The 20th Anniversary of Pharmaceuticals—Emerging Trends in Biopharmaceuticals

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 16131

Special Issue Editors


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Guest Editor

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Guest Editor
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40292, USA
Interests: regulation of innate immunity; antimicrobial peptides; antifungal peptides; defensins; cathelicidins; novel antiviral compounds
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University, Shanghai, China
Interests: human pluripotent stem cell; stem cell differentiation; three-dimensional cell culture; organoid technology; tissue engineering; extracellular matrix; biomaterial; Endocrinology; functional maturation; cell-matrix interaction

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Guest Editor
Centro de Química Estrutural, Departamento de Química e Bioquímica, Faculdade de Ciências, Institute of Molecular Sciences, Universidade de Lisboa, Lisboa, Portugal
Interests: organic chemistry; medicinal chemistry; carbohydrate and nucleos(t)ide chemistry; bioactive molecules; enzyme inhibitors; anticancer agents; antimicrobial agents; anti-Alzheimer’s agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit high-quality and relevant manuscripts on research activities in pharmaceutical technology for this Special Issue entitled “The 20th Anniversary of Pharmaceuticals—Emerging Trends in Biopharmaceutical Area”. All research will be included in a book dedicated to the 20th anniversary of our journal. Manuscripts focusing on the therapeutic, diagnostic, prognostic and immunoprophylactic developments of important biological macromolecules built from amino acids, sugars, nucleic acids, comprising small basic units of which they are composed, and mimetics produced by chemical synthesis. Contributions focusing on biopharmaceutical applications of more complex entities, such as phages, viruses, exosomes and stem cells, among others, are also welcome. Also reports on structure and molecular interactions determinant for biopharmaceuticals bioactivity or pharmaceutical applications, e.g. by computational and NMR studies are also accepted.

Dr. Alfredo Berzal-Herranz
Prof. Dr. Gill Diamond
Prof. Dr. Yan-Ru Lou
Dr. Nuno Manuel Xavier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proteins
  • nucleic acids
  • aptamers
  • Glycans
  • macromolecules
  • antibodies
  • phages
  • viruses
  • therapeutic tools
  • peptidomimetics

Published Papers (13 papers)

