Conditions Of Oxygen Deprivation Research Articles

Source rock assessment and organic matter characterization of the Oligocene upper Shahejie and Dongying formations in the Nanpu depression of the saline lacustrine Bohai Bay basin, China: Geochemical, palynological, and mineralogical perspectives

The Bohai Bay Basin, located in eastern China, is a significant petroliferous, non-marine rift basin, underwent intricate tectonic activities throughout the Cenozoic. The Nanpu Depression in the Huanghua sub-basin in the northern part of the basin was controlled by Paleogene rifting and increased subsidence. These geological processes resulted in the deposition of the Shahejie and Dongying formations, which exhibited varying quantities and qualities of organic matter. Eighty drill cuttings samples of the Paleogene First Member (Es1) and the overlying Third (Ed3) and Second (Ed2) members of the Shahejie and Dongying formations, respectively, were investigated. An integrated approach including organic and inorganic geochemistry, palynology, and mineralogy was employed to assess the paleoredox and marine incursion conditions, source rock quality and levels of thermal maturity, and factors that governed organic matter accumulation. Results indicated that the Es1 Member was deposited under anoxic conditions, resulting in the accumulation of organic matter-rich mudstones in the Nanpu Depression. Abundant pollen grains and acritarchs were found in the Es1 Member yielded along with minor occurrences of dinoflagellate cysts, freshwater algae, and spores. Terrestrial palynomorph composition provided evidence of increased terrestrial runoff, while the high abundance of acritarchs, accompanied by some dinoflagellate cysts, confirmed episodes of marine incursion and deposition under hypersaline conditions in the lacustrine Bohai Bay Basin. The Ed2 Member exhibited poor to fair amounts of organic matter and a limited potential of hydrocarbon generation with a variety of kerogen Types, including IV, III, II/III, and II. The Ed3 Member shows fair to good organic matter richness and hydrocarbon potential of kerogen Types III, II/III, and II. The Es1 Member emerged as the most promising source rock within the studied interval, boasting good to excellent organic matter richness, and fair to good hydrocarbon generation potential of kerogen Types III and II/III. Evaluating the thermal maturity of organic matter, based on Tmax and VRo-Eq% and related cross-plots, revealed that the Shahejie and Dongying formations are still in the immature to the early stage of the oil window. The mineralogical composition of the Es1 Member primarily consists of clay and quartz with some carbonate and accessory minerals, such as epigenetic halite, dolomite, and plagioclase. Weak correlations observed between the total organic carbon (TOC) and mineral components indicated that the availability of organic matter was primarily controlled by enhanced production and preservation rather than limited dilution under saline lacustrine, oxygen-deprived, and well-stratified water column conditions. Regional investigations of the Es1 Member confirmed the widespread anoxia and deposition of organic-rich source rocks in the Bohai Bay Basin during the Oligocene.

A Microphysiological Model to Mimic the Placental Remodeling during Early Stage of Pregnancy under Hypoxia-Induced Trophoblast Invasion.

Placental trophoblast invasion is critical for establishing the maternal-fetal interface, yet the mechanisms driving trophoblast-induced maternal arterial remodeling remain elusive. To address this gap, we developed a three-dimensional microfluidic placenta-on-chip model that mimics early pregnancy placentation in a hypoxic environment. By studying human umbilical vein endothelial cells (HUVECs) under oxygen-deprived conditions upon trophoblast invasion, we observed significant HUVEC artery remodeling, suggesting the critical role of hypoxia in placentation. In particular, we found that trophoblasts secrete matrix metalloproteinase (MMP) proteins under hypoxic conditions, which contribute to arterial remodeling by the degradation of extracellular matrix components. This MMP-mediated remodeling is critical for facilitating trophoblast invasion and proper establishment of the maternal-fetal interface. In addition, our platform allows real-time monitoring of HUVEC vessel contraction during trophoblast interaction, providing valuable insights into the dynamic interplay between trophoblasts and maternal vasculature. Collectively, our findings highlight the importance of MMP-mediated arterial remodeling in placental development and underscore the potential of our platform to study pregnancy-related complications and evaluate therapeutic interventions.

The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration.

