophobic patch, specify how each class of UBD specifically contacts ubiquitin. Here, we describe the structural model of a novel ubiquitin-binding domain that we identified in NEDD4 binding protein 1 (N4BP1). By performing protein sequence analysis, mutagenesis, and nuclear magnetic resonance (NMR) spectroscopy of the ¹⁵N isotopically labeled protein, we demonstrate that a Phe-Pro motif in N4BP1 recognizes the canonical hydrophobic patch of ubiquitin. This recognition mode resembles the molecular mechanism evolved in the coupling of ubiquitin conjugation to endoplasmic-reticulum (ER) degradation (CUE) domain family, where an invariant proline, usually following a phenylalanine, is required for ubiquitin binding. Interestingly, this novel UBD, which is not evolutionary related to CUE domains, shares a 40% identity and 47% similarity with cullin binding domain associating with NEDD8 (CUBAN), a protein module that also recognizes the ubiquitin-like NEDD8. Based on these features, we dubbed the region spanning the C-terminal 50 residues of N4BP1 the CoCUN domain, for Cousin of CUBAN. By performing circular dichroism and ¹⁵N NMR chemical shift perturbation of N4BP1 in complex with ubiquitin, we demonstrate that the CoCUN domain lacks the NEDD8 binding properties observed in CUBAN. We also show that, in addition to mediating the interaction with ubiquitin and ubiquitinated substrates, both CUBAN and CoCUN are poly-ubiquitinated in cells. The structural and the functional characterization of this novel UBD can contribute to a deeper understanding of the molecular mechanisms governing N4BP1 function, providing at the same time a valuable tool for clarifying how the discrimination between ubiquitin and the highly related NEDD8 is achieved. Full article

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14 pages, 1077 KiB

Open AccessReview

The Role of Stabilin-1 in Lymphocyte Trafficking and Macrophage Scavenging in the Liver Microenvironment

by Daniel A. Patten and Shishir Shetty

Biomolecules 2019, 9(7), 283; https://doi.org/10.3390/biom9070283 - 16 Jul 2019

Cited by 20 | Viewed by 5493

Abstract

Chronic liver diseases are a major global health burden, and cases of these conditions continue to rise in many countries. A diverse range of insults can lead to chronic liver disease, but they are all characterised by the infiltration and accumulation of immune [...] Read more.

Chronic liver diseases are a major global health burden, and cases of these conditions continue to rise in many countries. A diverse range of insults can lead to chronic liver disease, but they are all characterised by the infiltration and accumulation of immune cells within liver tissue and, if progressive, can lead to tissue fibrosis and cirrhosis. In this review, we focus on the role of stabilin-1 in two key processes that contribute to liver disease, namely, the recruitment of lymphocytes into liver tissue and the response of macrophages to tissue injury. Stabilin-1 is constitutively expressed on the sinusoidal endothelium of the liver and contributes to the homeostatic scavenging function of these cells. Epithelial damage in the context of chronic liver disease leads to the upregulation of stabilin-1 at sites of tissue injury, specifically at sites of immune cell recruitment and on subpopulations of hepatic macrophages. Functionally, stabilin-1 has been shown to mediate transendothelial migration of lymphocyte subsets in the setting of pro-inflammatory-activated human liver endothelium. In experimental models of liver fibrosis, stabilin-1 promotes the uptake of products of chronic oxidative stress by a subset of hepatic macrophages and suppresses their release of pro-inflammatory mediators that regulate tissue remodelling. These studies highlight the active contribution that scavenger receptors such as stabilin-1 can make in regulating chronic inflammation and tissue fibrosis, and their potential as novel therapeutic targets for these conditions. Full article

(This article belongs to the Special Issue Physiological Functions of Stabilin Receptors)

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35 pages, 11948 KiB

Open AccessArticle

Exploring the Molecular Mechanism of the Drug-Treated Breast Cancer Based on Gene Expression Microarray

by Ali Mohamed Alshabi, Basavaraj Vastrad, Ibrahim Ahmed Shaikh and Chanabasayya Vastrad

Biomolecules 2019, 9(7), 282; https://doi.org/10.3390/biom9070282 - 15 Jul 2019

Cited by 16 | Viewed by 6391

Abstract

Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential [...] Read more.

