Pub Date : 2024-02-14DOI: 10.3390/biophysica4010006
A. Barbasz, Barbara Dyba
Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.
{"title":"Direct Interaction of Zirconia Nanoparticles with Human Immune Cells","authors":"A. Barbasz, Barbara Dyba","doi":"10.3390/biophysica4010006","DOIUrl":"https://doi.org/10.3390/biophysica4010006","url":null,"abstract":"Nanomaterials play a crucial role in various aspects of modern life. Zirconia nanoparticles, extensively employed in medicine for fortifying and stabilizing implants in reconstructive medicine, exhibit unique electrical, thermal, catalytic, sensory, optical, and mechanical properties. While these nanoparticles have shown antibacterial activity, they also exhibit cytotoxic effects on human cells. Our research focuses on understanding how the cells of the human immune system (both the innate response, namely HL-60 and U-937, and the acquired response, namely HUT-78 and COLO-720L) respond to the presence of zirconium (IV) oxide nanoparticles (ZrO2-NPs). Viability tests indicate that ZrO2-NPs exert the highest cytotoxicity on HL-60 > U-937 > HUT-78 > COLO 720L cell lines. Notably, concentrations exceeding 100 μg mL−1 of ZrO2-NPs result in significant cytotoxicity. These nanoparticles readily penetrate the cell membrane, causing mitochondrial damage, and their cytotoxicity is associated with heightened oxidative stress in cells. The use of ZrO2-NP-based materials may pose a risk to immune system cells, the first responders to foreign entities in the body. Biofunctionalizing the surface of ZrO2-NPs could serve as an effective strategy to mitigate cytotoxicity and introduce new properties for biomedical applications.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139776993","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 : 2024-02-07DOI: 10.3390/biophysica4010005
Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta
Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.
{"title":"Neurite Growth and Electrical Activity in PC-12 Cells: Effects of H3 Receptor-Inspired Electromagnetic Fields and Inherent Schumann Frequencies","authors":"Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta","doi":"10.3390/biophysica4010005","DOIUrl":"https://doi.org/10.3390/biophysica4010005","url":null,"abstract":"Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139796671","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 : 2024-02-07DOI: 10.3390/biophysica4010005
Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta
Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.
{"title":"Neurite Growth and Electrical Activity in PC-12 Cells: Effects of H3 Receptor-Inspired Electromagnetic Fields and Inherent Schumann Frequencies","authors":"Landon M. Lefebvre, Adam D. Plourde-Kelly, K. Saroka, B. Dotta","doi":"10.3390/biophysica4010005","DOIUrl":"https://doi.org/10.3390/biophysica4010005","url":null,"abstract":"Cells are continually exposed to a range of electromagnetic fields (EMFs), including those from the Schumann resonance to radio waves. The effects of EMFs on cells are diverse and vary based on the specific EMF type. Recent research suggests potential therapeutic applications of EMFs for various diseases. In this study, we explored the impact of a physiologically patterned EMF, inspired by the H3 receptor associated with wakefulness, on PC-12 cells in vitro. Our hypothesis posited that the application of this EMF to differentiated PC-12 cells could enhance firing patterns at specific frequencies. Cell electrophysiology was assessed using a novel device, allowing the computation of spectral power density (SPD) scores for frequencies between 1 Hz and 128 Hz. T-tests comparing SPD at certain frequencies (e.g., 29 Hz, 30 Hz, and 79 Hz) between the H3-EMF and control groups showed a significantly higher SPD in the H3 group (p < 0.050). Moreover, at 7.8 Hz and 71 Hz, a significant correlation was observed between predicted and percentages of cells with neurites (R = 0.542). Key findings indicate the efficacy of the new electrophysiology measure for assessing PC-12 cell activity, a significant increase in cellular activity with the H3-receptor-inspired EMF at specific frequencies, and the influence of 7.8 Hz and 71 Hz frequencies on neurite growth. The overall findings support the idea that the electrical frequency profiles of developing cell systems can serve as an indicator of their progression and eventual cellular outcomes.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139856563","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 : 2024-01-31DOI: 10.3390/biophysica4010004
Eliza Marie Steele, Zacheus L. Carr, E. Dosmar
Globally, thousands of people are affected by severe nerve injuries or neurodegenerative disorders. These conditions cannot always be cured because nerve tissue either does not regenerate or does so at a slow rate. Therefore, tissue engineering has emerged as a potential treatment approach. This review discusses 3D bioprinting for scaffold manufacturing, highlights the advantages and disadvantages of common bioprinting techniques, describes important considerations for bioinks, biomaterial inks, and scaffolds, and discusses some drug delivery systems. The primary goal of this review is to bring attention to recent advances in nerve tissue engineering and its possible clinical applications in peripheral nerve, spinal cord, and cerebral nerve regeneration. Only studies that use 3D bioprinting or 3D printing to manufacture hydrogel scaffolds and incorporate the sustained release of a drug or growth factor for nerve regeneration are included. This review indicates that 3D printing is a fast and precise scaffold manufacturing technique but requires printing materials with specific properties to be effective in nervous tissue applications. The results indicate that the sustained release of certain drugs and growth factors from scaffolds can significantly improve post-printing cell viability, cell proliferation, adhesion, and differentiation, as well as functional recovery compared with scaffolds alone. However, more in vivo research needs to be conducted before this approach can be used in clinical applications.