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent forms of neurodegeneration. To date, a substantial body of experimental evidence has strongly implicated hypoxia in the pathogenesis of numerous neurological disorders, including AD, PD, and other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) is a transcription factor that triggers a cell survival program in conditions of oxygen deprivation. The involvement of HIF-1α in neurodegenerative processes presents a complex and sometimes contradictory picture. This review aims to elucidate the current understanding of the interplay between hypoxia and the development of AD and PD, assess the involvement of HIF-1 in their pathogenesis, and summarize promising therapeutic approaches centered on modulating the activity of the HIF-1 complex.

SDF-1/CXCR4 axis participants in the pathophysiology of adult patients with moyamoya disease

BackgroundMoyamoya disease (MMD) is characterized by an abundance of moyamoya vessels; however, the precise mechanism driving the spontaneous angiogenesis of these compensatory vessels remains unclear. Previous research has established a link between the stromal cell-derived factor-1 (SDF-1)/ CXC receptor 4 (CXCR4) axis and angiogenesis under hypoxic conditions. Nevertheless, the alterations in this axis within the cerebrospinal fluid, arachnoid membranes and vascular tissue of MMD patients have not been fully investigated. MethodsOur study enrolled 66 adult MMD patients and 61 patients with atherosclerotic vascular disease (ACVD). We investigated the SDF-1 concentration in cerebrospinal fluid (CSF) and CXCR4 expression level on the arachnoid membranes and vascular tissue. We utilized enzyme-linked immunosorbent assay and immunohistochemistr. Additionally, we cultured and stimulated human brain microvascular endothelial cells (HBMECs) and smooth muscle cells (SMCs) under oxygen and glucose deprivation (OGD) conditions followed by reoxygenation, to examine any changes in the SDF-1/CXCR4 axis. ResultsThe results demonstrated an elevation in the level of SDF-1 in CSF among MMD patients compared to those with ACVD. Moreover, the expression of CXCR4 in arachnoid membranes and vascular tissue showed a similar trend. Furthermore, the content of CXCR4 in HBMECs and SMCs increased with the duration of ischemia and hypoxia. However, it was observed that the expression of CXCR4 decreased at OGD/R 24h compared to OGD 24h. The temporal pattern of SDF-1 expression in HBMECs and SMCs mirrored that of CXCR4 expression. ConclusionThese findings indicate a critical role for the SDF-1/CXCR4 axis in the angiogenesis of moyamoya disease.

Centella asiatica extract ameliorates deoxygenation-induced neurological dysfunction in zebrafish larvae

Background: Oxygen deprivation (OD) is a critical condition that can lead to brain damage and even death. Current hypoxia management approaches are limited in effectiveness. Centella asiatica, known for its neuroprotective properties, offers a potential alternative for OD treatment. Aim: This study aims to investigate the neuroprotective effects of Centella asiatica (CA) on the expression of Brain-Derived Neurotrophic Factor (BDNF) and Vesicular Glutamate Transporter 1 (VGLUT1) in zebrafish larvae under oxygen-deficient conditions. Methods: Zebrafish embryos were subjected to low oxygen levels (1.5 mg/L) 0-2 hours post-fertilization (hpf) until three days post-fertilization (dpf), simulating the early stages of OD. Subsequent treatment involved varying concentrations of CA (1.25-5 µg/ml) up to nine days post-fertilization. The expression levels of BDNF and VGLUT1 were measured using PCR methods. Statistical analysis was conducted using Two-way ANOVA to evaluate the impact of CA on the expression of BDNF and VGLUT1 in zebrafish larvae aged 3 and 9 dpf in oxygen-deprived conditions. Results: CA significantly influenced the expression of BDNF and VGLUT1 under oxygen deprivation (p<0.001). An increase in BDNF expression (p<0.001) and a decrease in VGLUT1 (p<0.01) were observed in zebrafish larvae experiencing OD and treated with CA. There was no significant difference in BDNF and VGLUT1 expression across age variations in zebrafish larvae at 3 dpf and 9 dpf in the treatment groups (p>0.05). CA concentration of 2.5 µg/ml effectively enhanced BDNF and reduced VGLUT1 in 3-9 dpf zebrafish larvae. Conclusion: CA demonstrates potential as a neuroprotective agent, modulating increased BDNF expression and reduced VGLUT1 under OD conditions. These findings lay a foundation for further research in developing therapies for oxygen deficiency.

