Pub Date : 2023-04-25DOI: 10.37349/emed.2023.00132
R. Parveen, Monalisha Samal, Nafis, H. Mukhtar, Sayeed Ahmad
Aim: The main objective of the study was to formulate, evaluate and perform an optimization study of chaulmoogra oil-loaded solid lipid nanoparticles (SLNs) based gel. Methods: The study involves isolation, identification, and quantification of hydnocarpic acid (HA), using high-performance thin-layer chromatography (HPTLC) and characterization using ultraviolet (UV), nuclear magnetic resonance (NMR), and mass spectroscopy (MS), and differential scanning calorimetry (DSC). Different concentration of assorted solid lipids and surfactants was used for the preparation of SLN gel with the improved transdermal application. Size distribution, entrapping efficiency, transmission electron microscopy (TEM), and percent yield were tested for the prepared SLN and the characterization of SLN gel was evaluated on the basis of in vitro diffusion study, stability studies, homogeneity, and skin irritancy test. Results: The amount of HA quantified in the oil sample was found to be 54.84% w/w. The percent yield and entrapment efficiency (EE) of HA SLNs were 96.176 ± 1.338% and 90.2 ± 0.5% respectively. The in vitro percent cumulative drug release was 80.89% for the developed SLN, the homogeneity test showed no grittiness, and the prepared gel was found to be effective as it shows no signs of erythema post-treatment of 10 days. The in vitro dissolution studies showed better results for SLN gel when compared to SLN suspension. Conclusions: The nano-gel could be a better option for the topical delivery of herbal drugs with improved bioavailability providing several benefits over conventional formulation.
{"title":"Development of solid lipid nanoparticle gel for transdermal delivery system of chaulmoogra oil","authors":"R. Parveen, Monalisha Samal, Nafis, H. Mukhtar, Sayeed Ahmad","doi":"10.37349/emed.2023.00132","DOIUrl":"https://doi.org/10.37349/emed.2023.00132","url":null,"abstract":"Aim: The main objective of the study was to formulate, evaluate and perform an optimization study of chaulmoogra oil-loaded solid lipid nanoparticles (SLNs) based gel.\u0000Methods: The study involves isolation, identification, and quantification of hydnocarpic acid (HA), using high-performance thin-layer chromatography (HPTLC) and characterization using ultraviolet (UV), nuclear magnetic resonance (NMR), and mass spectroscopy (MS), and differential scanning calorimetry (DSC). Different concentration of assorted solid lipids and surfactants was used for the preparation of SLN gel with the improved transdermal application. Size distribution, entrapping efficiency, transmission electron microscopy (TEM), and percent yield were tested for the prepared SLN and the characterization of SLN gel was evaluated on the basis of in vitro diffusion study, stability studies, homogeneity, and skin irritancy test.\u0000Results: The amount of HA quantified in the oil sample was found to be 54.84% w/w. The percent yield and entrapment efficiency (EE) of HA SLNs were 96.176 ± 1.338% and 90.2 ± 0.5% respectively. The in vitro percent cumulative drug release was 80.89% for the developed SLN, the homogeneity test showed no grittiness, and the prepared gel was found to be effective as it shows no signs of erythema post-treatment of 10 days. The in vitro dissolution studies showed better results for SLN gel when compared to SLN suspension.\u0000Conclusions: The nano-gel could be a better option for the topical delivery of herbal drugs with improved bioavailability providing several benefits over conventional formulation.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41424770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-25DOI: 10.37349/emed.2023.00133
Lindsey B. Cundra, Manasa Vallabhaneni, Michael Saadeh, Kevin V. Houston, B. Yoo, Steve M. D’Souza, David A. Johnsonv
The novel coronavirus disease-2019 (COVID-19) has created a major public health crisis. Various dietary factors may enhance immunological activity against COVID-19 and serve as a method to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dietary factors that are responsible for boosting immunity may provide a therapeutic advantage in patients with COVID-19. Investigators have demonstrated that vitamins B6, B12, C, D, E, and K, and trace elements like zinc, copper, selenium, and iron may serve as important tools for immunomodulation. Herein this is a review the peer-reviewed literature pertaining to dietary immunomodulation strategies against COVID-19. This review is intended to better define the evidence that dietary modifications and supplementation could positively influence the proinflammatory state in patients with COVID-19 and improve clinical outcomes. With appropriate insight, therapeutic interventions are discussed and directed to potentially modulate host immunity to mitigate the disease mechanisms of COVID-19.
