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Volume 21, 14 Issues, 2020
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Special Issue Submission
"Current Drug Metabolism is an important new source of current and comprehensive reviews that are of interest to drug metabolism scientists working in academia, industry and government."
David S. Riddick
Univ. of Toronto, Canada
Thank you very much for publishing our article ' Virus-Host Interactions: New Insights And Advances In Drug Development Against Viral Pathogens ' in your esteemed journal "Current Drug Metabolism". It was great experience working with Bentham Science Publishers
(Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar, Haryana, 125004, India)
22 Articles Ahead of Print are available electronically
Gastroenterology is an ever-improving field. It is essential to the gastroenterologists, hepatologists, and endoscopists to keep up-to-date
with the new therapeutic molecules and their metabolism. Research on the molecular mechanisms of some gastrointestinal diseases has led to
the introduction of targeted therapies that can block the key mediators selectively. The liver is a critical organ for drug metabolism; however,
it can often be affected by toxic metabolites. The liver produces mainly hydrophilic metabolites through oxidative and conjugative metabolism,
and on the other hand, gut microbiota primarily produces hydrophobic byproducts through reductive and hydrolytic metabolism. Multiple
studies have concentrated on explaining how drug bioavailability resulting from the solubility, permeability, and stability in the stomach
and duodenum affects drug availability. However, the drug metabolism by the gut microbiota has not been well studied.
This Special Thematic Issue of Current Drug Metabolism aims to discuss the recent therapeutic enhancements of digestive diseases, their
metabolism and to compare them to the standard management that is available for everyday practice. The contributions in this Special Issue
include a review by Macaluso and Rodrigues-Lago , which reviews the current data about the mechanism of action, the efficacy and safety
of Janus kinase inhibitors in inflammatory bowel disease. Nakov and Velikova  focus on one of the gut microbiota’s newly explored roles
in human biology – the ability to alter xenobiotics. They state that there is a growing body of evidence for the role of the gut microbiota on
xenobiotic metabolism, which can have an intense impact on the therapy for various diseases in the future. Drug-induced bile duct injury is
highlighted in the paper by Dobreva and Karagyozov  who have described etiology, predisposing factors, clinical manifestations, and
histopathological characteristics of bile duct injury as a consequence of drug treatment and have discussed the different bile duct pathologies
The Editors express their gratitude to all the authors for their contributions to the current Special Issue. Moreover, we thank the reviewers
for their time, expertise, and comments to help improve the quality of the manuscripts.
We believe that this Special Thematic Issue on New therapeutic molecules and their metabolism in gastroenterology will help gastroenterologists
to be in line with the newest drugs in their field, their metabolism, and potential adverse effects.
Nowadays, most of the researchers are focusing to fight against COVID-19, either
its testing, diagnosis, management, the discovery of vaccines, linkage with other health
issues such as neurodegenerative disorders and many diseases including cancer. In the
discipline of cancers, many scientists are working on an array of aspects, such as how
cancer cells can fib latent in the bones before the metastasising stage. Anyhow, one of
the foremost issues currently fronting in cancer therapy is the increase of drug
resistance either intrinsically or as a result of treatment. We are delighted to introduce
this special issue (Part IV) dedicated to the “Challenges in the discovery of novel
therapeutic agents for cancer treatment”, featuring authoritative review articles written
by reputed scientists from all over the world, highlighting cutting edge research. In this
special issue, the first article by Saeed et al. highlights human papillomavirus (HPV)
induced cervical and oropharyngeal cancers from mechanisms to potential immunotherapeutic strategies in detail . HPV associated
infections are the hallmark of cervical and neck cancer. Almost all the cases of cervical cancer (CC) and 70% of oropharyngeal cancer (OC)
are, more or less, caused by the persistent infection of HPV. CC is the fourth most common cancer globally and is commenced by the
persistent infection with human papillomaviruses (HPVs), predominantly HPV types; 16 and 18. In light of the above facts, there is an
immediate requirement to develop novel preventive and innovative therapeutic strategies that may help in lower the occurrences of HPV
mediated cancers. Currently, only radiation and chemical-based therapies are the available treatments for HPV mediated neck cancer (NC)
and CC. Recent advances in the field of immunotherapy are underway, which are expected to unravel the optimal treatment strategies for the
growing HPV mediated cancers. In this review, Saeed et al. interpret the mechanism of pathogenesis with current immunotherapeutic
advances in regressing the NC and CC, with an emphasis on immune-therapeutic strategies being tested in clinical trials and predominantly
focusing on defining the efficacy and limitations. Taken together, these immunological advances have enhanced the effectiveness of
immunotherapy and promise better treatment results in coming future .
Kamal et al. discuss the role of tubulin proteins in cancer resistance  in their review article. Cancer cells are altered with cell cycle
genes, or they are mutated, leading to a high rate of proliferation compared to healthy cells. Alteration in these genes leads to mitosis
dysregulation and become the basis of tumour progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest
the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to
as antimitotic agents. Microtubule proteins play an essential role in mitosis during cell division as a target site for Vinca alkaloids and
taxanes. These proteins are dynamic and composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in
expression within cancerous cells. Initially, these drugs were very useful in the treatment of cancer but failed to show their desired action after
initial chemotherapy. Kamal et al. highlight some of the critical targets and their mechanism of resistance offered by cancer cells with new
promising drugs derived from natural sources that can lead to the development of a new approach for chemotherapy .
Chavda et al. comprehensively focus on therapeutics and research related to advancements and future targets on glioblastoma (the most
common primary brain tumour), which has been recognized as one of the most lethal and fatal human tumours. It has a dismal prognosis, and
survival time after diagnosis is less than 15 months. Surgery and radiotherapy are the only available treatment options at present. However,
numerous approaches have been made to upgrade in vivo and in vitro models with the primary goal of assessing abnormal molecular
pathways that would be suitable targets for novel therapeutic approaches. Novel drugs, delivery systems, and immunotherapy strategies to
establish new multimodal therapies that target the molecular pathways involved in tumour initiation and progression in glioblastoma are being
studied. The goal of their review is to describe the pathophysiology, neurodegeneration mechanisms, signalling pathways, and future
therapeutic targets associated with glioblastomas. The key features have been detailed to provide an up-to-date summary of the advancement
required in current diagnosis and therapeutics for glioblastoma. The role of nanoparticulate system graphene quantum dots as suitable therapy
for glioblastoma has also been discussed .
Shafi et al. reviewed the literature on the decoding novel mechanisms and emerging therapeutic strategies in breast cancer (BC) resistance
. It is a complex and highly heterogeneous disorder, which has presently afflicted 2.09 million females globally. Chemoresistance remains
a paramount challenge in the treatment of BC. Owing to its varied nature, the chemoresistant mechanisms of BC still need intensive research.
Accumulating evidence suggests that abnormalities related to the biogenesis of cancer stem cells (CSCs) and microRNAs (miRNAs) are
associated with BC progression and chemoresistance. The presently available interventions are inadequate to target chemoresistance.