Abstract #1604668: Insulin-Like Growth Factor Binding Protein 4 Increases Under Stressful Conditions of Transient Oxygen Deprivation

Abstract #1604668: Insulin-Like Growth Factor Binding Protein 4 Increases Under Stressful Conditions of Transient Oxygen Deprivation

Screening of potential donors for anaerobic stress tolerance during germination in rice.

The rising cost of transplanting rice has made direct seeding an affordable alternative for rice establishment, particularly in Africa. However, direct seeding, while cost-effective, faces crop establishment challenges due to flooding. Uncontrolled water, driven by erratic rains in low-lying areas or uneven fields, limit germination. Rice possesses the unique ability of anaerobic germination, enabling it to sprout and emerge in oxygen-deprived conditions. Understanding rice's response to anaerobic stress during germination is crucial for resilience breeding. Africa, although relying on direct seeding, has made limited progress in addressing flooding during germination compared to Asia. Anaerobic stress tolerance ensures successful crop emergence even in oxygen-limited environments and can help suppress weeds, a significant challenge in direct-seeded rice cultivation. This study aims to contribute by screening for potential rice donors exhibiting anaerobic stress tolerance. We screened 200 rice genotypes at Sokoine University of Agriculture (SUA) in Morogoro, Tanzania, primarily focusing on landraces with untapped potential. Using an alpha lattice design, we conducted two anaerobic experiments in September and October 2022, adding 7cm of standing water immediately after dry seeding for flooded and maintaining a 2cm water level after germination in the control for duration of 21 days. We identified potential donors based on selection index computed from genomic estimated breeding values (GEBVs) using eight variables: germination at 14 DAS, germination at 21 DAS, seedling height at 14 DAS, seedling height at 21 DAS, shoot dry matter at 21 DAS, root dry matter at 21 DAS, culm diameter at 21 DAS, and root length at 21DAS. Ten genotypes emerged as the most promising, exhibiting at least 70% germination in floodwater at 21 DAS and greater selection indices. These genotypes were like: Afaa Mwanza 1/159, Rojomena 271/10, Kubwa Jinga, Wahiwahi, Magongo ya Wayungu, Mpaka wa Bibi, Mwangaza, Tarabinzona, IB126-Bug 2013A, and Kanamalia with respective percentages of 75, 74, 71, 86, 75, 80, 71, 80, 70, and 73. These findings contribute to global efforts to mitigate the impacts of flooding during germination. These donors, will be potential to enrich the gene pool for anaerobic germination, providing valuable resources for breeding for flooding tolerance.

LncRNAs and CircRNAs as Strategies against Pathological Conditions Caused by a Hypoxic/Anoxic State.

Brain damage can be induced by oxygen deprivation. It is known that hypoxic or anoxic conditions can lead to changes in the expression levels of non-coding RNAs (ncRNAs), which, in turn, can be related to Central Nervous System (CNS) injuries. Therefore, it could be useful to investigate the involvement of non-coding RNAs (ncRNAs), as well as the underlying mechanisms which are able to modulate them in brain damage induced by hypoxic or anoxic conditions. In this review, we focused on recent research that associates these conditions with long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). The results of this review demonstrate that the expression of both lncRNAs and circRNAs can be influenced by oxygen deprivation conditions and so they can contribute to inducing damage or providing neuroprotection by affecting specific molecular pathways. Furthermore, several experimental studies have shown that ncRNA activity can be regulated by compounds, thus also modifying their transcriptomic profile and their effects on CNS damages induced by hypoxic/anoxic events.

Actinidia chinensis Planch. root extract attenuates hypoxia-induced hepatic stellate cell activation and epithelial–mesenchymal transition in hepatocellular carcinoma by inhibiting inflammatory cytokine secretion

IntroductionHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Several studies have demonstrated the potency of Chinese herbs in protecting the liver from inflammation, hypoxia, fibrosis, and cancer. The roots of Actinidia chinensis Planch. exhibit strong anti-tumour effects; however, their mechanisms of action in HCC are not clearly understood. MethodsTo investigate the molecular mechanisms underlying the anti-cancer effect of A chinensis Planch. root extract (acRoot) in HCC and hepatic stellate cells (HSCs). The HSC line LX2 and HCC cell line MHCC97H were cultured under oxygen-rich or oxygen-deprived conditions and then exposed to various acRoot concentrations for different periods. Subsequently, cell viability, cytotoxicity, and enzyme-linked immunosorbent assays and western blotting were conducted to assess the effects of acRoot treatment. ResultsacRoot decreased the number of viable LX2 and MHCC97H cells in a concentration- and time-dependent manner. Under hypoxic and/or co-culture conditions, pro-inflammatory cytokine expression was up-regulated in both cell lines; however, the expression levels were significantly decreased following treatment with acRoot. Additionally, acRoot inhibited hypoxia-induced activation of LX2 cells and inflammation and epithelial–mesenchymal transition (EMT) in MHCC97H cells. Moreover, acRoot inhibited cross-talk between LX2 and MHCC97H cells, further inhibiting cellular activation, inflammation, and EMT. ConclusionThese results show the therapeutic potential of acRoot as an anti-cancer, anti-inflammatory, and anti-fibrotic agent, shedding new light on the medicinal properties of Chinese herbs.

The invasive twospot livebearer's biology, its current and potential global distribution.

Poeciliids are widely recognised as successful invaders, possessing traits associated with invasion success. Native to Central America and south-eastern Mexico, the twospot livebearer (Pseudoxiphophorus bimaculatus) is a species recently recognised as invasive in both Central and Northern Mexico. Despite its invasive status, limited research exists on its invasion process and the potential threats it poses to native species. In this study, we conducted a comprehensive review of the current knowledge on the twospot livebearer and mapped its current and potential distribution worldwide. The twospot livebearer shares similar traits with other successful invaders within the same family. Notably, it exhibits high fecundity throughout the year and demonstrates resilience to highly polluted and oxygen-deprived water conditions. This fish serves as a host for several parasites, including generalists, and has been extensively translocated for commercial purposes. Recently, it has also been used for biocontrol within its native range. Apart from existing outside its native range, the twospot livebearer, under current climate conditions and if transported there, could readily colonise biodiversity hotspots in tropical zones worldwide, including the Caribbean Islands, the Horn of Africa, North of the Madagascar Island, the south-eastern Brazil, and Asia-Pacific. Given that this fish is highly plastic and our Species Distribution Model, we consider that all areas with a habitat suitability >0.2 should prevent its arrival and establishment. Our findings underscore the urgent need to recognise this species as a threat to freshwater native topminnows and prevent its introduction and spread. This article is protected by copyright. All rights reserved.

Experimental application results of mesenchymal stem cell microvesicles in the mouse model of acute renal failure

An important role in restoration of damaged organs and tissues is played by mesenchymal stem cells (MSCs) and microvesicular particles (MV) produced by them. They can be a source of cytokines, anti- apoptotic and growth stimulating factors. In addition, MVs carry out transport of mRNA, miRNA, and signal proteins into damaged tissues. This increases the ability of cells to regenerate and to inhibit apoptosis, promote to angiogenesis and stimulate cell proliferation. The aim of our research was to study the immunoregulatory and pro-regenerative properties of mesenchymal stem cell microvesicles (MSC-MV) in a model of glycerol- induced acute renal failure (ARF) in mice. The experiments were carried out on CBA mice aged 3-4 months. AKI was induced by a single intramuscular injection of 50% glycerol. MSCs were obtained from the bone marrow of healthy animals and cultivated under standard conditions. Microvesicles were obtained by centrifugation at 12000g of MSC supernatant after induction of their apoptosis by culturing under oxygen deprivation conditions and in serum-free medium. MSC-MV was injected intravenously into the retroorbital sinus one day after induction of ARF. The MV dose was calculated as equivalent to (derived from) 1 million MSCs, which was 100 mL per mouse. Animals were taken out of the experiment on days 4 and 11 after MSC-MV injection. Blood plasma was taken to determine the level of creatinine, urine – for albumin analysis, kidneys – for histological examination. It has been shown that MVs induced by MSCs dose-dependently stimulated splenocyte proliferation in both spontaneous and Con-A induced tests. The addition of MV caused a decrease in doxorubicin-induced apoptosis of splenic lymphocytes in mice. Probably, in this case, MV produced by MSCs had an immunostimulatory and antiapoptotic effect. Also, MVs had a positive impact on the restoration of structure and function kidneys in a model of ARF in mice. The use of MSC-MV in treatment of acute renal failure induced by a single injection of 50% glycerol contributed to decrease albumin level urine and restoration of creatinine level in blood serum of animals. Morphological studies have shown decrease in the height cell and collecting duct diameter in the medulla and a decrease in the largest transverse diameter of superficial glomeruli in the renal cortex of sick mice. Thus, the obtained results indicate significant therapeutic and pro-regenerative properties of MSC-MV, which require further study.