{"title":"Immunomodulation strategies against COVID-19 evidence: key nutrients and dietary approaches","authors":"Lindsey B. Cundra, Manasa Vallabhaneni, Michael Saadeh, Kevin V. Houston, B. Yoo, Steve M. D’Souza, David A. Johnsonv","doi":"10.37349/emed.2023.00133","DOIUrl":"https://doi.org/10.37349/emed.2023.00133","url":null,"abstract":"The novel coronavirus disease-2019 (COVID-19) has created a major public health crisis. Various dietary factors may enhance immunological activity against COVID-19 and serve as a method to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dietary factors that are responsible for boosting immunity may provide a therapeutic advantage in patients with COVID-19. Investigators have demonstrated that vitamins B6, B12, C, D, E, and K, and trace elements like zinc, copper, selenium, and iron may serve as important tools for immunomodulation. Herein this is a review the peer-reviewed literature pertaining to dietary immunomodulation strategies against COVID-19. This review is intended to better define the evidence that dietary modifications and supplementation could positively influence the proinflammatory state in patients with COVID-19 and improve clinical outcomes. With appropriate insight, therapeutic interventions are discussed and directed to potentially modulate host immunity to mitigate the disease mechanisms of COVID-19.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48296301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-25DOI: 10.37349/emed.2023.00130
Kevin V. Houston, Ankit Patel, Michael Saadeh, Alejandra Vargas, Ana Rosa Vilela Sangay
The gastrointestinal (GI) microbiome remains an emerging topic of study and the characterization and impact on human health and disease continue to be an area of great interest. Similarly, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the healthcare system with active disease, lasting effects, and complications with the full impact yet to be determined. The most current evidence of the interaction between COVID-19 and the GI microbiome is reviewed, with a focus on key mediators and the microbiome changes associated with acute disease and post-acute COVID-19 syndrome (PACS).
{"title":"Gastrointestinal microbiome and coronavirus disease: evidence of a bidirectional association","authors":"Kevin V. Houston, Ankit Patel, Michael Saadeh, Alejandra Vargas, Ana Rosa Vilela Sangay","doi":"10.37349/emed.2023.00130","DOIUrl":"https://doi.org/10.37349/emed.2023.00130","url":null,"abstract":"The gastrointestinal (GI) microbiome remains an emerging topic of study and the characterization and impact on human health and disease continue to be an area of great interest. Similarly, the coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the healthcare system with active disease, lasting effects, and complications with the full impact yet to be determined. The most current evidence of the interaction between COVID-19 and the GI microbiome is reviewed, with a focus on key mediators and the microbiome changes associated with acute disease and post-acute COVID-19 syndrome (PACS).","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47329016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-25DOI: 10.37349/emed.2023.00131
Lisanne Vervoort, J. Vermeesch
DNA paralogs that have a length of at least 1 kilobase (kb) and are duplicated with a sequence identity of over 90% are classified as low copy repeats (LCRs) or segmental duplications (SDs). They constitute 6.6% of the genome and are clustering in specific genomic loci. Due to the high sequence homology between these duplicated regions, they can misalign during meiosis resulting in non-allelic homologous recombination (NAHR) and leading to structural variation such as deletions, duplications, inversions, and translocations. When such rearrangements result in a clinical phenotype, they are categorized as a genomic disorder. The presence of multiple copies of larger genomic segments offers opportunities for evolution. First, the creation of new genes in the human lineage will lead to human-specific traits and adaptation. Second, LCR variation between human populations can give rise to phenotypic variability. Hence, the rearrangement predisposition associated with LCRs should be interpreted in the context of the evolutionary advantages.