Breast cancer (BRCA) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers expressed during estradiol and tamoxifen treatment of BRCA. The microarray dataset of E-MTAB-4975 from Array Express database was downloaded, and the differential expressed genes (DEGs) between estradiol-treated BRCA sample and tamoxifen-treated BRCA sample were identified by limma package. The pathway and gene ontology (GO) enrichment analysis, construction of protein-protein interaction (PPI) network, module analysis, construction of target genes—miRNA interaction network and target genes-transcription factor (TF) interaction network were performed using bioinformatics tools. The expression, prognostic values, and mutation of hub genes were validated by SurvExpress database, cBioPortal, and human protein atlas (HPA) database. A total of 856 genes (421 up-regulated genes and 435 down-regulated genes) were identified in T47D (overexpressing Split Ends (SPEN) + estradiol) samples compared to T47D (overexpressing Split Ends (SPEN) + tamoxifen) samples. Pathway and GO enrichment analysis revealed that the DEGs were mainly enriched in response to lysine degradation II (pipecolate pathway), cholesterol biosynthesis pathway, cell cycle pathway, and response to cytokine pathway. DEGs (MCM2, TCF4, OLR1, HSPA5, MAP1LC3B, SQSTM1, NEU1, HIST1H1B, RAD51, RFC3, MCM10, ISG15, TNFRSF10B, GBP2, IGFBP5, SOD2, DHF and MT1H), which were significantly up- and down-regulated in estradiol and tamoxifen-treated BRCA samples, were selected as hub genes according to the results of protein-protein interaction (PPI) network, module analysis, target genes—miRNA interaction network and target genes-TF interaction network analysis. The SurvExpress database, cBioPortal, and Human Protein Atlas (HPA) database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. A comprehensive bioinformatics analysis was performed, and potential therapeutic applications of estradiol and tamoxifen were predicted in BRCA samples. The data may unravel the future molecular mechanisms of BRCA. Full article

(This article belongs to the Special Issue Systems Genomics Approaches for Understanding Multi-omics Data)

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15 pages, 3706 KiB

Open AccessArticle

A Hydroxypropyl Methylcellulose-Based Solid Dispersion of Curcumin with Enhanced Bioavailability and Its Hepatoprotective Activity

by Myoung-Sook Shin, Jun Sang Yu, Jaemin Lee, Young Seok Ji, Hee Joung Joung, Yu-Mee Han, Hye Hyun Yoo and Ki Sung Kang

Biomolecules 2019, 9(7), 281; https://doi.org/10.3390/biom9070281 - 15 Jul 2019

Cited by 32 | Viewed by 5050

Abstract

Curcumin is a polyphenol compound derived from the rhizomes of Curcuma longa that exhibits antioxidant, anti-inflammatory, anticancer, and antimicrobial properties. However, its low solubility in aqueous solutions, low absorption following oral administration, and rapid degradation limit its use as a functional food material. [...] Read more.

Curcumin is a polyphenol compound derived from the rhizomes of Curcuma longa that exhibits antioxidant, anti-inflammatory, anticancer, and antimicrobial properties. However, its low solubility in aqueous solutions, low absorption following oral administration, and rapid degradation limit its use as a functional food material. In this study, a hydroxypropyl methylcellulose-based solid dispersion of curcumin (DW-CUR 20) was prepared and its bioavailability was evaluated. In addition, its therapeutic efficacy as a hepatoprotective agent was investigated using the model of tert-butyl hydroperoxide (t-BHP)-induced hepatocyte damage. The rat plasma pharmacokinetic study showed that the oral curcumin bioavailability of DW-CUR 20 significantly increased compared to that of non-formulated curcumin. DW-CUR 20 showed a concentration-dependent hepatocyte protective effect on t-BHP-induced HepG2 cells. DW-CUR 20 inhibited the release of lactate dehydrogenase and decreased apoptosis-related proteins such as Poly (ADP-ribose) polymerase, cleaved caspase-7 and cleaved caspase-8 on t-BHP-treated HepG2 cells. These findings suggest that DW-CUR 20 could be a promising formulation for enhancing the therapeutic efficiency of curcumin and for improving the safety. Full article

(This article belongs to the Special Issue Carbohydrate Polymers: Science and Applications)

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13 pages, 1378 KiB

Open AccessArticle

Discovery and Rational Design of a Novel Bowman-Birk Related Protease Inhibitor

by Yuxi Miao, Guanzhu Chen, Xinping Xi, Chengbang Ma, Lei Wang, James F. Burrows, Jinao Duan, Mei Zhou and Tianbao Chen

Biomolecules 2019, 9(7), 280; https://doi.org/10.3390/biom9070280 - 14 Jul 2019

Cited by 13 | Viewed by 4558

Abstract

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family [...] Read more.

