ISSN (Print): 0929-8665
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Volume 28, 12 Issues, 2021
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Special Issue Submission
"Protein and Peptide Letters provides an excellent venue for communication of succinct reports of interesting research findings."
Jeffrey J. Gorman
Institute of Molecular Bioscience, Australia
Role of Protein catalysts in lignocellulosics digestibility to value added products
Guest Editor(s): Ikram ul Haq, Yong Xu
Submit Abstract via Email
Organic-Inorganic Hybrid Materials and Their Applications
Guest Editor(s): Kin-ya Tomizaki, Yoshio Hamada, Kenji Usui
It was a great experience working with Bentham Science Publishers. The reviews were fair, prompt and the suggestions given made us analyze our work more deeply and unearth important issues and their solutions.
The proof-reading process of Bentham Science was also prompt and author-friendly. They took utmost care to ensure that all of our concerns were addressed in the final published form of the paper. The discounts offered to authors were also most appreciated.
The fast communication and periodical updates made us submit another research paper to Bentham Science Publishers in their journal, Current Bioinformatics, which is currently under review
Thank you Bentham Science Publishers!
Assistant Professor. Shomona GJ (Department of CSE, SSN College of Engineering, Chenniai, India)
19 Abstract Ahead of Print are available electronically
2 Articles Ahead of Print are available electronically
Plants are exposed to environmental cues that affect their cellular, molecular, physiological, and developmental processes,
starting from seed germination and ending with harvesting. The omics approaches have emerged as an essential toolbox to
understand the molecular systems of plants and their functions. One of these approaches, proteomics, which refers to the study
of proteomes and the techniques used for the purification and analysis of proteins, has been used as a platform for improving
the understanding of biology. However, a highly considered opinion is that the abundance of a protein in a cell or an organism
cannot be predicted by the level of the corresponding mRNA, which happensin an integrative approach; the proteogenomics,
on the other hand, integrates the proteomics with genomics and transcriptomics, providing a unified understanding of cellular
functions. Though this approach has recently emerged, to fully utilize the data developed through genomics, transcriptomic,
and proteomics, the integration of bioinformatics (an umbrella of methods and software tools) and metabolomics (the study of
metabolites or a complete set of metabolites in a cell or organism, a metabolome) is required. In this thematic issue, two minireviews,
three reviews, and two research articles have been published.
It begins with article 1 entitled, “Genome-wide association studies (GWAS) for traits related to fodder quality and biofuel
in sorghum: progress and prospects.” Gupta and co-authors focus on GWAS studies on genetic architecture and dissection of
traits underpinning fodder quality and biofuel traits and their limited comparison with other related model crop species . In
article 2 entitled, “Plastid transcriptomics: An important tool for plastid functional genomics,” Ahmad et al. discuss the importance
of plastid transcriptomics for the acclimatization of plants under changing environmental conditions keeping in view
their tissue-specific dynamic morphology. Plastids, in addition to housing metabolic activities, serve as a global sensor for
both internal and external environmental cues and open dialogue with neighboring organelles to help the plant either respond
or adjust accordingly. Hence, normal plastid functioning is, therefore, critical for plant survival .
In article 3 entitled, “Potential application of CRISPR/Cas9 system to engineer abiotic stress tolerance in plants,” Professor
Li and co-authors explain the biology and the potential applications of the CRISPR/Cas9 (clustered regularly interspaced short
palindromic repeats/CRISPR-associated protein 9) system in improving the plant tolerance to abiotic stresses under changing
environmental cues while highlighting the genome editing using the CRISPR/Cas9-mediated approaches for sustainable agriculture
. In article 4 entitled, “Metabolomics: A powerful tool to study the complexity of wheat metabolome,” Razzaq et al.
discuss the applications of metabolomics to probe the stress-responsive metabolites and stress-inducive regulatory pathways
that govern abiotic/biotic stress tolerance in wheat and highlight the significance of metabolic profiling in characterizing the
wheat agronomics traits. Further, they describe the potential of metabolomics-assisted speed breeding and the need to fasttrack
the breeding by devising modern biotechnological tools for wheat improvement . In article 5 entitled, “Integration of
OMICS technologies for crop improvement,” Faryad et al. analyze the various technical challenges that arise while employing
OMICS technologies to crop plants .
In article 6 entitled, “Genome-wide association study for major biofuel traits in sorghum using minicore collection,” Rayaprolu
et al. comprehensively explain the high variability and heritability in sorghum minicore collection for agronomic and
biofuel traits. To analyze the agronomic traits and cell wall components, they used 245 sorghum minicore to perform a genome-
wide association study (GWAS), and candidate genes for each component were annotated. These genes were further
validated using in-silico approaches. The genome components were identified using the association analysis, and the identified
DNA fragments could be targeted to enhance the quality of biomass and yield. Consequently, the breeding efficiency is increased
for enhanced biofuel production . In article 7 entitled, “Characterization and expression analysis of resistance gene
analogs in elite sugarcane genotypes,” Parvaiz et al. explain that resistance gene analogs are present in most of the sugarcane
genotypes. RGA-specific primers have amplified fragments. Sequence characterization of these fragments has revealed 86-
99% sequence homology with the disease resistance proteins. Differential expression of five RGAs indicates their role in the
resistance development against diseases, and the identified fragments could be used as markers for the screening of diseaseresistant
genotypes . The use of such fragments to develop disease resistance using transgenic technology is further discussed.