{"title":"Low copy repeats in the genome: from neglected to respected","authors":"Lisanne Vervoort, J. Vermeesch","doi":"10.37349/emed.2023.00131","DOIUrl":"https://doi.org/10.37349/emed.2023.00131","url":null,"abstract":"DNA paralogs that have a length of at least 1 kilobase (kb) and are duplicated with a sequence identity of over 90% are classified as low copy repeats (LCRs) or segmental duplications (SDs). They constitute 6.6% of the genome and are clustering in specific genomic loci. Due to the high sequence homology between these duplicated regions, they can misalign during meiosis resulting in non-allelic homologous recombination (NAHR) and leading to structural variation such as deletions, duplications, inversions, and translocations. When such rearrangements result in a clinical phenotype, they are categorized as a genomic disorder. The presence of multiple copies of larger genomic segments offers opportunities for evolution. First, the creation of new genes in the human lineage will lead to human-specific traits and adaptation. Second, LCR variation between human populations can give rise to phenotypic variability. Hence, the rearrangement predisposition associated with LCRs should be interpreted in the context of the evolutionary advantages.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43656486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-20DOI: 10.37349/emed.2023.00135
S. Santonocito, S. Ferlito, Alessandro Polizzi, V. Ronsivalle, G. Reitano, A. Lo Giudice, G. Isola
The periodontium is an appropriate target for regeneration, as it cannot restore its function following disease. Significantly, the periodontium's limited regenerative capacity could be enhanced through the development of novel biomaterials and therapeutic approaches. Notably, the regenerative potential of the periodontium depends not only on its tissue-specific architecture and function but also on its ability to reconstruct distinct tissues and tissue interfaces, implying that the development of tissue engineering techniques can offer new perspectives for the organized reconstruction of soft and hard periodontal tissues. With their biocompatible structure and one-of-a-kind stimulus-responsive property, hydrogels have been utilized as an excellent drug delivery system for the treatment of several oral diseases. Furthermore, bioceramics and three-dimensional (3D) printed scaffolds are also appropriate scaffolding materials for the regeneration of periodontal tissue, bone, and cartilage. This work aims to examine and update material-based, biologically active cues and the deployment of breakthrough bio-fabrication technologies to regenerate the numerous tissues that comprise the periodontium for clinical and scientific applications.
{"title":"Impact exerted by scaffolds and biomaterials in periodontal bone and tissue regeneration engineering: new challenges and perspectives for disease treatment","authors":"S. Santonocito, S. Ferlito, Alessandro Polizzi, V. Ronsivalle, G. Reitano, A. Lo Giudice, G. Isola","doi":"10.37349/emed.2023.00135","DOIUrl":"https://doi.org/10.37349/emed.2023.00135","url":null,"abstract":"The periodontium is an appropriate target for regeneration, as it cannot restore its function following disease. Significantly, the periodontium's limited regenerative capacity could be enhanced through the development of novel biomaterials and therapeutic approaches. Notably, the regenerative potential of the periodontium depends not only on its tissue-specific architecture and function but also on its ability to reconstruct distinct tissues and tissue interfaces, implying that the development of tissue engineering techniques can offer new perspectives for the organized reconstruction of soft and hard periodontal tissues. With their biocompatible structure and one-of-a-kind stimulus-responsive property, hydrogels have been utilized as an excellent drug delivery system for the treatment of several oral diseases. Furthermore, bioceramics and three-dimensional (3D) printed scaffolds are also appropriate scaffolding materials for the regeneration of periodontal tissue, bone, and cartilage. This work aims to examine and update material-based, biologically active cues and the deployment of breakthrough bio-fabrication technologies to regenerate the numerous tissues that comprise the periodontium for clinical and scientific applications.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45075045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases.
