Interleukin-1 receptor antagonist:From synthesis to therapeutic applications

The cytokine channel’s mechanism for self-regulation involves the application of antagonistic cytokines that are synthesized to connect to the receptors and release soluble cytokine receptors.The very first receptor antagonist of cytokine that was naturally present was interleukin-1 receptor antagonist(IL-1Ra).The IL-1Ra protein forms are disinfected from supernatants of cultured monocytes on stacked IgG.The family of IL-1 consists of IL-1α,IL-1βand IL-1Ra.Human monocytes regulate the production of IL-Ra.IL-Ra takes part in normal physiological functions by using specific antibodies,and acts as an anti-inflammatory agent.IL-Ra is synthesized in the tissues during the period of active disease and can be systematically measured and/or estimated.Maintenance of the levels of IL-Ra and IL-1 is the main factor for host resistance in patients during diseased conditions,as IL-Ra acts as an inherent regulator of various inflammatory responses.In this article,we focuse on how IL-Ra is synthesized and performs its functions once the inflammatory responses are activated.

Therapeutic applications of collagenase(metalloproteases): A review

Non-invasive therapeutic methods have recently been used in medical sciences. Enzymes have shown high activity at very low concentrations in laboratories and pharmaceutical,enabling them to play crucial roles in different biological phenomena related to living organism, especially human medicine. Recently, using the therapeutic methods based on non-invasive approaches has been emphasized in medical society. Researchers have focused on producing medicines and tools reducing invasive procedures in medical.Collagenases are proteins which catalyze chemical processes and break the peptide bonds in collagen. Collagen may be generated more than the required amount or produced in unsuitable sites or may not degrade after a certain time. In such cases, using an injectable collagenase or its ointment can be helpful in collagen degradation. In both in vitro and in vivo tests, it has been revealed that collagenases have several therapeutic properties in wound healing, burns, nipple pain and some diseases including intervertebral disc herniation, keloid, cellulite, lipoma among others. This review describes the therapeutic application of collagenase in medical sciences and the process for its production using novel methods, paving the way for more effective and safe applications of collagenases.

Therapeutic applications of exosomes from adipose-derived stem cells in antifibrosis

Fibrosis is a condition in which connective tissue replaces normal parenchymal tissue,resulting in significant tissue remodeling.Fibrosis can affect several organs and pose a serious threat to human health and life.Adiposederived stem cells(ASCs)have been suggested as promising candidates for antifibrotic therapies.Paracrine secretion is one of the key processes in stem cell therapy due to its critical function in cellular communication.ASC-derived exosomes(ASC-exos)are used as tools for restoring and regenerating damaged tissue,and they are now thought to orchestrate antifibrosis-related events.In this review,we summarize the recent findings and present an extensive view of the therapeutic applications of ASC-exos in fibrotic diseases.

Gut microbes in cardiovascular diseases and their potential therapeutic applications

Microbial ecosystem comprises a complex community in which bacteria interact with each other. The potential roles of the intestinal microbiome play in human health have gained considerable attention. The imbalance of gut microbial community has been looked to multiple chronic diseases. Cardiovascular diseases (CVDs) are leading causes of morbidity worldwide and are influenced by genetic and environmental factors. Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome. In this review, we highlight the complex interplay between microbes, their metabolites, and the potential influence on the generation and development of CVDs. The therapeutic potential of using intestinal microbiomes to treat CVD is also discussed. It is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.

Brown adipose tissue and its therapeutic application

In addition to white adipose tissue （WAT） that stores energy, human and small mammals also have brown adipose tissue （BAT） that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2 diabetes.

Brown adipose tissue and its therapeutic application

In addition to white adipose tissue(WAT) that stores energy, human and small mammals also have brown adipose tissue(BAT) that dissipates chemical energy for thermogenesis. BAT contains multilocular lipid droplets and much higher numbers of mitochondria than WAT. The mitochondria in BAT uncouple large amounts of fuel oxidation from ATP for heat generation. Accumulating evidences have demonstrated that increased activity and/or amount of BAT can reverse obesity and improve insulin resistance, which highlights that BAT plays an important role in energy metabolism. In this review, we summarized recent findings that shows advantageous effects of BAT activation in metabolic diseases. In addition, we presented the function and role of brown and beige fat cells and regulatory factors for them. Finally, we discussed the potential application of brown adipocytes-based therapy and pharmacological intervention to increase BAT activity for the treatment of obesity and related diseases including insulin resistance, cardiovascular diseases and type 2diabetes.

An overview of leech and its therapeutic applications

Hirudotherapy has a broad spectrum of therapeutic application in the medical field ranging from cardiology,gynaecology,ophthalmology,plastic and reconstructive surgeries.In medieval and early modern medicine,leeches were used to remove blood from patients in an attempt to balance the biological humours.Leeches are widely used to treat venous congestion in microvascular replantation,free and conventional flap surgery and traumatology.Recently,Food and Drug Administration has approved the usage of live leeches as medical device for therapeutic applications.Presently,some of the leech species have declined dramatically in its population due to the over utilization of leech for medicinal purposes and also due to pollution in several parts of the world particularly in European and Asian countries.This review presents an overview of leech including the history,biology,classification,and its application as medical device.Further,it also covers the controversies and misconception related to leech species identification and complications of post hirudotherapy.

Applications of genetic code expansion technology in eukaryotes

Unnatural amino acids(UAAs)have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins.In eukaryotes,genetic code expansion(GCE)enables the incorporation of UAAs and facilitates posttranscriptional modification(PTM),which is not feasible in prokaryotic systems.GCE is also a powerful tool for cell or animal imaging,the monitoring of protein interactions in target cells,drug development,and switch regulation.Therefore,there is keen interest in utilizing GCE in eukaryotic systems.This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.