Anuran amphibian skin secretions are a rich source of peptides, many of which represent novel protease inhibitors and can potentially act as a source for protease inhibitor drug discovery. In this study, a novel bioactive Bowman-Birk type inhibitory hexadecapeptide of the Ranacyclin family from the defensive skin secretion of the Fukien gold-striped pond frog, Pelophlax plancyi fukienesis, was successfully isolated and identified, named PPF-BBI. The primary structure of the biosynthetic precursor was deduced from a cDNA sequence cloned from a skin-derived cDNA library, which contains a consensus motif representative of the Bowman-Birk type inhibitor. The peptide was chemically synthesized and displayed a potent inhibitory activity against trypsin (Ki of 0.17 µM), as well as an inhibitory activity against tryptase (Ki of 30.73 µM). A number of analogues of this peptide were produced by rational design. An analogue, which substituted the lysine (K) at the predicted P₁ position with phenylalanine (F), exhibited a potent chymotrypsin inhibitory activity (Ki of 0.851 µM). Alternatively, a more potent protease inhibitory activity, as well as antimicrobial activity, was observed when P¹⁶ was replaced by lysine, forming K¹⁶-PPF-BBI. The addition of the cell-penetrating peptide Tat with a trypsin inhibitory loop resulted in a peptide with a selective inhibitory activity toward trypsin, as well as a strong antifungal activity. This peptide also inhibited the growth of two lung cancer cells, H460 and H157, demonstrating that the targeted modifications of this peptide could effectively and efficiently alter its bioactivity. Full article

(This article belongs to the Special Issue Novel Natural-based Biomolecules Discovery for Tackling Chronic Diseases)

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23 pages, 2555 KiB

Open AccessEditor’s ChoiceReview

Flagella-Driven Motility of Bacteria

by Shuichi Nakamura and Tohru Minamino

Biomolecules 2019, 9(7), 279; https://doi.org/10.3390/biom9070279 - 14 Jul 2019

Cited by 236 | Viewed by 29298

Abstract

The bacterial flagellum is a helical filamentous organelle responsible for motility. In bacterial species possessing flagella at the cell exterior, the long helical flagellar filament acts as a molecular screw to generate thrust. Meanwhile, the flagella of spirochetes reside within the periplasmic space [...] Read more.

The bacterial flagellum is a helical filamentous organelle responsible for motility. In bacterial species possessing flagella at the cell exterior, the long helical flagellar filament acts as a molecular screw to generate thrust. Meanwhile, the flagella of spirochetes reside within the periplasmic space and not only act as a cytoskeleton to determine the helicity of the cell body, but also rotate or undulate the helical cell body for propulsion. Despite structural diversity of the flagella among bacterial species, flagellated bacteria share a common rotary nanomachine, namely the flagellar motor, which is located at the base of the filament. The flagellar motor is composed of a rotor ring complex and multiple transmembrane stator units and converts the ion flux through an ion channel of each stator unit into the mechanical work required for motor rotation. Intracellular chemotactic signaling pathways regulate the direction of flagella-driven motility in response to changes in the environments, allowing bacteria to migrate towards more desirable environments for their survival. Recent experimental and theoretical studies have been deepening our understanding of the molecular mechanisms of the flagellar motor. In this review article, we describe the current understanding of the structure and dynamics of the bacterial flagellum. Full article

(This article belongs to the Special Issue Perspectives on Bacterial Flagellar Motor)

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17 pages, 2970 KiB

Open AccessEditor’s ChoiceArticle

A Sesquiterpenoid from Farfarae Flos Induces Apoptosis of MDA-MB-231 Human Breast Cancer Cells through Inhibition of JAK–STAT3 Signaling

by Hyeri Jang, Hyejin Ko, Kwangho Song and Yeong Shik Kim

Biomolecules 2019, 9(7), 278; https://doi.org/10.3390/biom9070278 - 13 Jul 2019

Cited by 25 | Viewed by 5408

Abstract

Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching [...] Read more.

