David Pérez Abadía, Harley Quinto Mosquera, José María Del Arco
Environmental factors control the accumulation of aboveground biomass (AB) in tropical forests, along with the role of AB in climate change mitigation. As such, the objective of this study was to evaluate the influence of factors such as forest type, succession, abundance of individuals, species richness, height, diameter, texture, and soil nutrient levels on the AB in mature and postmining forests in Chocó, Colombia. Five plots each were set up in primary and postmining forests with 15 and 30 years of regeneration, in which the amount of AB was measured and related to the environmental factors. The AB was 178.32 t ha-1 in the mature forests and 35.17 and 56.3 t ha-1 after 15 and 30 years of postmining regeneration, respectively. Furthermore, the general AB level was determined by the ecosystem type, diameter, richness, abundance, Shannon evenness, and Margalef diversity. In mature forests, the AB amount was positively influenced by height and richness, and negatively influenced by dominance and evenness; in areas degraded by mining, the AB level was positively related to richness and equity, and negatively related to species diversity and soil silt. In summary, environmental factors determine the carbon storage in the forests in Chocó. Mining reduces the function of these ecosystems in mitigating climate change.
{"title":"Influence of Environmental Factors on the Aboveground Biomass of Mature and Postmining Forests in Chocó.","authors":"David Pérez Abadía, Harley Quinto Mosquera, José María Del Arco","doi":"10.3390/life15010098","DOIUrl":"10.3390/life15010098","url":null,"abstract":"<p><p>Environmental factors control the accumulation of aboveground biomass (AB) in tropical forests, along with the role of AB in climate change mitigation. As such, the objective of this study was to evaluate the influence of factors such as forest type, succession, abundance of individuals, species richness, height, diameter, texture, and soil nutrient levels on the AB in mature and postmining forests in Chocó, Colombia. Five plots each were set up in primary and postmining forests with 15 and 30 years of regeneration, in which the amount of AB was measured and related to the environmental factors. The AB was 178.32 t ha<sup>-1</sup> in the mature forests and 35.17 and 56.3 t ha<sup>-1</sup> after 15 and 30 years of postmining regeneration, respectively. Furthermore, the general AB level was determined by the ecosystem type, diameter, richness, abundance, Shannon evenness, and Margalef diversity. In mature forests, the AB amount was positively influenced by height and richness, and negatively influenced by dominance and evenness; in areas degraded by mining, the AB level was positively related to richness and equity, and negatively related to species diversity and soil silt. In summary, environmental factors determine the carbon storage in the forests in Chocó. Mining reduces the function of these ecosystems in mitigating climate change.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constantin Popazu, Alexandra Toma, Daniela Mihalache, Oana-Monica Duca, Dorel Firescu, Dragoș F Voicu
Background: Colonic obstructions present a serious medical emergency that requires prompt surgical intervention to prevent life-threatening complications. Cecostomy, a procedure involving the creation of an opening in the cecum to decompress the colon, serves as one surgical approach for managing these obstructions. The aim of this review is to evaluate the effectiveness and benefits of cecostomies in emergency surgical settings, with a focus on recent clinical studies and case reports. Cecostomy is highlighted as a bridge procedure in cases such as obstructive carcinomas, providing data on success rates, relative survival, and clinical effectiveness. The importance of the patient's condition and surgeon expertise in selecting cecostomy as a procedure is emphasized. Further comparative research is suggested to optimize the selection criteria, providing a strong, clinically oriented conclusion.
Methods: A comprehensive literature review was conducted to identify studies and case reports focusing on the application of cecostomies in cases of acute colonic obstruction. Articles were selected based on their relevance to emergency surgery, the effectiveness of cecostomies, and patient outcomes in various clinical scenarios, including obstructive carcinomas and colonic pseudo-obstructions.
Results: The analysis reveals that cecostomies provide rapid decompression and effective relief from colonic obstruction, particularly when immediate intervention is needed to prevent bowel perforation or ischemia. In several cases, cecostomies act as a bridge to more definitive surgical treatments, such as resection and anastomosis, and are associated with reduced morbidity and mortality. The selection of cecostomy as a preferred procedure depends on the patient's condition, location of the obstruction, and surgeon expertise.
