ISSN (Print): 1389-2037
ISSN (Online): 1875-5550
Volume 20, 12 Issues, 2019
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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550
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Ben M. Dunn Department of Biochemistry and Molecular Biology
University of Florida, College of Medicine,
P.O. Box 100245, Gainesville Florida, FL 32610-0245 USA
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3 Abstract Ahead of Print are available electronically
15 Articles Ahead of Print are available electronically
Dietary protein is of vital importance in mammals, which can serve as building blocks for tissue, fuels for small intestinal mucosa and
precursors of numerous essential substances such as enzymes, hormones and antibodies.
The digestion of dietary protein in mammals is mainly carried out in the stomach and small intestine. In mammals, protein is broken down
into amino acids (AAs), and then sent to the body through blood circulation. AAs that reach liver contribute to liver proteins and plasma proteins,
and the rest go through the systemic circulation from liver to other tissue cells for tissue proteins, and promote body tissue update,
growth and the formation of animal products . Lv et al. reported the regulatory role of dietary protein on bone metabolism via GH/IGF
axis. AAs can also compound antibodies, enzymes, nitrogen hormones and convert to nucleotides, choline and other active substances. The
escaped AAs will enter the large intestine for further fermentation by the vast gut microbiota and generates short chain fatty acids or amines.
He et al. revealed the gut mucus-microbial interplay under stress. Wang et al. reviewed the protein utilization by probiotics in gastrointestinal
tract. These metabolites elicit a wide range of biological functions via different receptors and mechanisms .
Bioavailability of protein in mammals is affected by many factors. Different kinds of animals have varied digestion and absorption mode
for the same dietary protein for their different physiological features of digestive system. The AA composition of the protein is closely related
to the nutritional value of the protein. It is necessary to consider AA imbalance and antagonism in order to ensure that the animals achieve the
maximum deposition rate of dietary protein. Kim et al. reported the significance of AAs supplementation on protein-restricted diets in pigs.
Zhao et al. proposed some nutritional approaches to improve the feed protein utilization in cattle. The composition of diets such as protein
and fiber level also matters. With the increase of fiber level, the rate of protein emptying in the digestive tract also increases, which reduces
the enzyme action time and the absorption by the intestinal tract .
There is increasing evidence that microbial ecosystem of the gastrointestinal tract is largely influenced by dietary factors. Ingested nutrients
can be digested and bio-conversed in the digestive tract by host and intestinal microbiota. Both level and source of proteins modulate
intestinal micobiota composition and function . Hao et al. summarized the physiological functions of lactoferrin. Different dietary protein
level alters the composition of gut microbiota and intestinal barrier function in adult pig model . Highly digestible protein sources can be
digested by enzymes in the proximal intestine, resulting in less possibility for microbial fermentation [6, 7]. In addition, proteins from different
sources in diet have specific AA composition, which can induce the transcription level of genes such as Cationic amino acid transporters
(CAT1) and Excitatory amino acid carrier (EAAC1), which plays a role in AA transporter in gut. Intestinal microbiota composition and function
are affected in this process by the alteration of AA balance [8, 9], and Zhao et al. reviewed the role of dietary protein on gut microbiota
composition and function. When these AA materials are transported to the liver, the hepatocytes play important metabolic and detoxifying
roles. Che et al. concluded the Xenosensors act in chemical detoxification metabolism.
In this theme issue, we focus on the bioavailability and turnover of dietary protein in mammals, as well as their interactions with microbiota,
which will shed light on highlighting their mechanisms of physiological functions in mammals.
Mixed-mode (multimodal) chromatography now occupies an important place in biopharmaceutical purification. It adds a new dimension
to such conventional chromatographies as ion-exchange, hydrophobic interaction, reverse-phase and size-exclusion. Mixed-mode chromatography
resins are composed of multiple functional groups that help protein binding and elution. These groups on resins confer hydrophobic,
aromatic, electrostatic and hydrogen-bonding interactions. Earlier version of mixed-mode resins was composed of aliphatic hydrophobic
groups and used extensively for extraction and purification of small organic compounds, but is not useful for proteins, as the protein binding
is too strong to elute without application of organic solvents. Namely, such aliphatic mixed-mode resins are essentially identical to the operational
procedure of reverse-phase chromatography. Later version of mixed-mode resin is composed of aromatic and charged groups, which
make protein binding salt-tolerant: namely, protein binding occurs in the presence of salt. Such multiple binding mechanisms of mixed-mode
chromatography offer various advantages, which are a topic of this special issue.
