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Biochimica Et Biophysica Acta Oct 2015Peptidyl-prolyl-cis/trans-isomerases (PPIases) are ubiquitously expressed and have been implicated in a wide range of biological functions. Their inhibition is... (Review)
Review
BACKGROUND
Peptidyl-prolyl-cis/trans-isomerases (PPIases) are ubiquitously expressed and have been implicated in a wide range of biological functions. Their inhibition is beneficial in immunosuppression, cancer treatment, treatment of autoimmune diseases, protozoan and viral infections.
SCOPE OF REVIEW
Three classes of PPIases are known, each class having their own specific inhibitors. This review will cover the present knowledge on the biosynthesis of the natural PPIase inhibitors. These include for the cyclophilins: the cyclosporins, the analogues of peptolide SDZ 214-103 and the sanglifehrins; for the FKBPs: ascomycin, rapamycin and FK506 and for the parvulins the naphtoquinone juglone.
MAJOR CONCLUSIONS
Over the last thirty years much progress has been made in understanding PPIase function and the biosynthesis of natural PPIase inhibitors. Non-immunosuppressive analogues were discovered and served as lead compounds for the development of novel antiviral drugs. There are, however, still unsolved questions which deserve further research into this exciting field.
GENERAL SIGNIFICANCE
As all the major natural inhibitors of the cyclophilins and FKBPs are synthesized by complex non-ribosomal peptide synthetases and/or polyketide synthases, total chemical synthesis is not a viable option. Thus, fully understanding the modular enzyme systems involved in their biosynthesis may help engineering enzymes capable of synthesizing novel PPIase inhibitors with improved functions for a wide range of conditions. This article is part of a Special Issue entitled Proline-directed Foldases: Cell signaling catalysts and drug targets.
Topics: Cyclosporine; Enzyme Inhibitors; Peptide Biosynthesis, Nucleic Acid-Independent; Peptidylprolyl Isomerase
PubMed: 25497210
DOI: 10.1016/j.bbagen.2014.12.009 -
Memory & Cognition Oct 2023Recent results demonstrate that inducing an abstract representation of target analogs at retrieval time aids access to analogous situations with mismatching surface...
Recent results demonstrate that inducing an abstract representation of target analogs at retrieval time aids access to analogous situations with mismatching surface features (i.e., the late abstraction principle). A limitation of current implementations of this principle is that they either require the external provision of target-specific information or demand very high intellectual effort. Experiment 1 demonstrated that constructing an idealized situation model of a target problem increases the rate of correct solutions compared with constructing either concrete simulations or no simulations. Experiment 2 confirmed that these results were based on an advantage for accessing the base analog, and not merely an advantage of idealized simulations for understanding the target problem in its own terms. This target idealization strategy has broader applicability than prior interventions based on the late abstraction principle because it can be achieved by a greater proportion of participants and without the need to receive target-specific information. We present a computational model, SampComp, that predicts successful retrieval of a stored situation to understand a target based on the overlap of a random, but potentially biased, sample of features from each. SampComp is able to account for the relative benefits of base and target idealization, and their interaction.
Topics: Humans; Problem Solving; Concept Formation
PubMed: 36943635
DOI: 10.3758/s13421-023-01411-9 -
Alimentary Pharmacology & Therapeutics Mar 2018Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB). (Review)
Review
BACKGROUND
Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).
AIM
To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues.
METHODS
Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature.
RESULTS
Nephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real-life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine-treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.
CONCLUSIONS
Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.