Conclusions: Cecostomies play a crucial role in the emergency management of colonic obstructions, offering a viable and sometimes lifesaving alternative for rapid decompression. Understanding the indications and appropriate use of cecostomies can enhance patient outcomes and provide surgeons with effective strategies for managing acute colonic obstructions. Further research is warranted to refine selection criteria and to compare outcomes between cecostomies and other decompressive techniques in emergency settings.
{"title":"Unlocking the Potential of Cecostomies: A Valuable Lifesaving Procedure in Emergency Surgery for Colonic Obstructions.","authors":"Constantin Popazu, Alexandra Toma, Daniela Mihalache, Oana-Monica Duca, Dorel Firescu, Dragoș F Voicu","doi":"10.3390/life15010101","DOIUrl":"10.3390/life15010101","url":null,"abstract":"<p><strong>Background: </strong>Colonic obstructions present a serious medical emergency that requires prompt surgical intervention to prevent life-threatening complications. Cecostomy, a procedure involving the creation of an opening in the cecum to decompress the colon, serves as one surgical approach for managing these obstructions. The aim of this review is to evaluate the effectiveness and benefits of cecostomies in emergency surgical settings, with a focus on recent clinical studies and case reports. Cecostomy is highlighted as a bridge procedure in cases such as obstructive carcinomas, providing data on success rates, relative survival, and clinical effectiveness. The importance of the patient's condition and surgeon expertise in selecting cecostomy as a procedure is emphasized. Further comparative research is suggested to optimize the selection criteria, providing a strong, clinically oriented conclusion.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted to identify studies and case reports focusing on the application of cecostomies in cases of acute colonic obstruction. Articles were selected based on their relevance to emergency surgery, the effectiveness of cecostomies, and patient outcomes in various clinical scenarios, including obstructive carcinomas and colonic pseudo-obstructions.</p><p><strong>Results: </strong>The analysis reveals that cecostomies provide rapid decompression and effective relief from colonic obstruction, particularly when immediate intervention is needed to prevent bowel perforation or ischemia. In several cases, cecostomies act as a bridge to more definitive surgical treatments, such as resection and anastomosis, and are associated with reduced morbidity and mortality. The selection of cecostomy as a preferred procedure depends on the patient's condition, location of the obstruction, and surgeon expertise.</p><p><strong>Conclusions: </strong>Cecostomies play a crucial role in the emergency management of colonic obstructions, offering a viable and sometimes lifesaving alternative for rapid decompression. Understanding the indications and appropriate use of cecostomies can enhance patient outcomes and provide surgeons with effective strategies for managing acute colonic obstructions. Further research is warranted to refine selection criteria and to compare outcomes between cecostomies and other decompressive techniques in emergency settings.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: High-velocity, low-amplitude (HVLA) manipulation is a common manual therapy technique used for treating pain and musculoskeletal dysfunction. An audible manipulation sound is commonly experienced by patients who undergo HVLA manipulation; however, there is little known about the effects and clinical relevance of the audible manipulation sound on cortical output and the autonomic nervous system. This study aimed to identify the immediate impact of the audible manipulation sound on brainwave activity and pupil diameter in asymptomatic subjects following an HVLA cervical manipulation.
Methods: 40 subjects completed this quasi-experimental repeated measure study design. Subjects were connected to electroencephalography and pupillometry simultaneously, and an HVLA cervical distraction manipulation was performed. The testing environment was controlled to optimize brainwave and pupillometry data acquisition. Pre-manipulation, immediately after manipulation, and post-manipulation data were collected. The presence of an audible manipulation sound was noted.
Results: Twenty subjects experienced an audible manipulation sound. Brainwave activity changes were significant (p < 0.05) in both the audible manipulation sound and non-manipulation sound groups. Pupil diameter changes (p < 0.05) occurred in both eyes of the non-manipulation sound group and in the left eye of the audible-manipulation sound group. Brainwave activity patterns were similar in both groups.
Conclusions: The presence of an audible manipulation sound is not required to produce central nervous system changes following an HVLA cervical manipulation; however, the audible manipulation sound does prolong the effects of brainwave activity, indicating a prolonged relaxation effect.
