Aim: Present study was done to understand the dimerization of HER2/ERBB2 in normal and cancer cells using in-silico study. Methods: Pathway analysis was done using Reactome. Structure of HER2/ERBB2 protein was obtained from PDB database, and using Schrödinger software protein structure was analysed and dimerization was done. Results: In normal cells, HER2/ERBB2 is present at low levels and forms a stable complex with HSP90 (heat shock protein 90), CDC37 (cell division cycle 37), and ERBIN (an adaptor protein of the HER2/ERBB2 receptor). HER2/ERBB2 lacks a ligand-binding site, so it cannot bind ligands to activate HER2/ERBB2 signaling directly. Instead, it heterodimerizes with other EGFR family members, using their ligand-binding sites to activate cell proliferation signaling cascades. In cancer, overexpression of HER2/ERBB2 leads to ligand-independent activation of signaling through dimerization. During this process, HER2/ERBB2 dissociates from the HSP90 complex. Normally, HSP90 helps to correct misfolded and aggregated proteins, but it fails to correct mutated HER2/ERBB2 in cancer cells. Conclusions: This discussion focuses on the structural changes that HER2/ERBB2 undergoes, particularly in the form of homodimers, under normal and cancerous conditions. This analysis highlights the mutated state of HER2/ERBB2 and the role of HSP90 in this context. Notably, a single-point mutation outside a protein’s active site can significantly alter its structure. This is a critical consideration in drug discovery, underscoring the need to evaluate the entire protein conformation during simulations.
{"title":"Structural biology of HER2/ERBB2 dimerization: mechanistic insights and differential roles in healthy versus cancerous cells","authors":"Jayasree Santhanakrishnan, Prabhu Meganathan, Hemamalini Vedagiri","doi":"10.37349/emed.2024.00237","DOIUrl":"https://doi.org/10.37349/emed.2024.00237","url":null,"abstract":"Aim: Present study was done to understand the dimerization of HER2/ERBB2 in normal and cancer cells using in-silico study. Methods: Pathway analysis was done using Reactome. Structure of HER2/ERBB2 protein was obtained from PDB database, and using Schrödinger software protein structure was analysed and dimerization was done. Results: In normal cells, HER2/ERBB2 is present at low levels and forms a stable complex with HSP90 (heat shock protein 90), CDC37 (cell division cycle 37), and ERBIN (an adaptor protein of the HER2/ERBB2 receptor). HER2/ERBB2 lacks a ligand-binding site, so it cannot bind ligands to activate HER2/ERBB2 signaling directly. Instead, it heterodimerizes with other EGFR family members, using their ligand-binding sites to activate cell proliferation signaling cascades. In cancer, overexpression of HER2/ERBB2 leads to ligand-independent activation of signaling through dimerization. During this process, HER2/ERBB2 dissociates from the HSP90 complex. Normally, HSP90 helps to correct misfolded and aggregated proteins, but it fails to correct mutated HER2/ERBB2 in cancer cells. Conclusions: This discussion focuses on the structural changes that HER2/ERBB2 undergoes, particularly in the form of homodimers, under normal and cancerous conditions. This analysis highlights the mutated state of HER2/ERBB2 and the role of HSP90 in this context. Notably, a single-point mutation outside a protein’s active site can significantly alter its structure. This is a critical consideration in drug discovery, underscoring the need to evaluate the entire protein conformation during simulations.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141830056","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 : 2024-07-14DOI: 10.37349/emed.2024.00236
Priyanka S. Waghmare, A. Chabukswar, Kunal G. Raut, Bhagyashree Gaikwad-Pawar, S. Jagdale
The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery.