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Research

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13 pages, 5232 KiB  
Article
Iterative In Silico Screening for Optimizing Stable Conformation of Anti-SARS-CoV-2 Nanobodies
by Wenyuan Shang, Xiujun Hu, Xiaoman Lin, Shangru Li, Shuchang Xiong, Bingding Huang and Xin Wang
Pharmaceuticals 2024, 17(4), 424; https://doi.org/10.3390/ph17040424 - 27 Mar 2024
Viewed by 565
Abstract
Nanobodies (Nbs or VHHs) are single-domain antibodies (sdAbs) derived from camelid heavy-chain antibodies. Nbs have special and unique characteristics, such as small size, good tissue penetration, and cost-effective production, making Nbs a good candidate for the diagnosis and treatment of viruses and other [...] Read more.
Nanobodies (Nbs or VHHs) are single-domain antibodies (sdAbs) derived from camelid heavy-chain antibodies. Nbs have special and unique characteristics, such as small size, good tissue penetration, and cost-effective production, making Nbs a good candidate for the diagnosis and treatment of viruses and other pathologies. Identifying effective Nbs against COVID-19 would help us control this dangerous virus or other unknown variants in the future. Herein, we introduce an in silico screening strategy for optimizing stable conformation of anti-SARS-CoV-2 Nbs. Firstly, various complexes containing nanobodies were downloaded from the RCSB database, which were identified from immunized llamas. The primary docking between Nbs and the SARS-CoV-2 spike protein receptor-binding domain was performed through the ClusPro program, with the manual screening leaving the reasonable conformation to the next step. Then, the binding distances of atoms between the antigen–antibody interfaces were measured through the NeighborSearch algorithm. Finally, filtered nanobodies were acquired according to HADDOCK scores through HADDOCK docking the COVID-19 spike protein with nanobodies under restrictions of calculated molecular distance between active residues and antigenic epitopes less than 4.5 Å. In this way, those nanobodies with more reasonable conformation and stronger neutralizing efficacy were acquired. To validate the efficacy ranking of the nanobodies we obtained, we calculated the binding affinities (∆G) and dissociation constants (Kd) of all screened nanobodies using the PRODIGY web tool and predicted the stability changes induced by all possible point mutations in nanobodies using the MAESTROWeb server. Furthermore, we examined the performance of the relationship between nanobodies’ ranking and their number of mutation-sensitive sites (Spearman correlation > 0.68); the results revealed a robust correlation, indicating that the superior nanobodies identified through our screening process exhibited fewer mutation hotspots and higher stability. This correlation analysis demonstrates the validity of our screening criteria, underscoring the suitability of these nanobodies for future development and practical implementation. In conclusion, this three-step screening strategy iteratively in silico greatly improved the accuracy of screening desired nanobodies compared to using only ClusPro docking or default HADDOCK docking settings. It provides new ideas for the screening of novel antibodies and computer-aided screening methods. Full article
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15 pages, 1602 KiB  
Article
The Potential Role of the Extracellular Matrix Glycoprotein Reelin in Glioblastoma Biology
by Erika Ongemach, Daniela Zerrinius, Philipp Heimann, Christian Rainer Wirtz, Klaus-Michael Debatin, Mike-Andrew Westhoff and Aurelia Peraud
Pharmaceuticals 2024, 17(3), 401; https://doi.org/10.3390/ph17030401 - 21 Mar 2024
Viewed by 666
Abstract
Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a [...] Read more.
Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a successful containment strategy can be found. Reelin, an extracellular matrix glycoprotein, plays an important role in neuronal migration and serves here as a natural stop signal. Interestingly, the expression of reelin is negatively associated with tumor grade and, within glioblastoma, correlates with increased overall survival. To further elucidate a potential biological reason for these findings, we looked at the cellular behavior of glioblastoma cell lines grown on a pure fibronectin matrix or a matrix with reelin inserts. While reelin had no significant effects on cellular metabolism, proliferation, or resistance to chemotherapeutic agents, it did significantly affect the cells’ interaction with fibronectin. Both matrix attachment and detachment were modulated by reelin, and thus, the invasion and motility of cells interacting with a reelin-containing matrix were altered. The data presented in this work strongly suggest that reelin might be a potential modulator of underlying molecular mechanisms that contribute to glioblastoma invasion. Full article
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15 pages, 2769 KiB  
Article
Esterase-Responsive Polyglycerol-Based Nanogels for Intracellular Drug Delivery in Rare Gastrointestinal Stromal Tumors
by Sebastian Schötz, Adele K. Griepe, Björn B. Goerisch, Sally Kortam, Yael Shammai Vainer, Mathias Dimde, Hanna Koeppe, Stefanie Wedepohl, Elisa Quaas, Katharina Achazi, Avi Schroeder and Rainer Haag
Pharmaceuticals 2023, 16(11), 1618; https://doi.org/10.3390/ph16111618 - 16 Nov 2023
Viewed by 932
Abstract
