Elvia Haroen, Dina Alia, Gilbran Ayyubi Osman, Khalilullah Khalilullah
Berdasarkan data Riset Kesehatan Dasar (Riskesdas) 2018, prevalensi penyakit jantung koroner sebagai etiologi utama sindrom koroner akut (SKA) di Indonesia sebesar 1,5%. Sekitar 5,4% pasien dengan penyakit arteri koroner (PAD) dan 0,9% pasien dengan SKA didiagnosis dengan trombositopenia. Menurut American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) dan European Society of Cardiology (ESC), pemberian dual antiplatelet therapy (DAPT) yang terdiri dari aspirin dan antagonis reseptor P2Y12 adalah komponen mendasar dari manajemen SKA. Selain itu, terapi definitif berupa intervensi koroner perkutan (IKP), harus disertai dengan kombinasi obat antiplatelet dan antikoagulan untuk mencegah pembentukan trombus di lokasi intervensi koroner. Studi melaporkan bahwa trombositopenia yang diinduksi agen antiplatelet berkorelasi dengan mortalitas dan komorbiditas jangka pendek dan jangka panjang yang lebih tinggi pada pasien dengan SKA. Pada pasien dengan SKA dan trombositopenia, manajemen terapi pemberian antiplatelet masih sulit untuk dipertimbangkan dan saat ini tidak ada pedoman rekomendasi atau laporan konsensus untuk memandu dokter tentang manajemen pada kelompok ini. Oleh karena itu, kami berusaha untuk menjelaskan dari berbagai macam studi literatur tentang penggunaan DAPT pada pasien SKA dengan trombositopenia.
{"title":"Hubungan Faktor Risiko Tuli Kongenital Pada Anak Dengan Hasil Pemeriksaan Fungsi Pendengaran di RSUDZA","authors":"Elvia Haroen, Dina Alia, Gilbran Ayyubi Osman, Khalilullah Khalilullah","doi":"10.55572/jms.v4i2.89","DOIUrl":"https://doi.org/10.55572/jms.v4i2.89","url":null,"abstract":"Berdasarkan data Riset Kesehatan Dasar (Riskesdas) 2018, prevalensi penyakit jantung koroner sebagai etiologi utama sindrom koroner akut (SKA) di Indonesia sebesar 1,5%. Sekitar 5,4% pasien dengan penyakit arteri koroner (PAD) dan 0,9% pasien dengan SKA didiagnosis dengan trombositopenia. Menurut American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) dan European Society of Cardiology (ESC), pemberian dual antiplatelet therapy (DAPT) yang terdiri dari aspirin dan antagonis reseptor P2Y12 adalah komponen mendasar dari manajemen SKA. Selain itu, terapi definitif berupa intervensi koroner perkutan (IKP), harus disertai dengan kombinasi obat antiplatelet dan antikoagulan untuk mencegah pembentukan trombus di lokasi intervensi koroner. Studi melaporkan bahwa trombositopenia yang diinduksi agen antiplatelet berkorelasi dengan mortalitas dan komorbiditas jangka pendek dan jangka panjang yang lebih tinggi pada pasien dengan SKA. Pada pasien dengan SKA dan trombositopenia, manajemen terapi pemberian antiplatelet masih sulit untuk dipertimbangkan dan saat ini tidak ada pedoman rekomendasi atau laporan konsensus untuk memandu dokter tentang manajemen pada kelompok ini. Oleh karena itu, kami berusaha untuk menjelaskan dari berbagai macam studi literatur tentang penggunaan DAPT pada pasien SKA dengan trombositopenia.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139316255","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}
Ajao Folasade Omobolanle, Iyedupe Marcus Olaoye, Adegbola Raphael Oneosinina, Kalejaiye Noheem Olaolu, Adelusi Temitope Isaac
Background. The contemporary antidiabetic drugs have side effects and adverse reactions. This demand to search for less toxic and effective treatments for diabetes from medicinal plants using computational methods. The present research investigated the molecular docking of Anacadium occidentale nut methanolic extract compounds with selected proteins related to diabetes and the compounds’ AMDET properties. Material and Methods. The compounds were identified using Gas chromatography-mass spectrometry analysis. The compounds'2-dimensional structure was retrieved from the PubChem compound database. Three-dimensional crystallographic structure of selected proteins; B-cell-lymphoma-2 (Bcl-2), caspase-3, glucocorticoids, interleukin-1β, myeloperoxidase and tumor necrosis factor-alpha (TNF-α) was downloaded from Protein Data Bank. Molecular docking was performed using Autodoc kvina and the active site of binding interactions was detected with the Computed Atlas of Surface Topography of proteins (CAST-P). The compounds' drug-likeness, physicochemical and ADMET were evaluated using molininspiration and admetSAR online tools. Results. Ten compounds were identified from the Anacardium occidentale nut methanolic extract. All the compounds exhibited drug-likeness properties with violation of one Lipinski’s rule. Two compounds, oleic acid and 3-(p-methoxyphenyl)-propionic acid exhibited the best binding energy with the active receptors site of Bcl-2, caspase-3, TNF-α and glucocorticoid. Also, tridecanoic acid exhibited good binding energy with the active site of glucocorticoid receptors. Only 3-(p-methoxyphenyl)-propionic acid exhibited moderate binding energy with the active receptors site of interleukin-1β and myeloperoxidase. All the compounds displayed excellent ADMET properties. Conclusions. Antidiabetic drugs with the least side effects could be explored from these compounds.