{"title":"Nanoparticle-based targeted therapy through EGFR tyrosine kinase inhibitors and their recent advances in lung cancer therapy","authors":"Priyanka S. Waghmare, A. Chabukswar, Kunal G. Raut, Bhagyashree Gaikwad-Pawar, S. Jagdale","doi":"10.37349/emed.2024.00236","DOIUrl":"https://doi.org/10.37349/emed.2024.00236","url":null,"abstract":"The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"46 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141650100","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 : 2024-07-10DOI: 10.37349/emed.2024.00234
Domenico Baldi, Jason Motta Jones, Enrico Lertora, Chiara Burgio, A. Lugas, G. Schierano, J. Colombo
{"title":"Correction: Influence of dental implant site preparation method on three aspects of the site: magnetodynamic mallet versus conventional drill","authors":"Domenico Baldi, Jason Motta Jones, Enrico Lertora, Chiara Burgio, A. Lugas, G. Schierano, J. Colombo","doi":"10.37349/emed.2024.00234","DOIUrl":"https://doi.org/10.37349/emed.2024.00234","url":null,"abstract":"","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"70 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141662723","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 : 2024-07-10DOI: 10.37349/emed.2024.00235
O. Hørsdal
{"title":"Exploring the cardiovascular effects of hypertonic lactate: a systematic review of animal studies","authors":"O. Hørsdal","doi":"10.37349/emed.2024.00235","DOIUrl":"https://doi.org/10.37349/emed.2024.00235","url":null,"abstract":"","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"24 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141662172","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 : 2024-07-05DOI: 10.37349/emed.2024.00233
F. Gorassini, L. Fiorillo, M. M. Marrapodi, C. D’amico, Michela Basile, Marco Cicciù, G. Cervino
Background: This systematic review aims to critically assess the literature on the debonding process of orthodontic brackets from enamel surfaces. The review evaluates Randomized Controlled Trials (RCTs) to determine the effectiveness and implications of various debonding techniques and materials. Methods: The study followed PRISMA guidelines, selecting RCTs published from 1999 onwards that compared the outcomes of various orthodontic bracket debonding techniques. Selection criteria included studies utilizing human teeth, with outcomes such as enamel surface roughness and Adhesive Remnant Index (ARI) analyzed. Data sources included PubMed, Scopus, Web of Science, and the Cochrane Library. Results: Out of 1,587 records identified, five studies met the inclusion criteria. These studies provided comparative data on the effectiveness of various debonding techniques, including tungsten carbide and diamond burs, in minimizing enamel damage and optimizing adhesive removal. Findings indicated that tungsten carbide burs produced the least enamel roughness. Discussion: Utilizing tungsten carbide burs for debonding orthodontic brackets significantly minimizes enamel surface roughness and potential damage, thereby enhancing the preservation of enamel integrity post-treatment. The systematic review highlights current debonding techniques are effective in adhesive removal, and the choice of instrument significantly affects enamel integrity and clinical outcomes. The findings support the need for continuous improvement and innovation in removing braces to improve orthodontic treatment results and patient satisfaction.
{"title":"Debonding issues in orthodontics: an RCTs systematic review","authors":"F. Gorassini, L. Fiorillo, M. M. Marrapodi, C. D’amico, Michela Basile, Marco Cicciù, G. Cervino","doi":"10.37349/emed.2024.00233","DOIUrl":"https://doi.org/10.37349/emed.2024.00233","url":null,"abstract":"Background: This systematic review aims to critically assess the literature on the debonding process of orthodontic brackets from enamel surfaces. The review evaluates Randomized Controlled Trials (RCTs) to determine the effectiveness and implications of various debonding techniques and materials. Methods: The study followed PRISMA guidelines, selecting RCTs published from 1999 onwards that compared the outcomes of various orthodontic bracket debonding techniques. Selection criteria included studies utilizing human teeth, with outcomes such as enamel surface roughness and Adhesive Remnant Index (ARI) analyzed. Data sources included PubMed, Scopus, Web of Science, and the Cochrane Library. Results: Out of 1,587 records identified, five studies met the inclusion criteria. These studies provided comparative data on the effectiveness of various debonding techniques, including tungsten carbide and diamond burs, in minimizing enamel damage and optimizing adhesive removal. Findings indicated that tungsten carbide burs produced the least enamel roughness. Discussion: Utilizing tungsten carbide burs for debonding orthodontic brackets significantly minimizes enamel surface roughness and potential damage, thereby enhancing the preservation of enamel integrity post-treatment. The systematic review highlights current debonding techniques are effective in adhesive removal, and the choice of instrument significantly affects enamel integrity and clinical outcomes. The findings support the need for continuous improvement and innovation in removing braces to improve orthodontic treatment results and patient satisfaction.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141674027","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 : 2024-07-05DOI: 10.37349/emed.2024.00232
Domenico Baldi, Jason Motta James, Enrico Lertora, Chiara Burgio, A. Lugas, G. Schierano, J. Colombo