Therefore more efficient alternatives are urgently needed to improvise existing therapeutic regimens. A myriad of strategies is being explored,
such as immunotherapy, gene therapy, and combination treatment to surmount chemoresistance. Additionally, nanoparticles as
chemotherapeutic carriers put forward the options to encapsulate numerous drugs, alone as well as in combination with cancer theranostics.
Shafi et al. summarized the chemoresistance mechanisms of miRNAs and CSCs as well as the most recently documented therapeutic approaches for the treatment of chemoresistance in BC. By unravelling the underpinning mechanism of BC chemoresistance, researchers
could develop more efficient treatment strategies towards BC .
Kancharla et al. addressed the meta-analysis of NFKB1-94 ATTG Ins/Del polymorphism and risk of breast cancer (BC), which accounts
for one of the most prevalent malignancies in the world . Inflammatory molecules modulate tumour microenvironment in BC that
promotes tumour growth and metastasis. NF-κB (a transcription factor) regulates multiple immune functions and acts as a crucial mediator of
inflammatory responses. Their study aims to quantitatively summarise the relation of NFKB1-94 ATTG (nsertion/deletion or I/D) variant and
risk of BC. Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D
polymorphism, and BC patients. Databases from Web of Science, PubMed and Embase were used to retrieve relevant data. OR and 95%
confidence interval of pooled studies were analyzed by using the MetaGenyo web tool. Kancharla et al. also revealed a high heterogeneity. In
all three genetic comparison models, the NFKB1-94 ATTG I/D variant was not related to the risk of BC. Further, no publication bias on the
connection between NFKB-94 ATTG I/D variant and the risk of BC was observed. Their meta-analysis demonstrates that the NFKB1-94
ATTG I/D polymorphism is not a significant risk factor for BC .
Durthi et al. insight into potent therapeutical antileukemic agent l-glutaminase under solid-state fermentation (SSF) to review its
applications and production studies . An amidohydrolase that gained economic importance because of its wide range of applications in the
pharmaceutical industry, as well as the food industry, is L-glutaminase. The medical applications utilised it as an anti-tumour agent as well as
an antiretroviral agent. L-glutaminase is employed in the food industry as an acrylamide degradation agent, as a flavour enhancer and for the
synthesis of theanine. Another application includes its use in hybridoma technology as a biosensing agent. Because of its diverse applications,
scientists are now focusing on enhancing the production and optimisation of L-glutaminase from various sources by both SSF and submerged
fermentation studies. Of both types of fermentation processes, SSF has gained importance because of its minimal cost and energy
requirement. L-glutaminase can be produced by SSF from both bacteria and fungi. Single-factor studies, as well as multi-level optimisation
studies, were employed to enhance L-glutaminase production. It was concluded that L-glutaminase activity achieved by SSF was 1690 U/g
using wheat bran and Bengal gram husk by applying feed-forward artificial neural network and genetic algorithm. The highest L-glutaminase
activity achieved under SSF was 3300 U/gds from Bacillus sp., by mixture design. Purification and kinetics studies were also reported to find
the molecular weight as well as the stability of L-glutaminase. Their review is focused on the production of L-glutaminase by SSF from both
bacteria and fungi. It was concluded from reported literature that optimisation studies enhanced L-glutaminase production. Researchers have
also confirmed antileukemic and anti-tumour properties of the purified L-glutaminase on various cell lines .
On a personal level, we wish to end this editorial by thanking Dr. Ming Hu, the Editor-in-Chief of CDM, as well as Ms. Ashmal Afif, the
Assistant Publication Manager, and all the contributing authors who have passionately responded to our request to provide thought-provoking
articles. We furthermore extend our thanks to all peer-reviewers for their time and expertise in constructively evaluating and revising
individual contributions to a consistently high level of excellence. Last but not least, I (MAK) am highly appreciative of Nigel H. Greig
(Chief, Drug Design & Development Section, Intra
One of the major challenges currently facing cancer therapy is the development of drug resistance either intrinsically or as a result of
treatment. Treatment evasion is mediated by an intricate web of signalling cascades and adaptations caused by selective therapeutic pressure,
leading to metastatic spread and patient death. Hence, discovering and designing novel therapeutic compounds and regimens based on specific
alterations in the cancer microenvironment and capable of overcoming resistance to traditional therapies is necessary to improve cancer
survival outcomes. These new therapeutic modalities should exhibit improved solubility, penetration capacity and bioavailability in tumour
microenvironment, as well as enhanced target specificity as compared to old generation compounds. The success of this endeavour will
contribute to the advent of precision medicine leading to personalised therapeutic approaches for patients.
We are pleased to introduce this special issue (Part III) dedicated to “Challenges in the Discovery of Novel Therapeutic Agents for Cancer
Treatment”, featuring authoritative review articles written by reputed scientists from all over the world highlighting cutting edge research.
In this special issue, the first article by Rokkam et al. highlighted Glioma-associated oncogene homolog 1 (GLI1) as an amplified gene in
human glioblastoma cells . The primary function of GLI1 is normal neural development in various stages of human lives. The GLI1 gene
was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a
region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates
a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also governs
tumour tolerance, chemoresistance and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients.
GLI1 mediated HH pathway can induce apoptosis. These GLI1 can be a future diagnostic, prognostic marker and as well as potential target of
therapeutics in breast cancer .
Mukund discussed the role of genistein in breast cancer growth and metastasis . Genistein being a phytoestrogen imitates the characteristics
of estrogen, which can be useful to treat conditions by reducing the estrogen levels at the time of menopause, osteoporosis and high risk
for breast cancer. The superior binding of genistein to ERβ might help in reducing breast malignancy risk. Genistein induces cell cycle arrest,
anti-metastatic properties and ultimately affects the breast cancer cell growth by multiple mechanisms. Genistein-mediated anti-proliferative
or anti-growth effects are usually observed at higher concentrations. These signalling pathways involve the decrease of NF-κB, HIF-1α,
VEGF, and an increase of tumour suppressor p21. This will provide further insight into understanding the biology of transcription factors NF-
κB, and HIF-1α in breast cancer .
Malla and Vempati comprehensively focused on Talin as a potential drug target for cancer therapy . Talin is an intracellular cytoskeletal
protein and one of the major components of the focal adhesion complex. It mainly acts as an interlink between transmembrane integrin
receptors and cytosolic F-actin. Apart from integrins and actin, it also interacts with various other proteins in the adhesion complex to regulate
their functional dynamics. Talin undergoes a variety of post-translational modifications and they are implicated in the control of cell motility.
There are two talin isoforms (talin1 and talin2) in mammals and they are encoded by TLN1 and TLN2 genes. Recent studies showed that both
the isoforms have some mechanistic dissimilarities in terms of their interaction with membrane-bound Integrins. Among the two isoforms,
talin1 was well studied and most of the information available till now comes from talin1. This review was aimed to provide an updated overview
of the cellular significance of talin in normal and cancerous cells .