Plants play an essential role in the life and health of human beings. The last few decades have witnessed great interest in
their use. Several plants demonstrated beneficial medicinal effects due to their phytochemical compounds, which include several
combinations of plant’s secondary products. Phytochemicals are bioactive chemical structures, naturally found in roots,
leaf, fruits, vegetables, grains, nuts, tea and seeds that are able to promote human health and prevent diseases . Their therapeutic
effects are then associated with the phytochemical composition, especially with the substances such as flavonoids, alkaloids,
sterols, terpenoids, phenolic acids, stilbenes, lignans, tannins and saponins.
Chronic diseases, such as obesity, liver diseases, diabetes, cardiovascular diseases, cancer and chronic respiratory diseases
are the leading cause of mortality in the world [2, 3]. There is an increasing amount of scientific data on the effects of the bioactive
compounds and biological properties such as: antioxidant activity, antimicrobial action, modulation of detoxification
enzymes, stimulation of the immune system, decrease of platelet aggregation, modulation of hormone metabolism/microbiome
and anticancer effects .
In this context, the aim of the present Special Issue is to bring new insights and understanding on the use of plants and
their bioactive compounds on treating and modulating chronic diseases and also review the main findings. The present thematic
issue has three review articles and three research articles covering the new tendencies and advances in plants and phytochemical
relevant studies for the drug development with new treatment perspective in the near future.
Starting with the effects of flavonoids, Hilzendeger Zilli reviewed the evidence and perspectives of this class of bioactive
compounds to modulate Metabolic Syndrome and neurodegenerative diseases. Their biological activity is commonly associated
with a potent antioxidant and anti-inflammatory response. Alternative mechanisms of action, such as changes in the gut
microbiota or modulation of the toxic proteins production are also discussed in this study .
Moving on to the liver diseases, Ribeiro et al. showed that Lafoensia pacari A. St. Hil. (Lythraceae), a savanna plant leave
extract, may induce hepatotoxic effects if orally administered. The Pacari is commonly used in the folk medicine culture despite
its toxicology being poorly studied. The data indicates that immense care is necessary for the plants . In the context of
Brazilian Savanna (Cerrado) biome, Guimarães et al. investigated the Solanum lycocarpum A. St. Hil. (Solanaceae) leave extract
ability to treat diabetes in a mice model. The plant popularly known as “Lobeira” has being commonly used to treat glycemic
disorders. The main results confirmed the metabolic improvements without significant toxicity effects at low doses .
Considering that cardiovascular diseases still are the leading cause of death worldwide, Ribeiro et al. reviewed the properties
of terpenes for treating cardiometabolic disorders. Terpenes are also known as terpenoids and are naturally produced by
plants and chemically characterized as “natural alkenes” with carbon-carbon double bond, which is considered as an unsaturated
hydrocarbon. The authors also show the great pharmacological potential of the plant terpenes compounds on drug development
Given the growing clinical relevance of the cancer treatment, Xavier et al. reviewed the main pathways related to the anticancer
effects of metabolites derived from Cerrado biome (savanna) plants with bioinformatics analysis on oral squamous cell
carcinoma. The authors indicate that five compounds commonly find in Cerrado plants (i.e., flavonoids, vinblastine, irinotecan,
etoposide and paclitaxel) are able to regulate cell proliferation with great potential on the tumorigenesis control .
Finally, Mendes et al. described the beneficial effects of oral association use of Lactococcus lactis probiotic and resveratrol
(3,5,40-trihydroxystilbene) on decreasing body weight and increasing beneficial gastrointestinal microbiota in mice.
Resveratrol is a nutraceutical compound found in grape skin and red wine possessing anti-obesity properties. The probiotic
association potentiate the microbiome improvement, thereby reducing IgA production .
We thank all the plant investigators who contributed to this Special Issue- it is always your commitment and hard work
that has made the science progress, bringing new perspectives and optimism for new chronic disease treatments.
In the past two decades molecular biomarkers have achieved importance in the field of medicine as diagnostic molecules
for the diagnosis and prognosis stratification of the diseases. Proteomics has proven to be a promising tool for discovering
biomarkers linked to several diseases, including endocrine dysfunctions. Furthermore the use of protemic technologies represents
an interesting tool in the characterization of the pathophysiology of several endocrine diseases, permitting to unveil the
molecular machinaries involved in the hormonal action and regulation. In this thematic issue, three review articles, five minireview
articles, one systematic review article and one letter are published.
At first, Maffezzoni et al., reviewed and summarized the current state in the field of the identification of new potential biomarkers
for acromegaly and GH use/abuse . Both acromegaly and growth hormone deficiency (GHD) are pathological
conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for
the definition of treatment, treatment monitoring and follow-up. Although GH and IGF-I are widely validated biomarkers of
acromegaly and GHD, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore,
new biological markers for acromegaly and GH replacement therapy are strongly needed.
Furthermore two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence
of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted
isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-
GHR). Chiloiro et al. evaluated in their review article the role of GH receptor polymorphisms in skeletal fragility in patients
affected by GHD and acromegaly .
Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by three cardinal symptoms: alacrimia,
achalasia and adrenal insufficiency due to ACTH insensitivity. Early identification of the syndrome is challenging, given the
rarity of the condition and high phenotypic heterogeneity even among members of the same family. In their mini-review,
Pogliaghi et al. aimed to summarize the current knowledge of clinical and molecular profile of patients with TAS and recommendations
for the diagnosis, management, and follow-up of patients .
Proteomics study have been performed moreover in endocrine cancers, aimed to identify and characterize functional proteins
that drive the transformation of malignancy, and to discover biomarkers to detect early-stage cancer, predict prognosis,
identify novel therapeutical targets, in a perspective of personalized medicine. Pancreatic neuroendocrine tumors (PanNETs)
are rare tumors having usually an indolent behavior, but sometimes with unpredictable aggressiveness. Diagnostic and prognostic
markers, but also new therapeutic targets of PanNETs, are still lacking. Bianchi et al. conducted a systematic review to
summarize the state of the art of proteomics in PanNETs .