{"title":"The Effect of Audible Joint Manipulation Sounds in the Upper Cervical Spine on Brain Wave and Autonomic Nervous System Activity.","authors":"Dalton Whitman, Rob Sillevis, Matthew Frommelt","doi":"10.3390/life15010103","DOIUrl":"10.3390/life15010103","url":null,"abstract":"<p><strong>Background: </strong>High-velocity, low-amplitude (HVLA) manipulation is a common manual therapy technique used for treating pain and musculoskeletal dysfunction. An audible manipulation sound is commonly experienced by patients who undergo HVLA manipulation; however, there is little known about the effects and clinical relevance of the audible manipulation sound on cortical output and the autonomic nervous system. This study aimed to identify the immediate impact of the audible manipulation sound on brainwave activity and pupil diameter in asymptomatic subjects following an HVLA cervical manipulation.</p><p><strong>Methods: </strong>40 subjects completed this quasi-experimental repeated measure study design. Subjects were connected to electroencephalography and pupillometry simultaneously, and an HVLA cervical distraction manipulation was performed. The testing environment was controlled to optimize brainwave and pupillometry data acquisition. Pre-manipulation, immediately after manipulation, and post-manipulation data were collected. The presence of an audible manipulation sound was noted.</p><p><strong>Results: </strong>Twenty subjects experienced an audible manipulation sound. Brainwave activity changes were significant (<i>p</i> < 0.05) in both the audible manipulation sound and non-manipulation sound groups. Pupil diameter changes (<i>p</i> < 0.05) occurred in both eyes of the non-manipulation sound group and in the left eye of the audible-manipulation sound group. Brainwave activity patterns were similar in both groups.</p><p><strong>Conclusions: </strong>The presence of an audible manipulation sound is not required to produce central nervous system changes following an HVLA cervical manipulation; however, the audible manipulation sound does prolong the effects of brainwave activity, indicating a prolonged relaxation effect.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekaterina Bezpalaya, Svetlana Kurilova, Nataliya Vorobyeva, Elena Rodina
Inorganic pyrophosphatases, or PPases, are ubiquitous enzymes whose activity is necessary for a large number of biosynthetic reactions. The catalytic function of PPases is dependent on certain conformational changes that have been previously characterized based on the comparison of the crystal structures of various complexes. The current work describes the conformational dynamics of a structural model of human mitochondrial pyrophosphatase hPPA2 using molecular dynamics simulation, all-atom principal component analysis, and coarse-grained normal mode analysis. In addition to the wild-type enzyme, four mutant variants of hPPA2 were characterized that correspond to the natural pathogenic variants causing severe mitochondrial dysfunction and cardio pathologies. As a result, we identified the global type of flexible motion that seems to be shared by other dimeric PPases. This motion is discussed in terms of the allosteric behavior of the protein. Analysis of the observed conformational dynamics revealed the formation of a binding site for anionic ligands in the active site that could be relevant to enzyme catalysis. Based on the comparison of the wild-type and mutant PPases dynamics, we suggest the possible molecular mechanisms of the functional incompetence of hPPA2 caused by mutations. The results of this work allow for deeper insight into the structural basis of PPase function and the possible effects of pathogenic mutations on the protein structure and function.