{"title":"Bioprinting of Hydrogel-Based Drug Delivery Systems for Nerve Tissue Regeneration","authors":"Eliza Marie Steele, Zacheus L. Carr, E. Dosmar","doi":"10.3390/biophysica4010004","DOIUrl":"https://doi.org/10.3390/biophysica4010004","url":null,"abstract":"Globally, thousands of people are affected by severe nerve injuries or neurodegenerative disorders. These conditions cannot always be cured because nerve tissue either does not regenerate or does so at a slow rate. Therefore, tissue engineering has emerged as a potential treatment approach. This review discusses 3D bioprinting for scaffold manufacturing, highlights the advantages and disadvantages of common bioprinting techniques, describes important considerations for bioinks, biomaterial inks, and scaffolds, and discusses some drug delivery systems. The primary goal of this review is to bring attention to recent advances in nerve tissue engineering and its possible clinical applications in peripheral nerve, spinal cord, and cerebral nerve regeneration. Only studies that use 3D bioprinting or 3D printing to manufacture hydrogel scaffolds and incorporate the sustained release of a drug or growth factor for nerve regeneration are included. This review indicates that 3D printing is a fast and precise scaffold manufacturing technique but requires printing materials with specific properties to be effective in nervous tissue applications. The results indicate that the sustained release of certain drugs and growth factors from scaffolds can significantly improve post-printing cell viability, cell proliferation, adhesion, and differentiation, as well as functional recovery compared with scaffolds alone. However, more in vivo research needs to be conducted before this approach can be used in clinical applications.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140475399","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 : 2024-01-23DOI: 10.3390/biophysica4010003
A. Drozd-Rzoska, S. Rzoska, J. Łoś
The long-range supercritical changes of dielectric constant, resembling ones observed in the isotropic liquid phase of liquid crystalline compounds, are evidenced for linseed oil—although in the given case, the phenomenon is associated with the liquid–solid melting/freezing discontinuous phase transitions. This ‘supercriticality’ can be an additional factor supporting the unique pro-health properties of linseed oil. Broadband dielectric spectroscopy studies also revealed the ‘glassy’ changes of relaxation times, well portrayed by the ‘activated and critical’ equation recently introduced. In the solid phase, the premelting effect characteristic for the canonic melting/freezing discontinuous transition, i.e., without any pretransitional effect in the liquid phase, has been detected. It is interpreted within the grain model, and its parameterization is possible using the Lipovsky model and the ‘reversed’ Mossotti catastrophe concept. For the premelting effect in the solid state, the singular ‘critical’ temperature correlates with the bulk discontinuous melting and freezing temperatures. Consequently, the report shows that linseed oil, despite its ‘natural and complex’ origins, can be considered a unique model system for two fundamental problems: (i) pretransitional (supercritical) effects in the liquid state associated with a weakly discontinuous phase transition, and (ii) the premelting behavior in the solid side of the discontinuous melting/freezing discontinuous transition.