Aim: Magnetodynamic surgery has assumed increasing importance in recent years. The purpose of the present study was to compare in vitro, using dry porcine ribs, two methods of dental implant site preparation (conventional drill and magnetic mallet) on three aspects of the site. These were the difference between the diameter of the site and the diameter of the last drill used (an index of the accuracy of the preparation), the weight loss of the specimen on which the site was prepared (index of the bone loss in the site), and the change of temperature at the site (an index of the change to the material at the site). Methods: Eight preformed pork ribs were chosen for the study. Four implant preparations were made on each rib, two with Magnetic Mallet (Meta Ergonomica, Turbigo, Italy) and two with traditional drills. Each bone sample was weighed before and after implant site preparation in order to calculate the amount of bone lost during preparation. The diameter of preparations was analyzed with the aid of an optical microscope (MZ6, Leica, Wetzlar, Germany) connected to a dedicated measurement software. For the evaluation of the temperature, eight preparation sites were marked. In correspondence of each preparation site, on the opposite side of the rib, a hole was made for the thermocouple (HI 91530K, Hanna Instruments, Padova, Italy). During the preparations, the thermocouple was kept inserted inside the control hole to record the temperature variation. The results were analyzed using appropriate statistical methods, such as the Kolmogorov-Smirnoff test and the Wilcoxon test. Results: It was found that mallet drill provided significantly higher accuracy of preparation, lower amount of damage at the site, and less change to the porcine rib test material at the preparation site. Conclusions: A possible clinical implication of this finding is discussed.
{"title":"Influence of dental implant site preparation method on three aspects of the site: magnetodynamic mallet versus conventional drill","authors":"Domenico Baldi, Jason Motta James, Enrico Lertora, Chiara Burgio, A. Lugas, G. Schierano, J. Colombo","doi":"10.37349/emed.2024.00232","DOIUrl":"https://doi.org/10.37349/emed.2024.00232","url":null,"abstract":"Aim: Magnetodynamic surgery has assumed increasing importance in recent years. The purpose of the present study was to compare in vitro, using dry porcine ribs, two methods of dental implant site preparation (conventional drill and magnetic mallet) on three aspects of the site. These were the difference between the diameter of the site and the diameter of the last drill used (an index of the accuracy of the preparation), the weight loss of the specimen on which the site was prepared (index of the bone loss in the site), and the change of temperature at the site (an index of the change to the material at the site). Methods: Eight preformed pork ribs were chosen for the study. Four implant preparations were made on each rib, two with Magnetic Mallet (Meta Ergonomica, Turbigo, Italy) and two with traditional drills. Each bone sample was weighed before and after implant site preparation in order to calculate the amount of bone lost during preparation. The diameter of preparations was analyzed with the aid of an optical microscope (MZ6, Leica, Wetzlar, Germany) connected to a dedicated measurement software. For the evaluation of the temperature, eight preparation sites were marked. In correspondence of each preparation site, on the opposite side of the rib, a hole was made for the thermocouple (HI 91530K, Hanna Instruments, Padova, Italy). During the preparations, the thermocouple was kept inserted inside the control hole to record the temperature variation. The results were analyzed using appropriate statistical methods, such as the Kolmogorov-Smirnoff test and the Wilcoxon test. Results: It was found that mallet drill provided significantly higher accuracy of preparation, lower amount of damage at the site, and less change to the porcine rib test material at the preparation site. Conclusions: A possible clinical implication of this finding is discussed.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":" 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141676058","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 : 2024-06-06DOI: 10.37349/emed.2024.00227
C. Calia, Mario A. Parra
Aim: The present study investigated whether commonly used screening tools and assessments for dementia were culturally appropriate for older adults from ethnic minorities (EM) groups living in the UK. Methods: Both South Asian and British participants (N = 43) were assessed using the Cross-Linguistic Naming Test, Mini Addenbrooke’s Cognitive Examination, Visual Short-Term Memory Binding Test (VSTMBT), and the Rowland Universal Dementia Assessment Scale. Multi-Ethnic Acculturation Scale and English proficiency, measured with a self-rated scale, were associated with the four respective. No interpreters were used. Results: While members from EM significantly differed from members of the ethnic majority group in traditional neuropsychological tasks, their performance on the VSTMBT yielded results comparable to those drawn from the ethnic majority group. Complex influences seem to drive the sensitivity of traditional neuropsychological tasks to sociocultural factors. Conclusions: This is the first study that subjects the VSTMBT to investigation in EM groups. Older adults from EM showed no impact of their sociocultural backgrounds on the function assessed by this test. However, other tests widely used for the assessment of EM populations proved sensitive to the investigated sociocultural factors. Our results lend support to the suggestion that neuropsychological assessments must abandon the one-size-fits-all notion when it comes to dementia risk detection among EM groups.