{"title":"Conformational Dynamics of Mitochondrial Inorganic Pyrophosphatase hPPA2 and Its Changes Caused by Pathogenic Mutations.","authors":"Ekaterina Bezpalaya, Svetlana Kurilova, Nataliya Vorobyeva, Elena Rodina","doi":"10.3390/life15010100","DOIUrl":"10.3390/life15010100","url":null,"abstract":"<p><p>Inorganic pyrophosphatases, or PPases, are ubiquitous enzymes whose activity is necessary for a large number of biosynthetic reactions. The catalytic function of PPases is dependent on certain conformational changes that have been previously characterized based on the comparison of the crystal structures of various complexes. The current work describes the conformational dynamics of a structural model of human mitochondrial pyrophosphatase hPPA2 using molecular dynamics simulation, all-atom principal component analysis, and coarse-grained normal mode analysis. In addition to the wild-type enzyme, four mutant variants of hPPA2 were characterized that correspond to the natural pathogenic variants causing severe mitochondrial dysfunction and cardio pathologies. As a result, we identified the global type of flexible motion that seems to be shared by other dimeric PPases. This motion is discussed in terms of the allosteric behavior of the protein. Analysis of the observed conformational dynamics revealed the formation of a binding site for anionic ligands in the active site that could be relevant to enzyme catalysis. Based on the comparison of the wild-type and mutant PPases dynamics, we suggest the possible molecular mechanisms of the functional incompetence of hPPA2 caused by mutations. The results of this work allow for deeper insight into the structural basis of PPase function and the possible effects of pathogenic mutations on the protein structure and function.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The scorpion Buthus martensii Karsch is edible and has been an essential resource in traditional Chinese medicine for treating numerous diseases. In this study, two small peptides from B. martensii hydrolysates were examined to elucidate their potential against gastric cancer. The small peptides (AK and GK) were identified using the LC-QTOF-MS-based approach. In silico prediction of therapeutic targets, MGC-803 cells and transgenic zebrafish models, and immunoblotting experiments were used to reveal the molecular mechanism of action of the peptides. The peptides AK and GK competitively bound to the receptor to modulate the TNF/TNFR-signaling cascade and alter the tumor microenvironment. EGFR, TP53, MYC, PTEN, and STAT3 were also identified as major functional targets of the peptides. Mechanistically, AK and GK inactivated the TNF-α/EGFR/STAT3-signaling pathway, decreased c-myc protein expression levels, and upregulated p53 and PTEN expression, thereby preventing TNF-α-induced tumor growth. Our findings indicated that AK and GK played a pivotal role in offsetting the inflammatory stimuli that caused gastric cancer cell invasion and highlighted the use of B. martensii resources as functional products with health benefits.
{"title":"Two Small Peptides from <i>Buthus martensii</i> Hydrolysates Exhibit Antitumor Activity Through Inhibition of TNF-α-Mediated Signal Transduction Pathways.","authors":"Mengshuang Zhu, Shanshan Zhang, Jiyang Tang, Hairong Hou, Lizhen Wang, Houwen Lin, Xuanming Zhang, Meng Jin","doi":"10.3390/life15010105","DOIUrl":"10.3390/life15010105","url":null,"abstract":"<p><p>The scorpion <i>Buthus martensii</i> Karsch is edible and has been an essential resource in traditional Chinese medicine for treating numerous diseases. In this study, two small peptides from <i>B. martensii</i> hydrolysates were examined to elucidate their potential against gastric cancer. The small peptides (AK and GK) were identified using the LC-QTOF-MS-based approach. In silico prediction of therapeutic targets, MGC-803 cells and transgenic zebrafish models, and immunoblotting experiments were used to reveal the molecular mechanism of action of the peptides. The peptides AK and GK competitively bound to the receptor to modulate the TNF/TNFR-signaling cascade and alter the tumor microenvironment. EGFR, TP53, MYC, PTEN, and STAT3 were also identified as major functional targets of the peptides. Mechanistically, AK and GK inactivated the TNF-α/EGFR/STAT3-signaling pathway, decreased c-myc protein expression levels, and upregulated p53 and PTEN expression, thereby preventing TNF-α-induced tumor growth. Our findings indicated that AK and GK played a pivotal role in offsetting the inflammatory stimuli that caused gastric cancer cell invasion and highlighted the use of <i>B. martensii</i> resources as functional products with health benefits.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The diversity and complexity of RNA include sequence, secondary structure, and tertiary structure characteristics. These elements are crucial for RNA's specific recognition of other molecules. With advancements in biotechnology, RNA-ligand structures allow researchers to utilize experimental data to uncover the mechanisms of complex interactions. However, determining the structures of these complexes experimentally can be technically challenging and often results in low-resolution data. Many machine learning computational approaches have recently emerged to learn multiscale-level RNA features to predict the interactions. Predicting interactions remains an unexplored area. Therefore, studying RNA-ligand interactions is essential for understanding biological processes. In this review, we analyze the interaction characteristics of RNA-ligand complexes by examining RNA's sequence, secondary structure, and tertiary structure. Our goal is to clarify how RNA specifically recognizes ligands. Additionally, we systematically discuss advancements in computational methods for predicting interactions and to guide future research directions. We aim to inspire the creation of more reliable RNA-ligand interaction prediction tools.