Rare gastrointestinal stromal tumors (GISTs) are caused by mutations in the KIT and PDGFRA genes. Avapritinib (BLU-285) is a targeted selective inhibitor for mutated KIT and PDGFRA receptors that can be used to treat these tumors. However, there are subtypes of GISTs that [...] Read more.
Rare gastrointestinal stromal tumors (GISTs) are caused by mutations in the KIT and PDGFRA genes. Avapritinib (BLU-285) is a targeted selective inhibitor for mutated KIT and PDGFRA receptors that can be used to treat these tumors. However, there are subtypes of GISTs that exhibit resistance against BLU-285 and thus require other treatment strategies. This can be addressed by employing a drug delivery system that transports a combination of drugs with distinct cell targets. In this work, we present the synthesis of esterase-responsive polyglycerol-based nanogels (NGs) to overcome drug resistance in rare GISTs. Using inverse nanoprecipitation mediated with inverse electron-demand Diels–Alder cyclizations (iEDDA) between dPG-methyl tetrazine and dPG-norbornene, multi-drug-loaded NGs were formed based on a surfactant-free encapsulation protocol. The obtained NGs displayed great stability in the presence of fetal bovine serum (FBS) and did not trigger hemolysis in red blood cells over a period of 24 h. Exposing the NGs to Candida Antarctica Lipase B (CALB) led to the degradation of the NG network, indicating the capability of targeted drug release. The bioactivity of the loaded NGs was tested in vitro on various cell lines of the GIST-T1 family, which exhibit different drug resistances. Cell internalization with comparable uptake kinetics of the NGs could be confirmed by confocal laser scanning microscopy (CLSM) and flow cytometry for all cell lines. Cell viability and live cell imaging studies revealed that the loaded NGs are capable of intracellular drug release by showing similar IC50 values to those of the free drugs. Furthermore, multi-drug-loaded NGs were capable of overcoming BLU-285 resistance in T1-α-D842V + G680R cells, demonstrating the utility of this carrier system. Full article
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11 pages, 14537 KiB  
Article
Profiling Analysis of Tryptophan Metabolites in the Urine of Patients with Parkinson’s Disease Using LC–MS/MS
by So Hyeon Chung, Dallah Yoo, Tae-Beom Ahn, Wonwoong Lee and Jongki Hong
Pharmaceuticals 2023, 16(10), 1495; https://doi.org/10.3390/ph16101495 - 20 Oct 2023
Cited by 1 | Viewed by 1253
Abstract
Although Parkinson’s disease (PD) is a representative neurodegenerative disorder and shows characteristic motor impediments, the pathophysiological mechanisms and treatment targets for PD have not yet been clearly identified. Since several tryptophan metabolites produced by gut microbiota could pass the blood–brain barrier and, furthermore, [...] Read more.
Although Parkinson’s disease (PD) is a representative neurodegenerative disorder and shows characteristic motor impediments, the pathophysiological mechanisms and treatment targets for PD have not yet been clearly identified. Since several tryptophan metabolites produced by gut microbiota could pass the blood–brain barrier and, furthermore, might influence the central nervous system, tryptophan metabolites within the indole, kynurenine, and serotonin metabolic pathways might be the most potent targets for PD development. Furthermore, most metabolites are circulated via the blood, play roles in and/or are metabolized via the host organs, and finally are excreted into the urine. Therefore, profiling the overall tryptophan metabolic pathways in urine samples of patients with PD is important to understanding the pathological mechanisms, finding biomarkers, and discovering therapeutic targets for PD. However, the development of profiling analysis based on tryptophan metabolism pathways in human urine samples is still challenging due to the wide physiological ranges, the varied signal response, and the structural diversity of tryptophan metabolites in complicated urine matrices. In this study, an LC–MS/MS method was developed to profile 21 tryptophan metabolites within the indole, kynurenine, and serotonin metabolic pathways in human urine samples using ion-pairing chromatography and multiple reaction monitoring determination. The developed method was successfully applied to urine samples of PD patients (n = 41) and controls (n = 20). Further, we investigated aberrant metabolites to find biomarkers for PD development and therapeutic targets based on the quantitative results. Unfortunately, most tryptophan metabolites in the urine samples did not present significant differences between control and PD patients, except for indole-3-acetic acid. Nonetheless, indole-3-acetic acid was reported for the first time for its aberrant urinary levels in PD patients and tentatively selected as a potential biomarker for PD. This study provides accurate quantitative results for 21 tryptophan metabolites in biological samples and will be helpful in revealing the pathological mechanisms of PD development, discovering biomarkers for PD, and further providing therapeutic targets for various PD symptoms. In the near future, to further investigate the relationship between gut microbial metabolites and PD, we will employ studies on microbial metabolites using plasma and stool samples from control and PD patients. Full article
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Review