Durthi et al. reviewed the literature on the versatile and valuable utilisation of amidohydrolase l-glutaminase in pharma and food industries
. L-Glutaminase has versatile applications in pharma and food industries. In the pharmaceutical industry, L-Glutaminase can be used
as an anti-oxidant and anti-cancer agent to treat Acute Lymphocytic Leukaemia (ALL). Whereas, in food industry, L-Glutaminase is used for
acrylamide degradation, theanine production, flavour enhancement, soy sauce and many other uses. The other applications include nitrogen
metabolism and its use as a biosensor in hybridoma technology. Both intracellular and extra-cellular L-Glutaminases from a wide range of
sources were identified. Because of diverse applications of L-Glutaminase, there is a need to improve the production of L-Glutaminase by
enzyme engineering technology. The effect of recombination of L-Glutaminase production was also reported. Researchers also confirmed the
antitumor properties of L-Glutaminase by conducting in vitro, in vivo and in silico studies. Bacillus sps. and Aspergillus sps. are the commercial
producers of L-Glutaminase. In this review, the applications, different sources of L-Glutaminase, anti-cancer properties were discussed
Birru et al. addressed the major challenge in osteosarcoma treatment because stem cells in tumour microenvironment aid in a prolonged
survival rate of cancer cells and developed drug resistance . Osteosarcoma is an aggressive bone cancer found in children and adolescents.
The combined treatment strategy, which includes surgical removal of the tumour and subsequent chemotherapy to prevent the reoccurrence,
has been a widely accepted approach. However, the drug resistance developed by tumour cells causes recurrence of cancer. It is imperative to
understand the molecular mechanism involved in the development of drug resistance and tumour progression for developing potential therapy.
Tumour microenvironment and cellular cross-talk via activation of various signalling pathways are responsible for tumour progression
and metastasis. The comprehensive reviews are already available on the tumour microenvironment, signalling cascades responsible for tumour
progression, and cellular crosstalk between malignant cells and immune cells. Therefore, we intend to provide comprehensive review
postulating the importance of mesenchymal stem cells (MSCs) in osteosarcoma progression and metastasis. Their paper is aimed to provide
information sequentially includes tumour microenvironment, MSCs role in osteosarcoma progression, the hypoxic environment in MSCs
recruitment at the tumour site and the importance of exosomes in tumorigenesis, progression and metastasis. Overall, their review may enlighten
the research on the role of MSCs and MSCs derived exosome in osteosarcoma progression and drug resistance. This possibly may
result in developing novel therapeutic approaches to combat the osteosarcoma effectively and contributes to the development of prognosis
tools for early diagnosis .
On a personal level, we wish to end this editorial by thanking Ming Hu, the Editor-in-Chief of CDM, as well as Ashmal Afif, the Assistant
Publication Manager, and all the contributing authors who have passionately responded to our request to provide thought-provoking articles.
We furthermore extend our thanks to all peer-reviewers for their time and expertise in constructively evaluating and revising individual contributions to a consistently high level of excellence. Last but not least, I (MAK) is highly appreciative of Nigel H. Greig (Chief, Drug
Design & Development Section, Intramural Research Program, National Institute on Aging, National Institute Health, USA) for his support in
motivating me for my scientific career.
Although the invention of a new drug molecule is a very rigorous, specialized, time-consuming and costly process, it is vital for identifying
the solutions to modern age-associated, complex and lifestyle-related diseases. The primary hurdle in the invention of a new drug molecule
is to predict and analyze its effects on the metabolism of the drug itself and its effect on the metabolism of the person. The interaction of
drug molecules with different tissues and organs is highly dynamic, multifold, influenced by several factors and most of the time, it is unpredictable.
Hence, the application of drugs for the treatment of the disease may be associated with several undesirable effects. It is therefore
essential to understand the factors that influence the dynamics of the drug in the biological system. Both pharmacodynamics and pharmacokinetics
are important in understanding the interactions of the drug with living organisms and are essential in determining the drug dose, benefits,
and adverse effects. Furthermore, the determination of toxicity is of utmost importance, given the fact that several blockbuster drugs are
being withdrawn from the market.
Several factors regulate the dynamicity of the drug molecule in the living organism and it is not limited to environment, drug delivery
methods, the gender of the individual, the form of the drug, route and time of drug administration. This special issue has reviewed certain
factors that can influence the efficacy of the drug in the living organism and have envisaged the way to curtail their effects in order to make
the drug safe to the patient [1-6].
Several environmental factors such as radiation and pollutants can influence the activity of several drug-metabolizing enzymes and hence
the metabolism of drugs . Furthermore, the individual-specific factors such as genetic polymorphisms, physiological condition, pathological
conditions and life-style related factors such as smoking, alcohol consumption, nutrition, etc. can modulate the metabolism of a drug in a
person’s body. Sex and gender of a person are involved in the metabolism of drug molecules and they are usually the most neglected factors
in predicting and analyzing the effect of a drug. The influence of sex and gender is essential in understanding and avoiding sex-related adverse
effects of drugs. Specific emphasis is required to understand the involvement of genomic and non-genomic action of sex hormones .
Phytochemicals have been used for a long time for the treatment of various diseases, however, poor bioavailability is a major concern.
Poor bioavailability may be due to the metabolism of phytochemicals that are mostly dependent on the form of phytochemicals and individual-
specific variations. Therefore, understanding the metabolism and pharmacokinetics of phytochemicals might extend their therapeutic use
Poor bioavailability and severe side effects are the major limitations in the therapeutic use of many types of drugs. This can be efficiently
overcome by employing nanocarrier or nanoparticle-based drug delivery systems and it can not only improve the quality of life and lead to a
reduction in the overall cost of treatment [4, 5]. Due to increasing interest in the nanoparticles-based delivery of drugs, it has become more
efficient and less toxic. However, still, efforts are required to understand the differential metabolism of the nanoform of a drug versus a native
drug that may further reduce their side effects and enhance safety.
Amongst many diseases related to modern lifestyle, age and environmental effect, cancer is posing increasing pressure on the medicine
and health care systems for the invention of new therapeutic ways. Drug resistance in cancer is the probable reason behind the increasing risk
of cancer and may warrant parallel attention as that of antibiotic-resistant bacteria. Drug resistance in cancer may be due to an altered gene
expression, modulated gene expression regulation and altered DNA repair mechanisms of the major drug transporter proteins. Cancer cells
achieve this by epigenetic mechanisms, particularly, the methylation of the promoter region of the drug transporter proteins, expression of
specific microRNAs, etc. . Therefore, understanding these mechanisms may suggest us future directions for better treatment. Cancer
cachexia is a major complication of advanced cancers and is associated with many complications, particularly, the skeletal muscle wasting.
Mitochondria play a very important role in the development of cancer cachexia, particularly, in the regulation of total protein turnover in
skeletal muscles . Hence, mitochondria are a very important target in the prevention and treatment of cancer cachexia.
