Oceans as a Source of Immunotherapy

Marine flora is taxonomically diverse, biologically active, and chemically unique. It is an excellent resource, which offers great opportunities for the discovery of new biopharmaceuticals such as immunomodulators and drugs targeting cancerous, inflammatory, microbial, and fungal diseases. The ability of some marine molecules to mediate specific inhibitory activities has been demonstrated in a range of cellular processes, including apoptosis, angiogenesis, and cell migration and adhesion. Immunomodulators have been shown to have significant therapeutic effects on immune-mediated diseases, but the search for safe and effective immunotherapies for other diseases such as sinusitis, atopic dermatitis, rheumatoid arthritis, asthma and allergies is ongoing. This review focuses on the marine-originated bioactive molecules with immunomodulatory potential, with a particular focus on the molecular mechanisms of specific agents with respect to their targets. It also addresses the commercial utilization of these compounds for possible drug improvement using metabolic engineering and genomics.

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Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases

Cells ◽

10.3390/cells8121605 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1605 ◽

Cited By ~ 40

Author(s):

Carl Randall Harrell ◽

Nemanja Jovicic ◽

Valentin Djonov ◽

Nebojsa Arsenijevic ◽

Vladislav Volarevic

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Extracellular Vesicles ◽

Immune Cells ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Experimental Studies ◽

Bioactive Molecules ◽

Therapeutic Effects

There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) that regulate phenotype, function and homing of immune cells. In this review article we emphasized current knowledge regarding molecular mechanisms responsible for the therapeutic effects of MSC-EVs in attenuation of autoimmune and inflammatory diseases. We described the disease-specific cellular targets of MSC-EVs and defined MSC-sourced molecules, which were responsible for MSC-EV-based immunosuppression. Results obtained in a large number of experimental studies revealed that both local and systemic administration of MSC-EVs efficiently suppressed detrimental immune response in inflamed tissues and promoted survival and regeneration of injured parenchymal cells. MSC-EVs-based anti-inflammatory effects were relied on the delivery of immunoregulatory miRNAs and immunomodulatory proteins in inflammatory immune cells (M1 macrophages, dendritic cells (DCs), CD4+Th1 and Th17 cells), enabling their phenotypic conversion into immunosuppressive M2 macrophages, tolerogenic DCs and T regulatory cells. Additionally, through the delivery of mRNAs and miRNAs, MSC-EVs activated autophagy and/or inhibited apoptosis, necrosis and oxidative stress in injured hepatocytes, neurons, retinal cells, lung, gut and renal epithelial cells, promoting their survival and regeneration.

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Anticancer Activity of Propolis and Its Compounds

Nutrients ◽

10.3390/nu13082594 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2594

Author(s):

Ewa Forma ◽

Magdalena Bryś

Keyword(s):

Anticancer Activity ◽

Honey Bees ◽

Molecular Mechanisms ◽

Chemotherapeutic Agents ◽

Biologically Active ◽

Natural Material ◽

Cellular Processes ◽

Potential Benefits ◽

New Chemotherapeutic Agents ◽

Research Show

Propolis is a natural material that honey bees (Apis mellifera) produce from various botanical sources. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. Cancer is one of the major burdens of disease worldwide, therefore, numerous studies are being conducted to develop new chemotherapeutic agents and treatments for cancer. Propolis is a rich source of biologically active compounds, which affect numerous signaling pathways regulating crucial cellular processes. The results of the latest research show that propolis can inhibit proliferation, angiogenesis, and metastasis of cancer cells and stimulate apoptosis. Moreover, it may influence the tumor microenvironment and multidrug resistance of cancers. This review briefly summarizes the molecular mechanisms of anticancer activity of propolis and its compounds and highlights the potential benefits of propolis to reduce the side effects of chemotherapy and radiotherapy.

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Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF-α–Induced NF-κB and MAPK Signaling

Plants ◽

10.3390/plants10112273 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2273

Author(s):

Peraphan Pothacharoen ◽

Rujirek Chaiwongsa ◽

Theerawut Chanmee ◽

Orapin Insuan ◽

Thanchanok Wongwichai ◽

...