Triple-negative breast cancers (TNBCs) are hard-to-treat breast tumors with poor prognosis, which need to be treated by chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in proliferation, metastasis, and invasion of cancer cells. Therefore, research on searching for promising compounds with metabolism that suppress phosphorylation or transcription of STAT3 in TNBC cells is important. Farfarae Flos is well known as a traditional medicine for treating inflammation. However, few studies have shown that sesquiterpenoids from Farfarae Flos have an anticancer effect. In this study, efficient separation methods and an MTT assay were conducted to isolate an anticancer compound from Farfarae Flos against TNBC MDA-MB-231 cells. Here, 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a compound isolated from Farfarae Flos showed a potent cytotoxic effect on MDA-MB-231 cells. ECN inhibited JAK–STAT3 signaling and suppressed the expression of STAT3 target genes. In addition, ECN induced apoptosis through both extrinsic and intrinsic pathways. Furthermore, we investigated that ECN inhibited the growth of tumors by intraperitoneal administration in mice injected with MDA-MB-231 cells. Therefore, ECN can be an effective chemotherapeutic agent for breast cancer treatment. Full article

(This article belongs to the Special Issue Antitumor Agents from Natural Sources)

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10 pages, 230 KiB

Open AccessArticle

Association of Asymmetric Dimethylarginine and Diastolic Dysfunction in Patients with Hypertrophic Cardiomyopathy

by Kathrin Cordts, Doreen Seelig, Natalie Lund, Lucie Carrier, Rainer H. Böger, Maxim Avanesov, Enver Tahir, Edzard Schwedhelm and Monica Patten

Biomolecules 2019, 9(7), 277; https://doi.org/10.3390/biom9070277 - 13 Jul 2019

Cited by 8 | Viewed by 3660

Abstract

Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of [...] Read more.

Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of NOS. This study aimed to analyze the association of Arg and its derivates, i.e., l-homoarginine (hArg), ADMA and symmetric dimethylarginine (SDMA), with DD in HCM patients. In 215 HCM patients (mean age 54 ± 15 years, 58% male) transmitral and mitral annulus velocities were echocardiographically analyzed. Plasma concentrations of Arg derivatives were measured by liquid chromatography tandem-mass spectrometry. In 143 (70%) patients suffering from DD, ADMA showed the strongest association with DD (0.66 ± 0.16, 0.72 ± 0.24, and 0.76 ± 0.26 µmol/L, p < 0.01 for trend). In linear regression analyses, positive association per standard deviation increase of ADMA was found with E-wave (beta coefficient (95% confidence interval): 4.72 (0.43–9.01); p < 0.05) and mean E/E’ (1.76 (0.73–2.79) p < 0.001). Associations were adjusted for age, sex, body mass index (BMI), diabetes mellitus, coronary artery disease, and arterial hypertension. Elevated ADMA is associated with the severity of DD in HCM. Higher ADMA level might lead to decreased NO production and thus an impaired myocardial relaxation pattern. Full article

(This article belongs to the Section Molecular Medicine)

11 pages, 1871 KiB

Open AccessArticle

High-Throughput Screening of Chlorella Vulgaris Growth Kinetics inside a Droplet-Based Microfluidic Device under Irradiance and Nitrate Stress Conditions

by Marwa Gamal Saad, Noura Sayed Dosoky, Muhammad Shuja Khan, Mohamed Shafick Zoromba, Laila Mekki, Magdy El-Bana, David Nobles and Hesham Mohamed Shafik

Biomolecules 2019, 9(7), 276; https://doi.org/10.3390/biom9070276 - 12 Jul 2019

Cited by 14 | Viewed by 4183

Abstract

Biodiesel is an eco-friendly renewable fuel that can be derived from microalgae. Maximization of biomass and lipid productivities are considered the main challenges for algal biodiesel production. Since conventional batch cultures are time-, space-, and reagent-consuming with many restrictions to apply many replicates, [...] Read more.

