-
Marine Drugs Sep 2020Autophagy is an elegant and complex biological process that has recently attracted much attention from the scientific community. The compounds which are capable of... (Review)
Review
Autophagy is an elegant and complex biological process that has recently attracted much attention from the scientific community. The compounds which are capable of control and modulation of this process have a promising potential as therapeutics for a number of pathological conditions, including cancer and neurodegenerative disorders. At the same time, due to the relatively young age of the field, there are still some pitfalls in the autophagy monitoring assays and interpretation of the experimental data. This critical review provides an overview of the marine natural compounds, which have been reported to affect autophagy. The time period from the beginning of 2016 to the middle of 2020 is covered. Additionally, the published data and conclusions based on the experimental results are re-analyzed with regard to the guidelines developed by Klionsky and colleagues (Autophagy. 2016; 12(1): 1-222), which are widely accepted by the autophagy research community. Remarkably and surprisingly, more than half of the compounds reported to be autophagy activators or inhibitors could not ultimately be assigned to either category. The experimental data reported for those substances could indicate both autophagy activation and inhibition, requiring further investigation. Thus, the reviewed molecules were divided into two groups: having validated and non-validated autophagy modulatory effects. This review gives an analysis of the recent updates in the field and raises an important problem of standardization in the experimental design and data interpretation.
Topics: Animals; Aquatic Organisms; Autophagy; Biological Products; Humans; Neoplasms; Neurodegenerative Diseases
PubMed: 32967369
DOI: 10.3390/md18090482 -
Nutrients Aug 2023Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a... (Review)
Review
Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.
Topics: Humans; Animals; Phytochemicals; Sirtuins; Biological Products; Curcumin; Quercetin; Resveratrol
PubMed: 37630770
DOI: 10.3390/nu15163578 -
Medicine Oct 2023Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as... (Meta-Analysis)
Meta-Analysis
Comparative of the effectiveness and safety of biological agents, small molecule drugs, and microbiome therapies in ulcerative colitis: Systematic review and network meta-analysis.
BACKGROUND
Biological agents are commonly used for the first-line treatment of ulcerative colitis (UC). However, small-molecule drugs and microbiome therapies are now being used as new treatments for ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics, small-molecule drugs, and microbiome therapies for the treatment of patients with moderate-to-severe ulcerative colitis.
METHODS
We searched the Cochrane, Embase, and PubMed databases from their inception to December 2022. RCTs that recruited patients with moderate-to-severe ulcerative colitis treated with biological agents, small-molecule drugs, and microbiome therapies. Efficacy outcomes were induction of clinical remission and mucosal healing; safety outcomes were adverse events and serious adverse events. A network meta-analysis with multivariate consistency model random-effect meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety.
RESULTS
A total of 31 RCTs comprising 7933 UC patients were included in our studies. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib ranked highest for induction of clinical remission (SUCRA, 0.83) and mucosal healing (SUCRA, 0.44). Moreover, no treatments were found to increase the occurrence of adverse events compared with placebos. Ustekinumab ranked lowest for adverse events (SUCRA 0.26) and probiotic ranked lowest for serious adverse events (0·21), whereas tofacitinib ranked highest for adverse events (0·43) and upadacitinib ranked highest for serious adverse events (0·43).
CONCLUSION
In this systematic review and network meta-analysis, we found upadacitinib to be ranked highest for the induction of clinical remission and mucosal healing, but the worst performing agent in terms of adverse events in UC patients. Probiotics were the best-performing agent for safety outcomes. More trials of direct comparisons are needed to inform clinical decision-making with greater confidence.
Topics: Humans; Biological Factors; Colitis, Ulcerative; Network Meta-Analysis; Ustekinumab; Biological Products
PubMed: 37904440
DOI: 10.1097/MD.0000000000035689 -
World Journal of Gastroenterology May 2017Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds...
Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds of human diseases for thousands of years. The treatment protocols of natural medicine are integrative in nature, and are required to utilize the most appropriate therapies to address the needs of the individual patient. Because of the relative convenience, safety and efficacy, natural medicine is now increasing worldwide. Naturopathic doctors are licensed in many areas of the world and regulated partly by law in these areas, which is quite different from various other forms of complementary and alternative medicine. Liver diseases, such as hepatitis, liver cirrhosis and liver carcinoma, are serious health problems worldwide. Nearly half of the natural agents used in treatment of liver diseases today are natural products and their derivatives. Although natural medicine is beneficial and safe, physicians should pay close attention to the potential side-effects of the naturopathic agents, which lead to liver injury, interstitial pneumonia and acute respiratory failure. Therefore, when administrating naturopathic protocols to patients for the treatment of liver diseases, we should try our best to prevent and avoid as much as possible the negative impact of these medicines. This article highlights the current practice and recommended improvement of natural medicines in the treatment of liver diseases and gives some specific examples to emphasize the prevention and management of adverse reactions of the natural agents and suggests that natural medicine should be cautiously used to treat liver problems.
Topics: Animals; Biological Products; Carcinoma, Hepatocellular; Coffee; Dietary Supplements; Fruit; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Naturopathy; Ocimum basilicum; Plant Extracts; Sesquiterpenes; Silymarin; Phytoalexins
PubMed: 28596675
DOI: 10.3748/wjg.v23.i19.3388 -
Chemical Reviews Apr 2017[4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic pathways of many structurally complex natural products. A relatively small collection of... (Review)
Review
[4 + 2]-Cycloadditions are increasingly being recognized in the biosynthetic pathways of many structurally complex natural products. A relatively small collection of enzymes from these pathways have been demonstrated to increase rates of cyclization and impose stereochemical constraints on the reactions. While mechanistic investigation of these enzymes is just beginning, recent studies have provided new insights with implications for understanding their biosynthetic roles, mechanisms of catalysis, and evolutionary origin.
Topics: Alkyl and Aryl Transferases; Biological Products; Cycloaddition Reaction; Stereoisomerism
PubMed: 28441874
DOI: 10.1021/acs.chemrev.6b00578 -
International Journal of Oncology Sep 2020In a relatively short period of time, treatment strategies for metastatic melanoma have radically changed leading to an unprecedented improvement in patient survival. In... (Review)
Review
In a relatively short period of time, treatment strategies for metastatic melanoma have radically changed leading to an unprecedented improvement in patient survival. In this period, immunotherapy options have evolved from cytokine‑based approaches to antibody‑mediated inhibition of immune checkpoints, cancer vaccines and pharmacological modulation of the melanoma microenvironment. Combination of immunotherapy strategies and the association of immune checkpoint inhibitors (ICIs) with BRAF V600 targeted therapy show encouraging results. The future of drug development in this field is promising. The comprehension of primary and acquired resistance mechanisms to ICIs and the dissection of melanoma immunobiology will be instrumental for the development of new treatment strategies and to improve clinical trial design. Moreover, biomarker discovery will help patient stratification and management during immunotherapy treatment. In this review, we summarize landmark clinical trials of immune checkpoint inhibitors in advanced melanoma and discuss the rational for immunotherapy combinations. Immunotherapy approaches at early stage of clinical development and recent advances in melanoma immunotherapy biomarker development are also discussed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biological Products; Biomarkers, Tumor; CTLA-4 Antigen; Cancer Vaccines; Herpesvirus 1, Human; Humans; Immune Checkpoint Inhibitors; Immunity, Innate; Immunotherapy; Melanoma; Microbiota; Molecular Targeted Therapy; Programmed Cell Death 1 Receptor; Skin Neoplasms; Tumor Microenvironment; Melanoma, Cutaneous Malignant
PubMed: 32582963
DOI: 10.3892/ijo.2020.5088 -
Cells Dec 2022The variety of drugs available to treat neurodegenerative diseases is limited. Most of these drug's efficacy is restricted by individual genetics and disease stages and... (Review)
Review
The variety of drugs available to treat neurodegenerative diseases is limited. Most of these drug's efficacy is restricted by individual genetics and disease stages and usually do not prevent neurodegeneration acting long after irreversible damage has already occurred. Thus, drugs targeting the molecular mechanisms underlying subsequent neurodegeneration have the potential to negate symptom manifestation and subsequent neurodegeneration. Neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, and is associated with the activation of the NLRP3 inflammasome, which in turn leads to neurodegeneration. Inflammasome activation and oligomerisation is suggested to be a major driver of disease progression occurring in microglia. With several natural products and natural product derivatives currently in clinical trials, mushrooms have been highlighted as a rich and largely untapped source of biologically active compounds in both in vitro and in vivo neurodegenerative disease models, partially supported by successful clinical trial evaluations. Additionally, novel high-throughput methods for the screening of natural product compound libraries are being developed to help accelerate the neurodegenerative disease drug discovery process, targeting neuroinflammation. However, the breadth of research relating to mushroom natural product high-throughput screening is limited, providing an exciting opportunity for further detailed investigations.
