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Heliyon Feb 2024The augmented prevalence of Se (Se) pollution can be attributed to various human activities, such as mining, coal combustion, oil extraction and refining, and... (Review)
Review
The augmented prevalence of Se (Se) pollution can be attributed to various human activities, such as mining, coal combustion, oil extraction and refining, and agricultural irrigation. Although Se is vital for animals, humans, and microorganisms, excessive concentrations of this element can give rise to potential hazards. Consequently, numerous approaches have been devised to mitigate Se pollution, encompassing physicochemical techniques and bioremediation. The recognition of Se volatilization as a potential strategy for mitigating Se pollution in contaminated environments is underscored in this review. This study delves into the volatilization mechanisms in various organisms, including plants, microalgae, and microorganisms. By assessing the efficacy of Se removal and identifying the rate-limiting steps associated with volatilization, this paper provides insightful recommendations for Se mitigation. Constructed wetlands are a cost-effective and environmentally friendly alternative in the treatment of Se volatilization. The fate, behavior, bioavailability, and toxicity of Se within complex environmental systems are comprehensively reviewed. This knowledge forms the basis for developing management plans that aimed at mitigating Se contamination in wetlands and protecting the associated ecosystems.
PubMed: 38390045
DOI: 10.1016/j.heliyon.2024.e26023 -
Cell Stem Cell Apr 2024Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the...
Traumatic brain injury (TBI) strongly correlates with neurodegenerative disease. However, it remains unclear which neurodegenerative mechanisms are intrinsic to the brain and which strategies most potently mitigate these processes. We developed a high-intensity ultrasound platform to inflict mechanical injury to induced pluripotent stem cell (iPSC)-derived cortical organoids. Mechanically injured organoids elicit classic hallmarks of TBI, including neuronal death, tau phosphorylation, and TDP-43 nuclear egress. We found that deep-layer neurons were particularly vulnerable to injury and that TDP-43 proteinopathy promotes cell death. Injured organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients displayed exacerbated TDP-43 dysfunction. Using genome-wide CRISPR interference screening, we identified a mechanosensory channel, KCNJ2, whose inhibition potently mitigated neurodegenerative processes in vitro and in vivo, including in C9ORF72 ALS/FTD organoids. Thus, targeting KCNJ2 may reduce acute neuronal death after brain injury, and we present a scalable, genetically flexible cerebral organoid model that may enable the identification of additional modifiers of mechanical stress.
Topics: Humans; Amyotrophic Lateral Sclerosis; Brain; Brain Injuries, Traumatic; C9orf72 Protein; DNA-Binding Proteins; Frontotemporal Dementia; Neurodegenerative Diseases; Potassium Channels, Inwardly Rectifying
PubMed: 38579683
DOI: 10.1016/j.stem.2024.03.004 -
Frontiers in Immunology 2023Although both COVID-19 and non-COVID-19 ARDS can be accompanied by significantly increased levels of circulating cytokines, the former significantly differs from the...
INTRODUCTION
Although both COVID-19 and non-COVID-19 ARDS can be accompanied by significantly increased levels of circulating cytokines, the former significantly differs from the latter by its higher vasculopathy, characterized by increased oxidative stress and coagulopathy in lung capillaries. This points towards the existence of SARS-CoV2-specific factors and mechanisms that can sensitize the endothelium towards becoming dysfunctional. Although the virus is rarely detected within endothelial cells or in the circulation, the S1 subunit of its spike protein, which contains the receptor binding domain (RBD) for human ACE2 (hACE2), can be detected in plasma from COVID-19 patients and its levels correlate with disease severity. It remains obscure how the SARS-CoV2 RBD exerts its deleterious actions in lung endothelium and whether there are mechanisms to mitigate this.
METHODS
In this study, we use a combination of studies in RBD-treated human lung microvascular endothelial cells (HL-MVEC), including electrophysiology, barrier function, oxidative stress and human ACE2 (hACE2) surface protein expression measurements with studies in transgenic mice globally expressing human ACE2 and injected with RBD.