{"title":"Supercriticality, Glassy Dynamics, and the New Insight into Melting/Freezing Discontinuous Transition in Linseed Oil","authors":"A. Drozd-Rzoska, S. Rzoska, J. Łoś","doi":"10.3390/biophysica4010003","DOIUrl":"https://doi.org/10.3390/biophysica4010003","url":null,"abstract":"The long-range supercritical changes of dielectric constant, resembling ones observed in the isotropic liquid phase of liquid crystalline compounds, are evidenced for linseed oil—although in the given case, the phenomenon is associated with the liquid–solid melting/freezing discontinuous phase transitions. This ‘supercriticality’ can be an additional factor supporting the unique pro-health properties of linseed oil. Broadband dielectric spectroscopy studies also revealed the ‘glassy’ changes of relaxation times, well portrayed by the ‘activated and critical’ equation recently introduced. In the solid phase, the premelting effect characteristic for the canonic melting/freezing discontinuous transition, i.e., without any pretransitional effect in the liquid phase, has been detected. It is interpreted within the grain model, and its parameterization is possible using the Lipovsky model and the ‘reversed’ Mossotti catastrophe concept. For the premelting effect in the solid state, the singular ‘critical’ temperature correlates with the bulk discontinuous melting and freezing temperatures. Consequently, the report shows that linseed oil, despite its ‘natural and complex’ origins, can be considered a unique model system for two fundamental problems: (i) pretransitional (supercritical) effects in the liquid state associated with a weakly discontinuous phase transition, and (ii) the premelting behavior in the solid side of the discontinuous melting/freezing discontinuous transition.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139605751","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 : 2024-01-12DOI: 10.3390/biophysica4010002
Thais P. Pivetta, Paulo A. Ribeiro, M. Raposo
As a vital biomolecule, DNA is known as a target of antineoplastic drugs for cancer therapy. These drugs can show different modes of interaction with DNA, with intercalation and groove binding being the most common types. The intercalation of anticancer drugs with DNA can lead to the disruption of its normal function, influencing cell proliferation. Methylene blue (MB) and acridine orange (AO) are examples of DNA-intercalating agents that have been studied for their application against some types of cancer, mainly for photodynamic therapy. In this work, the impact of light irradiation on these compounds in the absence and presence of DNA was analyzed by means of UV-vis spectroscopy. Bathochromic and hypochromic shifts were observed in the absorbance spectra, revealing the intercalation of the dyes with the DNA base pairs. Dyes with and without DNA present different profiles of photodegradation, whereby the dyes alone were more susceptible to degradation. This can be justified by the intercalation of the dyes on the DNA base pairs allowing the DNA molecule to partially hinder the molecules’ exposition and, therefore, reducing their degradation.
作为一种重要的生物大分子，DNA 是抗肿瘤药物治疗癌症的靶点。这些药物与 DNA 的相互作用方式各不相同，其中最常见的是插层作用和沟结合作用。抗癌药物与 DNA 的插层作用会破坏 DNA 的正常功能，影响细胞增殖。亚甲基蓝（MB）和吖啶橙（AO）就是 DNA 插层剂的例子，它们已被研究用于抗击某些类型的癌症，主要是光动力疗法。在这项工作中，我们通过紫外可见光谱分析了在 DNA 不存在和存在的情况下，光照射对这些化合物的影响。在吸光度光谱中观察到了双色和低色偏移，揭示了染料与 DNA 碱基对的插层作用。含 DNA 和不含 DNA 的染料呈现出不同的光降解特征，其中单独的染料更容易降解。这是因为染料插层在 DNA 碱基对上，使 DNA 分子部分阻碍了分子的暴露，从而减少了降解。
{"title":"The Effect of UV-Vis Radiation on DNA Systems Containing the Photosensitizers Methylene Blue and Acridine Orange","authors":"Thais P. Pivetta, Paulo A. Ribeiro, M. Raposo","doi":"10.3390/biophysica4010002","DOIUrl":"https://doi.org/10.3390/biophysica4010002","url":null,"abstract":"As a vital biomolecule, DNA is known as a target of antineoplastic drugs for cancer therapy. These drugs can show different modes of interaction with DNA, with intercalation and groove binding being the most common types. The intercalation of anticancer drugs with DNA can lead to the disruption of its normal function, influencing cell proliferation. Methylene blue (MB) and acridine orange (AO) are examples of DNA-intercalating agents that have been studied for their application against some types of cancer, mainly for photodynamic therapy. In this work, the impact of light irradiation on these compounds in the absence and presence of DNA was analyzed by means of UV-vis spectroscopy. Bathochromic and hypochromic shifts were observed in the absorbance spectra, revealing the intercalation of the dyes with the DNA base pairs. Dyes with and without DNA present different profiles of photodegradation, whereby the dyes alone were more susceptible to degradation. This can be justified by the intercalation of the dyes on the DNA base pairs allowing the DNA molecule to partially hinder the molecules’ exposition and, therefore, reducing their degradation.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139533079","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 : 2024-01-02DOI: 10.3390/biophysica4010001
David A Hart
Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and the ability to synthesize other needed chemicals. The latter includes the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF) of the planet. How complex life forms have accommodated the GMF is not known in detail, considering that Homo sapiens evolved a neurological system, a neuromuscular system, and a cardiovascular system that developed electromagnetic fields as part of their functioning. Therefore, all of these could be impacted by magnetic fields. In addition, many proteins and physiologic processes utilize iron ions, which exhibit magnetic properties. Thus, complex organisms, such as humans, generate magnetic fields, contain significant quantities of iron ions, and respond to exogenous static and electromagnetic fields. Given the current body of literature, it remains somewhat unclear if Homo sapiens use exogenous magnetic fields to regulate function and what can happen if the boundary condition of the GMF no longer exerts an effect. Proposed deep space flights to destinations such as Mars will provide some insights, as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights into the role of magnetic fields on human functioning. This review will discuss the literature regarding the involvement of magnetic fields in various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer present to impact host systems, as well as the limitations in the current knowledge. The GMF has been present throughout evolution, but many details of its role in human functioning remain to be elucidated, and how humans have adapted to such fields in order to develop and retain function remains to be elucidated. Why this understudied area has not received the attention required to elucidate the critical information remains a conundrum for both health professionals and those embarking on space flight. However, proposed deep space flights to destinations such as Mars may provide the environments to test and assess the potential roles of magnetic fields in human functioning.