Halan et al. provide an overview of various mixed-mode ligands and their application for separation of peptides, proteins, nucleic acids
and small molecules . Santarelli and Cabanne describe application of mixed-mode chromatography for antibody purification and its selectivity
, followed by Cabanne and Santarelli who describe the development of a high-throughput screening to fully utilize mixed-mode
chromatography technique . Arakawa et al.  describe solvents to selectively elute the bound proteins during MEP chromatography, as an
alternative to the conventional low pH elution. Solvents, or elution modifiers, play a critical role in separation and recovery during mixedmode
chromatography. Arakawa and Kita describe fundamental mechanism of the effects of solvents on macromolecular interactions based
on protein-solvent interaction analysis. Among the elution modifiers used, arginine has been extensively used for washing and elution in
mixed-mode chromatography . Hirano et al. describe the mechanism by which arginine exerts its effects on disrupting interactions between
proteins and mixed-mode ligands . Nucleic acids also have both electrostatic and hydrophobic properties and hence are potential candidates
for purification by mixed-mode chromatography, in particular due to their different conformational states. Matos and Bülow compare
mixed-mode chromatography with ion-exchange or hydrophobic interaction chromatography for nucleic acid purification . In two papers
Arakawa et al. and Arakawa demonstrate the usefulness of mixed-mode chromatography in separation of protein isoforms [8, 9]. He et al.
report use of mixed-mode chromatography in removal of contaminants, which have similar properties to the target antibody, IgM . Yoshimoto
et al. report the selectivity of hydroxyapatite chromatography utilizing its electrostatic and metal affinity properties. I believe that
these papers provide readers comprehensive views of mixed-mode chromatography .
I wish to thank the staff of Current Peptide and Protein Science for their assistance in developing this Hot Topics issue and Professor Ben
Dunn, Editor-in-Chief of CPPS, for his encouragement.
Transforming Growth Factor beta (TGF-β) family of peptides is compose by the subfamilies of TGF-β,
BMP and Activins. This broad and versatile family of peptide has several physiological and pathological
functions in many tissues. The importance of these functions has been demonstrated in a wide variety
of processes, including development, differentiation, angiogenesis, apoptosis and survival. Moreover a
dysregulated expression or aberrant signaling associated to peptides of (TGF-β) family can contribute to
the development and progression of multiple human pathophysiological processes such as diabetes,
cancer, and cardiovascular, skeletal muscle and renal disease. These pathological status can be
potentiated by aging which is highly relevant considering that the population affected by chronic disease
and aging is increasing in the last decades.
We encourage investigators to contribute reviews articles that summarize recent findings in both basic
and clinical research in the field of the role of TGF-β family of peptides in both physiological and
pathological status that will help to discuss current outcome and to understand the cellular and
molecular mechanism involved. The potential topics include, but are not limited to:
β New mechanisms involved on the deleterious effect of TGF-β family of peptides in aging and
β Recent advances on cellular and molecular aspects of mechanism, therapy or prevention of
diseases in which TGF-β family is involved and potentially can be a target for interventions.
β Studies directed to find and develop new drugs anti- TGF-β family for prevention of pathological
β Signaling pathways that contribute effect of TGF-β family of peptides during development or
Protein and peptide based therapy of various human diseases has been the backbone of healthy society. Over the years, this
approach has yielded rich dividends in terms of scientific achievements and medical accomplishments. This hot topic issue
covers new emerging trends in protein and peptide based therapeutic approaches.
The part-II of this issue has incorporated the review articles covering new dimensions of protein and peptide based vaccine
development with articles exploring new dimensions of chemotherapeutic drugs and plasma proteins, protein-protein interaction
in various diseases, immunogenicity in protein and peptide based therapeutics, and polymer based protein therapeutics,
urotensin based pathophysiological regulation of various disorders. These articles provide a detailed account of the usage and
applications of the above-mentioned approaches in therapeutics of various human diseases.
Zia et al. contributed an article describing a detailed view of the interaction of a number of clinically important therapeutic
drugs currently in use that show covalent or non-covalent interaction with serum proteins.
Rabbani et al. contributed an article describing the role of protein-protein interactions in various diseases and their prediction
Fernández et al. contributed an article describing the overview of immunogenicity in protein and peptide based-therapeutics.
Bhawani et al. contributed an article describing the challenges in formulation of therapeutic proteins, synthetic routes of
conjugates, smart polymer–proteins conjugates and some advantages/disadvantages of polymers as a carrier system of proteins.
These review articles would expectedly make a wonderful read for the researchers and clinicians working for the quest of
protein and peptide based therapeutics.
I, as Guest Editor, would like to express my heartfelt gratitude to the many authors who contributed to this special issue,
reporting investigations on various aspects concerning New Emerging Trends in Protein and Peptide Based Therapeutic
Protein and peptide based therapy of various human diseases has been the backbone of healthy society. Over the years, this approach has
yielded rich dividends in terms of scientific achievements and medical accomplishments. This hot topic issue covers new emerging trends in
protein and peptide based therapeutic approaches.
