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Aims Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. Methods and results We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites—D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with β-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/β-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. Conclusion Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2–3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects. [ABSTRACT FROM AUTHOR]

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)–stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3β (GSK3β) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α–stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis. [ABSTRACT FROM AUTHOR]

In this study, we developed a XGBoost-based algorithm to downscale 2 km-resolution land surface temperature (LST) data from the GOES satellite to a finer 70 m resolution, using ancillary variables including NDVI, NDBI, and DEM. This method demonstrated a superior performance over the conventional TsHARP technique, achieving a reduced RMSE of 1.90 °C, compared to 2.51 °C with TsHARP. Our approach utilizes the geostationary GOES satellite data alongside high-resolution ECOSTRESS data, enabling hourly LST downscaling to 70 m—a significant advancement over previous methodologies that typically measure LST only once daily. Applying these high-resolution LST data, we examined the hottest days in Chicago and their correlation with ethnic inequality. Our analysis indicated that Hispanic/Latino communities endure the highest LSTs, with a maximum LST that is 1.5 °C higher in blocks predominantly inhabited by Hispanic/Latino residents compared to those predominantly occupied by White residents. This study highlights the intersection of urban development, ethnic inequality, and environmental inequities, emphasizing the need for targeted urban planning to mitigate these disparities. The enhanced spatial and temporal resolution of our LST data provides deeper insights into diurnal temperature variations, crucial for understanding and addressing the urban heat distribution and its impact on vulnerable communities. [ABSTRACT FROM AUTHOR]

Acidogenic fermentation is an emerging biotechnology that allows for the utilization of food waste as a feedstock to produce high-value products such as short-chain fatty acids (SCFAs), effectively offering a tangible solution for food waste management as well as resource recovery. The objectives of the current study were to identify the ideal inoculum, waste-activated sludge (WAS) or anaerobic digester sludge (AD), for the acidogenic fermentation of food waste at room temperature, as well as to evaluate the impact of heat pretreatment of these inoculums on fermentation performance. The maximum hydrolysis yield of 399 g sCOD/kg VS added was obtained when untreated AD was used as the inoculum, whereas the pretreated AD inoculum provided the highest SCFA yield and conversion efficiency of 238 g sCODSCFA/kg VS added and 71%, respectively. Heat pretreatment had a detrimental impact on the WAS inoculum, leading to lower hydrolysis and SCFA yields, but exerted a positive influence on the AD inoculum. The microbial community showed that heat pretreatment negatively impacted the abundance of non-spore-forming hydrolytic and acidogenic microorganisms. Overall, this study demonstrates the critical role of inoculum type and heat pretreatment in optimizing the acidogenic fermentation process, laying the groundwork for future refinements in SCFA production from food waste through inoculum design. [ABSTRACT FROM AUTHOR]

Excessive lipid accumulation in adipocytes is a primary contributor to the development of metabolic disorders, including obesity. The consumption of bioactive compounds derived from natural sources has been recognized as being safe and effective in preventing and alleviating obesity. Therefore, we aimed to explore the antilipidemic effects of pennogenin 3-O-β-chacotrioside (P3C), a steroid glycoside, on hypertrophied 3T3-L1 adipocytes. Oil Red O and Nile red staining demonstrated a P3C-induced reduction in lipid droplet accumulation. Additionally, the increased expression of adipogenic and lipogenic factors, including PPARγ and C/EBPα, during the differentiation process was significantly decreased by P3C treatment at both the protein and mRNA levels. Furthermore, P3C treatment upregulated the expression of fatty acid oxidation-related genes such as PGC1α and CPT1a. Moreover, mitochondrial respiration and ATP generation increased following P3C treatment, as determined using the Seahorse XF analyzer. P3C treatment also increased the protein expression of mitochondrial oxidative phosphorylation in hypertrophied adipocytes. Our findings suggest that P3C could serve as a natural lipid-lowering agent, reducing lipogenesis and enhancing mitochondrial oxidative capacity. Therefore, P3C may be a promising candidate as a therapeutic agent for obesity-related diseases. [ABSTRACT FROM AUTHOR]

We compare high‐resolution land‐surface temperature (LST) estimates from the GOES‐16/17 (GOES) satellites to ERA‐5 Land (ERA‐5) reanalysis data across nine large US cities. We quantify the offset and find that ERA‐5 generally overestimates LST compared to GOES by 1.63°C. However, this overestimation is less pronounced in urban areas, underscoring the limitations of ERA‐5 in capturing the LST gradient between urban and non‐urban areas. We then examine three quantities: Surface Urban Heat Island Intensity (SUHII), extreme LST events, and LST exposure by population. We find that ERA‐5 does not accurately represent the diurnal variation and magnitude of SUHII in GOES. Furthermore, while ERA‐5 was on average too warm, ERA‐5 underestimates extreme heat by an average of 2.40°C. Our analysis reveals higher population exposure to high LST in the GOES data set across the cities studied. This discrepancy is especially pronounced when estimating the population fraction that are most exposed to heat. Key Points: Land‐surface temperature (LST) from ERA‐5 Land are on average warmer than GOES‐16 and 17 estimates, but for extremely hot conditions, ERA‐5 underestimates LSTERA‐5 Land does not accurately represent the magnitude and diurnal cycle of surface urban heat island effectGOES‐16 and 17 show higher population exposure to extreme LST compared to ERA‐5 Land [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of Poncirus trifoliata aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT. [ABSTRACT FROM AUTHOR]