RESULTS
We show that SARS-CoV2 RBD impairs endothelial ENaC activity, reduces surface hACE2 expression and increases reactive oxygen species (ROS) and tissue factor (TF) generation in monolayers of HL-MVEC, as such promoting barrier dysfunction and coagulopathy. The TNF-derived TIP peptide (a.k.a. solnatide, AP301) -which directly activates ENaC upon binding to its a subunit- can override RBD-induced impairment of ENaC function and hACE2 expression, mitigates ROS and TF generation and restores barrier function in HL-MVEC monolayers. In correlation with the increased mortality observed in COVID-19 patients co-infected with S. pneumoniae, compared to subjects solely infected with SARS-CoV2, we observe that prior intraperitoneal RBD treatment in transgenic mice globally expressing hACE2 significantly increases fibrin deposition and capillary leak upon intratracheal instillation of S. pneumoniae and that this is mitigated by TIP peptide treatment.
Topics: Animals; Mice; Humans; Endothelial Cells; Angiotensin-Converting Enzyme 2; RNA, Viral; Reactive Oxygen Species; Spike Glycoprotein, Coronavirus; COVID-19; SARS-CoV-2; Endothelium
PubMed: 37638055
DOI: 10.3389/fimmu.2023.1241448 -
IScience Sep 2023Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated...
Radiation therapy can lead to late radiation-induced skin fibrosis (RISF), causing movement restriction, pain, and organ dysfunction. This study evaluated adipose-derived extracellular matrix (Ad-ECM) as a mitigator of RISF. Female C57BL/6J mice that were irradiated developed fibrosis, which was mitigated by a single local Ad-ECM injection, improving limb movement and reducing epithelium thickness and collagen deposition. Ad-ECM treatment resulted in decreased expression of pro-inflammatory and fibrotic genes, and upregulation of anti-inflammatory cytokines, promoting M2 macrophage polarization. Co-culture of irradiated human fibroblasts with Ad-ECM down-modulated fibrotic gene expression and enhanced bone marrow cell migration. Ad-ECM treatment also increased interleukin (IL)-4, IL-5, and IL-15 expression in endothelial cells, stimulating M2 macrophage polarization and alleviating RISF. Prophylactic use of Ad-ECM showed effectiveness in mitigation. This study suggests Ad-ECM's potential in treating chronic-stage fibrosis.
PubMed: 37705953
DOI: 10.1016/j.isci.2023.107660 -
Biological Reviews of the Cambridge... Dec 2023The conservation, restoration, and improved management of terrestrial forests significantly contributes to mitigate climate change and its impacts, as well as providing... (Review)
Review
The conservation, restoration, and improved management of terrestrial forests significantly contributes to mitigate climate change and its impacts, as well as providing numerous co-benefits. The pressing need to reduce emissions and increase carbon removal from the atmosphere is now also leading to the development of natural climate solutions in the ocean. Interest in the carbon sequestration potential of underwater macroalgal forests is growing rapidly among policy, conservation, and corporate sectors. Yet, our understanding of whether carbon sequestration from macroalgal forests can lead to tangible climate change mitigation remains severely limited, hampering their inclusion in international policy or carbon finance frameworks. Here, we examine the results of over 180 publications to synthesise evidence regarding macroalgal forest carbon sequestration potential. We show that research efforts on macroalgae carbon sequestration are heavily skewed towards particulate organic carbon (POC) pathways (77% of data publications), and that carbon fixation is the most studied flux (55%). Fluxes leading directly to carbon sequestration (e.g. carbon export or burial in marine sediments) remain poorly resolved, likely hindering regional or country-level assessments of carbon sequestration potential, which are only available from 17 of the 150 countries where macroalgal forests occur. To solve this issue, we present a framework to categorize coastlines according to their carbon sequestration potential. Finally, we review the multiple avenues through which this sequestration can translate into climate change mitigation capacity, which largely depends on whether management interventions can increase carbon removal above a natural baseline or avoid further carbon emissions. We find that conservation, restoration and afforestation interventions on macroalgal forests can potentially lead to carbon removal in the order of 10's of Tg C globally. Although this is lower than current estimates of natural sequestration value of all macroalgal habitats (61-268 Tg C year ), it suggests that macroalgal forests could add to the total mitigation potential of coastal blue carbon ecosystems, and offer valuable mitigation opportunities in polar and temperate areas where blue carbon mitigation is currently low. Operationalizing that potential will necessitate the development of models that reliably estimate the proportion of production sequestered, improvements in macroalgae carbon fingerprinting techniques, and a rethinking of carbon accounting methodologies. The ocean provides major opportunities to mitigate and adapt to climate change, and the largest coastal vegetated habitat on Earth should not be ignored simply because it does not fit into existing frameworks.