Proteomic techniques have been widely applied in the last decade in the field of andrology. The entire sperm proteome carry
crucial information for fertilization and embryo development. Altogether, 6871 proteins have been reported in spermatozoa
so far. In their letter Cannarella et al. underlined the role of the sperm proteome in fertilization, preimplantation embryo development
and paternal epigenetic inheritance .
Seminal plasma proteome has moreover a pivotal role in fertilization, reflecting moreover the androgenic status of sexual
accessory glands. In their mini-review Grande et al. discuss the role of seminal proteins as a seminal fingerprint of male hypogonadism,
usefull for the diagnosis of patients with moderate grades of testosterone reduction and in the follow-up of testosterone
replacement treatment .
Apart from testosterone, Leydig cells secretes two other hormones: 25-OH vitamin D and Insulin-like factor 3 (INSL3).
INSL3 has endocrine anabolic functions on the bone-skeletal muscle unit. INSL3 moreover reflects the number and the differentiation
state of Leydig cells and therefore it represents the ideal marker of Leydig cell function. Facondo et al. in their minireview
focused on the role of INSL3 as a marker of both Leydig cell function and testis-bone-skeletal muscle network .
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone
tissue. Biomarkers of bone turnover have been used for years in bone disease management. Recently, new approaches for the
detection of bone physiology and pathology biomarkers have been proposed, among which proteomics, with particular interest
in osteoporosis. Porcelli et al. reviewed current knowledge on proteomics applied to osteoporosis in vivo .
During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed
to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic
functions. De Toni et al. in their review article, discuss current experimental data supporting the inter-organ communication
roles of this protein are discussed, including the possible significance the OCN as a template agonist on its receptor
GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states
Adipose tissue is nowadays considered a complex organ with lots of endocrine and metabolic functions. Both adipocytes
and surrounding resident cells (macrophages, endothelial cells and others) produce a huge number of molecules, or adipokines,
with endocrine or paracrine functions, that regulate various aspects of metabolism whose clinical relevance is emerging.
In their mini-review Parrettini et al. summarized scientific evidence about adipokines' effects on human metabolism, by
focusing on their role on either Metabolic Syndrome, or insulin-resistance in pregnancy, or finally, reproductive function disorders
In summary, experts from the differents fields of endocrinology have reviewed the current advances in their specific area
in this special thematic issue of Protein & Peptide Letters. As the guest editors, we wish that this diverse collection of articles
will gain broad readership.
We would like to express our sincere gratitude to all authors and referees for their contribution to this issue. We would also
like to extend our appreciation to the Editor-in-Chief, Professor Ben M. Dunn and the editorial staff of Protein & Peptide Letters,
especially Ms. Syeda Mehak Fatima, for their excellent support and for providing us with the opportunity to pursue this
hot topic issue.
The Renin–Angiotensin System (RAS) consists of a complex enzymatic cascade which produces diverse angiotensin
peptides. Over the past few years, experimental and clinical evidences indicate that these peptides have actions that go beyond
the cardiovascular and renal systems. Several studies have associated cerebrovascular, neurodegenerative and psychiatric
diseases with important alterations in systemic and local/tissue RAS. For this reason, in this thematic issue “Renin-Angiotensin
System: Role in cerebrovascular, neurodegenerative and psychiatric disease”, we covered the relation between some of the
cerebrovascular, neurodegenerative and psychiatric diseases with key components of RAS, besides address the most important
aspects of its interactions and implications for research progress, drug developments and new treatments in a near future.
It is known that RAS components affect blood pressure, cerebral blood flow, neuroinflammation and oxidative stress.
Overactivity of the classical axis, composed by angiotensin (Ang) converting enzyme (ACE)/Ang II/AT1 receptor axis, may
promote brain tissue damage. In contrast, stimulation of AT2 receptors in the brain has been demonstrated to elicit beneficial
effects. Likewise, activation of the counter-regulatory RAS axis composed by ACE2/Ang-(1-7)/Mas receptor seems to elicit
In a mini-review, Mohite et al.  integrated basic and clinical studies showing the associations between RAS and mood
disorders. Animal studies on mood disorders models - either depression or mania - were focused on the reversal of behavioral
and/or cognitive symptoms through ACE inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs). ACE polymorphisms
were linked to mood disorders and suicidal behavior, while hypertension was associated with neurocognitive deficits in mood
disorders, which was reversed with RAS inhibition. Low levels of RAS components (renin activity or aldosterone) and mood
symptoms improvement with ACEi and ARBs were also observed in mood disorders.
Machado and colleagues  reviewed the participation of the RAS components in Huntington’s disease (HD). They showed
that alterations in brain RAS components are seen in this disease, suggesting that this system participates in the
pathophysiology of HD, although the results are still inconclusive and need further investigation. Kangussu et al.  summarize
and discuss recent findings related to the modulation of RAS components in cerebrovascular diseases (CVD). Despite CVD
being a leading cause of morbidity and mortality worldwide, therapy for these conditions are very limited and the precise
mechanisms underlying CVD are still a matter of debate. Clinical trials with ACEi or ARBs, like in AD, have generally shown
a beneficial role in patients with stroke, leading to a reduction of brain damage with limitation of stroke area, less
neuroinflammation and oxidative stress, but the mechanisms of this neuroprotection are also not fully elucidated.