Cancer refers to the uncontrolled growth of abnormal cells in the body . As estimated by from the American Cancer Society, there are
about 1,762,450 new cancer cases and 606,880 cancer deaths cases in 2019 . With the numerous advances in cancer therapy research, the
survival rate has improved by five percent. Due to chemoresistance developed by the tumor cells, there is no definite cure for many cancers;
multidrug resistance allows for metastasis and disease recurrence . Phytochemical extracts are highly effective against cancers and various
degenerative diseases [4, 5]. They possess potentiating features including antioxidant, anti-inflammatory, and anti-tumor properties . Regular
intake of phytochemicals has shown to improve an individual’s health status [4, 6]. Additionally, phytochemical combinational therapy is
less toxic to healthy cells, produces fewer symptoms, and preferentially sensitizes tumor cells to chemo drugs. Non-coding RNAs makeup an
emerging strategy expected to decrease chemoresistance by altering the regulation of various tumor suppressor genes and oncogenes against.
Thus, these ncRNA can be used as biomarkers or therapeutic target for cancers . Although the advanced therapeutic strategies are yet to be
developed, including natural products a patient’s daily diet may help decrease cancer incidence.
In continuation of volume 20 issue 12, we would like to potentiate our volume with more serious malignant diseases and the chemoresistance
developed by the cancer cells. This volume focuses mostly on neuroblastoma, lung cancer, and cervical cancer correlated with their
biology, therapy, and resistance development. Neuroblastoma is a common pediatric disease diagnosed in children of ages 1 to 5. This cancer,
generally arises in adrenal glands or within a bundle of neural cells often in the chest, neck, or spine. Secondly, lung cancer is the second most
common cancer detected in men and women. As per the estimation of the American Cancer Society, for the year 2020, about 228,820 new
cases and 135,720 deaths are expected. Cervical cancer is another serious cancer; it is the fourth most frequently diagnosed disease in females,
with as an estimated percentile of about 6.6% for the year 2018. Metabolic fluctuations, including insulin resistance, triglyceride levels,
obesity, and irregularity of adiponectin cause cervical cancer. Adiponectin is a hormone secreted from adipose tissue and found in blood
plasma. Moreover, the concentration of adiponectin is inversely associated with the an increased risk of cancers like cervical cancer. This
volume focuses on adiponectin and its role in cervical cancer. Previous research has shown that adiponectin downregulates the expression of
cyclin D1 and c-myc while upregulating p53, allowing for apoptosis cell proliferation the inhibition. Thus, adiponectin expression can be
taken as a biomarker for cervical cancer diagnosis.
In addition to the cancers, we focus on Alzheimer disease as well. This disease is an irreversible and progressive age-related neurodegenerative
disease detected worldwide. There are no current reliable therapies for this disease; acetylcholinesterases are somewhat effective for
neuropsychiatric symptoms. However, the new therapeutically plant derived agents have demonstrated improved results. Various studies on
phytochemicals have determined that their use of these may reduce the onset and progression of the disease, including age and insulin related
neuropathology in Alzheimer’s disease.
Chemoresistance remains a major obstacle in the therapy of cancer and presents a challenge for improvising the clinical research for a
better outcome. Phytochemicals are naturally occurring plant-based compounds that exhibit anti-cancer properties and reduce chemoresistance
development, thereby reducing relapse and metastasis. Chemoresistance mostly occurs due to aberrantly acting transporter pump proteins,
mitochondrial alterations, EMT, oncogenes, DNA repair proteins, and cancer stemness. Our volume includes the biology of the molecular
mechanisms behind as to determine which genes function abnormally and which can be targeted for therapy. Understanding how the cells
develop resistance is essential for enhancing therapy and sensitizing the cells to the chemodrug. As phytochemicals are natural extracts that
interfere with the self-renewal, drug resistance, they may be useful in combinational therapies. Our volume will describe phytochemicals and
their mechanisms in the drug resistance pathway. This is a potential milestone in the cancer therapy as, the synthetic drugs currently are toxic
to healthy cells and weaken a patient’s immune system. Additionally, our volume includes topics about the noncoding RNAs (ncRNAs).
These ncRNAs are large segments of the human transcriptome that play a crucial role in cellular physiology and pathogenesis. At present,
they are widely explored and encouraged for the cancer therapy, ncRNAs help regulate transcription; they work as transcriptional activators,
RNA polymerase, and duplex DNA to regulate genes that develop drug resistance pathways. Thus, targeting ncRNA could be an effective
novel therapeutic strategy for various cancers like lung cancer. The discussed topics herein would summarize the research done previously
and would describe how phytochemicals may be used to overcome chemoresistance in cancer therapy as well as degenerative diseases.
It is our pleasure to present this comprehensive summary of revised therapeutic strategies of cancer to the research community for a clear
and holistic understanding. Thus, we hope our work on these volumes reflects novel therapeutic ideas for improved patient care.
One of the major challenges currently facing cancer therapy is the development of drug resistance either intrinsically or as a
result of treatment. Treatment evasion is mediated by an intricate web of signalling cascades and adaptations caused by selective therapeutic
pressure, leading to metastatic spread and patient death. Hence, discovering and designing novel therapeutic compounds and regimens
based on specific alterations in the cancer microenvironment and capable of overcoming resistance to traditional therapies is necessary
to improve cancer survival outcomes. These new therapeutic modalities should exhibit improved solubility, penetration capacity and
bioavailability in the tumor microenvironment as well as enhanced target specificity compared to old generation compounds. The success
of this endeavour will contribute to the advent of precision medicine leading to personalized therapeutic approaches for patients.
Exosomes are cell-derived Nano vesicles, which can mediate intracellular communication by transferring exosome messages such
as mRNA, miRNA, protein, and etc. It has been reported that exosomes play important roles in antigen presentation, occurrence and
progress of tumors, and signal transduction of neurons. Besides, exosome acts as a carrier for targeted drug delivery, carrying mRNA
and miRNA to places where diseases are located and reaching the goal of targeted therapy. Therefore, it can be used as drug delivery
vehicle for numerous diseases. However, the hypothesis of using exosomes to deliver therapeutic cargo is still in initial stage considering
the heterogeneity and individualized genetic background of the tumor cells. Numerous studies showed that multiple types of cells
secrete exosomes, including immunocytes, cardiovascular cells, neurocytes, stem cells, cancer cells and so on, to play biological or
pathological effect like antigen presentation, RNA transport, tissue reconstruction, neurodegenerative disorder, tumor metastasis, metabolism
and so on. Some signal molecules like specific proteins, lipid or nucleic acids have a biological effect through exosomes
transportation. The universality of exosome and convenience of obtaining them make exosome as a potential way to diagnose and
treat diseases. It shows a promising prospect in the development of precision medicine. In this thematic issues, we collected latest
research and review papers in this field and hope it will be helpful to the readers who are interested in exosomes as drug delivery
The integration of nanotechnology with biology is poised to address current biomedical and human health problems [1, 2]. Recent developments
at such interfacial research have shaped novel concepts and products in the area of nanodevices and nanomedicines. It is well established
that the advances in the areas of bio-mimetic/bio-inspired nanotechnology, bio-imaging, disease diagnosis, and treatment, would progress
with either improvement in existing methods using integration of nanoparticles or development of novel methods for the preparation of
nanomaterials [3, 4].