Research Progress of the Antiviral Bioactivities of Natural Flavonoids

Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications.Most recent researches have focused on the health aspects of flavonoids for humans.Especially,different flavonoids have been investigated for their potential antiviral activities,and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo.This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids,highlights the cellular and molecular mechanisms of natural flavonoids on viruses,and presents the details of most reported flavonoids.Meanwhile,future perspectives on therapeutic applications of flavonoids against viral infections were discussed.

Incorporation of Bromelain into Dermatological Bases： Accelerated Stability Studies

This work aimed the incorporation of the enzyme bromelain from pineapple peel into dermatological bases for potential therapeutic application. The enzyme was incorporated into Lanette cream and lotion, as well as Carbopol gel and Chemyunion cream and lotion, at a concentration of 0.5% （w/w）. These bases were subjected to centrifugation test and accelerated stability test during 90 days at 25 ℃（with and without sunlight）, 37 ℃ and 4 ℃, in order to evaluate bromelain stability in dermatological bases. Total protein content and enzymatic activity were measured. The bases were stable as its organoleptic characteristics （appearance, color, smell and sensitivity to touch） only when kept at 4 ℃ with activity remaining 95.5%, 84,9%. 77.7%, 73.8% and 72.3%, alter 90 days of testing in Carbopol gel, Lanette and Chemyunion cream, and Lanette and Chemyunion lotion, respectively. Based on the results, it was possible to incorporate bromelain into dermatological bases, and the activity was well preserved when these bases were kept in refrigerator at 4 ℃.

A Review on General Nutritional Compounds and Pharmacological Properties of the Lentinula edodes Mushroom

Lentinula edodes?is a macrofungus with great potential for therapeutic applications and serves as a model for investigating functional fungi properties and isolating pure compounds for pharmaceutical use. Mushrooms have a great nutritional value and present medicinal molecules including polysaccharides, terpenoids, sterols and lipids, that participate actively in several human disorders and modulate mechanisms involved in the immune system regulation. This review will focus on general nutritional compounds and pharmacological properties of L. edodes.

Base editors:development and applications in biomedicine

Base editor(BE)is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase,enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break(DSB)or requiring donor DNA templates in living cells.Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems,such as CRISPR/Cas9,as the DSB induced by Cas9 will cause severe damage to the genome.Thus,base editors have important applications in the field of biomedicine,including gene function investigation,directed protein evolution,genetic lineage tracing,disease modeling,and gene therapy.Since the development of the two main base editors,cytosine base editors(CBEs)and adenine base editors(ABEs),scientists have developed more than 100 optimized base editors with improved editing efficiency,precision,specificity,targeting scope,and capacity to be delivered in vivo,greatly enhancing their application potential in biomedicine.Here,we review the recent development of base editors,summarize their applications in the biomedical field,and discuss future perspectives and challenges for therapeutic applications.

Cancer recognition of artificial intelligence

The recognition mechanism of artificial intelligence(AI)is an interesting topic in understanding AI neural networks and their application in therapeutics.A number of multilayered neural networks can recognize cancer through deep learning.It would be interesting to think about whether human insights and AI attention are associated with each other or should be translated,which is one of the main points in this editorial.The automatic detection of cancer with computeraided diagnosis is being applied in the clinic and should be improved with feature mapping in neural networks.The subtypes and stages of cancer,in terms of progression and metastasis,should be classified with AI for optimized therapeutics.The determination of training and test data during learning and selection of appropriate AI models will be essential for therapeutic applications.

Artificial intelligence in gastrointestinal diseases

Artificial intelligence(AI)applications are growing in medicine.It is important to understand the current state of the AI applications prior to utilizing in disease research and treatment.In this review,AI application in the diagnosis and treatment of gastrointestinal diseases are studied and summarized.In most cases,AI studies had large amounts of data,including images,to learn to distinguish disease characteristics according to a human’s perspectives.The detailed pros and cons of utilizing AI approaches should be investigated in advance to ensure the safe application of AI in medicine.Evidence suggests that the collaborative usage of AI in both diagnosis and treatment of diseases will increase the precision and effectiveness of medicine.Recent progress in genome technology such as genome editing provides a specific example where AI has revealed the diagnostic and therapeutic possibilities of RNA detection and targeting.

Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

Methods of DNA introduction for the engineering of commensal microbes

The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes.Over the past decades,the accumulated observational evidence reveals a close correlation between the micro-biome and human health and disease.Many groups are now manipulating individual microbial strains,species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome.Here,we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria,including transformation,transduction,and conjugation.We provide an overview of these approaches and describe the advantages and limitations of each method.In addition,we highlight examples of human mi-crobiome engineering using these approaches.Finally,we provide perspectives for the future of microbiome engineering.

Triboelectric nanogenerators for clinical diagnosis and therapy:A report of recent progress

Triboelectric nanogenerators(TENGs)are considered as an ideal platform for power harvesting for living organisms,thanks to their unique characteristics like flexibility,conversion efficient,and manufacturing cost.Recent advances in TENGs have brought innovative solutions for clinical healthcare.Particularly,TENGs offer novel solutions of continues power supply for wearable and implantable medical devices with lightweight,thinness,good biocompatibility,and excellent soft tissue conformability.In this review,we discuss(1)The working principle and representative structure of TENGs,(2)the material selection of TENGs,(3)the recent progression of application of TENG in the medical field of cardiovascular system,nervous system,respiratory system,microbial inactivation,antibiofouling,disinfection,and tissue repair,(4)challenges and future perspectives of TENG-based medical devices.The emerging TENGs and their applications in medicine cannot simply be seen as an alternative to conventional power supplies,it provides a revolutionary solution for wearable and implantable medical devices,and they will surely change the paradigm of disease diagnosis and treatment in the future.