Unfortunately, evidence on the beneficial role of ACE2/Ang/(1-7)/Mas receptor axis in CVD was almost exclusively provided
by animal models. Therefore, studies with patients are necessary to investigate the potential therapeutic role of the alternative
RAS axis in CVD.
de Melo and Almeida-Santos  described that the ACE2/Ang-(1-7)/Mas receptor pathway induces anxiolytic and antidepressive
effects. Overall, these studies reiterate the strong and under-researched connection between RAS and mood
disorders, which justifies further investigation into this system as a possible new therapeutic target in the management of
anxiety, depression and other neuropsychiatric disorders. In Alzheimer's disease (AD), a neurodegenerative disease, Ribeiro
and colleagues  discusses the pathophysiology of the disease and its possible interaction with RAS, looking for potential
therapeutic approaches. The link between AD and clinical conditions related to classical RAS axis hyperactivation
(hypertension, heart failure, and chronic kidney disease) supports the hypothesized role of this system in AD. Additionally,
RAS-targeting drugs, like ACEi or ARBs, seem to exert beneficial effects on AD. Results of randomized controlled trials
testing ACEi or ARBs in AD are awaited to elucidate whether AD-RAS interaction has implications on AD therapeutics.
Sassi and colleagues  did a systematic review of the studies evaluating the involvement of RAS in patients with migraine.
There is evidence from genetic studies exploring the relation between migraine and RAS-related genes and from clinical trials
evaluating the efficacy of ACEi and ARBs in migraine prophylaxis. RAS seems to play a role in the pathophysiology of
migraine, but more direct evidences are still missing. Completing our thematic issue, Barbosa et al.  investigated the
modulation of RAS components in Bipolar Disorder (BD) through a systematic review. BD patients presented higher plasma
renin activity in comparison with controls, but the studies evaluating the RAS molecules in BD are very scarce and
heterogeneous. The literature suggests a potential role of RAS in BD, although further studies are necessary to investigate this
In summary, although, after a period of vast and important discoveries about RAS, some researchers considered this an
exhausted subject, today we know that it is a very complex system, with multiple effectors, present in all tissues and with
influence on several pathophysiology aspects. Thus, many studies will still be needed to better understand and characterize the
RAS components, with the objective to expand strategies for the treatment of cerebrovascular, neurodegenerative and
Proteins are an important components that makes up all the cells and tissues of the human body. Proteins play an important
role in the life activities of cells and organisms, such as the principal catalytic agents, structural elements, signal transmitters,
transporters and molecular machines. However, proteins cannot show their biological functions as individuals. They need to
interact with other molecules, such as other proteins, RNAs, DNAs and small molecule compounds, to carry out their cellular
During the past decades, computational method has become an important strategy in the understanding and study of
biological sciences. With the more and more proteomics data generation, it is urgent to develop and apply various
computational resources and methods to handle these protein data. In this thematic issue, two review articles, seven research
papers and one letter are published.
At first, Chen et al.  reviewed the development of machine learning methods applied in bacteriophage virion protein
identification. The phage virion proteins play important roles in virus capsid and budding. Several works have developed to
identify the proteins. Chen et al. work provides a summary of the field. Subsequently, Han et al.  focused on the proteinprotein
interaction. They summarized many useful tools and visualization programs including databases, computational
methods for annotating and analyzing biological networks.
In most of proteins, disordered regions are important regions for protein function. Xie and Feng  developed a support
vector machine -based method to identify the six classes of intrinsically disordered proteins. Four kinds of descriptors were
extracted to formulate protein samples. In cross-validation, their model could produce a very high accuracy.
It is very important for protein classification to formulate a protein sample with a valid mathematical descriptor. Zhang and
Kong  introduced an amino acid properties selection technique and applied it in protein fold classification. Comparison with
published results showed that their model is better.
Multiple sequence alignment is a fundamental task in computational biology. Traditional methods do not consider the
different conserve regions in protein sequences, which results in a poor alignment. Zhan et al.  developed a novel refinement
method to solve the problem. Their method is based on splitting-splicing vertically, namely separating a sequence vertically
into three parts, and then performing alignment.
Protein fold is also a fundamental topic in protein study. Li et al.  focused on the influence of palindromes in mRNA on
protein folding rate. They found that palindromes play an important role in protein folding. Another two papers [7, 8] also
focused on protein folding. Li et al.  used the effective cumulative torsion angles model to predict protein folding rate. This
is an important progress for protein folding rate prediction from physical insight. Especially, their model based on such physical
parameter can produce better results than other published methods. Xiao et al.  presented a machine learning model to
predict protein quaternary structure. The gene ontology information was used in their model.
The machine learning method was also applied in protein function prediction. Cell wall lytic enzyme is a potential protein
drug for anti-bacteria. Endolysin and autolysin are two kinds of enzymes which could destroy cell wall. Xu et al.  introduced
a computational method to discriminate the two kinds of enzymes. By using feature selection technique, they dramatically
improved the accuracy of proposed model. Wang et al.  developed a model to recognize cleavage sites of neuropeptide
precursors. In 5-fold cross-validation, their model could produce the accuracy of >90%.
In summary, computational methods have been widely applied in protein function and structure prediction. We hope more
accurate tools can appear for providing convenience to most of the scholars.
Recombinant Proteins: Emerging Production Trends and Applications
A wide range of solvent accessibility methods to investigate structural features and conformational changes of macro-molecules in
solution are described in the articles in this issue. These methods have grown substantially of the past few decades, and are highly
complementary to other more widely used structural elucidation techniques for biological macromolecules, such as x-ray diffraction, cryoelectron
microscopy, and nuclear magnetic resonance. While these more widely known methods are all excellent techniques for studying
protein structure, they often require protein engineering, high concentrations of sample, or non-physiological sample environments, and in
addition, can be limited by the size and/or complexity of the molecule. Solvent accessibility methods have their own unique advantages and
disadvantages, and are increasingly used as stand-alone methods or as part of a suite of tools to characterize macromolecules.