Biodiesel is an eco-friendly renewable fuel that can be derived from microalgae. Maximization of biomass and lipid productivities are considered the main challenges for algal biodiesel production. Since conventional batch cultures are time-, space-, and reagent-consuming with many restrictions to apply many replicates, microfluidic technology has recently emerged as an alternative low-cost and efficient technology with high throughput repeatability and reproducibility. Different applications of microfluidic devices in algal biotechnology have been reported, including cell identification, sorting, trapping, and metabolic screening. In this work, Chlorella vulgaris was investigated by encapsulating in a simple droplet-based micro-array device at different light intensities of 20, 80, and 200 µmol/m²/s combined with different nitrate concentrations of 17.6, 8.8, and 4.4 mM. The growth results for C. vulgaris within microfluidic device were compared to the conventional batch culture method. In addition, the effect of combined stress of deficiencies in irradiance and nitrogen availability were studied to illustrate their impact on the metabolic profiling of microalgae. The results showed that the most optimum favorable culturing conditions for Chlorella vulgaris growth within the microfluidic channels were 17.6 mM and 80 µmol/m²/s. Full article

(This article belongs to the Section Synthetic Biology and Bioengineering)

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0 pages, 4409 KiB

Open AccessArticle

RETRACTED: Ailanthone Induces Cell Cycle Arrest and Apoptosis in Melanoma B16 and A375 Cells

by Wenjing Liu, Xiaona Liu, Zhaohai Pan, Dan Wang, Minjing Li, Xiaoyu Chen, Ling Zhou, Maolei Xu, Defang Li and Qiusheng Zheng

Biomolecules 2019, 9(7), 275; https://doi.org/10.3390/biom9070275 - 11 Jul 2019

Cited by 25 | Viewed by 6812 | Retraction

Abstract

Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of [...] Read more.

Malignant melanoma is the most lethal type of skin cancer. Previous studies have shown that ailanthone has potent antitumor activity in a variety of cell lines. However, the anti-tumor effect of ailanthone on malignant melanoma remains unclear. To investigate the anti-tumor mechanisms of ailanthone in human melanoma B16 and mouse melanoma A375 cells, the cell counting kit-8 assay, colony formation assay, DNA content analysis, Hoechst 33258, and Annexin V-FITC/PI staining were used to assess cell proliferation, cell cycle distribution, and cell apoptosis, respectively. Western blotting was performed to evaluate the expression of cell cycle- and apoptosis-related proteins and regulatory molecules. The results showed that ailanthone significantly inhibited melanoma B16 and A375 cell proliferation as well as remarkably induced cell cycle arrest at the G0–G1 phase in B16 cells and the G2–M phase in A375 cells in a dose-dependent manner. Further investigation revealed that ailanthone promoted the expression of p21 and suppressed the expression of cyclin E in B16 cells or cyclin B in A375 cells through the PI3K-Akt signaling pathway. In addition, ailanthone induced B16 and A375 cell apoptosis via a caspase-dependent mechanism. Further studies showed that ailanthone remarkably downregulated Bcl-2 and upregulated Apaf-1 and Bax, and subsequently increased mitochondrial membrane permeabilization and released cytochrome c from the mitochondria in B16 cells and A375 cells. Taken together, ailanthone induces cell cycle arrest via the PI3K-Akt signaling pathway as well as cell apoptosis via the mitochondria-mediated apoptotic signaling pathway. Ailanthone may be potentially utilized as an anti-tumor agent in the management of malignant melanoma. Full article

(This article belongs to the Section Molecular Medicine)

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8 pages, 1157 KiB

Open AccessCommunication

tRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis

by Linyuan Shen, Zhendong Tan, Mailin Gan, Qiang Li, Lei Chen, Lili Niu, Dongmei Jiang, Ye Zhao, Jinyong Wang, Xuewei Li, Shunhua Zhang and Li Zhu

Biomolecules 2019, 9(7), 274; https://doi.org/10.3390/biom9070274 - 11 Jul 2019

Cited by 43 | Viewed by 6984

Abstract

tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high [...] Read more.

tRNA-derived fragments (tRFs), a novel type of non-coding RNA derived from tRNAs, play an important part in governing gene expressions at a post-transcriptional level. To date, the regulatory mechanism of tRFs governing fat deposition and adipogenesis is completely unknown. In this study, high fat diet was employed to induce an obese rat model, and tRFs transcriptome sequencing was conducted to identify differentially expressed tRFs that response to obesity. We found out that tRF^GluTTC, which promoted preadipocyte proliferation by increasing expressions of cell cycle regulatory factors, had the highest fold change in the 296 differentially expressed tRFs. Moreover, tRF^GluTTC also suppressed preadipocyte differentiation by reducing triglyceride content and lipid accumulation, and by decreasing expressions of genes that related to fatty acid synthesis. According to results of luciferase activity analysis, tRF^GluTTC directly targeted Kruppel-like factor (KLF) 9, KLF11, and KLF12, thus significantly suppressing mRNA expressions of these target genes. Moreover, tRF^GluTTC suppressed adipogenesis, accompanying by suppressing expressions of adipogenic transcription factors (aP2, PPARγ, and C/EBPα). In conclusion, these results imply that tRF^GluTTC may act as a novel epigenetic molecule regulating adipogenesis and could provide a new strategy for the intervention treatment of obesity. Full article