{"title":"Advances and Mechanisms of RNA-Ligand Interaction Predictions.","authors":"Chen Zhuo, Chengwei Zeng, Haoquan Liu, Huiwen Wang, Yunhui Peng, Yunjie Zhao","doi":"10.3390/life15010104","DOIUrl":"10.3390/life15010104","url":null,"abstract":"<p><p>The diversity and complexity of RNA include sequence, secondary structure, and tertiary structure characteristics. These elements are crucial for RNA's specific recognition of other molecules. With advancements in biotechnology, RNA-ligand structures allow researchers to utilize experimental data to uncover the mechanisms of complex interactions. However, determining the structures of these complexes experimentally can be technically challenging and often results in low-resolution data. Many machine learning computational approaches have recently emerged to learn multiscale-level RNA features to predict the interactions. Predicting interactions remains an unexplored area. Therefore, studying RNA-ligand interactions is essential for understanding biological processes. In this review, we analyze the interaction characteristics of RNA-ligand complexes by examining RNA's sequence, secondary structure, and tertiary structure. Our goal is to clarify how RNA specifically recognizes ligands. Additionally, we systematically discuss advancements in computational methods for predicting interactions and to guide future research directions. We aim to inspire the creation of more reliable RNA-ligand interaction prediction tools.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Bettinsoli, Gloria Melzi, Angelica Crea, Lorenzo Degli Esposti, Michele Iafisco, Daniele Catalucci, Paolo Ciana, Emanuela Corsini
Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns-particularly those specific to this class of drugs-is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs. Human peripheral blood mononuclear cells (PBMCs), purified from buffy coats of healthy donors, were used to investigate the ability of NA-drugs to trigger toxicity pathways and inappropriate immune stimulation. PBMCs were selected for their ability to represent potential human responses, given their likelihood of interacting with administered drugs. As proof of concept, a small interfering RNA (siRNA) targeting Ryanodine Receptor mRNA (RyR2) identified by the Italian National Center for Gene Therapy and Drugs based on RNA Technology as a potential therapeutic target for dominant catecholaminergic polymorphic ventricular tachycardia, was selected. This compound and its scramble were formulated within a calcium phosphate nanoparticle-based delivery system. Positive controls for four toxicity pathways were identified through literature review, each associated with a specific type of cellular stress: oxidative stress (tert-butyl hydroperoxide), mitochondrial stress (rotenone), endoplasmic reticulum stress (thapsigargin), and autophagy (rapamycin). These controls were used to define specific mRNA signatures triggered in PBMCs, which were subsequently used as indicators of off-target effects. To assess immune activation, the release of pro-inflammatory cytokines (interleukin-6, interleukin-8, tumor necrosis factor-α, and interferon-γ) was measured 24 h after exposure. The proposed approach provides a rapid and effective screening method for identifying potential unintended effects in a relevant human model, which also allows to address gender effects and variability in responses.
{"title":"A Novel Approach for In Vitro Testing and Hazard Evaluation of Nanoformulated RyR2-Targeting siRNA Drugs Using Human PBMCs.","authors":"Valeria Bettinsoli, Gloria Melzi, Angelica Crea, Lorenzo Degli Esposti, Michele Iafisco, Daniele Catalucci, Paolo Ciana, Emanuela Corsini","doi":"10.3390/life15010095","DOIUrl":"10.3390/life15010095","url":null,"abstract":"<p><p>Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns-particularly those specific to this class of drugs-is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs. Human peripheral blood mononuclear cells (PBMCs), purified from buffy coats of healthy donors, were used to investigate the ability of NA-drugs to trigger toxicity pathways and inappropriate immune stimulation. PBMCs were selected for their ability to represent potential human responses, given their likelihood of interacting with administered drugs. As proof of concept, a small interfering RNA (siRNA) targeting Ryanodine Receptor mRNA (RyR2) identified by the Italian National Center for Gene Therapy and Drugs based on RNA Technology as a potential therapeutic target for dominant catecholaminergic polymorphic ventricular tachycardia, was selected. This compound and its scramble were formulated within a calcium phosphate nanoparticle-based delivery system. Positive controls for four toxicity pathways were identified through literature review, each associated with a specific type of cellular stress: oxidative stress (tert-butyl hydroperoxide), mitochondrial stress (rotenone), endoplasmic reticulum stress (thapsigargin), and autophagy (rapamycin). These controls were used to define specific mRNA signatures triggered in PBMCs, which were subsequently used as indicators of off-target effects. To assess immune activation, the release of pro-inflammatory cytokines (interleukin-6, interleukin-8, tumor necrosis factor-α, and interferon-γ) was measured 24 h after exposure. The proposed approach provides a rapid and effective screening method for identifying potential unintended effects in a relevant human model, which also allows to address gender effects and variability in responses.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mshari Alghadier, Reem M Basuodan, Afnan Gmmash, Reem A Albesher
Background: The COVID-19 pandemic may have had long-lasting detrimental effects on children's physical health. Previous studies have shown that children's participation in physical activity (PA) declined during the pandemic. This study examined the effect of the COVID-19 pandemic on PA type selection and the influence of gender, number of siblings, residence type, and caregiver education level on PA.