The concept of footprinting refers to the method of delineating interactions between macromolecules, i.e., the "footprint" of one molecule
on another. Some of the earliest footprinting methods used enzymatic digestion to define the areas on nucleic acid which were solvent
protected by binding partners, i.e., a protein protected a specific region on the nucleic acid from digestion, thereby delineating a "footprint" on
the nucleic acid . Chemical methods for determining solvent accessibility, such as methylation, were developed around the same time, and
had the advantage of using a smaller probe, thus yielding higher resolution footprints. Many variations on enzymatic and chemical
footprinting for both nucleic acid and proteins have been developed in the last several decades. Protein footprinting in particular, has
historically been deployed using proteases  and antibodies  as well as other modification methods such as hydroxyl radical footprinting
using reagents . More recently, hydroxyl radical footprinting has been developed using an external energy source for the generation of
hydroxyl radicals, as in electron , laser-induced , X-ray [7, 8], and very recently, plasma-induced radical formation . The hydroxyl
radical, in particular, is an excellent probe for determining protein-protein and protein-nucleic acid interactions, because of its small size and
high reactivity. The method is variously referred to as Radical Probe Mass Spectrometry (RP-MS), Hydroxyl Radical Footprinting (HRF),
Fast Photochemical Oxidative Footprinting (FPOP), X-ray Footprinting (XRF), or X-ray Footrpinting with Mass Spectrometry (XF-MS)
depending on the radical source and method.
In this thematic issue, the first review article is by Maleknia & Downard and covers the development of RP-MS over the last two decades,
describing the technological advances of the different methods of hydroxyl generation through the years. In contrast to the hydroxyl radical
reaction with protein sidechains, the method of Hydrogen Exchange Mass Spectrometry (HDX-MS), as described in the second review by
Benhaim et al., relies on the modification of protein backbone amide groups. This method is well-developed, increasingly used in industrial
applications, and provides a natural complement to the other side-chain labeling footprinting methods described in this issue. FPOP is
reviewed by Shi & Gross, and describes the recent development of a lab-based radical generating method using an excimer laser to induce
radical formation. A review by Garcia et al., then describes the application of the method for characterization of biotherapeutics. Specific
applications to membrane proteins are described in the review by Gupta, while Bohon describes the history of the development of an X-ray
footprinting beamline at the Brookhaven National Laboratory on the East Coast of the United States.
In the research article section, Leser et al., describe a novel approach for oxidative footprinting, a "lab on a chip" method which enables
many different chemical environments to be probed quickly and simultaneously, and will be of particular interest for biotechnology
applications. Morton et al., describe the new development of an X-ray footprinting beamline at Lawrence Berkeley national Laboratory on the
West Coast of the United States.
The primary aim is to cover the most exciting and promising new areas of research in peptide science as
applied to therapeutic discovery and development. The strengths of peptides as drug targets are their high
potency, specificity and good safety profile. These positive attributes of peptides along with advances in
drug delivery technologies have afforded a renewed interest in the discovery, optimization and
development of peptides as therapeutics. In this themed issue, the most compelling indications and targets
for peptide therapeutics are reviewed and discussed with the intent to demonstrate that peptides have
broad applicability in many therapeutic areas. Target selection for peptide therapeutics is challenging due
to the inherent properties of peptides. Therefore, identifying a clear differentiation strategy for a new
peptide program over a small molecule or antibody program from the outset is critical for successful
navigation of drug development hurdles. The latest techniques for overcoming some of the perceived
limitations of peptides to increase their druggability will be reviewed and discussed. Emerging
technologies for stabilizing peptides for sufficient in vivo half-life will be described and evaluated, as
well as novel technologies for getting peptides across cell membranes to reach intracellular targets and
across the blood brain barrier to reach central nervous system targets. Capitalizing on the strengths of
peptides in this issue, the latest advancements in therapeutic peptidic hormones, peptides targeting
protein-protein interactions especially for oncology indications, venom peptides as therapeutics as well as
diagnostics, and antimicrobial peptide progress will be covered with emphasis on the distinctive
properties peptides have compared to other therapeutics.
Proteins are the material basis of life, and the basic organic matter that constitutes cells. In cells, proteins are the principal
catalytic agents, structural elements, signal transmitters, transporters and molecular machines. But individual proteins do not
function alone, they must interact with other molecules, such as proteins, RNAs, DNAs and small molecule compounds, to
carry out their cellular roles.
Studying these interactions has very important biological implications. Typically, interactions of proteins are identified and
characterized by a number of biochemical or biophysical experimental methods. Although these experiments are very valuable
and contribute significantly to our understanding of the mechanisms of protein interactions, technical challenges make these
experiments both labor intensive and time consuming. Therefore, reliable computational methods are more and more widely
recognized by researchers.
In recent years, computational techniques have been successfully applied to predict the interactions between protein and
various kinds of molecules. Especially, protein–protein interactions prediction, protein–RNA interactions prediction and
protein–drug interactions prediction based on heterogeneous biological data have become critical topics in the search of
functions of proteins and therapeutic targets for various diseases. With the development and application of many new
computational techniques, such as machine learning, deep learning, new feature extraction methods and network methods, a
great progress has been made in the field of protein interactions prediction.
The following pages of this issue are four papers presenting current computational models for various interactions related to
proteins, representing only a small portion of current research. The following is a brief description of these papers.