Topics: Ecosystem; Carbon Sequestration; Climate Change; Seaweed; Forests; Carbon
PubMed: 37437379
DOI: 10.1111/brv.12990 -
Health Affairs (Project Hope) Oct 2023In August 2022 the Department of Health and Human Services (HHS) issued a notice of proposed rulemaking prohibiting covered entities, which include health care providers... (Review)
Review
In August 2022 the Department of Health and Human Services (HHS) issued a notice of proposed rulemaking prohibiting covered entities, which include health care providers and health plans, from discriminating against individuals when using clinical algorithms in decision making. However, HHS did not provide specific guidelines on how covered entities should prevent discrimination. We conducted a scoping review of literature published during the period 2011-22 to identify health care applications, frameworks, reviews and perspectives, and assessment tools that identify and mitigate bias in clinical algorithms, with a specific focus on racial and ethnic bias. Our scoping review encompassed 109 articles comprising 45 empirical health care applications that included tools tested in health care settings, 16 frameworks, and 48 reviews and perspectives. We identified a wide range of technical, operational, and systemwide bias mitigation strategies for clinical algorithms, but there was no consensus in the literature on a single best practice that covered entities could employ to meet the HHS requirements. Future research should identify optimal bias mitigation methods for various scenarios, depending on factors such as patient population, clinical setting, algorithm design, and types of bias to be addressed.
Topics: Humans; Health Equity; Racial Groups; Delivery of Health Care; Health Personnel; Algorithms
PubMed: 37782868
DOI: 10.1377/hlthaff.2023.00553 -
The Journal of Clinical Investigation Mar 2024Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor with a need for novel therapies. So far, monotherapies have failed to prolong survival for these...
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor with a need for novel therapies. So far, monotherapies have failed to prolong survival for these patients, and combinatorial strategies have often shown severe, dose-limiting toxicities. In this issue of the JCI, Duchatel, Jackson, and colleagues address this challenge by introducing a drug combination that mitigates side effects and overcomes resistance. After identifying the PI3K/mTOR pathway as a therapeutic vulnerability, they treated DIPG-bearing mice with paxalisib and saw responses but also observed hyperglycemia as a severe side effect. Combining paxalisib with metformin mitigated this toxicity, but also upregulated protein kinase C (PKC) signaling. To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.
Topics: Humans; Mice; Animals; Brain Stem Neoplasms; Glioma; Metformin; Signal Transduction; Protein Kinase Inhibitors; Drug Combinations
PubMed: 38488006
DOI: 10.1172/JCI179144 -
Current Opinion in Infectious Diseases Aug 2023This review summarizes existing data on health inequities in antimicrobial stewardship, identifies data gaps and barriers, and reflects on mitigating factors for... (Review)
Review
PURPOSE OF REVIEW
This review summarizes existing data on health inequities in antimicrobial stewardship, identifies data gaps and barriers, and reflects on mitigating factors for achieving inclusion, diversity, access, and equity in antimicrobial stewardship.