Keyword(s):

Synovial Fibroblast ◽

Molecular Mechanisms ◽

Synovial Fibroblasts ◽

Cartilage Degradation ◽

Biological Properties ◽

Mapk Signaling ◽

Oncostatin M ◽

Biologically Active ◽

Therapeutic Effects ◽

Tnf Α

Bromelain, a mixture of proteases in pineapple rhizome, has beneficial biological properties. Following absorption, the compound remains biologically active in mammalian blood and tissues. Bromelain has multiple clinical and therapeutic applications because of its anti-arthritic activities. Anti-inflammation is one of the putative therapeutic effects of bromelain on osteoarthritis (OA) and rheumatoid arthritis (RA), but the molecular mechanisms in cartilage and synovial fibroblast has not been reported. Thus, in this study, interleukin (IL)-1β/oncostatin M-induced porcine cartilage and TNF-α–induced synovial fibroblast were used as the inflamed OA and RA models, respectively. The results demonstrated the chondroprotective effects of bromelain on cartilage degradation and the downregulation of inflammatory cytokine (tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-8) expression in TNF-α–induced synovial fibroblasts by suppressing NF-κB and MAPK signaling. The evidence from this study supported and explained the anti-inflammatory and analgesic effects of bromelain on arthritis in animal models and clinical studies.

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Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer

Cells ◽

10.3390/cells9030564 ◽

2020 ◽

Vol 9 (3) ◽

pp. 564 ◽

Cited By ~ 4

Author(s):

Saber H. Saber ◽

Hamdy E. A. Ali ◽

Rofaida Gaballa ◽

Mohamed Gaballah ◽

Hamed I. Ali ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Membrane Vesicles ◽

Cell Types ◽

Bioactive Molecules ◽

Therapeutic Interventions ◽

Target Cells ◽

Molecular Signatures ◽

Cellular Processes

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

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Molecular Insights into Potential Contributions of Natural Polyphenols to Lung Cancer Treatment

Cancers ◽

10.3390/cancers11101565 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1565 ◽

Cited By ~ 2

Author(s):

Zhou ◽

Pan ◽

Keyword(s):

Lung Cancer ◽

Molecular Mechanisms ◽

Large Body ◽

Molecular Medicine ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Cellular Processes ◽

Natural Polyphenols ◽

Multiple Protein ◽

Lung Cancer Therapy

Naturally occurring polyphenols are believed to have beneficial effects in the prevention and treatment of a myriad of disorders due to their anti-inflammatory, antioxidant, antineoplastic, cytotoxic, and immunomodulatory activities documented in a large body of literature. In the era of molecular medicine and targeted therapy, there is a growing interest in characterizing the molecular mechanisms by which polyphenol compounds interact with multiple protein targets and signaling pathways that regulate key cellular processes under both normal and pathological conditions. Numerous studies suggest that natural polyphenols have chemopreventive and/or chemotherapeutic properties against different types of cancer by acting through different molecular mechanisms. The present review summarizes recent preclinical studies on the applications of bioactive polyphenols in lung cancer therapy, with an emphasis on the molecular mechanisms that underlie the therapeutic effects of major polyphenols on lung cancer. We also discuss the potential of the polyphenol-based combination therapy as an attractive therapeutic strategy against lung cancer.

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Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

Current Medicinal Chemistry ◽

10.2174/0929867326666191212102407 ◽

2020 ◽

Vol 28 (2) ◽

pp. 360-376 ◽

Cited By ~ 7

Author(s):

Atefeh Amiri ◽

Maryam Mahjoubin-Tehran ◽

Zatollah Asemi ◽

Alimohammad Shafiee ◽

Sarah Hajighadimi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Antioxidant Activities ◽

Natural Compounds ◽

Therapeutic Effects ◽

Inflammatory Disorder ◽

Inflammatory Disorders ◽

Therapeutic Modalities ◽

Anti Cancer ◽

Current Therapies ◽

Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

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A Comprehensive Review on Pharmacology and Toxicology of Bioactive Compounds of Lagerstroemia Speciosa (L.) Pers.