{"title":"Screening tools for dementia assessment in UK based ethnic minorities","authors":"C. Calia, Mario A. Parra","doi":"10.37349/emed.2024.00227","DOIUrl":"https://doi.org/10.37349/emed.2024.00227","url":null,"abstract":"Aim: The present study investigated whether commonly used screening tools and assessments for dementia were culturally appropriate for older adults from ethnic minorities (EM) groups living in the UK. Methods: Both South Asian and British participants (N = 43) were assessed using the Cross-Linguistic Naming Test, Mini Addenbrooke’s Cognitive Examination, Visual Short-Term Memory Binding Test (VSTMBT), and the Rowland Universal Dementia Assessment Scale. Multi-Ethnic Acculturation Scale and English proficiency, measured with a self-rated scale, were associated with the four respective. No interpreters were used. Results: While members from EM significantly differed from members of the ethnic majority group in traditional neuropsychological tasks, their performance on the VSTMBT yielded results comparable to those drawn from the ethnic majority group. Complex influences seem to drive the sensitivity of traditional neuropsychological tasks to sociocultural factors. Conclusions: This is the first study that subjects the VSTMBT to investigation in EM groups. Older adults from EM showed no impact of their sociocultural backgrounds on the function assessed by this test. However, other tests widely used for the assessment of EM populations proved sensitive to the investigated sociocultural factors. Our results lend support to the suggestion that neuropsychological assessments must abandon the one-size-fits-all notion when it comes to dementia risk detection among EM groups.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"100 S397","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141377139","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 : 2024-05-16DOI: 10.37349/emed.2024.00224
I. Chikileva, Polina Fedorova, I. Shubina, Stanislav Pshenichnikov, Kateryna Levada, Vyacheslav Abramov, M. Kiselevskiy
Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.
{"title":"Can magnetic nanoparticles enhance adoptive cell therapy via driving migration of lymphocytes into tumors?","authors":"I. Chikileva, Polina Fedorova, I. Shubina, Stanislav Pshenichnikov, Kateryna Levada, Vyacheslav Abramov, M. Kiselevskiy","doi":"10.37349/emed.2024.00224","DOIUrl":"https://doi.org/10.37349/emed.2024.00224","url":null,"abstract":"Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"19 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967431","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 : 2024-05-10DOI: 10.37349/emed.2024.00223
F. Tayeb
During cellular stress, the master regulators of intrinsic self-death (apoptosis) are BCL-2 family proteins. The BCL-2 family proteins play a key role in apoptosis and are tightly regulated via other BCL-2 family proteins, non-BCL-2 protein suppressors, and epigenetic modifications. As the name implies, these proteins possess one or two of the four BCL-2 homology domains (BH1–BH4). According to their roles, they are classified as pro-apoptotic or pro-survival proteins. BH-3-only proteins possess a single BH3 domain and are specific/key effector proteins for intracellular death commitment, particularly in the context of cell survival and programmed cell death. This delicate interplay among the BCL-2 family members is essential for maintaining the primary hemostasis, or balance, of cell fate. The anti-apoptotic proteins, such as BCL-2 and BCL-XL, promote cell survival by inhibiting apoptosis. On the other hand, the pro-apoptotic proteins, such as BAX and BAK, drive apoptosis. It ensures that cells are able to respond appropriately to various internal and external signals, ultimately determining whether a cell survives or undergoes programmed cell death. Understanding and targeting this delicate balance is a promising avenue for developing therapeutic strategies to modulate cell fate and treat various diseases. The molecular pathogenesis of BCL-2 family proteins in blood disorders involves differential expression of these components resulting in the dysregulation of the pathway contributing to cell survival and resistance to apoptosis as observed in follicular lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Such dysregulation is a major impediment to standard therapies and aids in chemo resistance. Studies show some promising clinical outcomes with antineoplastic agent venetoclax either as a monotherapy or in combination with other agents. This review discusses recent studies on the regulation of BCL-2 family proteins which might provide a molecular landscape for their clinical implications in blood disorders.