(This article belongs to the Special Issue Obesity and Hormones)

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14 pages, 1270 KiB

Open AccessReview

Ligand Binding and Signaling of HARE/Stabilin-2

by Edward N. Harris and Fatima Cabral

Biomolecules 2019, 9(7), 273; https://doi.org/10.3390/biom9070273 - 11 Jul 2019

Cited by 23 | Viewed by 4352

Abstract

The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external [...] Read more.

The Stabilin receptors are a two-member family in the type H class of scavenger receptors. These dynamic receptors bind and internalize multiple ligands from the cell surface for the purpose of clearing extracellular material including some synthetic drugs and for sensing the external environment of the cell. Stabilin-1 was the first receptor to be cloned, though the biological activity of Hyaluronic Acid Receptor for Endocytosis (HARE)/Stabilin-2 was observed about 10 years prior to the cloning of Stabilin-1. Stabilin-1 has a more diverse expression profile among the tissues than HARE/Stabilin-2. This review will focus on HARE/Stabilin-2 and its interactions with hyaluronan, heparin, and phosphorothioate antisense oligonucleotides and what is known about how this receptor participates in signaling upon ligand binding. Full article

(This article belongs to the Special Issue Physiological Functions of Stabilin Receptors)

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16 pages, 3243 KiB

Open AccessArticle

Analysis and Identification of Active Compounds from Gami-Soyosan Toxic to MCF-7 Human Breast Adenocarcinoma Cells

by Mi-Yeon Jung, Chang-Seob Seo, Seon-Eun Baek, Jaemin Lee, Myoung-Sook Shin, Ki Sung Kang, Sullim Lee and Jeong-Eun Yoo

Biomolecules 2019, 9(7), 272; https://doi.org/10.3390/biom9070272 - 10 Jul 2019

Cited by 11 | Viewed by 4066

Abstract

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy [...] Read more.

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy is a big burden. However, little is known about the components and their mechanism of action that exhibit these beneficial effects of Gami-soyosan. The aim of this study was to simultaneously analyze compounds of Gami-soyosan, and determine their cytotoxic effects on estrogen receptor (ER)-positive MCF-7 human breast adenocarcinoma cells. We established a simultaneous analysis method of 18 compounds contained in Gami-soyosan and found that, among the various compounds in Gami-soyosan, gallic acid (1), decursin (17), and decursinol angelate (18) suppressed the viability of MCF-7 cells. Gallic acid (1), decursin (17), and decursinol angelate (18) induced apoptotic cell death and significantly increased poly (ADP-ribose) polymerase (PARP) cleavage and the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) ratio. Decursin (17) increased the expression of cleaved caspases-8, -9, -7, and -3. Decursinol angelate (18) increased the expression of cleaved caspase-8 and -7. These three components altered the different apoptosis signal pathways. Collectively, gallic acid (1), decursin (17), and decursinol angelate (18) may be used to inhibit cell proliferation synergistically in patients with ER-positive breast cancer. Full article

(This article belongs to the Section Natural and Bio-derived Molecules)

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23 pages, 1264 KiB

Open AccessReview

Role of Dietary Supplements in the Management of Parkinson’s Disease

by Michele Ciulla, Lisa Marinelli, Ivana Cacciatore and Antonio Di Stefano

Biomolecules 2019, 9(7), 271; https://doi.org/10.3390/biom9070271 - 10 Jul 2019

Cited by 70 | Viewed by 14325

Abstract

The use of food supplements or functional food has significantly increased in the past decades, especially to compensate both the modern lifestyle and the food shortages of the industrialized countries. Despite food supplements are habitually intended to correct nutritional deficiencies or to support [...] Read more.