In the opening paper of this issue, Xu et al. gave the process for prediction of posttranslational modification sites including
feature construction, algorithms, evaluation measurements and online web-servers. There are two types of posttranslational
modifications in proteins, and this paper summarized the methods and steps in the prediction of single and multiple PTM sites,
Hasan et al. discussed the latest developments and challenges in protein S-sulfenylation site prediction from available data
sets, algorithms and accessible services, and demonstrated the limitations and future prospects of computational prediction tools
One of the most important steps in developing functional genomics and proteomics prediction methods is to represent
biological sequences in fixed-length digital form, which can be further analyzed using machine learning algorithms. Several
software tools have been developed to apply these algorithms, and Zhao et al. reviewed the technical aspects of these software
Zhao et al. introduced a semi-supervised learning algorithm prediction model called random walk for lncRNA-protein
association prediction. This approach successfully avoided the difficulty of extracting negative data sets and features and
achieved better results than previous algorithms .
We would like to express our sincere gratitude to all authors and reviewers for their contribution to this issue. We would
also like to extend our appreciation to the Editor-in-Chief, Professor Ben M. Dunn and the editorial staff of Protein & Peptide
Letters for their excellent support and for providing us with the opportunity to pursue this hot topic issue.
In 1843, the nephew of Napoleon Bonaparte (i.e. Charles Lucien Bonaparte) established for the first time the proteinaceous
nature of snake venom, a complex substance secreted by glands to paralyze and kill either for predatory or defensive purposes.
Snake venoms represent a cocktail of thousands of diverse molecules, mainly proteins accounting for up to 95% of venom’s
dry weight. These proteins are mainly enzymes such as oxidoreductases e.g. catalase and oxidase; transferases such as ALT;
hydrolases including phospholipases, phosphodiesterases and hyaluronidases; lyases; (metalloproteinases) as well as peptides
(e.g. cardiotoxins, cytotoxin, hemotoxins alias hemorrhagins such as mucrotoxin or PLA2; postsynaptic neurotoxins, such as
cobratoxin or taipoxin). In addition to free amino acids, there are nucleosides, lipids, carbohydrates and metals coupled to
proteins, which account for the 5% of venom’s dry weight . The difference in chemical constituents of venoms among
various species is both topographical and onto-genic. Now-a-days, Omics technologies are contributing to a qualitative and
quantitative progress in the road map towards reconstruction of the natural history of venoms, which is of great interest in
diverse fields such as evolutionary ecology and biotechnology .
Snake venoms exert potent, selective and pleiotropic biological functions, which can lead to deleterious/toxic effects or
beneficial/exploitable solutions for biotechnological/medicinal applications .
It is worth noting that animal venoms have been used for a long time in folk medicine, mostly in Asian and Middle-East
countries and their applications are well documented as diuretic, cardiotonic, anesthetic or anti-cancers agents. For a bit more
than four decades, venoms and toxins of animals have been extensively explored for the management of human ailments like
hypertension, diabetes, long-lasting pains, cancers and HIV . Therefore, the complex chemical cocktail of venoms represents
a rich source of discovery and development of lead compounds.
An increasing number of in vitro and in vivo investigations have revealed the anti-carcinogenic properties of snake venoms
and purified toxins in various types of cancer (e.g. colorectal, cervical and breast cancers), produced mostly via the blocking of
progress of cancer, stopping of cell cycle, initiation of oxidative-stress mediated apoptosis, inhibition of pro-inflammatory
cytokines, and suppression of cancer metastasis. Thereby, anti-angiogenic effects by inhibiting Vascular Endothelial Growth
Factors (VEGF) were displayed by the Disintegrin Lebein isolated from snake venom [5-7]. Interestingly, those venoms or
purified venom toxins may be either an alternative or a complementary alternative to the currently available chemotherapeutic
The current and future challenges towards encapsulation of venoms or purified proteins in functionalized nanoparticles (e.g.
biocompatible and biodegradable liposomes/nanovesicles) are entailing in enhancing the anti-cancer potential while minimizing
the side effects (e.g. efficacy versus systemic or local toxicities) of free venom or free pure venom proteins . Various novel
nanoformulations are being tested, and their transfer from the benchmark to the bedside will certainly constitute a new hope for
more accurate theranostic strategies.
The crucial emphasis of our special thematic issue of Protein and Peptide Letters concerns the theranostic applications of
venom proteins isolated from different organisms (e.g. snakes, frogs, bees, spiders, scorpions, jellyfish, leeches, snails) to
diagnostic procedures like hemostasis testing and in therapeutics as anti-thrombotic agents in peripheral arterial thrombosis,
deep-vein thrombosis, myocardial infarction, stroke, HIV, diabetes, neurodegenerative disorders, hypertension and cancers.
We are thankful to all the Venomics researchers for their valuable contribution to this Special Issue. The stout efforts and
promise of the researchers always made the advancement of science to bring innovative perspectives and expectation for the
management of emerging chronic and complex disorders
The health threat caused by kidney diseases such as kidney cancer, chronic kidney disease and acute kidney failure, have a
high prevalence and represent a large burden of health care cost. Intensive research to develop novel strategies on various
aspects have been conducted in order to detect kidney function and treat kidney disease. One potential risk of Chronic Kidney
Disease (CKD) is end-stage renal disease, which requires costly renal replacement therapy such as dialysis and transplantation.