Overexpression of DAPK1 and Beclin1 under oxygen and glucose deprivation conditions promotes excessive autophagy and apoptosis in A549 cells

AbstractIn this study, we aimed to determine the specific roles of death‐associated protein kinase 1 (DAPK1) and Beclin1 in non‐small cell lung cancer (NSCLC) under oxygen and glucose deprivation (OGD). We found that OGD caused most cells to shrink, aggregate, and produce many vacuoles in the cytoplasm. Transmission electron microscopy revealed the presence of autophagic vesicles in the OGD group but not in the Control group. Moreover, the cell counting kit‐8 assay showed that cell proliferation was reduced in the OGD group. Quantitative reverse transcription‐polymerase chain reaction, western blot, and cell function assays showed that DAPK1 overexpression under OGD promoted apoptosis and autophagy in A549 cells. The coimmunoprecipitation assay confirmed the interaction between DAPK1 and Beclin1 protein. Moreover, knockdown of Beclin1 inhibited autophagy, but its overexpression promoted apoptosis in A549 cells. In vivo tumorigenesis experiment revealed that overexpression of DAPK1 promoted A549 cell apoptosis. Collectively, overexpression of DAPK1 and Beclin1 under OGD promoted excessive autophagy and apoptosis in A549 cells. Our study may provide a novel therapeutic target and theoretical basis for NSCLC treatment.

HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia

The prevalence of non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is rising rapidly, yet its underlying mechanisms remain unclear. Herein, we aim to determine the role of hypoxia-inducible lipid droplet associated protein (HILPDA)/hypoxia-inducible gene 2 (HIG2), a selective inhibitor of intracellular lipolysis, in NASH-driven HCC. The clinical significance of HILPDA was assessed in human NASH-driven HCC specimens by immunohistochemistry and transcriptomics analyses. The oncogenic effect of HILPDA was assessed in human HCC cells and in 3D epithelial spheroids upon exposure to free fatty acids and either normoxia or hypoxia. Lipidomics profiling of wild-type and HILPDA knockout HCC cells was assessed via shotgun and targeted approaches. Wild-type (Hilpdafl/fl) and hepatocyte-specific Hilpda knockout (HilpdaΔHep) mice were fed a Western diet and high sugar in drinking water while receiving carbon tetrachloride to induce NASH-driven HCC. In patients with NASH-driven HCC, upregulated HILPDA expression is strongly associated with poor survival. In oxygen-deprived and lipid-loaded culture conditions, HILPDA promotes viability of human hepatoma cells and growth of 3D epithelial spheroids. Lack of HILPDA triggered flux of polyunsaturated fatty acids to membrane phospholipids and of saturated fatty acids to ceramide synthesis, exacerbating lipid peroxidation and apoptosis in hypoxia. The apoptosis induced by HILPDA deficiency was reversed by pharmacological inhibition of ceramide synthesis. In our experimental mouse model of NASH-driven HCC, HilpdaΔHep exhibited reduced hepatic steatosis and tumorigenesis but increased oxidative stress in the liver. Single-cell analysis supports a dual role of hepatic HILPDA in protecting HCC cells and facilitating the establishment of a pro-tumorigenic immune microenvironment in NASH. Hepatic HILPDA is a pivotal oncometabolic factor in the NASH liver microenvironment and represents a potential novel therapeutic target. Non-alcoholic steatohepatitis (NASH, chronic metabolic liver disease caused by buildup of fat, inflammation and damage in the liver) is emerging as the leading risk factor and the fastest growing cause of hepatocellular carcinoma (HCC), the most common form of liver cancer. While curative therapeutic options exist for HCC, it frequently presents at a late stage when such options are no longer effective and only systemic therapies are available. However, systemic therapies are still associated with poor efficacy and some side effects. In addition, no approved drugs are available for NASH. Therefore, understanding the underlying metabolic alterations occurring during NASH-driven HCC is key to identifying new cancer treatments that target the unique metabolic needs of cancer cells.

PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR.

Maintaining the integrity and protecting the stability of tight junctions in endothelial cells is a potential therapeutic strategy against myocardial ischaemia. Laminin receptors (67LR) are highly expressed on endothelial cell membranes and are associated with endothelial barrier function. Herein, we sought to demonstrate the direct effects of pigment epithelial-derived factor (PEDF) on tight junctions between endothelial cells via 67LR during acute myocardial infarction (AMI) and elucidate its underlying mechanisms. We detected that PEDF directly increased the level of the tight junction protein zonula occludens protein 1 (ZO-1) after overexpression in vitro and in vivo using Western blotting. Evans Blue/TTC staining showed that PEDF significantly reduced the size of the infarcted myocardium. Immunofluorescence and the transwell cellular experiments suggested that PEDF significantly upregulated PI3K-AKT permeability and the distribution of ZO-1 between endothelial cells under OGD conditions. Interestingly, PEDF significantly upregulated the phosphorylation levels of PI3K-AKT-mTOR under oxygen and glucose deprivation conditions but had no significant effects on the total protein expression. The protective effect of PEDF on ZO-1 was significantly inhibited following the inhibition of PI3K-AKT-mTOR. The activation of phosphorylation of PI3K-AKT-mTOR by PEDF was blocked after silencing 67LR, as were the protective effects of PEDF on ZO-1. Therefore, we have reason to believe that PEDF increased ZO-1 expression through the 67LR-dependent PI3K-AKT-mTOR signaling pathway, thus maintaining tight junction stability and protecting cardiac function.

LncRNA AC005332.7 Inhibited Ferroptosis to Alleviate Acute Myocardial Infarction Through Regulating miR-331-3p/CCND2 Axis.

Acute myocardial infarction (AMI) often occurs suddenly and leads to fatal consequences. Ferroptosis is closely related to the progression of AMI. However, the specific mechanism of ferroptosis in AMI remains unclear. We constructed a cell model of AMI using AC16 cells under oxygen and glucose deprivation (OGD) conditions and a mice model of AMI using the left anterior descending (LAD) ligation. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide was employed to determine cell viability. The levels of lactate dehydrogenase, creatine kinase, reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and iron were measured using corresponding kits. Dual luciferase reporter gene assay, RNA-binding protein immunoprecipitation, and RNA pull-down were performed to validate the correlations among AC005332.7, miR-331-3p, and cyclin D2 (CCND2). Hematoxylin and eosin staining was employed to evaluate myocardial damage. AC005332.7 and CCND2 were lowly expressed, while miR-331-3p was highly expressed in vivo and in vitro models of AMI. AC005332.7 sufficiency reduced ROS, MDA, iron, and ACSL4 while boosting the GSH and GPX4, indicating that AC005332.7 sufficiency impeded ferroptosis to improve cardiomyocyte injury in AMI. Mechanistically, AC005332.7 interacted with miR-331-3p, and miR-331-3p targeted CCND2. Additionally, miR-331-3p overexpression or CCND2 depletion abolished the suppressive impact of AC005332.7 on ferroptosis in OGD-induced AC16 cells. Moreover, AC005332.7 overexpression suppressed ferroptosis in mice models of AMI. AC005332.7 suppressed ferroptosis in OGD-induced AC16 cells and LAD ligation-operated mice through modulating miR-331-3p/CCND2 axis, thereby mitigating the cardiomyocyte injury in AMI, which proposed novel targets for AMI treatment.

Molecular investigation of the multi-phase photochemistry of Fe(III)-citrate in aqueous solution.