{"title":"Molecular docking and admet properties of anacardium occidentale methanolic nut extract against inflammatory, oxidative and apoptotic markers of diabetes","authors":"Ajao Folasade Omobolanle, Iyedupe Marcus Olaoye, Adegbola Raphael Oneosinina, Kalejaiye Noheem Olaolu, Adelusi Temitope Isaac","doi":"10.20883/medical.e885","DOIUrl":"https://doi.org/10.20883/medical.e885","url":null,"abstract":"Background. The contemporary antidiabetic drugs have side effects and adverse reactions. This demand to search for less toxic and effective treatments for diabetes from medicinal plants using computational methods. The present research investigated the molecular docking of Anacadium occidentale nut methanolic extract compounds with selected proteins related to diabetes and the compounds’ AMDET properties. Material and Methods. The compounds were identified using Gas chromatography-mass spectrometry analysis. The compounds'2-dimensional structure was retrieved from the PubChem compound database. Three-dimensional crystallographic structure of selected proteins; B-cell-lymphoma-2 (Bcl-2), caspase-3, glucocorticoids, interleukin-1β, myeloperoxidase and tumor necrosis factor-alpha (TNF-α) was downloaded from Protein Data Bank. Molecular docking was performed using Autodoc kvina and the active site of binding interactions was detected with the Computed Atlas of Surface Topography of proteins (CAST-P). The compounds' drug-likeness, physicochemical and ADMET were evaluated using molininspiration and admetSAR online tools. Results. Ten compounds were identified from the Anacardium occidentale nut methanolic extract. All the compounds exhibited drug-likeness properties with violation of one Lipinski’s rule. Two compounds, oleic acid and 3-(p-methoxyphenyl)-propionic acid exhibited the best binding energy with the active receptors site of Bcl-2, caspase-3, TNF-α and glucocorticoid. Also, tridecanoic acid exhibited good binding energy with the active site of glucocorticoid receptors. Only 3-(p-methoxyphenyl)-propionic acid exhibited moderate binding energy with the active receptors site of interleukin-1β and myeloperoxidase. All the compounds displayed excellent ADMET properties. Conclusions. Antidiabetic drugs with the least side effects could be explored from these compounds.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135696194","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}
Marcin Skotnicki, Emilia Jakubowska, Wojciech Smułek, Sharon Davin, Lidia Tajber, Janina Lulek
The Open Research Biopharmaceutical Internships Support project (ORBIS) was a response to the scientific, economic, and social challenge of increasing the effectiveness and productivity of the drug development process, both for innovative and (super)generic drugs. The overarching objective of the ORBIS project was to form a transnational and intersectoral cooperation network of academic and industrial organisations delivering a joint research programme. The research aimed at improving the preclinical pathway of drug development and manufacturing, focusing on technological and methodological improvements of the existing processes. The participating staff from all institutions have developed new skills, were exposed to new work and research environments, and have significantly broadened their career perspectives. More than 450 months of secondments were completed, and over 175 early-stage and experienced researchers participated in the exchange. This review aims to present some aspects of the scientific, training, and organisational activities of the consortium, bringing together representatives of both the academic sector as well as small and medium-sized pharmaceutical enterprises.
