-
The Journal of Investigative Dermatology Jul 2022Since the foundation of the European Society for Dermatological Research, pathogenesis of psoriasis has been studied by many research groups, focusing on various... (Review)
Review
Since the foundation of the European Society for Dermatological Research, pathogenesis of psoriasis has been studied by many research groups, focusing on various compartments of the skin. Understanding of the pathogenesis of psoriasis has evolved into a branching model of innate and acquired immunity. Insights in the genetics of psoriasis proved to be compatible with this model. Inspired by these insights, pathogenesis-based treatments have emerged with unprecedented efficacy and sustainability. In particular, the cytokine network harbors major treatment targets for biologics with TNF-α, the IL-17 family, IL-23 and, in the case of generalized pustular psoriasis, IL-36. Furthermore, the Jak TYK2, PDE-4, and AHR are targets for new small molecules in the treatment of psoriasis. Psoriasis research is a showcase par excellence of translational medicine, resulting in pathogenesis-based treatments.
Topics: Adaptive Immunity; Biological Products; Humans; Psoriasis; Skin; Tumor Necrosis Factor-alpha
PubMed: 35249726
DOI: 10.1016/j.jid.2022.01.014 -
Journal of Pharmacy & Pharmaceutical... 2007Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often... (Review)
Review
PURPOSE
Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often complicate study of the biological effects of the main ingredient. The presence of small amounts of endotoxin in recombinant protein preparations can cause side effects in host organism such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove endotoxins from drugs, injectables, and other biological and pharmaceutical products. An overview of this subject is provided by this article.
METHODS
An extensive review of literature with regard to methods for removal of endotoxin from biotechnological preparations was carried out.
RESULTS
A short history of endotoxin is presented first. This is followed by a review of chemical and physical properties of endotoxin and its pathophysiological effects when the body is exposed to LPS excessively or systemically. The techniques of endotoxin determination and interaction of endotoxin with proteins is also presented, taking into consideration the established techniques as well as the state of the art technology in this field. A review of techniques of endotoxin removal from biotechnological preparations is described, emphasizing how endotoxin removal can be carried out in an economical way based on a number of processes discussed in the literature (e.g., adsorption, two-phase partitioning, ultrafiltration and chromatography). Different methods are mentioned with relatively high protein recoveries; however, special attention is given to two-phase aqueous micellar systems, which are valuable tools for endotoxin removal from pharmaceutical proteins on a small scale because they provide a mild environment for biological materials.
CONCLUSIONS
Efficient and cost-effective removal of endotoxins from pharmaceutical and biotechnology preparations is challenging. Despite development of novel methods, such as the two-phase aqueous micellar systems, in recent years, more research is needed in this field.
Topics: Biological Products; Chromatography, Liquid; Cost-Benefit Analysis; Drug Contamination; Endotoxins; History, 19th Century; History, 20th Century; Micelles; Octoxynol; Polyethylene Glycols; Quality Control; Ultrafiltration
PubMed: 17727802
DOI: No ID Found -
International Journal of Rheumatic... Apr 2020As glucocorticoids and immunosuppressive drugs are non-specific therapeutic agents that cause many adverse reactions, the development of biologicals aiming to control... (Review)
Review
As glucocorticoids and immunosuppressive drugs are non-specific therapeutic agents that cause many adverse reactions, the development of biologicals aiming to control specific molecular targets is anticipated for the treatment of systemic lupus erythematosus (SLE). The antibody targeting B cell-activating factor belonging to the tumor necrosis factor family (BAFF) belimumab was the first biological approved for SLE. At present, many biologicals, such as anifrolumab (anti-type I interferon receptor antibody) and ustekinumab (antibody against interleukin 12/23 [p40]), are in clinical trials. Thus, successful treatments with biologicals targeting "bridging cytokines" produced by dendritic cells, which form a bridge between the innate and acquired immune/autoimmune systems, is of particular interest. Moreover, a phase IIb clinical trial of baricitinib, a low-molecular-weight compound targeting Janus kinase 1/2, in patients with SLE revealed that baricitinib was significantly more effective for relieving arthritis and skin manifestations than placebo, and the trial met the primary endpoint. In the future, it is expected that drugs with better efficacy and safety profiles will be used to apply therapeutic strategies, such as precision medicine, in which different molecular target drugs are used for patients classified by their conditions, and to set a therapeutic goal of the discontinuation of glucocorticoids.
Topics: Biological Products; Glucocorticoids; Humans; Immunosuppressive Agents; Janus Kinase Inhibitors; Lupus Erythematosus, Systemic; Molecular Targeted Therapy; Treatment Outcome
PubMed: 32134201
DOI: 10.1111/1756-185X.13817 -
Journal of Industrial Microbiology &... Mar 2016Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop... (Review)
Review
Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.