{"title":"The Influence of Magnetic Fields, Including the Planetary Magnetic Field, on Complex Life Forms: How Do Biological Systems Function in This Field and in Electromagnetic Fields?","authors":"David A Hart","doi":"10.3390/biophysica4010001","DOIUrl":"https://doi.org/10.3390/biophysica4010001","url":null,"abstract":"Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and the ability to synthesize other needed chemicals. The latter includes the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF) of the planet. How complex life forms have accommodated the GMF is not known in detail, considering that Homo sapiens evolved a neurological system, a neuromuscular system, and a cardiovascular system that developed electromagnetic fields as part of their functioning. Therefore, all of these could be impacted by magnetic fields. In addition, many proteins and physiologic processes utilize iron ions, which exhibit magnetic properties. Thus, complex organisms, such as humans, generate magnetic fields, contain significant quantities of iron ions, and respond to exogenous static and electromagnetic fields. Given the current body of literature, it remains somewhat unclear if Homo sapiens use exogenous magnetic fields to regulate function and what can happen if the boundary condition of the GMF no longer exerts an effect. Proposed deep space flights to destinations such as Mars will provide some insights, as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights into the role of magnetic fields on human functioning. This review will discuss the literature regarding the involvement of magnetic fields in various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer present to impact host systems, as well as the limitations in the current knowledge. The GMF has been present throughout evolution, but many details of its role in human functioning remain to be elucidated, and how humans have adapted to such fields in order to develop and retain function remains to be elucidated. Why this understudied area has not received the attention required to elucidate the critical information remains a conundrum for both health professionals and those embarking on space flight. However, proposed deep space flights to destinations such as Mars may provide the environments to test and assess the potential roles of magnetic fields in human functioning.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139390853","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 : 2023-12-18DOI: 10.3390/biophysica3040046
B. Sonkodi
This opinion manuscript outlines how the hippocampal theta rhythm could receive two novel peripheral inputs. One of the ways this could be achieved is through Piezo2 channels and atypical hippocampal-like metabotropic glutamate receptors coupled to phospholipase D containing proprioceptive primary afferent terminals. Accordingly, activated proprioceptive terminal Piezo2 on Type Ia fibers synchronizes to the theta rhythm with the help of hippocampal Piezo2 and medial septal glutamatergic neurons. Second, after baroreceptor Piezo2 is entrained to activated proprioceptive Piezo2, it could turn on the Cav1.3 channels, which pace the heart rhythm and regulate pacemaker cells during cardiac sympathetic activation. This would allow the Cav1.3 channels to synchronize to theta rhythm pacemaker hippocampal parvalbumin-expressing GABAergic neurons. This novel Piezo2-initiated proton–proton frequency coupling through VGLUT2 may provide the ultrafast long-range signaling pathway for the proposed Piezo2 synchronization of the low-frequency glutamatergic cell surface membrane oscillations in order to provide peripheral spatial and speed inputs to the space and speed coding of the hippocampal theta rhythm, supporting locomotion, learning and memory. Moreover, it provides an ultrafast signaling for postural and orthostatic control. Finally, suggestions are made as to how Piezo2 channelopathy could impair this ultrafast communication in many conditions and diseases with not entirely known etiology, leading to impaired proprioception and/or autonomic disbalance.