The part-I of this issue has incorporated the review articles covering latest updates on the therapeutic role of proteins and peptides in various
human diseases like breast cancer, neurodegenerative disorders like Autism Spectrum Disorders and Alzheimer’s disease, systemic lupus
erythematosus, leprosy, and obesity. One review article explores urotensin based pathophysiological regulation of various disorders. These
articles effectively update the latest findings on the role of protein and peptide based therapeutic approaches for these major human diseases.
Rizvi et al. contributed an article describing therapeutic targeting of amyloid precursor protein and its processing enzymes for breast cancer
Alexiou et al. contributed an article describing several pieces of evidence associated with the correlations of misfolding proteins and neurodegenerative
diseases, and presented computational analysis of the various essential proteins.
Fatima et al. contributed an article describing emerging targets and latest proteomics based therapeutic approaches in neurodegenerative
Alexiou et al. contributed an article describing significant correlations between proteins linked to Autism Spectrum Disorders and Alzheimer’s
Khan et al. contributed an article describing the impact of hydroxyl radical modified-human serum albumin autoantigens in Systemic
Tarique et al. contributed an article describing the role of various subtypes of T-cell and their cytokines in the pathogenesis of leprosy.
Guilherme et al. contributed an article focusing on the genes that confer susceptibility with a perspective on vaccine development to prevent
the rheumatic heart disease.
Queen et al. contributed an article describing the role and mechanism of carbonic anhydrase V in obesity and its therapeutic implications.
Svistunov et al. contributed an article describing the targets at Urotensin system for pharmacological intervention of a number of pathological
statuses and diseases.
These review articles would expectedly make a wonderful read for the researchers and clinicians working for the quest of protein and
peptide based therapeutics.
I, as Guest Editor, would like to express my heartfelt gratitude to the many authors who contributed to this special issue, reporting investigations
on various aspects concerning New Emerging Trends in Protein and Peptide Based Therapeutic Approaches– Part I.
Sarcopenia, the age-related loss of muscle mass and strength/function, is increasingly recognized as a major issue in geriatric
medicine. It is noteworthy that the study of this condition has recently extended beyond the boundaries of geriatrics, highlighting
the relevance of muscle physiology to the overall health status. Indeed, the assessment of sarcopenia is increasingly
invoked as an important tool for the risk stratification of patients suffering from a variety of medical conditions, such as liver
disease, cancer, cardiovascular disease, chronic kidney failure, among others. The wide range of negative health-related events
to which sarcopenia contributes has instigated intensive research efforts in the attempt to decipher its complex pathophysiology
and develop effective treatments. This mini thematic issue has been conceived as a fairly comprehensive overview of the state
of art on sarcopenia, including operational definition, pathogenic processes, candidate biomarkers, and potential therapeutic
interventions [1-6]. The contribution by Ponziani & Gasbarrini  on the relevance of sarcopenia in advanced liver disease has
been included to acknowledge the growing interest in muscle decline outside the original field of geriatric medicine.
The opening article by Landi et al.  provides an overview on current definitions, diagnosis, and treatment of sarcopenia.
Special emphasis is placed on the ongoing debate regarding the need of adopting an univocal definition of sarcopenia as an essential
requisite to promote its clinical implementation and the development of new treatments. As pointed out by Calvani et al.
, the lack of a unique definition of sarcopenia impacts the identification of meaningful biomarkers for the condition. Such a
task is also challenged by the multifaceted and only partly understood pathophysiology of sarcopenia. The complexity of muscle
aging is epitomized by the controversial role played by oxidative stress in this process, as discussed by Fougère et al. .
While the free radical theory of aging provides a strong rationale for the use of antioxidants as a countermeasure for sarcopenia,
the evidence of benefits is still inconclusive. On the other hand, the review by Anton et al.  reports on the efficacy of multimodal
interventions combining exercise and specific nutritional supplementation regimens at improving muscle mass and
strength in old age. β-hydroxy-β-methylbutyrate, a metabolite of leucine, and taurine, a pleiotropic amino acid, are two promising
nutritional agents against age-related muscle loss, as reviewed by Cruz-Jentoft  and Scicchitano & Sica , respectively.
The last contribution discusses the importance of the assessment of sarcopenia in the clinical management of patients with advanced
liver disease . The authors also illustrate similarities and differences in the pathogenesis of sarcopenia of aging and
liver disease-associated muscle wasting.
As the guest editors, we wish that the collection of articles chosen for this mini thematic issue will stimulate the interest not
only of those working in the field, but also of scientists from other biomedical disciplines. Finally, we would like to sincerely
thank all of the authors and referees who have contributed to this issue.
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