Methods: Parents of Saudi children (ages 6-9 years) were recruited through convenience sampling and completed an online survey between July and August 2020. The parent-reported survey included demographics and PA types across three time periods (pre-, during, and post-lockdown). Chi-squared tests and logistic regression with pairwise comparisons were used to analyze the differences.
Results: Parents reported that children (n = 361, mean age 7.7 ± 1.1 years) selected different PA types pre-COVID-19 pandemic more often than during the COVID-19 lockdown, such as swimming (16.9% vs. 12.8%), high-intensity jumping (9.8% vs. 6.6%), cycling (12.8% vs. 9.6%), football (14.3% vs. 6.1%), running (9.3% vs. 5.5%), virtual gaming exercise (5% vs. 3.2%), and playground activity (11.3% vs. 5.8%) (p < 0.05). Additionally, PA type was shown to be influenced by gender and residence type, with girls being 55% more likely to be physically active during COVID-19 compared to boys, and participants living in houses without private yards being less physically active compared to those who lived in houses with private yards.
Conclusions: Children's gender (boy vs. girl) and residence type (with private yards vs. without private yards) affected their PA level during the COVID-19 lockdown. These findings suggest that more effort should be directed toward understanding the influence of gender and house types in the selection of PA types.
{"title":"Physical Activity Types Among School-Aged Children During COVID-19 Pandemic in Saudi Arabia: A Cross-Sectional Study.","authors":"Mshari Alghadier, Reem M Basuodan, Afnan Gmmash, Reem A Albesher","doi":"10.3390/life15010091","DOIUrl":"10.3390/life15010091","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic may have had long-lasting detrimental effects on children's physical health. Previous studies have shown that children's participation in physical activity (PA) declined during the pandemic. This study examined the effect of the COVID-19 pandemic on PA type selection and the influence of gender, number of siblings, residence type, and caregiver education level on PA.</p><p><strong>Methods: </strong>Parents of Saudi children (ages 6-9 years) were recruited through convenience sampling and completed an online survey between July and August 2020. The parent-reported survey included demographics and PA types across three time periods (pre-, during, and post-lockdown). Chi-squared tests and logistic regression with pairwise comparisons were used to analyze the differences.</p><p><strong>Results: </strong>Parents reported that children (<i>n</i> = 361, mean age 7.7 ± 1.1 years) selected different PA types pre-COVID-19 pandemic more often than during the COVID-19 lockdown, such as swimming (16.9% vs. 12.8%), high-intensity jumping (9.8% vs. 6.6%), cycling (12.8% vs. 9.6%), football (14.3% vs. 6.1%), running (9.3% vs. 5.5%), virtual gaming exercise (5% vs. 3.2%), and playground activity (11.3% vs. 5.8%) (<i>p</i> < 0.05). Additionally, PA type was shown to be influenced by gender and residence type, with girls being 55% more likely to be physically active during COVID-19 compared to boys, and participants living in houses without private yards being less physically active compared to those who lived in houses with private yards.</p><p><strong>Conclusions: </strong>Children's gender (boy vs. girl) and residence type (with private yards vs. without private yards) affected their PA level during the COVID-19 lockdown. These findings suggest that more effort should be directed toward understanding the influence of gender and house types in the selection of PA types.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irena Plahuta, Žan Šarenac, Medeja Golob, Špela Turk, Bojan Ilijevec, Tomislav Magdalenić, Stojan Potrč, Arpad Ivanecz