{"title":"ORBIS project – where have we arrived?","authors":"Marcin Skotnicki, Emilia Jakubowska, Wojciech Smułek, Sharon Davin, Lidia Tajber, Janina Lulek","doi":"10.20883/medical.e936","DOIUrl":"https://doi.org/10.20883/medical.e936","url":null,"abstract":"The Open Research Biopharmaceutical Internships Support project (ORBIS) was a response to the scientific, economic, and social challenge of increasing the effectiveness and productivity of the drug development process, both for innovative and (super)generic drugs. The overarching objective of the ORBIS project was to form a transnational and intersectoral cooperation network of academic and industrial organisations delivering a joint research programme. The research aimed at improving the preclinical pathway of drug development and manufacturing, focusing on technological and methodological improvements of the existing processes. The participating staff from all institutions have developed new skills, were exposed to new work and research environments, and have significantly broadened their career perspectives. More than 450 months of secondments were completed, and over 175 early-stage and experienced researchers participated in the exchange. This review aims to present some aspects of the scientific, training, and organisational activities of the consortium, bringing together representatives of both the academic sector as well as small and medium-sized pharmaceutical enterprises.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136344072","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}
Teemu Tomberg, Alba Maria Arbiol Enguita, Clare Strachan
Microscopic chemical and solid-state structures and their changes in solid drugs and dosage forms can profoundly affect pharmaceutical performance and patient safety. Despite this, their detailed spatially-resolved analysis can be difficult or impossible with established analytical technologies. Multimodal non-linear optical imaging represents opportunities for sensitive and specific chemical and solid-state pharmaceutical imaging. Non-linear optical imaging encompasses several nonlinear optical phenomena, including coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), and sum frequency/second harmonic generation (SFG/SHG). Imaging in 3D with (sub)micron resolution is rapid, non-destructive, possible in situ in aqueous media, and generally does not require prior sample preparation. This mini-review explores several applications of non-linear optical imaging for solid drug and dosage form analysis.
{"title":"Insights into solid dosage forms with nonlinear optical imaging","authors":"Teemu Tomberg, Alba Maria Arbiol Enguita, Clare Strachan","doi":"10.20883/medical.e914","DOIUrl":"https://doi.org/10.20883/medical.e914","url":null,"abstract":"Microscopic chemical and solid-state structures and their changes in solid drugs and dosage forms can profoundly affect pharmaceutical performance and patient safety. Despite this, their detailed spatially-resolved analysis can be difficult or impossible with established analytical technologies. Multimodal non-linear optical imaging represents opportunities for sensitive and specific chemical and solid-state pharmaceutical imaging. Non-linear optical imaging encompasses several nonlinear optical phenomena, including coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS), and sum frequency/second harmonic generation (SFG/SHG). Imaging in 3D with (sub)micron resolution is rapid, non-destructive, possible in situ in aqueous media, and generally does not require prior sample preparation. This mini-review explores several applications of non-linear optical imaging for solid drug and dosage form analysis.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199829","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}
Piotr Rudzki, Olga Czerepow-Bielik, Marta Karaźniewicz-Łada
Public policies and regulations strongly influence research and manufacturing in pharmaceutical sector. Therefore, it is of critical importance that these policies and regulations are of high quality as well as appropriately balanced between general rules and detailed solutions. The process of public consultations prolongs adoption of novel documents. On the other hand, comments from different stakeholders like academia, industry, public administration and patients allow 360-degree critical evaluation of the document and a better understanding of the topic. This mini-review summarizes the contributions of numerous members of ORBIS project team in open consultations of draft regulatory documents published by European Medicines Agency (EMA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ORBIS project feedback on the Pharmaceutical Strategy for Europe is also presented. ORBIS project members contributed to open consultations of two ICH draft guidelines, and three EMA draft documents. ORBIS project was also active during the European Commission’s efforts to develop Pharmaceutical Strategy for Europe. The interaction between representatives of academic and industrial sectors allowed to form balanced comments. We hope that this paper will inspire more researchers to participate in future open consultations on public policies.