RECENT FINDINGS
Studies show variable antimicrobial prescribing patterns and adverse events according to race/ethnicity, rurality, socioeconomic status, and other factors. Most studies demonstrating these inequities typically do not address their upstream drivers or interventions to mitigate them.
SUMMARY
Approaching antimicrobial stewardship through a lens of equity can allow antimicrobial stewardship programs (ASPs) opportunities to reach a wider population, and in doing so reduce health inequities. These opportunities include expanding ASPs beyond highly resourced institutions, educational outreach efforts, equity monitoring tools, incentivized equity metrics, and leadership diversification. Clinical research in this area also needs to address drivers of inequities and innovative approaches to mitigating and reducing them.
Topics: Humans; Antimicrobial Stewardship; Anti-Infective Agents
PubMed: 37284770
DOI: 10.1097/QCO.0000000000000934 -
EBioMedicine Oct 2023
Topics: Humans; Senotherapeutics; Cellular Senescence; Aging
PubMed: 37833009
DOI: 10.1016/j.ebiom.2023.104837 -
Journal of Ethnopharmacology Jan 2024As a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced...
ETHNOPHARMACOLOGICAL RELEVANCE
As a traditional Chinese anti-emetic formula, Xiao-Ban-Xia decoction (XBXD) was recorded in Golden Chamber, and has promising anti-emetic effect on chemotherapy-induced nausea and vomiting (CINV).
AIM OF THE STUDY
This study aimed to determine whether the underlying mechanism of XBXD against CINV is correlated to the restoration of cisplatin-induced PINK1/Parkin mediated mitophagy deficiency and mitigation of gastrointestinal inflammation.
MATERIALS AND METHODS
The rat pica model was established by intraperitoneal injection of cisplatin 6 mg/kg. The daily kaolin consumption, food intake and body weight were recorded every 24 h. The pathological damage of gastric antrum and ileum were observed by hematoxylin-eosin staining. The levels of serum reactive oxygen species (ROS), interleukin-1β (IL-1β) and interleukin-1β (IL-18) were detected by ELISA. The expression of microtubule-associated protein 1 light chain 3 (LC3) in gastric antrum and ileum was detected by Immunofluorescence staining. The levels of LC3II, P62/SQSTM1, PTEN-induced putative protein kinases (PINK1), E3 ubiquitin ligase (Parkin), AMP-dependent protein kinases (AMPK), phosphorylated AMPK (p-AMPK), nuclear factor erythroid 2-related factor (Nrf2) and kelch like ECH Associated Protein 1 (Keap1) in gastric antrum and ileum were assayed by western blotting.
RESULTS
At 24 h and 72 h following cisplatin challenge, XBXD inhibited cisplatin-induced elevation of kaolin consumption, and improved the daily food intake and body weight loss in rats. Cisplatin-induced gastrointestinal histopathological damages were alleviated, and serum levels of ROS, IL-1β and IL-18 increases were mitigated following XBXD treatments. In gastric antrum and ileum, XBXD activated AMPK-Nrf2 signaling pathway and restored cisplatin-induced PINK1/Parkin mediated mitophagy deficiency.
CONCLUSIONS
XBXD significantly ameliorated CINV in a cisplatin-induced rat pica model. The underlying anti-emetic mechanism of XBXD might be related to the activation of AMPK-Nrf2 signaling pathway and the restoration of cisplatin-induced PINK1/Parkin-mediated mitophagy deficiency in the gastrointestinal tract.
Topics: Rats; Animals; Mitophagy; Cisplatin; Kelch-Like ECH-Associated Protein 1; Interleukin-18; Interleukin-1beta; AMP-Activated Protein Kinases; Antiemetics; Kaolin; Pica; Pinellia; Reactive Oxygen Species; NF-E2-Related Factor 2; Ubiquitin-Protein Ligases; Vomiting
PubMed: 37422100
DOI: 10.1016/j.jep.2023.116882