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25 pages, 3267 KiB  
Review
Long-Acting Gel Formulations: Advancing Drug Delivery across Diverse Therapeutic Areas
by Hossein Omidian and Renae L. Wilson
Pharmaceuticals 2024, 17(4), 493; https://doi.org/10.3390/ph17040493 - 12 Apr 2024
Viewed by 464
Abstract
This multifaceted landscape of long-acting gels in diverse medical fields, aims to enhance therapeutic outcomes through localized treatment and controlled drug release. The objective involves advancements spanning cancer treatment, immunotherapy, diabetes management, neuroendocrine disorders, ophthalmic applications, contraception, HIV/AIDS treatment, chronic diseases, wound care, [...] Read more.
This multifaceted landscape of long-acting gels in diverse medical fields, aims to enhance therapeutic outcomes through localized treatment and controlled drug release. The objective involves advancements spanning cancer treatment, immunotherapy, diabetes management, neuroendocrine disorders, ophthalmic applications, contraception, HIV/AIDS treatment, chronic diseases, wound care, and antimicrobial treatments. It explores the potential of long-acting gels to offer sustained and extended drug release, targeted therapy, and innovative administration routes while addressing limitations such as scalability challenges and regulatory hurdles. Future directions focus on personalized therapies, biodegradability, combination therapies, interdisciplinary innovation, regulatory considerations, and patient-centric development. This comprehensive review highlights the pivotal role of long-acting gels in transforming therapeutic approaches and improving patient outcomes across various medical conditions. Full article
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27 pages, 1030 KiB  
Review
The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina
by Dario Rusciano and Cristina Russo
Pharmaceuticals 2024, 17(4), 441; https://doi.org/10.3390/ph17040441 - 29 Mar 2024
Viewed by 501
Abstract
Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin [...] Read more.
Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects. Full article
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16 pages, 1914 KiB  
Review
BRCA1 and Its Vulnerable C-Terminal BRCT Domain: Structure, Function, Genetic Mutations and Links to Diagnosis and Treatment of Breast and Ovarian Cancer
by Tala Ismail, Safa Alzneika, Emna Riguene, Salwa Al-maraghi, Aya Alabdulrazzak, Noof Al-Khal, Sara Fetais, Angelos Thanassoulas, Halema AlFarsi and Michail Nomikos
Pharmaceuticals 2024, 17(3), 333; https://doi.org/10.3390/ph17030333 - 04 Mar 2024
Viewed by 1144
Abstract
The BRCA1 is a tumor suppressor gene that encodes for the BRCA1 protein, which plays a vital role in DNA repair, cell cycle regulation, and the maintenance of genomic stability. The BRCA1 protein interacts with a variety of other proteins that play essential [...] Read more.
The BRCA1 is a tumor suppressor gene that encodes for the BRCA1 protein, which plays a vital role in DNA repair, cell cycle regulation, and the maintenance of genomic stability. The BRCA1 protein interacts with a variety of other proteins that play essential roles in gene regulation and embryonic development. It is a large protein composed of multiple domains. The C-terminal region of the BRCA1 protein consists of two BRCT domains connected by a short linker. The BRCT domains are crucial in protein–protein interactions as well as in DNA damage response and cell cycle regulation through their phosphoprotein binding modules that recognize the phosphorylated protein sequence motif of other kinases. Mutations within the BRCT domain can disrupt the normal function of BRCA1 and lead to an increased risk of developing breast and ovarian cancer. Herein, we explore the structural characteristics of BRCA1, focusing on the BRCT domain, its interactions with key cellular components, and its involvement in various cellular processes. In addition, the impact of BRCT domain mutations on breast and ovarian cancer susceptibility, prognosis, and treatment options is discussed. By providing a comprehensive understanding of the BRCT domain of BRCA1, this review aims to shed light on the role of this important domain in the pathogenesis and potential therapeutic approaches for breast and ovarian cancer. Full article
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14 pages, 1163 KiB  
Review
The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases
by Ming-Cheng Chang, Chun-Tang Chen, Ping-Fang Chiang and Ying-Cheng Chiang
Pharmaceuticals 2024, 17(3), 307; https://doi.org/10.3390/ph17030307 - 27 Feb 2024
Viewed by 774
Abstract
Chitinase-3-like protein-1 (CHI3L1), also known as YKL40, is a glycoprotein that belongs to the chitinase protein family. It is involved in various biological functions, including cell proliferation and tissue remodeling, with inflammatory and immunomodulatory capabilities. Several studies have shown that CHI3L1 [...] Read more.
Chitinase-3-like protein-1 (CHI3L1), also known as YKL40, is a glycoprotein that belongs to the chitinase protein family. It is involved in various biological functions, including cell proliferation and tissue remodeling, with inflammatory and immunomodulatory capabilities. Several studies have shown that CHI3L1(YKL40) is upregulated in various diseases, such as cancer, asthma, and inflammatory bowel disease, among others. Although the expression level of CHI3L1(YKL40) is associated with disease activity, severity, and prognosis, its potential as a therapeutic target is still under investigation. In this review, we summarize the biological functions, pathological roles, and potential clinical applications of specific inhibitors and targeted therapies related to CHI3L1(YKL40). Full article
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15 pages, 1771 KiB  
Review
Antiviral Potential of Azathioprine and Its Derivative 6- Mercaptopurine: A Narrative Literature Review
by Carolina Rios-Usuga, Marlen Martinez-Gutierrez and Julian Ruiz-Saenz
Pharmaceuticals 2024, 17(2), 174; https://doi.org/10.3390/ph17020174 - 30 Jan 2024
Viewed by 853
Abstract
The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the [...] Read more.