Kidney disease is conventionally assessed in terms of both overall renal function (glomerular filtration rate) and the presence of
kidney damage ascertained by either kidney biopsy or other markers of kidney damage such as proteinuria, abnormal urinary
sediment and abnormalities on imaging studies. Urinary proteome analysis has improved the current state of the art of CKD
detection and prediction. Additionally, in attempt to prevent or retard the progression of further kidney damage from CKD,
kidney specific drug targeting or renal drug delivery systems are used as an attractive strategy to reduce unwanted side effects
and to improve drug efficacy in the kidney tissue. Renal Cell Carcinoma (RCC) is the most prevailing kidney cancer. On one
hand, targeted therapies dramatically improved progression-free survival towards RCC patients compared with other traditional
chemotherapies and radiotherapies; on the other hand, immunotherapy has become an effective approach in the management of
RCC patient with metastatic disease because RCC has a high resistance of both chemotherapies and radiotherapies.
An increase in interesting preliminary results is being reported in aforementioned subtopics. As witnesses and practitioners
in this exciting area, however, we notice that the related communication in public domain is still limited due to the relatively
small number of scientists involved. Thus, we feel the necessity to compile a timely issue about the special topic “Protein and
Peptide Studies in Kidney Disease”, covering state-of-the-art research papers and expert reviews from this field. We are pleased
that Protein & Peptide Letters is willing to realize the idea with us.
The opening paper of this issue by Dr. Wu and co-author discusses several approaches to prolong the half-life of protein and
peptide drugs based on the unique structures of the glomerular capillary wall and mechanisms of glomerular filtration, such as
increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; and increasing plasma
protein binding to decrease plasma clearance . Next, Dr. Xu and coauthors describe current low molecular weight proteins
and peptide carriers for kidney targeted drug delivery systems, and outline the current status as well as give an outlook on the
further study .
The following two papers discuss the treatment of RCC. RCC, a type of kidney cancers, is one of the common malignant
tumors and accounts for approximately 4% of all cancers with high rates of morbidity and mortality. Dr. Yang and coauthors
discuss the role of therapeutic drug monitoring in the individual targeted treatment of RCC . The breakthroughs in the
understanding of tumor immune biology and the development of newer generation of cancer immunotherapies have provided a
new strategy for battling tumors. Recent progress of the use of immunotherapy with different agents for RCC are presented by
Dr. Gong and coauthors. In addition, the combination of different novel immunotherapeutic agents and other immune therapies
are also discussed .
The last review of this issue by Dr. Zeng and co-worker provide an overview of the varied probes from small molecular to
nanoparticle-based sensors that have been applied to the detection of various proteins from bench to bedside . The
quantitative measurement of protein and peptides will be benefit for the diagnosis and monitoring of kidney diseases in the
In summary, experts from different fields have showcased new results and expressed their opinions in this special thematic
issue of Protein & Peptide Letters. As the guest editor, I wish that this diverse collection of valuable intellectual contributions
will positively influence this emerging area and gain broad readership.
At the end, we would like to express our sincerest gratitude to all authors and referees for their invaluable contribution to
this issue. We would also like to extend our appreciation to Editor-in-Chief, Professor Ben M. Dunn and the staff of Protein &
Peptide Letters, especially Ms. Rukhshanda Rehman, for their excellent support and for providing us with the opportunity to
pursue this exciting project.
In developed countries, subfertility has become an increasing problem. Infertility is the inability to conceive after 12 months
of regular, unprotected intercourse. It is a worldwide problem, affecting 15% of couples that have unprotected intercourse. In
general, 50% of infertility cases are due to a solely female factor, pure male factor accounts for 20-30% of the problem, and the
remaining 20-30% is due to a combination of both male and female factors.
Again, one of the common complications of pregnancy is spontaneous pregnancy loss which occurs in an estimated 5-15%
of pregnancies. Although pregnancy loss has been associated to various hematologic, anatomic, hormonal, immune, and genetic
defects, in 30% of the cases, screening tests performed in cases of Repeated Pregnancy Loss (RPL) give negative results.
The last 10 to 15 years have witnessed rapid advances in approaches for the analyses of DNA sequence and structure. The
amount of information currently available about the genomes in human and animal reproduction has increased dramatically in
the past few years and the rate of its accumulation will continue to increase.
Also, proteomics has been widely used over recent years in almost all relevant biological samples (tissues, fluids, cells) to
depict both physiological and pathological states, and has yielded important results, including the significance of posttranslational
modifications in sperm and the intense immunological-inflammatory processes that take place during ovulation
and implantation. Proteomics represents a state-of-the-art, technology-driven science, which, in a high-throughput mode,
studies proteins and their post-translational modifications and interactions. This approach provides the opportunity to elucidate
complex biological processes and conditions, including fertilization, embryo implantation and differentiation and pregnancy.
Proteomics is providing useful insights into physiology of human reproduction and it is leading to the identification of
numerous proteins in biological tissues and fluids related to human reproduction that may be potential biomarkers and/or
treatment targets. In the area of reproduction, this approach seems to be the most promising and powerful platform that has
been recently applied in order to widely study the physiology and pathophysiology of reproduction and to identify novel
markers of diseases.
In the diagnostic of male infertility, semen analysis represents the cornerstone for the assessment of the male partner in subfertile
couples. Many studies, however, criticized the thresholds used to define male factor infertility using sperm concentration,
motility and morphology, the three classical sperm parameters measured by all laboratories. Additional markers of male fertility
have been proposed including the evaluation of anti-sperm antibodies, biochemical tests, kinematic parameters, sperm DNA
integrity and oxidative stress markers. However, due to the lack of a standardized and universally accepted assays and the
expensive or time-consuming techniques, these parameters did not reveal a role in the clinical workout of male infertility.
Therefore, several sources of clinical biomarkers have been proposed for female reproductive tract disease and cervical
mucus represents the most promising source of biomarkers reflecting the health of the male tract.