This special issue includes seven articles delving around to provide a comprehensive overview of recent trends and developments of
nanotechnology towards multidimensional aspects of biomedical applications.
The first contribution covers an overview of nanobiotechnology and cancer nanotechnology submitted by Chaturvedi et al. . This
manuscript summarizes the use of nanomaterials for early cancer detection by sensing the targeted biomolecules such as proteins, antibody
fragments, and nucleotide (DNA/RNA) fragments serve as cancer biomarkers. Nanoparticles as drug delivery vehicles for the treatment of
cancer has been at the frontier of the cancer nanotechnology, which has found to develop novel strategies and smart ways to deal with cancer
cells. Several of these examples are covered in this article as well as in the second contribution written by Patel et al. . Topical application
of drug-delivering nanoparticles has shown promise towards the treatment of several autoimmune disorders such as Rheumatoid Arthritis,
which deals with symptoms such as chronic progressive inflammation and destruction of cartilage and bones. A concise report about the different
types of nanomaterials exhibited positive results for Rheumatoid Arthritis treatment has also been presented. Safe delivery of anesthetic
agents to the patients remains one of the challenging tasks; therefore, utilizing the capabilities of nanotechnology has been recently realized
for the site specific delivery of such drugs. Therefore, we have also included a comprehensive report by Liu et al. describing the synthesis of
various nanoformulations of anesthetic drugs and their applications.
Today’s medical diagnostics research aims towards molecular imaging to facilitate early diagnosis, identification of disease type, stage of
disease and provide fundamental information about pathological processes. The paradigm shift exploits nanomaterial-based probes over traditional
single molecule-based contrast agents. Although quantum dots, fluorophore-doped nanomaterials, and other metal-oxides hold excellent
promise, development of nanomaterials as artificial enzymes (nanozymes), animal imaging probes such as molecular imaging with X-ray
based computerized tomography, ultrasound, and magnetic resonance imaging will be of great use for human health [7-9]. Further, considering
the broad spectrum applications of iron oxide nanoparticles, two articles prepared by Shakil et al.  and Karakoti and co-workers 
systematically summarize the current progress and future promises of these magnetic nanoparticles.
Protozoan parasites mediated morbidity and mortality has been a serious threat to humans and animals. Among them, Leishmaniasis is a
dreaded disease caused by a protozoan parasites Leishmania donovani. Owing to the absence of vaccines for the treatment of leishmaniasis,
chemotherapy remains the mainstay for anti-leishmanial therapeutics, which face several limitations and thus results in poor therapeutic efficacy.
Several of anti-leishmanial drugs are conjugated with nanoparticles to offer better therapeutic results than naked drugs. In this context,
Shah et al have contributed an article summarizing available targeted delivery of pharmacological agents which are expected to enhance the
bioavailability, reduce toxicity and circumvent the issues of chemoresistance .
Recent developments in the pharmaceutical sector have led to the discharge of drugs in wastewater which could pose threat to the aquatic
species and humans. Although recent awareness about the presence of such contaminants in drinking water has raised substantial concerns,
very little is known about the fate and ecological impacts of these pollutants. As a result, these pollutants are inevitably introduced to our food
chain at trace concentrations and eventually induce toxicity. Focusing on this issue, Agnihotri and co-workers  have contributed an article
which covers the essential insights about applications of various nanomaterials for the removal of pharmaceutical contaminants from wastewater
and soil samples.
Undoubtedly, nanotechnology would have a tremendous future due to the unflinching growth and potential to be used as an alternative to
solve several of the current generation problems. Incorporation of nanomaterials has led to the construction of new sensors as well as an increase
in the sensitivity and performance of existing biosensors. Signal transduction based technologies using nanomaterials has allowed the
invention of several novel biosensors. Additionally, the nanoscale dimension further assists the development of nanosensors for rapid and
simple detection in vivo. Due to these capabilities, nanotechnology is being looked as the potential technology to provide portable instruments
capable of multiplexed analysis of components in extremely low concentrations. However, the release of nanoparticles from consumer products
into the environment has been suspected as one of the biggest limitations of nanotechnology. Therefore, it is imperative to fully understand
the properties and activities of nanomaterials before it is used for any biomedical applications. In this context, Gupta et al.  have
summarized potential toxicities aroused by nanoparticles and their possible remedies by considering carbon-based nanomaterials as a model
nanoparticle system. The strategies described in this article is not only limited to carbon-based materials and could also be extended to other
nanomaterials of biomedical interests.
All the valuable contributions presented in this special issue depict the present status and future perspectives in the area by leading experts
of the field. This comprehensive issue will be a valuable asset for researchers from all fields which encompasses the expertise from materials
science, medicines, engineering, and radiologists together to make nanobiotechnology most rewarding.
With the development of high-throughput sequencing techniques, more and more sequencing data is available, including genomics reads,
transcriptomes data, and proteomics sequences, which provide us an opportunity for disease treatment and prevention that takes into account
individual variability in environment, lifestyle and genes for each person. Thus, it is critical to develop protein drugs and identify protein drug
targets. Application of machine learning techniques in protein drugs and drugs targets discovery is more and more popular because these
techniques can extract the essential characteristics of research object and improve accuracies of models, which is needed by all biological
scholars [1, 2]. This special issue was hosted in various aspects of the development and application of machine learning techniques in protein
drugs and drug targets data analysis.
In this special issue, ten works were published for describing the development of drug design and drug target discovery by using machine
learning methods. Drug discovery is very important for pharmaceutical industries. At its current stage, it is still an expensive and timeconsuming
process for discovering new drugs. Machine learning techniques have been widely applied in the field. Stephenson et al. reviewed
the potential application of Artificial Intelligent (AI) techniques in the field of drug discovery . This review provides a survey to understand
the current status of machine learning techniques in the drug discovery field within both academic and industrial settings. They also
discussed the AI potential future applications and several interesting patterns in drug discovery fields.
Peptide-Fc fusion drugs are a category of biological therapeutics in which the Fc region of antibody is fused genetically to a peptide of
interest. Ning et al. summarized the key steps of peptide-Fc fusion technology and stressed the main computational resources, tools, and
methods that were helpful for the rational design of peptide-Fc fusion drugs . Moreover, they raised open questions about the computeraided
molecular design of peptide-Fc fusions. Heat Shock Proteins (HSPs) are molecular chaperones. They are associate with multiple kinds
of diseases. Chen et al. summarized the development of HSP families’ classification and prediction by using machine learning methods .
Several published online servers were listed which will provide convenience to most of wet-experimental scholars.
Protein–peptide recognition and interaction plays an essential role in the orchestration and regulation of cell signaling networks. Li et al.
presented a systematic review of applying machine learning techniques to perform the quantitative modeling and prediction of protein–
peptide binding affinity, particularly focusing on its implications for therapeutic peptide design . They briefly introduce the physical quantities
used to characterize protein–peptide affinity and extend the content of generalized machine learning methods. They also discussed the
existing issues and future perspective on the computational prediction of protein–peptide binding affinity.