{"title":"Dysregulation of BCL-2 family proteins in blood neoplasm: therapeutic relevance of antineoplastic agent venetoclax","authors":"F. Tayeb","doi":"10.37349/emed.2024.00223","DOIUrl":"https://doi.org/10.37349/emed.2024.00223","url":null,"abstract":"During cellular stress, the master regulators of intrinsic self-death (apoptosis) are BCL-2 family proteins. The BCL-2 family proteins play a key role in apoptosis and are tightly regulated via other BCL-2 family proteins, non-BCL-2 protein suppressors, and epigenetic modifications. As the name implies, these proteins possess one or two of the four BCL-2 homology domains (BH1–BH4). According to their roles, they are classified as pro-apoptotic or pro-survival proteins. BH-3-only proteins possess a single BH3 domain and are specific/key effector proteins for intracellular death commitment, particularly in the context of cell survival and programmed cell death. This delicate interplay among the BCL-2 family members is essential for maintaining the primary hemostasis, or balance, of cell fate. The anti-apoptotic proteins, such as BCL-2 and BCL-XL, promote cell survival by inhibiting apoptosis. On the other hand, the pro-apoptotic proteins, such as BAX and BAK, drive apoptosis. It ensures that cells are able to respond appropriately to various internal and external signals, ultimately determining whether a cell survives or undergoes programmed cell death. Understanding and targeting this delicate balance is a promising avenue for developing therapeutic strategies to modulate cell fate and treat various diseases. The molecular pathogenesis of BCL-2 family proteins in blood disorders involves differential expression of these components resulting in the dysregulation of the pathway contributing to cell survival and resistance to apoptosis as observed in follicular lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Such dysregulation is a major impediment to standard therapies and aids in chemo resistance. Studies show some promising clinical outcomes with antineoplastic agent venetoclax either as a monotherapy or in combination with other agents. This review discusses recent studies on the regulation of BCL-2 family proteins which might provide a molecular landscape for their clinical implications in blood disorders.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":" 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140993594","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 : 2024-05-06DOI: 10.37349/emed.2024.00222
Mohd Javed Naim
Mushrooms, due to their many medical, preventive, and nutraceutical purposes, as well as their reputation as a folk remedy, have long been an integral part of traditional cuisines. The therapeutic advantages of mushrooms may be attributed to their bioactive components, including polysaccharides (both low and high molecular weight), terpenoids, phenolic compounds, fatty acids, lectins, and glucans. The bioactive components have been discovered to possess various health advantages, including antibacterial, antifungal, anticancer, radical scavenging, cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects. These effects have gained worldwide attention and stimulated interest in further investigating their potential applications. Functional foods have the dual purpose of serving as both nourishment and medication. They may assist in the management and prevention of health disorders that are not functioning optimally, as well as mitigate some adverse effects of life-threatening diseases. Further evaluation is necessary to fully understand the mechanisms via which mushrooms operate and improve their therapeutic properties. This review delves into the possible medicinal potential of mushrooms and the advantages they may provide to human health.
{"title":"A review on mushrooms as a versatile therapeutic agent with emphasis on its bioactive constituents for anticancer and antioxidant potential","authors":"Mohd Javed Naim","doi":"10.37349/emed.2024.00222","DOIUrl":"https://doi.org/10.37349/emed.2024.00222","url":null,"abstract":"Mushrooms, due to their many medical, preventive, and nutraceutical purposes, as well as their reputation as a folk remedy, have long been an integral part of traditional cuisines. The therapeutic advantages of mushrooms may be attributed to their bioactive components, including polysaccharides (both low and high molecular weight), terpenoids, phenolic compounds, fatty acids, lectins, and glucans. The bioactive components have been discovered to possess various health advantages, including antibacterial, antifungal, anticancer, radical scavenging, cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects. These effects have gained worldwide attention and stimulated interest in further investigating their potential applications. Functional foods have the dual purpose of serving as both nourishment and medication. They may assist in the management and prevention of health disorders that are not functioning optimally, as well as mitigate some adverse effects of life-threatening diseases. Further evaluation is necessary to fully understand the mechanisms via which mushrooms operate and improve their therapeutic properties. This review delves into the possible medicinal potential of mushrooms and the advantages they may provide to human health.","PeriodicalId":507580,"journal":{"name":"Exploration of Medicine","volume":"57 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141008869","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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