Iron (Fe) is ubiquitous in nature and found as FeII or FeIII in minerals or as dissolved ions Fe2+ or Fe3+ in aqueous systems. The interactions of soluble Fe have important implications for fresh water and marine biogeochemical cycles, which have impacts on global terrestrial and atmospheric environments. Upon dissolution of FeIII into natural aquatic systems, organic carboxylic acids efficiently chelate FeIII to form [FeIII-carboxylate]2+ complexes that undergo a wide range of photochemistry-induced radical reactions. The chemical composition and photochemical transformations of these mixtures are largely unknown, making it challenging to estimate their environmental impact. To investigate the photochemical process of FeIII-carboxylates at the molecular level, we conduct a comprehensive experimental study employing UV-visible spectroscopy, liquid chromatography coupled to photodiode array and high-resolution mass spectrometry detection, and oil immersion flow microscopy. In this study, aqueous solutions of FeIII-citrate were photolyzed under 365 nm light in an experimental setup with an apparent quantum yield of (φ) ∼0.02, followed by chemical analyses of reacted mixtures withdrawn at increment time intervals of the experiment. The apparent photochemical reaction kinetics of Fe3+-citrates (aq) were expressed as two generalized consecutive reactions of with the experimental rate constants of j1 ∼ 0.12 min-1 and j2 ∼ 0.05 min-1, respectively. Molecular characterization results indicate that R and I consist of both water-soluble organic and Fe-organic species, while P compounds are a mixture of water-soluble and colloidal materials. The latter were identified as Fe-carbonaceous colloids formed at long photolysis times. The carbonaceous content of these colloids was identified as unsaturated organic species with low oxygen content and carbon with a reduced oxidation state, indicative of their plausible radical recombination mechanism under oxygen-deprived conditions typical for the extensively photolyzed mixtures. Based on the molecular characterization results, we discuss the comprehensive reaction mechanism of FeIII-citrate photochemistry and report on the formation of previously unexplored colloidal reaction products, which may contribute to atmospheric and terrestrial light-absorbing materials in aquatic environments.

Simultaneously deplete reactive oxygen species and inhibit pyroptosis by dopamine/thioketal-containing polymers delivering disulfiram in combination with Cu(II) for acute glaucoma

Glaucoma is a worldwide prominent cause of irreversible vision damage, which is characterized by progressive loss of retinal ganglion cells (RGCs) and currently no effective treatment is available till far. Overexpression of reactive oxygen species (ROS) contribute to RGCs death. Moreover, pyroptosis mediate RGCs death also played a key role in neurodegeneration of glaucoma. However, there is no treatment available for glaucoma that can simultaneously prevent ROS generation and inhibit pyroptosis. Herein, bioinformatics analysis was firstly applied to identify the upregulation of a key protein N-terminal gasdermin D (N-GSDMD) can result in membrane pore formation in RGCs, leading to pyroptosis. Thereafter, disulfiram (DSF), a novel N-GSDMD inhibitor, was screened out which could be in combination with Cu(II) (DSF+Cu(II)) to significantly inhibit RGCs pyroptosis. To translate this effect in vivo, a ROS scavenging biodegradable polymer containing dopamine and thioketal bonds was designed to deliver DSF as nanoparticles (DSF-NPs). Once DSF-NPs were internalized by RGCs, the high intracellular ROS could break up the thioketal bonds to release dopamine for depleting ROS and simultaneously release DSF which could work in combination with Cu(II) for inhibiting RGCs pyroptosis. In vitro, DSF-NPs+Cu(II) was proved to protect R28 cells significantly better than DSF+Cu(II) under oxygen and glucose deprivation (OGD) conditions. In vivo, DSF-NPs could accumulate in the RGCs of an ischemia/reperfusion (I/R) mouse model after intravitreal injection, which further worked together with Cu(II) to significantly inhibit RGCs pyroptosis. Taken together, DSF-NPs+Cu(II) can selectively inhibit pyroptosis of RGCs, resulting in considerable protection from high intraocular pressure injury, providing a new therapeutic strategy for acute glaucoma.

Tanshinone IIA reduces AQP4 expression and astrocyte swelling after OGD/R by inhibiting the HMGB1/RAGE/NF-κB/IL-6 pro-inflammatory axis