Topics: Administration, Oral; Antiviral Agents; Drug-Related Side Effects and Adverse Reactions; Female; Hepatitis B, Chronic; Humans; Male; Nucleosides; Pregnancy; Renal Insufficiency; Time Factors; Treatment Outcome
PubMed: 29359487
DOI: 10.1111/apt.14497 -
Molecules (Basel, Switzerland) Sep 2020Calixarene-analogous metacyclophanes (CAMs) are a special class of cyclophanes that are cyclic polyaromatic hydrocarbons containing three or more aromatic rings linked... (Review)
Review
Calixarene-analogous metacyclophanes (CAMs) are a special class of cyclophanes that are cyclic polyaromatic hydrocarbons containing three or more aromatic rings linked by one or more methylene bridging groups. They can be considered to be analogues of calixarenes, since, in both types of molecules, the component aromatic rings are linked by methylene groups, which are meta to each other. Since the prototype or classical calix[4]arene consists of four benzene rings each linked by methylene bridges, which are also meta to each other, it can be considered to be an example of a functionalized [1.1.1.1]metacyclophane. A metacyclophane (MCP) that consists of three individual hydroxyl-group functionalized aromatic rings linked by methylene groups, e.g., a trihydroxy[1.1.1]MCP may therefore, by analogy, be termed in the broadest sense as a "calix[3]arene" or a "calix[3]arene-analogous metacyclophane". Most of the CAMs reported have been synthesized by fragment coupling approaches. The design, synthesis and development of functionalized CAMs, MCPs, calixarenes and calixarene analogues has been an area of great activity in the past few decades, due their potential applications as molecular receptors, sensors and ligands for metal binding, and for theoretical studies, etc. In this review article, we focus mainly on the synthesis, structure and conformational properties of [1.1.1]CAMs, i.e., "calix[3]arenes" and their analogues, which contain three functionalized aromatic rings and which provide new scaffolds for further explorations in supramolecular and sensor chemistry.
Topics: Benzene Derivatives; Calixarenes; Chemistry, Organic; Cyclization; Drug Design; Hydrocarbons; Ligands; Metals; Methane; Molecular Conformation; Molecular Structure; Stereoisomerism
PubMed: 32937796
DOI: 10.3390/molecules25184202 -
Pituitary Apr 2016In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals... (Review)
Review
INTRODUCTION
In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the increased mortality to normal rates. Therapeutic strategies aim to minimize tumor mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical treatment of choice in acromegaly, as first-line or post-surgical therapy, and have proven efficacy in pituitary tumor volume reduction (TVR).
METHODS
Here we review the effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly.
RESULTS
TVR with somatostatin analogues may be mediated by direct anti-proliferative effects via activation of somatostatin receptors, or by indirect effects, such as angiogenesis inhibition, and is more pronounced when they are administered as first-line therapy. Various studies of first-line treatment with octreotide LAR have shown significant TVR in ≥73% of patients. First-line treatment with lanreotide Autogel has shown evidence of TVR, although more studies are needed. In a recent randomized, double-blind, 12-month trial in 358 medical-treatment-naïve acromegaly patients, significant TVR was achieved by 81% of patients administered pasireotide LAR and 77% administered octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR and improve post-operative disease control compared with surgery alone. TVR is progressive with prolonged treatment, and decreased IGF-1 levels may be its best predictor, followed by age and degree of GH decrease. However, TVR does not always correlate with degree of biochemical control.
CONCLUSION
Somatostatin analogues (first- or second-line treatment) are the mainstay of medical therapy and, as first-line medical therapy, are associated with significant pituitary TVR in most patients.
Topics: Acromegaly; Adenoma; Antineoplastic Agents, Hormonal; Growth Hormone-Secreting Pituitary Adenoma; Humans; Octreotide; Peptides, Cyclic; Somatostatin; Treatment Outcome; Tumor Burden
PubMed: 26290466
DOI: 10.1007/s11102-015-0677-y -
Nanomaterials (Basel, Switzerland) Dec 2022The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in...
The electromagnetic induced transparency (EIT) effect originates from the destructive interference in an atomic system, which contributes to the transparency window in its response spectrum. The implementation of EIT requires highly demanding laboratory conditions, which greatly limits its acceptance and application. In this paper, an improved harmonic spring oscillation (HSO) model with four oscillators is proposed as a classical analog for the tunable triple-band EIT effect. A more general HSO model including more oscillators is also given, and the analyses of the power absorption in the HSO model conclude a formula, which is more innovative and useful for the study of the multiple-band EIT effect. To further inspect the analogizing ability of the HSO model, a hybrid unit cell containing an electric dipole and toroidal dipoles in the metamaterials is proposed. The highly comparable transmission spectra based on the HSO model and metamaterials indicate the validity of the classical analog in illustrating the formation process of the multiple-band EIT effect in metamaterials. Hence, the HSO model, as a classical analog, is a valid and powerful theoretical tool that can mimic the multiple-band EIT effect in metamaterials.
PubMed: 36558255
DOI: 10.3390/nano12244405 -
Life Sciences Dec 2019Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer,... (Review)
Review
Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.