This special issue of Protein & Peptide Letters, entitled “Protein and peptide markers in reproduction” intends to showcase
new results and express the opinions of a selection of specialists who have expanded the field with their recent discoveries.
In the opening paper of this issue, Dr. Bibancos and co-authors discuss the potential use of proteomic platforms in the
workflow of couple infertility in clinical practice. Beyond the identification of the oocytes and embryos with the best
developmental potentials in assisted reproductive techniques or prediction of a pregnancy’s outcome, it may add significant
information for the diagnosis of both male and female infertility .
The most abundant sperm nuclear proteins are protamins. Dr. Oliva, in addition to briefly reviewing the studies available so
far about protamine alterations and male infertility, provided a very comprehensive protocol for the successful implementation
of protamine extraction and analysis into the laboratory routine, including protocol variations for specific procedure
The post-genomic approaches in the study of male sperm function, consisting of different methodologies for concurrently
testicular transcriptome studies, protein compositional analysis and metabolomics findings, have been reviewed by Dr. Dipresa
Dr. Luca summarized some of the recent findings regarding the immunomodulatory role of Sertoli cells, and especially the
key Sertoli cell regulatory proteins that are associated with the well-defined immune privileged status of the testis .
Dr. De Toni analyzed the most recent cues about the molecular bases of the known process of sperm thermotaxis, and the
possible pathophysiological and therapeutic repercussions deriving from the characterization of sperm proteins acting as
Furthermore, the expression in sperm surface of specific nicotine receptors might represent a marker of sperm smokingrelated
damage. Dr. La Vignera discussed in his manuscript the mechanism by which nicotine alters spermatozoa and the
expression pattern of nicotinic receptors subunits in human spermatozoa .
In addition Dr. Di Nicuolo reviewed the role of inflammosome in female reproduction and namely in RPL .
Dr. Fernandez-Hermida in her review article collected relevant knowledge about the physicochemical properties and
functions of the cervical mucus, including its important role as a clinical marker of female fertility, and draws attention to
cervical mucus as the best source of potential protein biomarkers to assess the health of female genital tract .
Proteomic platforms have been applied to identify novel markers of disease in seminal plasma. Dr. Grande reported a
research article aimed to identify, for the first time, novel seminal biomarkers for the male tract infection by Enterococcus
faecalis, using proteomic profiling, in order to understand the effect of E. faecalis on the physiopathology of male reproduction
Among the proposed markers of Male Accessory Gland Inflammation (MAGI), soluble urokinase-type plasminogen
activator receptor (suPAR) has been recently proposed as a reliable and sensitive marker. In the study by Milardi et al., the role
of suPAR as a protein marker of MAGI was confirmed in hypogonadism, supporting the hypothesis that hypogonadism induces
a state of inflammation in male accessory glands which is involved in male infertility .
In summary, experts from the field of male and female reproduction have presented new results and reviewed the current
advances in their specific area in this special thematic issue of Protein & Peptide Letters. As the guest editors, we wish that this
diverse collection of articles will gain broad readership.
The protein and peptide analysis provides a good starting point to discover new reproduction-related proteins; however,
further functional analyses should be conducted to gain a specific role for fertility traits in human reproduction metabolism. The
comprehensive proteomic profiling of human reproduction and its pathology constitutes a major challenge for the international
We would like to express our sincere gratitude to all authors and referees for their contribution to this issue. We would also
like to extend our appreciation to the Editor-in-Chief, Professor Ben M. Dunn and the editorial staff of Protein & Peptide
Letters, especially Ms Amna Sajid, for their excellent support and for providing us with the opportunity to pursue this hot topic
Global warming, diminishing fossil fuel resources and growing energy requirements have kindled the
research on alternative fuels. Moreover, cleaner production and sustainable consumption of industrial
products have become forefront research areas in recent years. The special issue “Recent trends in
biofuels and bio-industry” focusses on the emerging trends in this area. Original research articles
presenting the cornerstone technologies to address the bottleneck issues in biofuel and bio-industrial
processes, and critical review articles analyzing the challenges and discussing the future opportunities are
welcomed. The submissions focusing on the characterization/engineering of novel proteins/enzymes of
industrial/biofuel importance, identification/engineering/synthesis of metabolic pathways for biofuels and
industrial chemicals, would be highly appreciated.
In the last decade, materials synthesis and processing under conditions with low energy consumptions have been gathering attractive interests for building sustainable societies. Because biominerals are precisely-designed composite materials made from the combinations of inorganic minerals such as calcium carbonate, silica, hydroxyapatite and organic template molecules such as proteins and peptides under ambient conditions, biomimetic production of organic-inorganic hybrid nanomaterials would be one of the approaches to provide a variety of morphologies and arrangements of inorganic components for fabrications and applications. So far, many scientists/chemists have devoted their great efforts to control morphologies of inorganic precipitates using organic compounds such as polymers, surfactants, and so on. Proteins and peptides are promising organic template molecules for use in the biomimetic process because they confer several advantages: 1) proteins and peptides can offer milder conditions for the production, 2) proteins and peptides can impose on the size, shape, and crystal structure of the inorganic products, 3) proteins and peptides can offer the potential to produce materials with highly specific or multiple functions. Therefore, the rapid progress in the development of synthesis and processing of organic-inorganic hybrid materials is evident and the compilation of the subtopics listed below would appear to be timely. This theme issue intends to offer for understanding new knowledge on protein- and/or peptide-associated materials and propose unprecedented and fundamental concepts as well as some directions to their practical applications. The theme issue included in the following potential subtopics, but are not limited to:
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