{"title":"Impact of ORBIS on public policies – open consultations of draft regulatory documents and the Pharmaceutical Strategy for Europe","authors":"Piotr Rudzki, Olga Czerepow-Bielik, Marta Karaźniewicz-Łada","doi":"10.20883/medical.e890","DOIUrl":"https://doi.org/10.20883/medical.e890","url":null,"abstract":"Public policies and regulations strongly influence research and manufacturing in pharmaceutical sector. Therefore, it is of critical importance that these policies and regulations are of high quality as well as appropriately balanced between general rules and detailed solutions. The process of public consultations prolongs adoption of novel documents. On the other hand, comments from different stakeholders like academia, industry, public administration and patients allow 360-degree critical evaluation of the document and a better understanding of the topic. This mini-review summarizes the contributions of numerous members of ORBIS project team in open consultations of draft regulatory documents published by European Medicines Agency (EMA) and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). ORBIS project feedback on the Pharmaceutical Strategy for Europe is also presented. ORBIS project members contributed to open consultations of two ICH draft guidelines, and three EMA draft documents. ORBIS project was also active during the European Commission’s efforts to develop Pharmaceutical Strategy for Europe. The interaction between representatives of academic and industrial sectors allowed to form balanced comments. We hope that this paper will inspire more researchers to participate in future open consultations on public policies.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"221 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199406","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}
Water is omnipresent during pharmaceutical product manufacturing and may interact with the drug substance, excipients, and the drug product in either solvent or vapor form, resulting in several physico-chemical changes, ultimately affecting product performance. Therefore, understanding the mechanisms behind such moisture-induced changes is necessary at every stage of pharmaceutical development and manufacturing to obtain the target formulation. Characterization tools, such as water sorption, spectroscopy, thermal analysis, diffraction, and more sophisticated approaches like simulations and PAT techniques, can help in the selection of the appropriate solid form, manufacturing method, excipients, and storage conditions, enabling the manufacturing of a stable drug product formulation.
{"title":"Effect of moisture on solid state stability","authors":"Stanko Srčič, Zoran Lavrič","doi":"10.20883/medical.e908","DOIUrl":"https://doi.org/10.20883/medical.e908","url":null,"abstract":"Water is omnipresent during pharmaceutical product manufacturing and may interact with the drug substance, excipients, and the drug product in either solvent or vapor form, resulting in several physico-chemical changes, ultimately affecting product performance. Therefore, understanding the mechanisms behind such moisture-induced changes is necessary at every stage of pharmaceutical development and manufacturing to obtain the target formulation. Characterization tools, such as water sorption, spectroscopy, thermal analysis, diffraction, and more sophisticated approaches like simulations and PAT techniques, can help in the selection of the appropriate solid form, manufacturing method, excipients, and storage conditions, enabling the manufacturing of a stable drug product formulation.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199269","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}
Anna Paszel-Jaworska, Justyna Gornowicz-Porowska, Aleksandra Dańczak-Pazdrowska, Adriana Polańska, Violetta Krajka-Kuźniak, Maciej Stawny, Aleksandra Gostyńska, Michał Masternak, Błażej Rubiś
Senescence is accompanied by numerous processes that lead to alterations in cell metabolism, cell cycle arrest, and, increased production and secretion of senescence-associated secretory phenotype (SASP). Consequently, signaling pathways cascades are activated, leading to inflammation that can trigger multiple disorders, including cancer. Recently, a novel therapeutic approach was proposed based on targeting senescent cells using senolytics. This group of biologically active compounds includes fisetin, quercetin, dasatinib, and others. These compounds were shown to affect laboratory animals (rodents) by improving the quality of life and significantly increasing the length of life by reducing senescent cells pool in different organs. Based on these findings, we decided to evaluate the potential of these compounds in targeting senescent cells in human skin using in vitro model based on human-derived keratinocytes (HEKa) and fibroblasts (HDFa). Cytotoxicity assay revealed that the activity of the compounds was time- and dose-dependent as well as cell-type dependent. Further studies were performed to reveal the mechanistic aspect of these observations including assessment of the senescence marker, namely p16. However, it requires clarification before entering clinical trials to provide not only efficient but, first of all, safe application of senolytics to human skin.