Topics: Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Colonic Neoplasms; Curcumin; Humans
PubMed: 31704450
DOI: 10.1016/j.lfs.2019.117032 -
Gut Microbes Sep 2020Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are...
Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are currently under development to extend the key metabolic therapeutic actions of trehalose without adversely affecting host microbial communities. In the current study, we contrast the extent to which trehalose and its degradation-resistant analogue, lactotrehalose (LT), modulate microbial communities and host transcriptomic profiles. We demonstrate that trehalose and LT each exert adaptive metabolic and microbial effects that both overlap and diverge. We postulate that these effects depend both upon compound stability and bioavailability, and on stereospecific signal transduction. In context, the data suggest that trehalose is unlikely to be harmful, and yet it harbors unique effects that are not yet fully replicated by its analogues. These compounds are thus valuable probes to better define trehalose structure-function, and to offer as therapeutic metabolic agents.
Topics: Animals; Clostridioides difficile; Clostridium Infections; Dietary Sugars; Gastrointestinal Microbiome; Humans; Mice; Ribotyping; Stereoisomerism; Transcriptome; Trehalose
PubMed: 32329657
DOI: 10.1080/19490976.2020.1750273 -
Metabolism: Clinical and Experimental Jan 2022The first insulin preparation injected in humans in 1922 was short-acting, extracted from animal pancreas, contaminated by impurities. Ever since the insulin extracted... (Review)
Review
The first insulin preparation injected in humans in 1922 was short-acting, extracted from animal pancreas, contaminated by impurities. Ever since the insulin extracted from animal pancreas has been continuously purified, until an unlimited synthesis of regular human insulin (RHI) became possible in the '80s using the recombinant-DNA (rDNA) technique. The rDNA technique then led to the designer insulins (analogs) in the early '90s. Rapid-acting insulin analogs were developed to accelerate the slow subcutaneous (sc) absorption of RHI, thus lowering the 2-h post-prandial plasma glucose (PP-PG) and risk for late hypoglycemia as comparing with RHI. The first rapid-acting analog was lispro (in 1996), soon followed by aspart and glulisine. Rapid-acting analogs are more convenient than RHI: they improve early PP-PG, and 24-h PG and A1C as long as basal insulin is also optimized; they lower the risk of late PP hypoglycemia and they allow a shorter time-interval between injection and meal. Today rapid-acting analogs are the gold standard prandial insulins. Recently, even faster analogs have become available (faster aspart, ultra-rapid lispro) or are being studied (Biochaperone lispro), making additional gains in lowering PP-PG. Rapid-acting analogs are recommended in all those with type 1 and type 2 diabetes who need prandial insulin replacement.
Topics: Diabetes Mellitus; History, 20th Century; History, 21st Century; Humans; Hypoglycemic Agents; Insulin
PubMed: 34762931
DOI: 10.1016/j.metabol.2021.154935 -
Foods (Basel, Switzerland) Feb 2023Fish products are consumed by human beings as a high-quality protein source. However, overfishing, and pollution puts out an urgent call to seek a new strategy to... (Review)
Review
Fish products are consumed by human beings as a high-quality protein source. However, overfishing, and pollution puts out an urgent call to seek a new strategy to substitute fish protein for secure eco-sustainability. Plant-based fish analogs, which mimic the structure, texture, and flavor of fish meat products, are a rapid-growing segment of the food products. The purpose of this review is to discuss the feasibility and potential strategies for developing plant-based fish analog. The nutritional properties, especially the protein quality of plant-based fish analogs, were discussed. Furthermore, a thorough comparison was made between fish and terrestrial animal muscle structures, including both macroscopical and microscopical structures. Potential processing technologies for producing plant-based fish analogs from plant proteins and approaches for the characterization of the fish analog structures were elaborated. Comparing all the current processing techniques, extrusion is the predominately used technique in the current industry. At the same time, 3D-printing and electrospinning have shown the prominent potential of mimicking fish muscle structure as bottom-up approaches. Finally, key challenges and future research were discussed for the potential commercialization of plant-based fish analogues. The primary focus of this review covers the innovative works that were indexed in the Web of Science Core Collection in the past five years.
PubMed: 36766143
DOI: 10.3390/foods12030614