The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the hypothesis of an immunomodulatory effect. AZA is a prodrug that belongs to the thiopurine group of drugs that behave as purine analogs. After absorption, it is converted into 6-mercaptopurine. Subsequently, it can be degraded through various enzymatic pathways into inactive compounds and biologically active compounds related to the mechanism of action, which has been the subject of study to evaluate a possible antiviral effect. This study aims to examine the metabolism, mechanism of action, and antiviral potential of AZA and its derivatives, exploring AZA impact on antiviral targets and adverse effects through a narrative literature review. Ultimately, the review will provide insights into the antiviral mechanism, present evidence of its in vitro effectiveness against various DNA and RNA viruses, and suggest in vivo studies to further demonstrate its antiviral effects. Full article
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17 pages, 4955 KiB  
Review
Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy
by Sebastian Hasselbeck and Xinlai Cheng
Pharmaceuticals 2024, 17(1), 41; https://doi.org/10.3390/ph17010041 - 27 Dec 2023
Viewed by 1731
Abstract
In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprecedented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas systems, recent advancements have witnessed the [...] Read more.
In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprecedented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas systems, recent advancements have witnessed the integration of small molecules to augment their functionality, introducing new dimensions to the precision and versatility of gene editing applications. This review delves into the synergy between CRISPR-Cas technologies based specifically on Cas9 and small-molecule drugs, elucidating the pivotal role of chemicals in optimizing target specificity and editing efficiency. By examining a diverse array of applications, ranging from therapeutic interventions to agricultural advancements, we explore how the judicious use of chemicals enhances the precision of CRISPR-Cas9-mediated genetic modifications. In this review, we emphasize the significance of small-molecule drugs in fine-tuning the CRISPR-Cas9 machinery, which allows researchers to exert meticulous control over the editing process. We delve into the mechanisms through which these chemicals bolster target specificity, mitigate off-target effects, and contribute to the overall refinement of gene editing outcomes. Additionally, we discuss the potential of chemical integration in expanding the scope of CRISPR-Cas9 technologies, enabling tailored solutions for diverse genetic manipulation challenges. As CRISPR-Cas9 technologies continue to evolve, the integration of small-molecule drugs emerges as a crucial avenue for advancing the precision and applicability of gene editing techniques. This review not only synthesizes current knowledge but also highlights future prospects, paving the way for a deeper understanding of the synergistic interplay between CRISPR-Cas9 systems and chemical modulators in the pursuit of more controlled and efficient genetic modifications. Full article
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36 pages, 3585 KiB  
Review
At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment
by Tatyana V. Korneenko, Nikolay B. Pestov, Ivan A. Nevzorov, Alexandra A. Daks, Kirill N. Trachuk, Olga N. Solopova and Nickolai A. Barlev
Pharmaceuticals 2023, 16(12), 1675; https://doi.org/10.3390/ph16121675 - 01 Dec 2023
Cited by 1 | Viewed by 2395
Abstract
The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic DNA-sensing systems that is activated in response to viral invasion and/or damage to the integrity of the nuclear envelope. The key outcome of this pathway is the production [...] Read more.
The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic DNA-sensing systems that is activated in response to viral invasion and/or damage to the integrity of the nuclear envelope. The key outcome of this pathway is the production of interferon, which subsequently stimulates the transcription of hundreds of genes. In oncology, the situation is complex because this pathway may serve either anti- or pro-oncogenic roles, depending on context. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as DNA released from ruptured micronuclei, it results in the production of interferon, which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in terms of its association with cancer progression, giving special attention to pancreatic ductal adenocarcinoma and gliomas. As the development of new cGAS–STING-modulating small molecules and immunotherapies such as oncolytic viruses involves serious challenges, we highlight several recent fundamental discoveries, such as the proton-channeling function of STING. These discoveries may serve as guiding lights for potential pharmacological advancements. Full article
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20 pages, 418 KiB  
Review
Phage Therapy—Challenges, Opportunities and Future Prospects
by Beata Zalewska-Piątek
Pharmaceuticals 2023, 16(12), 1638; https://doi.org/10.3390/ph16121638 - 22 Nov 2023
Cited by 4 | Viewed by 2581
Abstract
The increasing drug resistance of bacteria to commonly used antibiotics creates the need to search for and develop alternative forms of treatment. Phage therapy fits this trend perfectly. Phages that selectively infect and kill bacteria are often the only life-saving therapeutic option. Full [...] Read more.
The increasing drug resistance of bacteria to commonly used antibiotics creates the need to search for and develop alternative forms of treatment. Phage therapy fits this trend perfectly. Phages that selectively infect and kill bacteria are often the only life-saving therapeutic option. Full legalization of this treatment method could help solve the problem of multidrug-resistant infectious diseases on a global scale. The aim of this review is to present the prospects for the development of phage therapy, the ethical and legal aspects of this form of treatment given the current situation of such therapy, and the benefits of using phage products in persons for whom available therapeutic options have been exhausted or do not exist at all. In addition, the challenges faced by this form of therapy in the fight against bacterial infections are also described. More clinical studies are needed to expand knowledge about phages, their dosage, and a standardized delivery system. These activities are necessary to ensure that phage-based therapy does not take the form of an experiment but is a standard medical treatment. Bacterial viruses will probably not become a miracle cure—a panacea for infections—but they have a chance to find an important place in medicine. Full article