Topics: Actinobacteria; Animals; Anti-Bacterial Agents; Biological Products; Computational Biology; Drug Discovery; Drug Industry; History, 20th Century; History, 21st Century; Humans; Secondary Metabolism
PubMed: 26739136
DOI: 10.1007/s10295-015-1723-5 -
The Journal of Allergy and Clinical... Oct 2022Biologics or molecularly targeted drugs are often highly effective for the treatment of allergic diseases and other immunologic disorders, and they are relatively safe... (Review)
Review
Biologics or molecularly targeted drugs are often highly effective for the treatment of allergic diseases and other immunologic disorders, and they are relatively safe for short-term use as compared with conventional approaches such as the systemic use of corticosteroids. A number of studies published in 2021 consistently demonstrated their effectiveness and also revealed unanticipated findings. Among them, clinical trials for asthma and chronic obstructive pulmonary disease using biologics targeting thymic stromal lymphopoietin, IL-33, and IL-33 receptor demonstrated that these type 2 alarmin cytokines are also involved in non-type 2, noneosinophilic inflammation. Randomized controlled trials reporting the efficacies of 2 small-molecule oral drugs targeting Janus kinase-1 had a substantial impact on the management of atopic dermatitis. These drugs demonstrated superiority over dupilumab, which has previously demonstrated efficacy and is in wide use in clinical practice. As a concern, biologics are generally costly, and it should be noted that racial/ethnic minority populations may be less likely to receive biologics in the real world. Here, we have reviewed recent clinical trials and related topics dealing with the effects of biologics on allergic and immunologic diseases; in addition, we discuss how our understanding of the pathophysiology of these disorders has progressed.
Topics: Adrenal Cortex Hormones; Alarmins; Biological Products; Ethnicity; Humans; Hypersensitivity; Interleukin-33; Janus Kinases; Minority Groups
PubMed: 36058723
DOI: 10.1016/j.jaci.2022.08.009 -
Journal of Natural Products May 2022Here, we describe two -acetyl-cysteinylated streptophenazines ( and ) produced by the soil-derived sp. ID63040 and identified through a metabolomic approach. These... (Review)
Review
Here, we describe two -acetyl-cysteinylated streptophenazines ( and ) produced by the soil-derived sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine sp. CNB-091. Compounds and were the main streptophenazine products from sp. ID63040 at all cultivation times but were not detected in sp. CNB-091. The lack of obvious candidates for cysteinylation in the sp. ID63040 biosynthetic gene cluster suggests that the -acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example of how to leverage metabolomics for the discovery of new natural products and point out the often-neglected contribution of house-keeping cellular functions to natural product diversification.
Topics: Anti-Bacterial Agents; Biological Products; Metabolomics; Multigene Family; Streptomyces
PubMed: 35422124
DOI: 10.1021/acs.jnatprod.1c01123 -
Journal of Periodontology Dec 2022A large variety of biomaterials, biologics and membranes have been utilized in the past 40 years for the regenerative treatment of periodontal infrabony defects.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A large variety of biomaterials, biologics and membranes have been utilized in the past 40 years for the regenerative treatment of periodontal infrabony defects. Biologic agents have progressively gained popularity among clinicians and are routinely used for periodontal regeneration. In alignment with the goals of the American Academy of Periodontology (AAP) Best Evidence Consensus (BEC) on the use of biologic mediators in contemporary clinical practice, the aim of this sytematic review was to evaluate the effect of biologic agents, specifically autogenous blood-dervied products (ABPs), enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB), on the regenerative outcomes of infrabony defects.
METHODS
A detailed systematic search was conducted to identify eligible randomized control trials (RCTs) reporting the outcomes of periodontal regenerative therapy using biologics for the treatment of infrabony defects. A frequentist mixed-modeling approach to network meta-analysis (NMA), characterized by the assessment of three individual components for the treatment of an infrabony defect (the bone graft material [BG], the biologic agent, the application of a barrier membrane) was performed to evaluate and compare the relative efficacy of the different components, on the outcomes of different therapeutic modalities of periodontal regeneration.