To understand the functions of target proteins binding and regulating by drugs is crucial to against the diseases. Two reviews focused on
the drug-target identification. Hu et al. provided a systematic overview of recent work on identifying drug targets . They summarized the
published drug-target database, wet- and dry-experimental techniques on drug targets discovery and published results obtained from machine
learning method. Zhang et al. focused on the recent advances of drug-target interaction prediction by using machine learning methods .
They also listed the published datasets, and introduced features for drugs and targets. Since similarity index are important for prediction, they
introduced how to calculate similarities based on training data or published features. Finally, they summarized and compared the performance
of different machine learning-based prediction methods.
Virus-host protein interactions play essential roles in viral infection and antiviral defenses. Targeting critical viral-host Protein-protein
Interactions (PPIs) has enormous application prospects for therapeutics. Using computational method to identify virus-host PPIs could provide
new opportunities for gaining biological insights, including applications in disease control. Zheng et al. provided an overview of recent
computational approaches for studying virus-host PPI interactions . The pivotal and representative features extracted from relevant sources
of biological data were described. They also introduced some state-of-the-art machine learning algorithms in the field and discussed their
abilities, weakness and future directions. Cervical cancer is the second most common cancer in women worldwide, which was caused by Human
Papillomavirus (HPV). Thus, Yao et al. focused on HPV identification. They discussed the advantage and disadvantage of several classical
approaches which have been applied for the risk type prediction of HPV . Especially, many computational methods were proposed for
this prediction issue.
Cell-penetrating Peptides (CPPs) are important short peptides that can transport drug molecules through the plasma membrane and send
these molecules to different cellular organelles. Thus, Wei et al. summarized the machine learning-based CPP identification methods and
compared the construction strategies of 11 different computational methods . Furthermore, they pointed out the limitations and difficulties
in predicting CPPs. The future development direction of CPP recognition with computational methods was finally discussed.
Drug metabolism is one of the most complicated pharmacokinetic properties to be understood and predicted. Xiong et al. reviewed the
computational study on cytochrome P450 enzymes which play a key role in the phase I metabolism of foreign compounds including most of
Humans and mammals must successfully evolve metabolic system, to effectively deal with the inevitable exposure to a lot of nutrients
and chemicals (xenobiotics) from the exogenous food and environment, especially endogenous toxic metabolic by-products, in order to maintain
homeostasis and survive in nature. This exogenous nutrients and chemical defense task are undertaken by the hepatic metabolism and
detoxification system mediated by the xenobiotic receptors, which at least include the Pregnane X Receptor (PXR), Constitutive Androstane
Receptor (CAR) and aryl hydrocarbon receptor (AhR) . PXR and CAR are the bona fide nuclear receptors, which have been cloned in all
vertebrates, indicating the evolutionary conservation for metabolic detoxification . AhR has been identified as ligand activated transcription
factor of the bHLH/PAS family, and mediating the toxic responses of dioxins, polycyclic aromatic hydrocarbons and other related compounds
It is reported that PXR plays a critical role in organism's metabolic detoxification system by sensing the presence of xenobiotics and triggering
detoxification responses. Additionally, PXR has pleiotropic functions in regulating immune and inflammatory responses, cell proliferation,
bile acid and cholesterol metabolism, glucose and lipid metabolism, steroid and endocrine homeostasis, as well as bone metabolism.
Pu et al. summarized the effects of xenobiotic nuclear receptors on metabolic syndromes. Chen et al. concluded how xenobiotic receptors
mediate hepatic glycolipid metabolism. Recent research suggests that the PXR is required for maintaining healthy commensalism between
microbiota and gut . Interestingly, the metabolites such as indole derivatives from commensal microbes serve as the ligands for the PXR in
intestinal epithelium forming an intricate mutualistic interaction between host and microbiota.
AhR recognizes xenobiotics as well as natural compounds such as tryptophan metabolites, dietary components and microbiota-derived
factors , and it is important for maintenance of homeostasis at mucosal surfaces. AhR activation induces cytochrome P450 1 (CYP1) enzymes,
which oxygenate AhR ligands, leading to their metabolic clearance and detoxification . Thus, CYP1 enzymes have an important
feedback role that curtails the duration of AhR signaling . It is reported that intestinal epithelial cells serve as gatekeepers for the supply of
AhR ligands to the host and emphasize the importance of feedback control in modulating AhR pathway activation . Tryptophan catabolites
from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via IL-22 . Tryptophan mediates the IDO1-AhR axis in
host-microbial symbiosis . Ji et al. reviewed the cross-regulatory circuit between AhR and microbiota. Tryptophan metabolite activation
of the aryl hydrocarbon receptor regulates IL-10 receptor expression on intestinal epithelia .
In addition, other factors have reported to be involved in the crosstalk between nutrients and xenobiotic receptors. Feng et al. concluded
Kisspeptin and its effect on mammalian spermatogensis. Zhang et al. summarized the role of E-cadherin in Helicobacter pylori-related gastric
diseases. Wang et al. summarized the amino acid metabolism in dairy cows and their regulation in milk synthesis. Zhou et al reviewed soy
isoflavones and their effects on xenobiotic metabolism. Abdallah et al. concluded application of traditional Chinese herbal medicine byproducts
as dietary feed supplements and antibiotic replacements in animal production.
This special issue collects and provides an overview of the current understanding of the pattern of the crosstalk between nutrients and
xenobiotic receptors, as well as its dysfunction induced metabolic diseases, particularly the critical signal pathways, which will shed light on
revealing potential targets for therapeutics.
A variety of factors can affect the patients' responses to therapeutic drugs, such as race, gender, age, etc., while genetic polymorphisms
are the main causes of individual differences in drug responses. The genetic polymorphisms are not only closely related to the incidence of
diseases such as tumors, Alzheimers, and Parkisnsons, but also affect the metabolism, activity, and toxicity of the drugs. The studies of genetic
polymorphisms on drug metabolizing enzymes, transporters, and targets are helpful to clarify the relationships between gene mutation
and efficacy or safety of drugs. Patients could be given different therapies according to different genotypes, which may significantly improve
the therapeutic effect. Genetic polymorphisms provide a new way for individualized treatments besides therapeutic drug monitoring. At present,
the relationships between genetic polymorphisms of many drugs and clinical outcomes have been very clear. For example, the guideline
emphasizes that genetic testing has the vital significance when taking warfarin. However, although genetic polymorphisms of many drugs
have been reported, some studies are controversial, it is also necessary to integrate various genetic factors for further research.
Therefore, this special issue of Current Drug Metabolism is to publish some valuable reviews on how genetic polymorphisms affect the
pharmacokinetics and pharmacodynamic parameters of several therapeutic drugs, including antitumor drugs, antiasthmatic drugs, immunosuppressive
agents, anti-infective drug, EGFR Tyrosine Kinase Inhibitors (EGFR-TKIs), and Recombinant Human Growth Hormone (rhGH),
new oral anticoagulant, humanized anti-α4 integrin monoclonal antibody, Platelet-Derived Growth Factor Receptor (PDGFR) kinase inhibitors.
We aim to provide current genetic research progress on these therapeutic drugs which are widely used in clinic therapy.