{"title":"Oxidative stress and inflammation: the root causes of aging","authors":"Sobhon Prasert, Savedvanich Gavin, Weerakiet Sawaek","doi":"10.37349/emed.2023.00129","DOIUrl":"https://doi.org/10.37349/emed.2023.00129","url":null,"abstract":"Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen free radicals [reactive nitrogen species (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, and catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, and nitric oxide synthases during drug catabolism, phagocytosis, and acute inflammation. Under normal circumstances, low levels of ROS and RNS provide redox signalings that control many essential physiological processes. As age progresses ROS and RNS increase excessively due to dysfunctional mitochondria, dysregulated NOX, and other free-radical generating sources, leading to oxidative stress, which causes oxidation and denaturation of key cellular components including DNA, proteins, and lipids, which become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ by immune cells, leading to inflammation which is mediated by nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase and Janus kinase-signal transducer and activator of transcription pathways. DAMPs are continuously released from damaged and senescent cells, causing an otherwise normally transient inflammation turning into systemic chronic inflammation, the root cause of aging and age-associated diseases (AADs). Cells restore redox balance by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway that induces the synthesis and release of antioxidation molecules and enzymes including haem oxygenase-1, which also inhibits the three inflammatory pathways. Furthermore, upregulation of autophagy (AP) can get rid of abnormal molecules, prevent the generation of DAMPs, and attenuate inflammation. Both AP and Nrf2 signalings decrease with age. The upregulations of Nrf2, AP, and downregulation of inflammation are controlled by sensors of energy and stress levels, i.e., adenosine monophosphate-activated protein kinase, silent information regulator 1, and Sestrins, as well as the extracellular matrix, while mammalian targets for rapamycin complex 1, a nutrient sensor, act in the opposite direction. If the balance of these sensor systems becomes dysregulated, aging process accelerates, and the risk of AADs increases.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41839652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-10DOI: 10.37349/emed.2023.00128
S. Rabkin
Aim: Hypertension (HTN) is a major cause of heart failure but the precise pathways by which HTN leads to heart failure are not resolved. Newer echocardiographic techniques permit assessment of myocardial contraction in different orientations defining left ventricular (LV) shortening as percentage longitudinal, circumferential and radial strain. Methods: A systematic search was conducted of Medline and Embase. The search was conducted from the inception of each database on June 30, 2022. Search terms “left ventricular strain” or speckle tracking AND heart failure with preserved ejection fraction or diastolic dysfunction AND HTN. Results: Six studies were identified and subject to detailed review. LV ejection fraction (LVEF) was not significantly different in patients with heart failure with preserved ejection fraction (HFpEF) and HTN compared to individuals with or without HTN. Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly (P < 0.0001) different (lower) in patients with HFpEF and HTN compared to patients with HTN without HFpEF and control individuals without HTN or other conditions. In contrast, global radial strain (GRS) was not significantly (P < 0.054) different in patients with HFpEF and HTN compared to individuals without HTN or other conditions. GRS was significantly (P < 0.01) different in individuals with HFpEF and HTN compared to individuals with HTN. Conclusions: Assessment of LV strain is an important advance in the assessment of LV function in patients with HTN and HFpEF as it identifies patients with reduced LV strain while there was no difference in LVEF. GLS and GCS provide the best separation between patients with HFpEF and HTN compared to individuals with HTN without HFpEF. This study advances the possibility of redefining the classification of heart function and heart failure for patients with HTN by either classifying patients mainly by LV strain or sub-classifying patients with HTN and HFpEF by LV strain.
{"title":"Assessing cardiac contractility in hypertension with heart failure with preserved ejection fraction: the value of left ventricular strain","authors":"S. Rabkin","doi":"10.37349/emed.2023.00128","DOIUrl":"https://doi.org/10.37349/emed.2023.00128","url":null,"abstract":"Aim: Hypertension (HTN) is a major cause of heart failure but the precise pathways by which HTN leads to heart failure are not resolved. Newer echocardiographic techniques permit assessment of myocardial contraction in different orientations defining left ventricular (LV) shortening as percentage longitudinal, circumferential and radial strain.\u0000Methods: A systematic search was conducted of Medline and Embase. The search was conducted from the inception of each database on June 30, 2022. Search terms “left ventricular strain” or speckle tracking AND heart failure with preserved ejection fraction or diastolic dysfunction AND HTN.\u0000Results: Six studies were identified and subject to detailed review. LV ejection fraction (LVEF) was not significantly different in patients with heart failure with preserved ejection fraction (HFpEF) and HTN compared to individuals with or without HTN. Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly (P < 0.0001) different (lower) in patients with HFpEF and HTN compared to patients with HTN without HFpEF and control individuals without HTN or other conditions. In contrast, global radial strain (GRS) was not significantly (P < 0.054) different in patients with HFpEF and HTN compared to individuals without HTN or other conditions. GRS was significantly (P < 0.01) different in individuals with HFpEF and HTN compared to individuals with HTN.