{"title":"Does Proprioception Involve Synchronization with Theta Rhythms by a Novel Piezo2 Initiated Ultrafast VGLUT2 Signaling?","authors":"B. Sonkodi","doi":"10.3390/biophysica3040046","DOIUrl":"https://doi.org/10.3390/biophysica3040046","url":null,"abstract":"This opinion manuscript outlines how the hippocampal theta rhythm could receive two novel peripheral inputs. One of the ways this could be achieved is through Piezo2 channels and atypical hippocampal-like metabotropic glutamate receptors coupled to phospholipase D containing proprioceptive primary afferent terminals. Accordingly, activated proprioceptive terminal Piezo2 on Type Ia fibers synchronizes to the theta rhythm with the help of hippocampal Piezo2 and medial septal glutamatergic neurons. Second, after baroreceptor Piezo2 is entrained to activated proprioceptive Piezo2, it could turn on the Cav1.3 channels, which pace the heart rhythm and regulate pacemaker cells during cardiac sympathetic activation. This would allow the Cav1.3 channels to synchronize to theta rhythm pacemaker hippocampal parvalbumin-expressing GABAergic neurons. This novel Piezo2-initiated proton–proton frequency coupling through VGLUT2 may provide the ultrafast long-range signaling pathway for the proposed Piezo2 synchronization of the low-frequency glutamatergic cell surface membrane oscillations in order to provide peripheral spatial and speed inputs to the space and speed coding of the hippocampal theta rhythm, supporting locomotion, learning and memory. Moreover, it provides an ultrafast signaling for postural and orthostatic control. Finally, suggestions are made as to how Piezo2 channelopathy could impair this ultrafast communication in many conditions and diseases with not entirely known etiology, leading to impaired proprioception and/or autonomic disbalance.","PeriodicalId":72401,"journal":{"name":"Biophysica","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138964401","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 : 2023-12-14DOI: 10.3390/biophysica3040045
Anders Brahme, Yvonne Lorat
Most ionizing radiation produces δ-rays of ≈1 keV that can impart MGy doses to 100 nm3 volumes of DNA. These events can produce severe dual double-strand breaks (DDSBs) on nucleosomes, particularly in dense heterochromatic DNA. This is the most common multiply damaged site, and their probabilities determine the biological effectiveness of different types of radiation. We discuss their frequency, effect on cell survival, DNA repair, and imaging by gold nanoparticle tracers and electron microscopy. This new and valuable nanometer resolution information can be used for determining the optimal tumor cure by maximizing therapeutic effects on tumors and minimizing therapeutic effects on normal tissues. The production of DDSBs makes it important to deliver a rather high dose and LET to the tumor (>2.5 Gy/Fr) and at the same time reach approximately 1.8–2.3 Gy of the lowest possible LET per fraction in TP53 intact normal tissues at risk. Therefore, their intrinsic low-dose hyper-sensitivity (LDHS)-related optimal daily fractionation window is utilized. Before full p53 activation of NHEJ and HR repair at ≈½ Gy, the low-dose apoptosis (LDA) and LDHS minimize normal tissue mutation probabilities. Ion therapy should thus ideally produce the lowest possible LET in normal tissues to avoid elevated DDSBs. Helium to boron ions can achieve this with higher-LET Bragg peaks, producing increased tumor DDSB densities. Interestingly, the highest probability of complication-free cure with boron or heavier ions requires a low LET round-up for the last 10–15 GyE, thereby steepening the dose response and further minimizing normal tissue damage. In conclusion, the new high-resolution DSB and DDSB diagnostic methods, and the new more accurate DNA-repair-based radiation biology, have been combined to increase our understanding of what is clinically important in curative radiation therapy. In fact, we must understand that we already passed the region of optimal LET and need to go back one step rather than forward, with oxygen being contemplated. As seen by the high overkill and severely high LET in the distal tumor and the increased LET to normal tissues (reminding of neutrons or neon ions), it is therefore preferable to use lithium–boron ions or combine carbon with an optimal 10–15 GyE photon, electron, or perhaps even a proton round-up, thus allowing optimized, fractionated, curative, almost complication-free treatments with photons, electrons, and light ions, introducing a real paradigm shift in curative radiation therapy with a potential 5 GyE tumor boost, 25% increase in complication-free cure and apoptotic–senescent Bragg Peak molecular light ion radiation therapy.