Diabetes is characterized by persistently high blood glucose levels and severe complications and affects millions of people worldwide. In this study, we explored the epigenetic landscape of diabetes using data from the Korean Genome and Epidemiology Study (KoGES), specifically the Ansung–Ansan (AS–AS) cohort. Using epigenome-wide association studies, we investigated DNA methylation patterns in patients with type 2 diabetes mellitus (T2DM) and those with normal glucose regulation. Differential methylation analysis revealed 106 differentially methylated probes (DMPs), with the 10 top DMPs prominently associated with TXNIP, PDK4, NBPF20, ARRDC4, UFM1, PFKFB2, C7orf50, and ABCG1, indicating significant changes in methylation. Correlation analysis highlighted the association between the leading DMPs (e.g., cg19693031 and cg26974062 for TXNIP and cg26823705 for NBPF20) and key glycemic markers (fasting plasma glucose and hemoglobin A1c), confirming their relevance in T2DM. Moreover, we identified 62 significantly differentially methylated regions (DMRs) spanning 61 genes. A DMR associated with PDE1C showed hypermethylation, whereas DMRs associated with DIP2C, FLJ90757, PRSS50, and TDRD9 showed hypomethylation. PDE1C and TDRD9 showed a strong positive correlation between the CpG sites included in each DMR, which have previously been implicated in T2DM-related processes. This study contributes to the understanding of epigenetic modifications in T2DM. These valuable insights can be utilized in identifying potential biomarkers and therapeutic targets for effective management and prevention of diabetes. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (Pgc1α), and downregulated adipogenic/lipogenic genes (Pparγ and C/ebpα) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (il-6, Tnf-α, Cox-2, and inos), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders. [ABSTRACT FROM AUTHOR]

Mortality due to extreme temperatures is one of the most worrying impacts of climate change. In this analysis, we use historic mortality and temperature data from 106 cities in the United States to develop a model that predicts deaths attributable to temperature. With this model and projections of future temperature from climate models, we estimate temperature‐related deaths in the United States due to climate change, changing demographics, and adaptation. We find that temperature‐related deaths increase rapidly as the climate warms, but this is mainly due to an expanding and aging population. For global average warming below 3°C above pre‐industrial levels, we find that climate change slightly reduces temperature‐related mortality in the U.S. because the reduction of cold‐related mortality exceeds the increase in heat‐related deaths. Above 3°C warming, whether the increase in heat‐related deaths exceeds the decrease in cold‐related deaths depends on the level of adaptation. Southern U.S. cities are already well adapted to hot temperatures and the reduction of cold‐related mortality drives overall lower mortality. Cities in the Northern U.S. are not well adapted to high temperatures, so the increase in heat‐related mortality exceeds the reduction in cold‐related mortality. Thus, while the total number of climate‐related mortality may not change much, climate change will shift mortality in the U.S. to higher latitudes. Plain Language Summary: Deaths due to extreme temperatures is one of the most important impacts of climate change. Here we estimate future temperature related deaths in the US using climate projection, population projection, and adaptation assumptions. We find that in 3°C of global warming level, temperature‐related deaths will increase by a factor of five, mostly due to aging and increasing population. Below 3°C warming, impact of climate change slightly decreases temperature‐related deaths, because the decrease in cold‐related deaths exceeds the increase in heat‐related deaths. Above 3°C warming, impact of climate change depends on the level of adaptation. Furthermore, we find that temperature‐related mortality shifts Northward. This is due to increase of heat‐related deaths in Northern cities, which are currently poorly adapted to heat. Key Points: Temperature‐related deaths in the U.S. will increase by a factor of 5 with 3°C of warming, mostly due to aging and increasing populationImpact of climate change is not significant until 3°C of global warming, and it depends on the level of adaptation beyond that pointTemperature‐related deaths will shift Northward, due to increasing heat‐related deaths in poorly heat‐adapted Northern cities [ABSTRACT FROM AUTHOR]

This study evaluated the hydrolysis and acidogenesis of food waste at different operating pHs (uncontrolled, 5.5, 6.5, 7.5, 8.5) in a leachate bed reactor (LBR) at room temperature. LBR operation at pH 6.5–8.5 resulted in a hydrolysis yield of 718–729 g SCOD/kg VSadded, which was statistically (p ≤ 0.05) higher than that obtained at pH 5.5 (577 g SCOD/kg VSadded) and the uncontrolled pH (462 g SCOD/kg VSadded). The hydrolysis rate at pH 6.5 was the highest amongst all the pH values. Stabilization at pH at 6.5 also resulted in a high fatty acid (FA) yield of 643 g CODFA/kg VSadded. Butyrate was the main FA at the pH of 5.5–6.5, while acetate was the main FA at the pH of 7.5–8.5. At the uncontrolled pH, lactate production was the highest, indicating a shift in the microbial community from fatty-acid-producing bacteria to lactate-producing bacteria. The compositions of medium-chain fatty acids, such as caproate, were the highest at pH of 5.5. [ABSTRACT FROM AUTHOR]