The use of food supplements or functional food has significantly increased in the past decades, especially to compensate both the modern lifestyle and the food shortages of the industrialized countries. Despite food supplements are habitually intended to correct nutritional deficiencies or to support specific physiological functions, they are often combined with common drug therapies to improve the patient’s health and/or mitigate the symptoms of many chronic diseases such as cardiovascular diseases, cystic fibrosis, cancer, liver and gastrointestinal diseases. In recent years, increased attentions are given to the patient’s diet, and the use of food supplements and functional food rich in vitamins and antioxidants plays a very important role in the treatment and prevention of neurodegenerative diseases such as Parkinson’s disease (PD). Natural compounds, phytochemicals, vitamins, and minerals can prevent, delay, or alleviate the clinical symptoms of PD in contrast to some of the main physiopathological mechanisms involved in the development of the disease, like oxidative stress, free radical formation, and neuroinflammation. The purpose of this review is to collect scientific evidences which support the use of specific biomolecules and biogenic elements commonly found in food supplements or functional food to improve the clinical framework of patients with PD. Full article

(This article belongs to the Special Issue Advances in Parkinson's Disease Drugs)

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14 pages, 904 KiB

Open AccessReview

Molecular Pathways Modulated by Curcumin Analogue, Diarylpentanoids in Cancer

by Felicia Paulraj, Faridah Abas, Nordin H. Lajis, Iekhsan Othman and Rakesh Naidu

Biomolecules 2019, 9(7), 270; https://doi.org/10.3390/biom9070270 - 10 Jul 2019

Cited by 42 | Viewed by 9821

Abstract

While curcumin has a range of therapeutic benefits, its potent anticancer activity remains an attractive avenue for anticancer research owing to the multifactorial nature of cancer itself. The structure of curcumin has thus been used as a lead to design more potent analogues, [...] Read more.

While curcumin has a range of therapeutic benefits, its potent anticancer activity remains an attractive avenue for anticancer research owing to the multifactorial nature of cancer itself. The structure of curcumin has thus been used as a lead to design more potent analogues, and diarylpentanoids in particular have shown improved cytotoxicity over curcumin. Investigations of diarylpentanoids have demonstrated that these compounds exert anti-cancer effects through several signalling pathways that are associated with cancer. This review focuses on selected diarylpentanoids and highlights molecular targets that modulate key pathways involved in cancer such as NF-κB, MAPK/ERK, and STAT signalling. Future research will need to focus on drug interactions to explore potential synergistic actions of diarylpentanoids and further establish the use of diverse animal models. Full article

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54 pages, 1623 KiB

Open AccessEditor’s ChoiceReview

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

by Marianna Tosato and Valerio Di Marco

Biomolecules 2019, 9(7), 269; https://doi.org/10.3390/biom9070269 - 9 Jul 2019

Cited by 56 | Viewed by 10034

Abstract

The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or [...] Read more.

The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant K_d (both computed at pH = 7.4 and at total metal and ligand concentrations of 10⁻⁶ and 10⁻⁵ mol/L, respectively), charge and stoichiometry of the most abundant metal–ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal–ligand speciation of PD drugs is underlined. Full article

(This article belongs to the Special Issue Advances in Parkinson's Disease Drugs)

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11 pages, 2047 KiB

Open AccessArticle

Carbon-Carbon Double Bond and Resorcinol in Resveratrol and Its Analogues: What Is the Characteristic Structure in Quenching Singlet Oxygen?

by Qingjun Kong, Xueyan Ren, Jianrui Qi, Jia Yu, Jun Lu and Shuo Wang

Biomolecules 2019, 9(7), 268; https://doi.org/10.3390/biom9070268 - 9 Jul 2019

Cited by 9 | Viewed by 3569

Abstract

Stilbenes, particularly resveratrol and resveratrol dimers, could effectively quench singlet oxygen (¹O₂). It was reported that both resorcinol and carbon-carbon double bond quenching ¹O₂ can participate in the mechanism. However, it is still not clear which structure [...] Read more.

Stilbenes, particularly resveratrol and resveratrol dimers, could effectively quench singlet oxygen (¹O₂). It was reported that both resorcinol and carbon-carbon double bond quenching ¹O₂ can participate in the mechanism. However, it is still not clear which structure plays a dominant role in quenching ¹O₂. To investigate the characteristic structure in the mechanism of quenching ¹O₂, the resveratrol, pterostilbene and piceatannol quenching ¹O₂ abilities were compared by UHPLC-QTOF-MS² and UHPLC-QQQ-MS². Results showed that catechol, carbon-carbon double bond and resorcinol participated in the quenching of ¹O₂. Catechol ring plays a leading role in the mechanism, and the contribution of the structures in quenching ¹O₂ activity are as follows: catechol ring > carbon-carbon double bond > resorcinol ring, which is supported by the calculation of energy. Our findings will contribute to the future screening of stilbenes with higher activity, and those stilbenes may have great therapeutic potential in ¹O₂-mediated diseases. Full article