\u0000Conclusions: Assessment of LV strain is an important advance in the assessment of LV function in patients with HTN and HFpEF as it identifies patients with reduced LV strain while there was no difference in LVEF. GLS and GCS provide the best separation between patients with HFpEF and HTN compared to individuals with HTN without HFpEF. This study advances the possibility of redefining the classification of heart function and heart failure for patients with HTN by either classifying patients mainly by LV strain or sub-classifying patients with HTN and HFpEF by LV strain.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45014638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.37349/emed.2023.00125
Dilpreet Singh, Amrinder Singh, P. Chawla
A large number of the population faces mortality as an effect of tuberculosis (TB). The line of treatment in the management of TB faces a jolt with ever-increasing multi-drug resistance (DR) cases. Further, the drugs engaged in the treatment of TB are associated with different toxicities, such as renal and hepatic toxicity. Different combinations are sought for effective anti-tuberculosis (anti-TB) effects with a decrease in toxicity. In this regard, drug repurposing has been very promising in improving the efficacy of drugs by enhancement of bioavailability and widening the safety margin. The success in drug repurposing lies in specified binding and inhibition of a particular target in the drug molecule. Different drugs have been repurposed for various ailments like cancer, Alzheimer’s disease, acquired immunodeficiency syndrome (AIDS), hair loss, etc. Repurposing in anti-TB drugs holds great potential too. The use of whole-cell screening assays and the availability of large chemical compounds for testing against Mycobacterium tuberculosis poses a challenge in this development. The target-based discovery of sites has emerged in the form of phenotypic screening as ethionamide R (EthR) and malate synthase inhibitors are similar to pharmaceuticals. In this review, the authors have thoroughly described the drug repurposing techniques on the basis of pharmacogenomics and drug metabolism, pathogen-targeted therapy, host-directed therapy, and bioinformatics approaches for the identification of drugs. Further, the significance of repurposing of drugs elaborated on large databases has been revealed. The role of genomics and network-based methods in drug repurposing has been also discussed in this article.
{"title":"An overview of current strategies and future prospects in drug repurposing in tuberculosis","authors":"Dilpreet Singh, Amrinder Singh, P. Chawla","doi":"10.37349/emed.2023.00125","DOIUrl":"https://doi.org/10.37349/emed.2023.00125","url":null,"abstract":"A large number of the population faces mortality as an effect of tuberculosis (TB). The line of treatment in the management of TB faces a jolt with ever-increasing multi-drug resistance (DR) cases. Further, the drugs engaged in the treatment of TB are associated with different toxicities, such as renal and hepatic toxicity. Different combinations are sought for effective anti-tuberculosis (anti-TB) effects with a decrease in toxicity. In this regard, drug repurposing has been very promising in improving the efficacy of drugs by enhancement of bioavailability and widening the safety margin. The success in drug repurposing lies in specified binding and inhibition of a particular target in the drug molecule. Different drugs have been repurposed for various ailments like cancer, Alzheimer’s disease, acquired immunodeficiency syndrome (AIDS), hair loss, etc. Repurposing in anti-TB drugs holds great potential too. The use of whole-cell screening assays and the availability of large chemical compounds for testing against Mycobacterium tuberculosis poses a challenge in this development. The target-based discovery of sites has emerged in the form of phenotypic screening as ethionamide R (EthR) and malate synthase inhibitors are similar to pharmaceuticals. In this review, the authors have thoroughly described the drug repurposing techniques on the basis of pharmacogenomics and drug metabolism, pathogen-targeted therapy, host-directed therapy, and bioinformatics approaches for the identification of drugs. Further, the significance of repurposing of drugs elaborated on large databases has been revealed. The role of genomics and network-based methods in drug repurposing has been also discussed in this article.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41540424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.37349/emed.2023.00127
Hiromichi Sato, T. Hara, Chihiro Otsuka, Yasuko Arao, Yoshiko Tsuji, Yumiko Hamano, Mirei Ogita, E. di Luccio, Takaaki Hirotsu, A. Vecchione, Hideshi Ishii
m6A RNA methylation, a predominant type of RNA modification, is involved in regulating mRNA splicing, stability, and translation as well as the interaction between nucleoproteins and noncoding RNAs. Recent studies have revealed that m6A RNA methylation plays a critical role in the self-to-non-self-recognition of immune cells against endogenous mutations in cancer and exogenous organism-related infections. As an epigenetic mechanism, m6A RNA modification induces immune cell signal transduction, which is altered in the tumor microenvironment, as detected in liquid biopsy. Furthermore, m6A RNA methylation-related inflammation is involved in the cellular response to viral infections, including the emerging severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Given the importance of the immune response in maintaining homeostasis in higher eukaryotes, m6A RNA methylation could be useful not only for the early detection of cancer but also for SARS-CoV-2 screening during a global pandemic.