{"title":"New therapies targeting aging cells in the skin","authors":"Anna Paszel-Jaworska, Justyna Gornowicz-Porowska, Aleksandra Dańczak-Pazdrowska, Adriana Polańska, Violetta Krajka-Kuźniak, Maciej Stawny, Aleksandra Gostyńska, Michał Masternak, Błażej Rubiś","doi":"10.20883/medical.e903","DOIUrl":"https://doi.org/10.20883/medical.e903","url":null,"abstract":"Senescence is accompanied by numerous processes that lead to alterations in cell metabolism, cell cycle arrest, and, increased production and secretion of senescence-associated secretory phenotype (SASP). Consequently, signaling pathways cascades are activated, leading to inflammation that can trigger multiple disorders, including cancer. Recently, a novel therapeutic approach was proposed based on targeting senescent cells using senolytics. This group of biologically active compounds includes fisetin, quercetin, dasatinib, and others. These compounds were shown to affect laboratory animals (rodents) by improving the quality of life and significantly increasing the length of life by reducing senescent cells pool in different organs. Based on these findings, we decided to evaluate the potential of these compounds in targeting senescent cells in human skin using in vitro model based on human-derived keratinocytes (HEKa) and fibroblasts (HDFa). Cytotoxicity assay revealed that the activity of the compounds was time- and dose-dependent as well as cell-type dependent. Further studies were performed to reveal the mechanistic aspect of these observations including assessment of the senescence marker, namely p16. However, it requires clarification before entering clinical trials to provide not only efficient but, first of all, safe application of senolytics to human skin.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"118 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199519","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}
Much of the priorities in drug delivery research are focused on targeted drug delivery for cancer therapies and a wide range of controlled drug release systems for commonly used active pharmaceutical ingredients (APIs). In this “thousand words article” we highlight some of the emerging health threats and future opportunities for drug delivery research. Important emerging health threats include viral pandemics beyond COVID, antibiotic-resistant pathogens, the need for new antifungal therapies, and emerging diseases caused by increasing pollution and climate change. Fundamentally new drugs may be needed. For example, one little known research effort focuses on the development of new antibiotics based on metal-organic frameworks. Finally, new delivery approaches will be needed. This is illustrated by the development of a topical peptide delivery system as a wound dressing for burn patients, combining biotechnology (a new peptide) with polymer science (a new topical delivery system) to address a medical need (burn injury) for which there is currently no effective treatment. Another important trend is the shift in our collective understanding of impact, moving away from “counting papers” to considering the societal benefit of the research including its potential for commercialization. To remain relevant in the coming decade, we need to anticipate and embrace future challenges. This is particularly important for younger scientists.
{"title":"Future Opportunities in the Field of Drug Delivery Research","authors":"Joachim Kohn, Bozena Michniak-Kohn","doi":"10.20883/medical.e925","DOIUrl":"https://doi.org/10.20883/medical.e925","url":null,"abstract":"Much of the priorities in drug delivery research are focused on targeted drug delivery for cancer therapies and a wide range of controlled drug release systems for commonly used active pharmaceutical ingredients (APIs). In this “thousand words article” we highlight some of the emerging health threats and future opportunities for drug delivery research. Important emerging health threats include viral pandemics beyond COVID, antibiotic-resistant pathogens, the need for new antifungal therapies, and emerging diseases caused by increasing pollution and climate change. Fundamentally new drugs may be needed. For example, one little known research effort focuses on the development of new antibiotics based on metal-organic frameworks. Finally, new delivery approaches will be needed. This is illustrated by the development of a topical peptide delivery system as a wound dressing for burn patients, combining biotechnology (a new peptide) with polymer science (a new topical delivery system) to address a medical need (burn injury) for which there is currently no effective treatment. Another important trend is the shift in our collective understanding of impact, moving away from “counting papers” to considering the societal benefit of the research including its potential for commercialization. To remain relevant in the coming decade, we need to anticipate and embrace future challenges. This is particularly important for younger scientists.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"64 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135246194","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}
Aging is a natural process leading to decline in physical function, reducing ability to adjust to everyday organismal stress and increased frailty. Recent studies of the mechanism of aging have brought attention to naturally occurring senescent cells in different organs throughout the body. This natural process of senescence is caused by cell cycle arrest due to cellular damage, which protects cells from apoptosis, while stimulating the production and secretion of different senescent associated secretory phenotypes (SASPs) causing low grade chronic inflammation. Emerging studies show that by targeting and eliminating these cells with a new class of senolytic drugs in old animals we can improve a variety of health conditions including reduction of inflammation, improvement of insulin sensitivity and metabolic status, increase of bone mineral density and enhanced physical function together with extended overall longevity. Ongoing clinical trials using Desatanib and Quarcetin (D+Q) and other classes of senolytic drugs indicate high translational potentials in targeting and clearing senescent cells to cure some age-related diseases; however, more in depth studies have to be completed to incorporate these therapies in general healthy elderly populations for safe anti-aging intervention.