Current Traditional Medicine ◽

10.2174/2215083806999201211213931 ◽

2020 ◽

Vol 06 ◽

Author(s):

Surya Kant Tripathi ◽

Sunayna Behera ◽

Munmun Panda ◽

Gokhan Zengin ◽

Bijesh K. Biswal

Keyword(s):

Molecular Mechanisms ◽

Biological Activities ◽

Health Benefit ◽

Biologically Active ◽

Pharmacological Properties ◽

Lagerstroemia Speciosa ◽

Novel Drugs ◽

Corosolic Acid ◽

Current Article ◽

Preclinical And Clinical Studies

Background: Lagerstroemia speciosa (L.) Pers is one of the most valuable plants due to its ornamental and pharmacological relevance. It is known for its anti-diabetic activity with proved potent blood sugar-lowering activity. The anti-diabetic activity is due to presence of its biologically active component corosolic acid. Moreover, L. speciosa and its novel purified compounds are also well-known for its several biological activities with beneficial health benefit on the human being. Objectives: This review provides a summary of pharmacokinetics, toxicity, and pharmacological properties of L. speciosa and its purified phytochemicals which may help researchers for building up new researches in near future. Methods: The current article is prepared by collecting through various online and offline databases. Preliminary source of study and data collection for outlining the review was research articles and reviews that have been already published by many reputed publishers, including Springer, Elsevier, Taylor & Francis imprints, BMC, Willy, The Norwegian Academy of Science and Letters, Environmental health prospective (EHP), and PLOS One. Result: The available studies results suggested that the L. speciosa and its phytochemicals showed antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiviral, anti-obesity, and cardio-protective activities. Pharmacokinetic stud-ies suggested the low bioavailability of its purified compounds. However, nano-encapsulation can improve the bioavaila-bility related issue and effectively potentiate the medicinal properties of its constituents. Conclusion: Considering the worthy pharmacological properties, L. speciosa is considered as a potent source of several novel drugs. Though, still preclinical and clinical studies are needed to reveal the targets, molecular mechanisms, bioavail-ability, and toxicity of its constituents.

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Role of Long Non-Coding RNA Polymorphisms in Cancer Chemotherapeutic Response

Journal of Personalized Medicine ◽

10.3390/jpm11060513 ◽

2021 ◽

Vol 11 (6) ◽

pp. 513

Author(s):

Zheng Zhang ◽

Meng Gu ◽

Zhongze Gu ◽

Yan-Ru Lou

Keyword(s):

Molecular Mechanisms ◽

Neurological Diseases ◽

Cellular Processes ◽

Dna And Rna ◽

Chemotherapeutic Response ◽

Non Coding Rna ◽

Response To Chemotherapy ◽

Personalized Oncology ◽

Long Non Coding Rna

Genetic polymorphisms are defined as the presence of two or more different alleles in the same locus, with a frequency higher than 1% in the population. Since the discovery of long non-coding RNAs (lncRNAs), which refer to a non-coding RNA with a length of more than 200 nucleotides, their biological roles have been increasingly revealed in recent years. They regulate many cellular processes, from pluripotency to cancer. Interestingly, abnormal expression or dysfunction of lncRNAs is closely related to the occurrence of human diseases, including cancer and degenerative neurological diseases. Particularly, their polymorphisms have been found to be associated with altered drug response and/or drug toxicity in cancer treatment. However, molecular mechanisms are not yet fully elucidated, which are expected to be discovered by detailed studies of RNA–protein, RNA–DNA, and RNA–lipid interactions. In conclusion, lncRNAs polymorphisms may become biomarkers for predicting the response to chemotherapy in cancer patients. Here we review and discuss how gene polymorphisms of lncRNAs affect cancer chemotherapeutic response. This knowledge may pave the way to personalized oncology treatments.

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DEAD-box helicases modulate dicing body formation in Arabidopsis

Science Advances ◽

10.1126/sciadv.abc6266 ◽

2021 ◽

Vol 7 (18) ◽

pp. eabc6266

Author(s):

Qi Li ◽

Ningkun Liu ◽

Qing Liu ◽

Xingguo Zheng ◽

Lu Lu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Turnip Mosaic Virus ◽

Liquid Droplets ◽

Phase Separations ◽

Body Formation ◽

Cellular Processes ◽

Dead Box ◽

Body Components ◽

Liquid Phase Separations ◽

Spatiotemporal Control

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana. We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

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A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

International Journal of Molecular Sciences ◽

10.3390/ijms22147390 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7390

Author(s):

Nicole Wesch ◽

Frank Löhr ◽

Natalia Rogova ◽

Volker Dötsch ◽

Vladimir V. Rogov

Keyword(s):

Cellular Localization ◽

Molecular Mechanisms ◽

Biochemical Characterization ◽

Effective Interaction ◽

Regulatory Region ◽

Titration Calorimetry ◽

Enzymatic Reactions ◽

Cellular Processes ◽

Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

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