This study aimed to investigate the role of tanshinone IIA (TSO IIA) in astrocytic swelling caused by ischemia–reperfusion-like injury in an in vitro model and the molecular mechanisms underlying this effect. Primary brain astrocytes were cultured under conditions of glucose and oxygen deprivation and reoxygenation (OGD/R). The study explored the effects of TSO IIA treatment on cell swelling and injury and the protein levels of aquaporin 4 (AQP4) in the plasma membrane. It then examined the involvement of the high-mobility group box protein 1 (HMGB1)/receptors for advanced-glycation end products (RAGE)/nuclear factor-kappa B (NF-κB)/interleukin-6 (IL-6) pro-inflammatory axis in TSO IIA-mediated protection. The treatment with TSO IIA alleviated OGD/R-induced astrocytic swelling and the overclustering of AQP4 protein in the plasma membrane. In addition, TSO IIA significantly reduced the overexpression of HMGB1 and the high levels of the NF-κB protein in the nucleus and of the IL-6 protein in the cytoplasm and extracellular media induced by OGD/R. The combination of TSO IIA and recombinant HMGB1 reversed these effects. The inhibition of the RAGE, the receptor of HMGB1, induced results similar to those of TSO IIA. In addition, exogenous IL-6 reversed TSO IIA-mediated effect on AQP4 overclustering and cell swelling. TSO IIA significantly reduced astrocyte swelling after OGD/R injury in vitro, via blocking the activation of the HMGB1/RAGE/NF-κB/IL-6 pro-inflammatory axis and thereby decreasing the expression of AQP4 in the plasma membrane.

Polystyrene Degradation by Exiguobacterium sp. RIT 594: Preliminary Evidence for a Pathway Containing an Atypical Oxygenase

The widespread use of plastics has led to their increasing presence in the environment and subsequent pollution. Some microorganisms degrade plastics in natural ecosystems and the associated metabolic pathways can be studied to understand the degradation mechanisms. Polystyrene (PS) is one of the more recalcitrant plastic polymers that is degraded by only a few bacteria. Exiguobacterium is a genus of Gram-positive poly-extremophilic bacteria known to degrade PS, thus being of biotechnological interest, but its biochemical mechanisms of degradation have not yet been elucidated. Based solely on genome annotation, we initially proposed PS degradation by Exiguobacterium sp. RIT 594 via depolymerization and epoxidation catalyzed by a ring epoxidase. However, Fourier transform infrared (FTIR) spectroscopy analysis revealed an increase of carboxyl and hydroxyl groups with biodegradation, as well as of unconjugated C-C double bonds, both consistent with dearomatization of the styrene ring. This excludes any aerobic pathways involving side chain epoxidation and/or hydroxylation. Subsequent experiments confirmed that molecular oxygen is critical to PS degradation by RIT 594 because degradation ceased under oxygen-deprived conditions. Our studies suggest that styrene breakdown by this bacterium occurs via the sequential action of two enzymes encoded in the genome: an orphan aromatic ring-cleaving dioxygenase and a hydrolase.

IFN-γ enhances the efficacy of mesenchymal stromal cell-derived exosomes via miR-21 in myocardial infarction rats

BackgroundMesenchymal stromal cells (MSCs) activated with IFN-γ elicit stronger physical effects. Exosomes (Exos) secreted from MSCs show protective effects against myocardial injury. This study aimed to determine whether Exos derived from IFN-γ-treated MSCs exhibit more potent cardioprotective function and the underlying mechanisms.MethodsH9c2 cells or human umbilical vein endothelial cells (HUVECs) were treated with Exos isolated from MSCs (Ctrl-Exo) or IFN-γ-primed MSCs (IFN-γ-Exo) under oxygen and glucose deprivation (OGD) conditions in vitro and in vivo in an infarcted rat heart. RNA sequencing was used to identify differentially expressed functional transcription factors (TFs). Quantitative reverse transcription-PCR (qPCR) was used to confirm the upregulated TFs and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay was used to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was determined by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD conditions.ResultIFN-γ-Exo accelerated migration and tube-like structure formation and prevented OGD-induced apoptosis in H9c2. Similarly, IFN-γ-Exo treatment caused a decrease in fibrosis, reduced cardiomyocyte apoptosis, and improved cardiac function compared to Ctrl-Exo treatment. MiR-21 was significantly upregulated in IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 could inhibit BTG anti-proliferation factor 2 (BTG2) expressions. BTG2 promoted H9c2 cell apoptosis and reversed the protective effects of miR-21 under OGD conditions.ConclusionIFN-γ-Exo showed enhanced therapeutic efficacy against acute MI, possibly by promoting angiogenesis and reducing apoptosis by upregulating miR-21, which directly targeted BTG2.