RESULTS
A total of 153 eligible RCTs were included, with 150 studies contributing to the NMA. The quantitative analysis showed that the addition of biologic agents to bone graft significantly improves the clinical and radiographic outcomes, as compared to BG and flap procedures alone. Barrier membranes enhanced the regenerative outcomes of BG but did not provide further benefits in combination with biologics. The type of BG (autogenous, allogeneic, xenogeneic or alloplastic) and the biologic agent (EMD, platelet-rich fibrin [PRF], platelet-rich plasma [PRP] or rhPDGF-BB) played a significant role on the final outcomes of infrabony defects. Allogeneic and xenogeneic BGs exhibited statistically significantly superior clinical gain than synthetic and autogenous BGs (p < 0.05 in all the comparisons), while rhPDGF-BB and PRF demonstrated significantly higher stability of the gingival margin (p < 0.01) and radiographic bone fill/gain (p < 0.05), together with greater, although not statistically significant, clinical attachment level gain and pocket depth reduction, than EMD and PRP. Overall, rhPDGF-BB exhibited the largest effect size for most parameters, including clinical attachment level gain, pocket depth reduction, less gingival recession and radiographic linear bone gain. Considering the relatively high number of trials presenting an unclear or high risk of bias, the strength of recommendation supporting the use of PRP was judged weak, while the recommendation for EMD, PRF and rhPDGF-BB was deemed in favor.
CONCLUSIONS
Biologics enhance the outcomes of periodontal regenerative therapy. Combination therapies involving BGs + biologics or BGs + barrier membrane demonstrated to be superior to monotherapies. The choice of the type of BG and biologic agent seems to have significant impact on the clinical and radiographic outcomes of infrabony defects.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Becaplermin; Alveolar Bone Loss; Network Meta-Analysis; Biological Products; Periodontal Attachment Loss
PubMed: 36279121
DOI: 10.1002/JPER.22-0120 -
Molecules (Basel, Switzerland) Aug 2022Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy.... (Review)
Review
Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy. Due to the potential toxicity and lack of selectivity of conventional chemotherapeutic agents, discovering alternative treatments is a top priority. Plant-derived natural products have high potential in cancer treatment due to their multiple mechanisms of action, diversity in structure, availability in nature, and relatively low toxicity. In this review, the anticancer mechanisms of the most common phytochemicals were analyzed. Furthermore, a detailed discussion of the anticancer effect of combinations consisting of natural product or natural products with chemotherapeutic drugs was provided. This review should provide a strong platform for researchers and clinicians to improve basic and clinical research in the development of alternative anticancer medicines.
Topics: Antineoplastic Agents; Biological Products; Humans; Neoplasms; Phytochemicals
PubMed: 36080219
DOI: 10.3390/molecules27175452 -
Nature Reviews. Rheumatology Feb 2021Biologic agents have become a core component of therapeutic strategies for many inflammatory rheumatic diseases. However, perhaps reflecting the specificity and... (Comparative Study)
Comparative Study Review
Biologic agents have become a core component of therapeutic strategies for many inflammatory rheumatic diseases. However, perhaps reflecting the specificity and generally high affinity of biologic agents, these therapeutics have been used by rheumatologists with less consideration of their pharmacokinetics than that of conventional synthetic DMARDs. Immunogenicity was recognized as a potential limitation to the use of biologic agents at an early stage in their development, although regulatory guidance was relatively limited and assays to measure immunogenicity were less sophisticated than today. The advent of biosimilars has sparked a renewed interest in immunogenicity that has resulted in the development of increasingly sensitive assays, an enhanced appreciation of the pharmacokinetic consequences of immunogenicity and the development of comprehensive and specific guidance from regulatory authorities. As a result, rheumatologists have a greatly improved understanding of the field in general, including the factors responsible for immunogenicity, its potential clinical consequences and the implications for everyday treatment. In some specialties, immunogenicity testing is becoming a part of routine clinical management, but definitive evidence of its cost-effectiveness in rheumatology is awaited.
Topics: Adaptive Immunity; Antirheumatic Agents; Biological Factors; Biosimilar Pharmaceuticals; Cost-Benefit Analysis; Humans; Rheumatic Diseases; Rheumatologists; Rheumatology
PubMed: 33318665
DOI: 10.1038/s41584-020-00540-8 -
American Journal of Clinical Dermatology Oct 2019Patients with hidradenitis suppurativa (HS) are often undertreated and there are limited efficacious therapies available for treating this population. Biologics are an... (Review)
Review
Patients with hidradenitis suppurativa (HS) are often undertreated and there are limited efficacious therapies available for treating this population. Biologics are an emerging therapeutic modality used in the management of many inflammatory conditions including HS. Implementation of biologics is typically reserved for moderate-to-severe cases or in those cases that are refractory to treatment. Though many biologics have been trialed for use in HS, only one biologic, adalimumab, is currently US FDA (Food and Drug Administration) approved for the treatment of moderate-to-severe HS. Limitations in the use of biologics for HS include the many scoring systems utilized in research studies and the relatively few well-designed, adequately powered clinical trials.
Topics: Adalimumab; Biological Factors; Biological Products; Clinical Trials as Topic; Hidradenitis Suppurativa; Humans; Severity of Illness Index; Treatment Outcome
PubMed: 31140067
DOI: 10.1007/s40257-019-00439-5