Other

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26 pages, 943 KiB  
Systematic Review
The Efficacy and Safety of Biologic Drugs in the Treatment of Moderate–Severe Crohn’s Disease: A Systematic Review
by Ana Avedillo-Salas, Sara Corral-Cativiela, Ana Fanlo-Villacampa and Jorge Vicente-Romero
Pharmaceuticals 2023, 16(11), 1581; https://doi.org/10.3390/ph16111581 - 08 Nov 2023
Viewed by 1475
Abstract
Conventional therapy is the most commonly used treatment for Crohn’s disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of [...] Read more.
Conventional therapy is the most commonly used treatment for Crohn’s disease (CD), but it does not always achieve disease control, which is why the use of biologic drugs is increasing. The aim of this study was to analyze the efficacy and safety of biologic drugs in adult patients diagnosed with moderate–severe CD. An intensive search was performed in PubMed, Web of Science and Medline to collect phase 2 or 3 clinical trials published between 2018 and 2023 that were randomized, placebo-controlled and double-blind trials analyzing the efficacy and safety of biologic drugs in adult patients diagnosed with CD. This systematic review was conducted according to the PRISMA statement. Thirteen clinical trials evaluating eight biologic drugs were included. Upadacitinib, vedolizumab, adalimumab, guselkumab, mirikizumab, ustekinumab and risankizumab showed statistically significant efficacy across different clinical, endoscopic, histological, genetic, biomarker or quality-of-life parameters. However, PF-00547659 only showed statistically significant results for the CDAI-70 at week 12. In terms of safety, the incidence and severity of adverse effects were analyzed, with all drugs being well tolerated and presenting a good safety profile since most adverse effects were mild. Biologic drugs can be considered an effective and safe option for the treatment of moderate–severe CD in adult patients with an inadequate response or intolerance to conventional therapy. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Prof. Juan C. Morales, CSIC - Instituto de Parasitologia y Biomedicina Lopez Neyra (IPBLN), Armilla, Spain

Dr. Kent Kirshenbaum, New York University, New York, NY, USA

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