Gamma-hydroxybutyrate (GHB) is a potent central nervous system depressant, used as a
recreational drug of abuse. It is quite frequently found in forensic investigations of subjects alive
or dead. GHB in the form of sodium salt is a registered therapeutic agent approved of by some
countries in treating narcolepsy-associated cataplexy and is an adjuvant medication for
detoxification and withdrawal in alcohol abusers. GHB is endogenously produced and traces can
be found (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a
precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid
(GABA). Information available indicates that GHB serves as a neurotransmitter or
neuromodulator in the GABAergic system, and in particular via binding to the GABA-B receptor
Taking into account the dual nature of this compound, endogenous and exogenous, various
points need to be clarified and this special issue aims to focus on them, trying to provide the
most updated scientific evidence in this field.
Moreover, the role of new GHB metabolites, such as GHB-glucuronide (GHB-Gluc) and the
sulfonated metabolite of GHB (GHB-SUL) and their detection window in biological samples,
with particular emphasis on alternative matrices, will be given for forensic purposes, especially
in cases of drug facilitated sexual assault (DFSA), and clinical purposes both in the short and
long-term monitoring of patients under sodium oxybate treatment.
Tumor is one of the most serious threats to human beings. Benefiting from the fast development of nanotechnology, many kinds of
nanoparticles that constructed from various nanomaterials were developed for tumor diagnosis and therapy. Nanoparticles have gained great
attention of both academy and industry. However, few nanoparticles were approved for clinical application although thousands were developed
in lab. Therefore, in this theme issue, we invited several contributors to discuss the application of various kinds of nanoparticles in tumor
targeting drug delivery, as well as their advantages and shortages.
Based on their good biocompatibility and low toxicity, polymeric nanoparticles have gained much attention in gene and drug delivery to
tumor. However, the drug delivery efficiency by polymeric nanoparticles is greatly hindered by the rapid opsonization, phagocytic uptake and
subsequent clearance from bloodstream. Therefore, in the first review, Hu et al. firstly discussed the factors that influence the blood circulation
of polymeric nanoparticles, including particle size, shape, zeta potential and hydrophilicity. Then some natural and synthetic polymers
used in the constructing of nanoparticles were reviewed, such as gelatin, polysaccharides, cyclodextrin, and synthetic polymers. While several
preparation methods were also discussed, including polymerization techniques, precipitation techniques, film extension techniques, and particle
replication in non-wetting templates. Finally, methods to achieve long blood circulation time were reviewed.
In the review provided by Zhang et al., authors further discussed the strategies in long circulating drug delivery by nanoparticles. To
achieve the long blood circulation time, PEGylation is widely used in modification surface of nanoparticles to inhibit the adsorption of opsonins
in blood. As an alternative of finding new nanomaterials especially new surface coating materials, biomimetic nanoparticles showed great
potential because they can adopt the intrinsic long circulation behavior of biological components, such as red blood cells, cancer cells, macrophages,
bacteria, viruses and lipoproteins. The application of these strategies and the constructed nanoparticles were detailed reviewed in the
Safety of nanomaterials is a great concern for clinical application, that is why only few formulations were approved by Food and Drug
Administration (FDA) of US. To meet the safety concern, natural polymers are good candidates to constructing nanoparticles. Polysaccharide
is one of the most widely explored and used natural polymers, and many kinds of derives were developed to provide excellent properties in
drug delivery. In the review, Dr. Tong and Dr. Ma summarized the representative examples of polysaccharides used in drug delivery, such as
chitosan, hyaluronic acid, dextran and pullulan. Because of their widely application in tumor targeting diagnosis and treatment, the reviewed
discussed several aspects of the application of polysaccharide, including gene delivery, small molecular drug delivery, no matter polysaccharide-
drug conjugates or drug encapsulation, combinational drug delivery, and finally theranostics. In the review, many examples were provided
with in-deep discussion.
As a supplement to the natural polymers, nature products could be directly used in treatment of cancers. Therefore, Dr. Cai and Dr. Yu
reviewed the application of natural products in cancer therapy by targeting the apoptosis pathways. In the review, key proteins involved in the
regulation of apoptosis were firstly summarized, including Cytochrome c, Bcl-2 family, p53, Fas, Survivin, Caspase family, Nuclear factor-
B, and Protein Kinase B. Then various kinds of natural products that can target these proteins were reviewed.
Gold nanoparticles are most widely used inorganic nanomaterials in cancer diagnosis and therapy, while many kinds of anisotropic gold
nanoparticles are developed, including gold nanospheres, gold nanoclusters, one-dimensional gold nanorods, two-dimensional gold nanoplates,
gold nanoshells, platonic gold nanoparticles, hollow gold nanoparticles and other types of gold nanoparticles. In the review provided
by Dr. Shevtsov et al., the various synthesis methods for these kinds of gold nanoparticles were summarized. Then the application of gold
nanoparticles in drug delivery was reviewed. Gold nanoparticles have been used in many aspects of tumor treatment and diagnosis, such as
modification tumor microenvironment, radiosensitization, photothermal therapy, and photodynamic therapy. All these researches demonstrated
the great potential of gold nanoparticles in tumor management.
At last, as a kind of cancers with highest incidence, lung cancer was paid with particular attention. Zheng et al. reviewed the nanoparticles
in management of lung cancer, including polymeric nanoparticles, lipid nanoparticles, human serum albumin nanoparticles, and inorganic
nanoparticles. Then the various models used for different application routes were reviewed. Finally, the clinical application of these administration
routes and formulations were discussed.
Mental disorders such schizophrenia, depression, bipolar and anxiety disorders are leading causes of disability and multimorbidity in the
modern society. In recent years, major advances were made in order to understand the molecular basis of these disorders aiming to discover
potential new drugs. Unfortunately, the majority of these efforts have been unsuccessful. Many other studies have been focused on understanding
the mechanism of action of drugs used for the treatment of neuropsychiatric disorders, such as antidepressants, mood stabilizers and
antipsychotics using isolated systems. Many incredible discoveries were made which allowed us to develop better treatment options to improve
the quality of life of patients struggling with these disorders.
Today, clinicians and scientists are combining forces to better understand different connections of the brain-body relationship that were
refuted for many years because of the general idea of the brain as an independent and isolated tissue. The concept of a two-way relationship
between depression and cardiovascular disease, or the gut-brain axis is only gaining more space and credibility. We are in the moment of
understanding how our complex body is interconnected in the way that a single insult in a remote part of our body could lead to molecular
changes in our brain.
We are also better understanding the side effects of distinct drugs, such as antidepressants, and their impact on a population with cardiovascular
disease or the relationship between long-term lithium intake and cancer proliferation. More studies are still needed to confirm these
suggestions; however, they are thought-provoking.