大多数电离辐射会产生≈1 keV 的 δ 射线，可对 100 nm3 体积的 DNA 产生 MGy 剂量。这些事件可在核小体上产生严重的双链断裂（DDSB），尤其是在密集的异染色质 DNA 中。这是最常见的多重损伤部位，其发生概率决定了不同类型辐射的生物有效性。我们将讨论它们的频率、对细胞存活的影响、DNA 修复以及金纳米粒子示踪剂和电子显微镜成像。这种新的、有价值的纳米分辨率信息可用于确定最佳的肿瘤治疗方法，最大限度地提高对肿瘤的治疗效果，同时最大限度地降低对正常组织的治疗效果。DDSBs 的产生使得向肿瘤提供相当高的剂量和 LET（>2.5 Gy/Fr），同时在 TP53 完整的受威胁正常组织中达到每部分约 1.8-2.3 Gy 的最低 LET 变得非常重要。因此，利用了其内在的低剂量高敏感性（LDHS）相关的最佳日分馏窗口。在 p53 完全激活 NHEJ 和 HR 修复（≈½ Gy）之前，低剂量凋亡（LDA）和 LDHS 可将正常组织的突变概率降至最低。因此，离子疗法最好能在正常组织中产生尽可能低的 LET，以避免 DDSB 的升高。氦到硼离子可以通过更高的 LET 布拉格峰来实现这一目标，从而增加肿瘤的 DDSB 密度。有趣的是，使用硼或更重的离子实现无并发症治愈的可能性最大，这需要在最后 10-15 GyE 采用低 LET 循环，从而使剂量反应陡峭化，进一步将正常组织损伤降至最低。总之，新的高分辨率 DSB 和 DDSB 诊断方法与新的更精确的基于 DNA 修复的放射生物学相结合，加深了我们对治疗性放射治疗的临床重要性的理解。事实上，我们必须明白，我们已经越过了最佳 LET 区域，需要后退一步，而不是向前迈进，目前正在考虑使用氧气。从远端肿瘤的高杀伤力和严重的高LET以及正常组织的LET增加（让人联想到中子或氖离子）可以看出，因此最好使用锂硼离子或将碳与最佳的10-15 GyE光子、电子或甚至质子辐照结合起来，从而实现优化的分次、根治性、近乎复杂的放射治疗、这样就可以利用光子、电子和光离子进行优化的、分次的、治疗性的、几乎无并发症的治疗，为治疗性放射治疗带来真正的范式转变，有可能提高肿瘤治疗效果 5 GyE，将无并发症治愈率提高 25%，并实现凋亡-衰减-布拉格峰分子光离子放射治疗。
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Pub Date : 2023-12-03DOI: 10.3390/biophysica3040044
Bojin Chen, J. Z. Zhang
Serine hydroxymethyltransferase 2 (SHMT2) has garnered significant attention as a critical catalytic regulator of the serine/glycine pathway in the one-carbon metabolism of cancer cells. Despite its potential as an anti-cancer target, only a limited number of inhibitors have been identified so far. In this study, we employed seven different scoring functions and skeleton clustering to screen the ChemDiv database for 38 compounds, 20 of which originate from the same skeleton structure. The most significant residues from SHMT2 and chemical groups from the inhibitors were identified using ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy), and the binding energy of each residue was quantitatively determined, revealing the essential features of the protein–inhibitor interaction. The two most important contributing residues are TYR105 and TYR106 of the B chain followed by LEU166 and ARG425 of the A chain. The findings will be greatly helpful in developing a thorough comprehension of the binding mechanisms involved in drug–SHMT2 interactions and offer valuable direction for designing more potent inhibitors.
丝氨酸羟甲基转移酶2 (SHMT2)作为癌细胞单碳代谢中丝氨酸/甘氨酸通路的关键催化调节剂，引起了人们的广泛关注。尽管它具有抗癌靶点的潜力，但到目前为止，只有有限数量的抑制剂被发现。在这项研究中，我们使用了7种不同的评分函数和骨架聚类来筛选ChemDiv数据库中的38个化合物，其中20个化合物来自相同的骨架结构。利用ASGBIE (Alanine Scanning with Generalized Born model and Interaction Entropy)对抑制剂中最显著的SHMT2残基和化学基团进行了鉴定，并定量测定了每个残基的结合能，揭示了蛋白-抑制剂相互作用的基本特征。两个最重要的贡献残基是B链的TYR105和TYR106，其次是A链的LEU166和ARG425。这些发现将极大地有助于深入了解药物- shmt2相互作用的结合机制，并为设计更有效的抑制剂提供有价值的指导。
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