(This article belongs to the Section Chemical Biology)

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22 pages, 5893 KiB

Open AccessArticle

High Proton Conducting Polymer Blend Electrolytes Based on Chitosan:Dextran with Constant Specific Capacitance and Energy Density

by Shujahadeen B. Aziz, M. H. Hamsan, Wrya O. Karim, M. F. Z. Kadir, M. A. Brza and Omed Gh. Abdullah

Biomolecules 2019, 9(7), 267; https://doi.org/10.3390/biom9070267 - 9 Jul 2019

Cited by 75 | Viewed by 4615

Abstract

Polymer blend electrolytes based on chitosan: dextran (CS:Dext) incorporated with various amounts of ammonium fluoride (NH₄F) with constant specific capacitance (12.4 F/g) and energy density over 100 cycles were prepared using a solution cast technique. The blend electrolyte samples exhibit broader [...] Read more.

Polymer blend electrolytes based on chitosan: dextran (CS:Dext) incorporated with various amounts of ammonium fluoride (NH₄F) with constant specific capacitance (12.4 F/g) and energy density over 100 cycles were prepared using a solution cast technique. The blend electrolyte samples exhibit broader amorphous humps in X-ray diffraction (XRD) spectra compared to pure CS:Dext film. The Fourier transform infrared (FTIR) study indicates the complex formation of the added ammonium salt with the polymer blend functional groups through the shifting and decrease in the intensity of FTIR bands. The impedance plots were used to determine the conductivity of the samples. The field emission scanning electron microscopy (FESEM) images support the conductivity behavior of the samples. The impedance plots were applied in the determination of the conductivity of the samples in which the relatively highest conductivity was gained to be 1 × 10⁻³ S/cm. The transference number measurement (TNM) of the conducting electrolyte was 0.88, which portrays the dominancy of ion in the conduction process. Linear sweep voltammetry (LSV) verified the chemical stability and showed it to be 1.7 V and an effective electrical double layer capacitor (EDLC) that is applicable in electrochemical devices. The performance of the EDLC cell was examined using both cyclic voltammetry and constant current charge–discharge techniques at ambient temperature. The semi-rectangular shape of the cyclic voltammetry (CV) plot and no redox peak was observed. The charge-discharge process of the fabricated EDLC is durable over 100 cycles with an equivalent circuit resistance and power density of 194.5 Ω and 428 W/kg, respectively. Two main outcomes, the specific capacitance and energy densities of 12.4 Farad/g and 1.4 Wh/kg, respectively, are almost constant over 100 cycles. Full article

(This article belongs to the Special Issue Carbohydrate Polymers: Science and Applications)

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10 pages, 1053 KiB

Open AccessReview

Endosymbiotic Evolution of Algae, Secondary Heterotrophy and Parasitism

by Miroslav Oborník

Biomolecules 2019, 9(7), 266; https://doi.org/10.3390/biom9070266 - 8 Jul 2019

Cited by 37 | Viewed by 8760

Abstract

Photosynthesis is a biochemical process essential for life, serving as the ultimate source of chemical energy for phototrophic and heterotrophic life forms. Since the machinery of the photosynthetic electron transport chain is quite complex and is unlikely to have evolved multiple independent times, [...] Read more.

Photosynthesis is a biochemical process essential for life, serving as the ultimate source of chemical energy for phototrophic and heterotrophic life forms. Since the machinery of the photosynthetic electron transport chain is quite complex and is unlikely to have evolved multiple independent times, it is believed that this machinery has been transferred to diverse eukaryotic organisms by endosymbiotic events involving a eukaryotic host and a phototrophic endosymbiont. Thus, photoautotrophy, as a benefit, is transmitted through the evolution of plastids. However, many eukaryotes became secondarily heterotrophic, reverting to hetero-osmotrophy, phagotrophy, or parasitism. Here, I briefly review the constructive evolution of plastid endosymbioses and the consequential switch to reductive evolution involving losses of photosynthesis and plastids and the evolution of parasitism from a photosynthetic ancestor. Full article

(This article belongs to the Special Issue Evolutionary and Molecular Aspects of Plastid Endosymbioses)

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