{"title":"Senescent cells as new pharmacological targets for age-related diseases and anti-aging therapy","authors":"Michal Masternak","doi":"10.20883/medical.e907","DOIUrl":"https://doi.org/10.20883/medical.e907","url":null,"abstract":"Aging is a natural process leading to decline in physical function, reducing ability to adjust to everyday organismal stress and increased frailty. Recent studies of the mechanism of aging have brought attention to naturally occurring senescent cells in different organs throughout the body. This natural process of senescence is caused by cell cycle arrest due to cellular damage, which protects cells from apoptosis, while stimulating the production and secretion of different senescent associated secretory phenotypes (SASPs) causing low grade chronic inflammation. Emerging studies show that by targeting and eliminating these cells with a new class of senolytic drugs in old animals we can improve a variety of health conditions including reduction of inflammation, improvement of insulin sensitivity and metabolic status, increase of bone mineral density and enhanced physical function together with extended overall longevity. Ongoing clinical trials using Desatanib and Quarcetin (D+Q) and other classes of senolytic drugs indicate high translational potentials in targeting and clearing senescent cells to cure some age-related diseases; however, more in depth studies have to be completed to incorporate these therapies in general healthy elderly populations for safe anti-aging intervention.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199025","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}
Background. The skin’s uppermost layer, the stratum corneum is a very effective barrier against the penetration of compounds including pharmaceuticals and cosmetic actives. To deliver higher amounts of drugs into the skin layers or to deliver drugs deeper into the skin (e.g., into the dermis), several enhancement techniques have been established. These techniques include chemical penetration enhancers as well as physical techniques such as iontophoresis and microneedles. In addition, one of the newer approaches includes the use of nano-based carriers such as metallic nanoparticles and polymeric self-assembling nanospheres. Methods. This mini-review explores this new approach of using nano-based drug carriers for skin penetration enhancement. In particular we will explore the use of gold nanoparticles as well as biocompatible tyrosine-derived polymeric nanoparticles known as Tyrospheres. Results. The most investigated carriers in the class of metallic carriers are gold nanoparticles that can be used for both medical as well as diagnostic uses. Many investigators have reported that gold nanoparticles are able to enhance the skin transport and delivery of macromolecular and hydrophilic drugs. Meanwhile, for challenging highly lipophilic and/or unstable compounds such as adapalene and Vitamin D3 packaging them into polymeric nanocarriers such as Tyrospheres enables drug delivery to hair follicles, significantly increased aqueous solubility and resulted in elevated amounts of drug in targeted skin layers. Conclusions. The relatively new approach of using nanotechnological approaches as a way of enhancement of drug delivery to skin shows significant promise over some other established techniques such as the addition of chemical penetration enhancers to formulations used for topical/transdermal uses.
{"title":"Overcoming the barrier of skin to drug permeation for localized dermatological therapies","authors":"Bozena Michniak-Kohn, Joachim Kohn","doi":"10.20883/medical.e926","DOIUrl":"https://doi.org/10.20883/medical.e926","url":null,"abstract":"Background. The skin’s uppermost layer, the stratum corneum is a very effective barrier against the penetration of compounds including pharmaceuticals and cosmetic actives. To deliver higher amounts of drugs into the skin layers or to deliver drugs deeper into the skin (e.g., into the dermis), several enhancement techniques have been established. These techniques include chemical penetration enhancers as well as physical techniques such as iontophoresis and microneedles. In addition, one of the newer approaches includes the use of nano-based carriers such as metallic nanoparticles and polymeric self-assembling nanospheres. Methods. This mini-review explores this new approach of using nano-based drug carriers for skin penetration enhancement. In particular we will explore the use of gold nanoparticles as well as biocompatible tyrosine-derived polymeric nanoparticles known as Tyrospheres. Results. The most investigated carriers in the class of metallic carriers are gold nanoparticles that can be used for both medical as well as diagnostic uses. Many investigators have reported that gold nanoparticles are able to enhance the skin transport and delivery of macromolecular and hydrophilic drugs. Meanwhile, for challenging highly lipophilic and/or unstable compounds such as adapalene and Vitamin D3 packaging them into polymeric nanocarriers such as Tyrospheres enables drug delivery to hair follicles, significantly increased aqueous solubility and resulted in elevated amounts of drug in targeted skin layers. Conclusions. The relatively new approach of using nanotechnological approaches as a way of enhancement of drug delivery to skin shows significant promise over some other established techniques such as the addition of chemical penetration enhancers to formulations used for topical/transdermal uses.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"132 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135245787","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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