Topics: Neurodegenerative Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Biological Products; Agaricales; Inflammasomes; Drug Discovery
PubMed: 36497196
DOI: 10.3390/cells11233938 -
Marine Drugs Apr 2016Like many fields of the biosciences, actinomycete natural products research has been revolutionised by next-generation DNA sequencing (NGS). Hundreds of new genome... (Review)
Review
Like many fields of the biosciences, actinomycete natural products research has been revolutionised by next-generation DNA sequencing (NGS). Hundreds of new genome sequences from actinobacteria are made public every year, many of them as a result of projects aimed at identifying new natural products and their biosynthetic pathways through genome mining. Advances in these technologies in the last five years have meant not only a reduction in the cost of whole genome sequencing, but also a substantial increase in the quality of the data, having moved from obtaining a draft genome sequence comprised of several hundred short contigs, sometimes of doubtful reliability, to the possibility of obtaining an almost complete and accurate chromosome sequence in a single contig, allowing a detailed study of gene clusters and the design of strategies for refactoring and full gene cluster synthesis. The impact that these technologies are having in the discovery and study of natural products from actinobacteria, including those from the marine environment, is only starting to be realised. In this review we provide a historical perspective of the field, analyse the strengths and limitations of the most relevant technologies, and share the insights acquired during our genome mining projects.
Topics: Actinobacteria; Biological Products; Chromosome Mapping; Genome, Bacterial; Genomics; High-Throughput Nucleotide Sequencing; Humans; Multigene Family; Sequence Analysis, DNA
PubMed: 27089350
DOI: 10.3390/md14040078 -
Marine Drugs Jun 2017Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However,... (Review)
Review
Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. Here, we focus on limitations of available technology as well as computational and experimental strategies to overcome them. We review the unique challenges and approaches in the study of symbiotic and uncultured systems, as well as those associated with biosynthetic gene cluster (BGC) assembly and product prediction. Finally, to explore sequencing parameters that affect the recovery and contiguity of large and repetitive BGCs assembled , we simulate Illumina and PacBio sequencing of the genome focusing on assembly of the salinilactam () BGC.
Topics: Biological Products; Computational Biology; Drug Discovery; Genome, Bacterial; Genomics; Metagenomics; Micromonosporaceae; Multigene Family
PubMed: 28587290
DOI: 10.3390/md15060165 -
Molecules (Basel, Switzerland) Jun 2021species (Syn. species) of the family are widely used in many countries as food and in trado-medicinal practice due to their wide geographical distribution and... (Review)
Review
species (Syn. species) of the family are widely used in many countries as food and in trado-medicinal practice due to their wide geographical distribution and medicinal properties. Peer reviewed journal articles and ethnobotanical records that reported the traditional knowledge, phytoconstituents, biological activities and toxicological profiles of species with a focus on metabolic and neuronal health were reviewed. It was observed that many of the plant species are used as food ingredients and in treating inflammation, pain, hypertension and brain diseases. Over 500 compounds have been isolated from species, and the biological activities of both the plant extracts and their phytoconstituents, including their mechanisms of action, are discussed. The phytochemicals responsible for the biological activities of some of the species are yet to be identified. Similarly, biological activities of some isolated compounds remain unknown. Taken together, the species extracts and compounds possess promising biological activities and should be further explored as potential sources of new nutraceuticals and drugs.
Topics: Animals; Dietary Supplements; Ethnobotany; Ethnopharmacology; Food Ingredients; Humans; Phytochemicals; Plant Extracts; Zanthoxylum
PubMed: 34209371
DOI: 10.3390/molecules26134023