This thematic issue, devoted to the study of current pharmacological treatments involved in mental disorders introduce an interesting interface
intended to explore (i) the safety limits of the use of antidepressants on cardiovascular function , (ii) the cross-talk between inflammation
in depression and cardiovascular disease , (iii) the involvement of microbiota in the etiopathogenesis of mental illness , (iv)
the relationship between lithium intake and cancer proliferation  and (v) the applicability of targeting GSK-3B for several incurable neuropsychiatric
It is evident that science reached a time where scientists and clinicians are combining strengths to better comprehend the molecular basis
of pharmacological treatments to study the diseases as they occur; in combination, and not isolated. In this new era of technology and information,
combining forces in a multidisciplinary environment to understand the pathological basis will only improve the treatment options and
the quality of life of patients with psychiatric disorders.
Chronic kidney disease (CKD) leading to kidney failure is becoming a global public health
problem. Acute kidney injury (AKI) is also a major kidney disease characterized by a rapid
decline of renal function. Drug-induced nephrotoxicity is a contributing factor to AKI in
19-25% of critically ill patients. Drugs exert their toxic effects to cause nephrotoxicity by one
or more common pathogenic mechanisms. The progressive loss of kidney function associated
with CKD not only leads to impaired renal excretion of numerous drugs and their metabolites
in the kidneys, but also alters the non-renal disposition of moieties that are extensively
metabolized by the liver. Various alterations in activity of metabolic enzyme system have
been reported in CKD models, for example, reductions in expression and activity of hepatic
cytochrome P450 (CYP) enzymes including CYP3A1, CYP3A2, CYP2C11, and other
enzymes such as N-acetyltransferases. What’s more, other mechanisms such as the
dysregulation of drug transporter systems are involved in decreasing the clearance of drugs in
renal failure. With the development of renal failure, the renal secretion of organic ions
mediated by organic anion transporters (OATs) and organic cation transporters (OCTs) is
decreased. Some organic anionic uremic toxins may directly inhibit the renal excretion of
various drugs and endogenous organic acids by competitively inhibiting OATs.
The objective of this mini-thematic issue is to report recent studies about most common
mechanisms of drug-induced nephrotoxicity and prevention strategies, the alterations of drug
enzymes and transporters in the kidney and liver in renal failure, the potential model systems
to predict drug efficacy, interactions, and drug-induced kidney injury in drug development.
Neurological disorders cover a wide range of diseases; suffering patients all around the world. A study in UK shows about six percent of
the population involved with neurological disorders . Also, investigations stated that the imposed cost of these disorders is an important
challenge for European societies . Therefore, there are too many investigations to find new medical approaches and remedies to treat or
manage neurological disorders. Natural products as well as complementary and alternative therapies are as the sources to find such therapeutics
that are going to be more popular in the society. There are too many traditional and complementary systems of medicine, mostly with
historical roots in ancient eras like Chinese medicine, Persian medicine, Ayurveda, Homeopathy, etc.  Alongside raising the popularity of
using natural and traditional medications, interest of researchers to evaluate their efficacy and safety is going to be raise up. On the other
hand, this popularity causes some concerns including the safety and probable interactions between these remedies with common drugs. Therefore,
investigations to find the efficacy and safety of them with the help of accepted and academic methods are too important.
World Health Organization (WHO) approves and encourages traditional therapies integrated with current and conventional medicine. It
means using the opportunities in both medical systems, traditional and conventional medicines . It is important to integrate Traditional and
Complementary Medicine (T&CM) approaches to current medical systems. It is not only necessary for using T&CM opportunities to manage
and treat neurological disorders and decrease the costs of treatment, but to find any probable side effects and interactions with such remedies.
Therefore, in the first step, it needs scientific investigations to find T&CM drugs’ efficacy, safety and toxicology and then, in the next step
training the neurologists and pharmacists is too important.
Therefore, this thematic issue of Current Drug Metabolism aims to publish some valuable reviews on the principles, suggestions, efficacy
of drugs and also herb-drug interactions of some types of T&CM systems in some neurological disorders; providing scientific data and discussions
for medical practitioners, pharmacists and researchers in this field.
This thematic issue will provide a platform to share comprehensive information on advances and recent trends
in various prophylactic and therapeutic regimens to effectively combat various diseases and other health
problems, both infectious and non-infectious posing challenge to the humans and their companion animals
(livestock & poultry). It will focus mainly on the novel, emerging and valuable alternate / complementary
frontier therapeutic options especially in the era of emerging and rising drug resistance in microbial pathogens
and increasing health disorders and conditions of high concerns due to changing life style and other various
predisposing factors. Advances and interdisciplinary approaches of biotechnology, molecular biology,
genetics, cellular immunology, immunomics, proteomics, pharmacology, bioinformatics, nanotechnology and
others for designing and developing newer and effective therapeutic modules would be given priority. These
will include phages, enzybiotics, apoptins, cytokines, monoclonal antibodies, egg yolk antibodies, TLR, stem
cells, si-RNA, nanomedicines, nutritional immunomodulation, probiotics, antioxidants, phytonutrients, and
herbal medicines, which could play promising role in curbing evolving pathogenic threats by their potent
antimicrobial potential, treating non-infectious diseases, metabolic disorders, cancers as well as various
general health problems. Other potential candidates being explored for targeting development of valuable
medicines, drugs, pharmaceuticals, immunotherapeutics, antitoxins, tissue growth factors, gene therapy,
regenerative medicines, therapeutic biologics, modern vaccines and vaccines based therapies will also be
considered. Trends and advances in pharmacogenomics aided drug development and therapeutics,
pharmacokinetics, pharmacodynamics and metabolism of effective/newer drugs and medicines, upcoming
drug designing and novel drug delivery methods will also be given due attention. The compilation will be
useful for medical and veterinary professionals, clinicians, researchers, students/scholars, public health
experts, animal producers, and pharmaceutical industry in designing and adapting effective and safer
therapeutics from clinics to the laboratory for countering important diseases. This thematic issue will accept
submissions of comprehensive review papers on above mentioned topics / theme with their basics, modes of
action, medicinal values, beneficial health applications, modern trends and advances, perspectives, which
could lead to designing and development of effective therapeutics, drugs/medicines, nutraceuticals and
pharmaceuticals in the area of biomedicine with an aim to safeguard health of both humans and animals in a
Recent developments in nanomaterials for the therapy of deadliest diseases have gained significant interest because of their
advantages, such as reduction in systemic toxicity, easy surface functionalization with passivation and targeting moieties, and
enhanced drug accumulation in specific tissue. Nanomedicines and nanomaterials can be administrated by different strategies,
including oral, local, intravenous, and transarterial administration, which are the underlying determinants for their therapeutic
efficacy, pharmacokinetics and pharmacodynamics. In order to optimize the therapeutic outcomes, careful design and synthesis
of nanomedicines are guided by the administration strategies. It requires a broad-system view for innovative nanomaterials and
their clinical applications. The aim and scope of the issue is to introduce Current Drug Metabolism readers to this important
topic of efficacy, toxicology, and PK/PD of nanomedicine administrated by different strategies.
I would like to thank Editor-in-Chief, Michael Sinz, for his support and all authors for their contribution to this special
issue. I am grateful for all peer reviewers’ time and expertise, which help to improve quality of articles. I also thank Maryam
Shaikh for the excellent coordination in publication process.
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