Laparoscopic distal pancreatectomy is a minimally invasive approach for the surgical treatment of neoplasms in the distal pancreas. This study aimed to compare this approach to the open procedure. A retrospective analysis of a prospectively maintained database of 400 pancreatectomies was performed. The laparoscopic distal pancreatectomy group (LDP) was compared to the open distal pancreatectomy group (ODP). A propensity score matching analysis (PSM) was performed. From 2016 to 2023, 108 distal pancreatectomies were carried out, 19 (17.6%) laparoscopically and 89 (82.4%) openly. The conversion rate was 13.6%. The severe morbidity rates were 28.1% in the ODP group, 47.4% in the LDP group, and 15.8% in the ODP-PSM group. The difference between the latter two was statistically significant (p = 0.034) due to the high rate of Clavien-Dindo grade 3a complications (42.1% versus 10.5%, p = 0.042) in the LDP group. The 90-day mortality rates were 3.3% in the ODP group and 5.3% in the other two groups. The LDP group had a shorter duration of intravenous narcotic analgesia (5 versus 7 days, p = 0.041). There was no difference in the R0 resection or postoperative pancreatic fistula rates. Our attention should be drawn to preventing postoperative complications because the oncological outcomes are already comparable with those of the open procedure, and postoperative pain management is promising.
{"title":"Laparoscopic and Open Distal Pancreatectomy-An Initial Single-Institution Experience with a Propensity Score Matching Analysis.","authors":"Irena Plahuta, Žan Šarenac, Medeja Golob, Špela Turk, Bojan Ilijevec, Tomislav Magdalenić, Stojan Potrč, Arpad Ivanecz","doi":"10.3390/life15010097","DOIUrl":"10.3390/life15010097","url":null,"abstract":"<p><p>Laparoscopic distal pancreatectomy is a minimally invasive approach for the surgical treatment of neoplasms in the distal pancreas. This study aimed to compare this approach to the open procedure. A retrospective analysis of a prospectively maintained database of 400 pancreatectomies was performed. The laparoscopic distal pancreatectomy group (LDP) was compared to the open distal pancreatectomy group (ODP). A propensity score matching analysis (PSM) was performed. From 2016 to 2023, 108 distal pancreatectomies were carried out, 19 (17.6%) laparoscopically and 89 (82.4%) openly. The conversion rate was 13.6%. The severe morbidity rates were 28.1% in the ODP group, 47.4% in the LDP group, and 15.8% in the ODP-PSM group. The difference between the latter two was statistically significant (<i>p</i> = 0.034) due to the high rate of Clavien-Dindo grade 3a complications (42.1% versus 10.5%, <i>p</i> = 0.042) in the LDP group. The 90-day mortality rates were 3.3% in the ODP group and 5.3% in the other two groups. The LDP group had a shorter duration of intravenous narcotic analgesia (5 versus 7 days, <i>p</i> = 0.041). There was no difference in the R0 resection or postoperative pancreatic fistula rates. Our attention should be drawn to preventing postoperative complications because the oncological outcomes are already comparable with those of the open procedure, and postoperative pain management is promising.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11767203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivana Shawkatova, Vladimira Durmanova, Juraj Javor
Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer's disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood-brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management.
{"title":"Alzheimer's Disease and <i>Porphyromonas gingivalis</i>: Exploring the Links.","authors":"Ivana Shawkatova, Vladimira Durmanova, Juraj Javor","doi":"10.3390/life15010096","DOIUrl":"10.3390/life15010096","url":null,"abstract":"<p><p>Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer's disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly <i>Porphyromonas gingivalis</i>, has garnered significant attention. <i>P. gingivalis</i>, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting <i>P. gingivalis</i> to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood-brain barrier disruption, neuroinflammation, and neuronal damage. <i>P. gingivalis</i>-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting <i>P. gingivalis</i> virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into <i>P. gingivalis</i>-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management.</p>","PeriodicalId":56144,"journal":{"name":"Life-Basel","volume":"15 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}