{"title":"m6 RNA methylation: an emerging common target in the immune response to cancer and severe acute respiratory syndrome-coronavirus-2 infection","authors":"Hiromichi Sato, T. Hara, Chihiro Otsuka, Yasuko Arao, Yoshiko Tsuji, Yumiko Hamano, Mirei Ogita, E. di Luccio, Takaaki Hirotsu, A. Vecchione, Hideshi Ishii","doi":"10.37349/emed.2023.00127","DOIUrl":"https://doi.org/10.37349/emed.2023.00127","url":null,"abstract":"m6A RNA methylation, a predominant type of RNA modification, is involved in regulating mRNA splicing, stability, and translation as well as the interaction between nucleoproteins and noncoding RNAs. Recent studies have revealed that m6A RNA methylation plays a critical role in the self-to-non-self-recognition of immune cells against endogenous mutations in cancer and exogenous organism-related infections. As an epigenetic mechanism, m6A RNA modification induces immune cell signal transduction, which is altered in the tumor microenvironment, as detected in liquid biopsy. Furthermore, m6A RNA methylation-related inflammation is involved in the cellular response to viral infections, including the emerging severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Given the importance of the immune response in maintaining homeostasis in higher eukaryotes, m6A RNA methylation could be useful not only for the early detection of cancer but also for SARS-CoV-2 screening during a global pandemic.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42548362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-28DOI: 10.37349/emed.2023.00126
Shikha Choudhary, Raminderjit Kaur, Aafrin Waziri, A. Garg, R. Kadian, M. Alam
Neuropathic pain (NP) remains maltreated for a wide number of patients by the currently available treatments and little research has been done in finding new drugs for treating NP. Ziconotide (PrialtTM) had been developed as the new drug, which belongs to the class of ω-conotoxin MVIIA. It inhibits N-type calcium channels. Ziconotide is under the last phase of the clinical trial, a new non-narcotic drug for the management of NP. Synthetically it has shown the similarities with ω-conotoxin MVIIA, a constituent of poison found in fish hunting snails (Conus magus). Ziconotide acts by selectively blocking neural N-type voltage-sensitized Ca2+ channels (NVSCCs). Certain herbal drugs also have been studied but no clinical result is there and the study is only limited to preclinical data. This review emphasizes the N-type calcium channel inhibitors, and their mechanisms for blocking calcium channels with their remedial prospects for treating chronic NP.
{"title":"N-type calcium channel blockers: a new approach towards the treatment of chronic neuropathic pain","authors":"Shikha Choudhary, Raminderjit Kaur, Aafrin Waziri, A. Garg, R. Kadian, M. Alam","doi":"10.37349/emed.2023.00126","DOIUrl":"https://doi.org/10.37349/emed.2023.00126","url":null,"abstract":"Neuropathic pain (NP) remains maltreated for a wide number of patients by the currently available treatments and little research has been done in finding new drugs for treating NP. Ziconotide (PrialtTM) had been developed as the new drug, which belongs to the class of ω-conotoxin MVIIA. It inhibits N-type calcium channels. Ziconotide is under the last phase of the clinical trial, a new non-narcotic drug for the management of NP. Synthetically it has shown the similarities with ω-conotoxin MVIIA, a constituent of poison found in fish hunting snails (Conus magus). Ziconotide acts by selectively blocking neural N-type voltage-sensitized Ca2+ channels (NVSCCs). Certain herbal drugs also have been studied but no clinical result is there and the study is only limited to preclinical data. This review emphasizes the N-type calcium channel inhibitors, and their mechanisms for blocking calcium channels with their remedial prospects for treating chronic NP.","PeriodicalId":72999,"journal":{"name":"Exploration of medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42125798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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