Background and aims
Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, the utility of which has not been tested and validated in real world. We aimed to compare the ...characteristics of MAFLD and non‐alcoholic fatty liver disease (NAFLD).
Methods
The data was retrieved from the third National Health and Nutrition Examination Surveys of the United States, which is an unbiased survey dataset and frequently used for the study of fatty liver disease.
Results
A total of 13 083 cases with completed ultrasonography and laboratory data were identified from the NHANES III database. MAFLD was diagnosed in 4087/13 083 (31.24%) participants, while NAFLD in 4347/13 083 (33.23%) amongst the overall population and 4347/12 045 (36.09%) in patients without alcohol intake and other liver diseases. Compared with NAFLD, MAFLD patients were significantly older, had higher BMI level, higher proportions of metabolic comorbidities (diabetes, hypertension) and higher HOMA‐IR, lipid and liver enzymes. MAFLD patients with alcohol consumption were younger than those without, and more likely to be male. They had less metabolic disorder but higher liver enzymes. There were more cases with advance fibrosis in MAFLD patients with alcohol consumption.
Conclusion
MAFLD definition is more practical for identifying patients with fatty liver disease with high risk of disease progression.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to ...integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy.
Hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites ...is unknown. We utilized adult male Sprague-Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT
) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus, Parabacteroides, Butyricimonas, SMB53, Akkermansia, Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas Prevotella, Prevotella, Kaistobacter, Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT
, and CORT with Prevotella, Kaistobacter, Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT
on Prevotella and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The relationship between vitamin D levels and non-alcoholic fatty liver disease (NAFLD) remains unestablished. In this study, we aimed to explore the relationship between vitamin D levels and NAFLD ...based on population survey data. This cross-sectional study was conducted based on data from the National Health and Nutrition Examination Survey. Liver steatosis was diagnosed by ultrasonography. Binary logistic regression analyses were performed to determine the relationship between vitamin D status and NAFLD. A total of 9,782 participants were identified in this analysis, with 46.8% male and an average age of 44.41±0.16 y old. Among them, 6,047 (61.8%) cases were without NAFLD, 1,357 (13.9%) had mild NAFLD, 1,594 (16.3%) had moderate and 784 (8.0%) had severe NAFLD. Compared to those with non-NAFLD or mild NAFLD, patients in the moderate to severe NAFLD group had higher vitamin D deficiency or insufficiency rates (12.4% vs 11.5% and 36.8% vs 33.2%, respectively). After adjustment for male gender, older age, race, BMI, history of diabetes and vitamin D intake, vitamin D levels were independently associated with the severity of NAFLD (vitamin D deficiency group OR: 1.314, 95% CI: 1.129 to 1.529, vitamin D insufficiency group OR: 1.203, 95% CI: 1.090 to 1.328). Besides that, cold season was also found to be an independent factor for NAFLD (OR: 0.896, 95% CI: 0.820 to 0.979). Lower vitamin D level is an independent risk factor for NAFLD. Vitamin D levels are inversely associated with the severity of NAFLD. Cold season increases the risk of NAFLD independently.
Background and objective
Root resorption is an unavoidable side effect of orthodontic tooth movement. The mechanism of root resorption is similar to bone resorption; the odontoclasts share similar ...characteristics with osteoclasts (OCs). MicroRNAs (miRNAs) such as miR‐155‐5p play an important role in OC differentiation, but the underlying molecular mechanism of miR‐155‐5p in this process is not fully understood. We found that the miR‐155‐5p seed sequences were complementary to a sequence conserved in the 3‐untranslated region of CXCR2 mRNA. In this study, we explored the molecular mechanism underlying the effect of miR‐155‐5p on OC differentiation by targeting CXCR2.
Materials and methods
In this study, we divided the orthodontic patients into mild, moderate, and severe groups according to the severity of root resorption. The gingival crevicular fluid (GCF) of patients in different groups was collected, and the expression levels of dentin phosphoprotein (DPP) were detected by ELISA, and the expression levels of CXCR2 and miR‐155‐5p in GCF were detected by real‐time quantitative PCR (qRT‐PCR). The relationship between miR‐155‐5p and CXCR2 was verified by double luciferase. We analyzed changes of CXCR2 and miR‐155‐5p expression after transfection of miR‐155‐5p mimic and inhibitor into RAW264.7 cells induced by receptor activator of nuclear factor‐κB ligand (RANKL) through qRT‐PCR and western blotting. The effect of miR‐155‐5p on OC differentiation was evaluated by tartrate‐resistant acid phosphatase (TRAP) staining. QRT‐PCR and western blotting were used to analyze expression of the osteoclastic bone resorption‐related enzymes carbonic anhydrase 2 (CA II), matrix metalloproteinase‐9 (MMP‐9), and cathepsin K. To further confirm the direct targeting effect of CXCR2 by miR‐155‐5p, we blocked CXCR2 using si‐CXCR2 in RANKL‐induced RAW264.7 cells.
Results
Dentin phosphoprotein levels were consistent with the trend of miR‐155‐5p changes, and the trend of CXCR2 expression was opposite to miR‐155‐5p changes. miR‐155‐5p can be directly targeted to act on CXCR2. The expression of miR‐155‐5p was significantly downregulated in differentiated OCs. MiR‐155‐5p inhibited OC differentiation, and downregulated CA II, MMP‐9, and cathepsin K expression at the protein and mRNA levels.
Conclusions
In summary, the results of this study suggested that miR‐155‐5p inhibited OC differentiation by targeting CXCR2, thus reducing root resorption in orthodontics. MiR‐155‐5p can be used as an effective target for avoiding or reducing the degree of root resorption in orthodontic treatment.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The function of the root system is crucial for plant survival, such as anchoring plants, absorbing nutrients and water from the soil, and adapting to stress. MYB transcription factors constitute one ...of the largest transcription factor families in plant genomes with structural and functional diversifications. Members of this superfamily in plant development and cell differentiation, specialized metabolism, and biotic and abiotic stress processes are widely recognized, but their roles in plant roots are still not well characterized. Recent advances in functional studies remind us that
genes may have potentially key roles in roots. In this review, the current knowledge about the functions of
genes in roots was summarized, including promoting cell differentiation, regulating cell division through cell cycle, response to biotic and abiotic stresses (e.g., drought, salt stress, nutrient stress, light, gravity, and fungi), and mediate phytohormone signals.
genes from the same subfamily tend to regulate similar biological processes in roots in redundant but precise ways. Given their increasing known functions and wide expression profiles in roots,
genes are proposed as key components of the gene regulatory networks associated with distinct biological processes in roots. Further functional studies of
genes will provide an important basis for root regulatory mechanisms, enabling a more inclusive green revolution and sustainable agriculture to face the constant changes in climate and environmental conditions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective Winter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system ...(ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions. Methods Fourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale. Results HRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval. Conclusion Prolonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pyroptosis is a newly discovered type of programmed cell death associated with inflammatory and fibrotic diseases. Macrophages play an important role in inducing early immune inflammation in systemic ...sclerosis (SSc).
To investigate the effect of macrophages pyroptosis on fibrosis of SSc.
Pyroptosis/inflammatory markers in serum and skin of SSc patients were detected. Bleomycin (BLM) was subcutaneously injected to establish SSc mouse model. The levels of pyroptosis markers, dermal thickness and collagen deposition in skin were assessed before and after the administration of pyroptosis inhibitors, including MCC950, Disulfiram and necrosulfonamide (NSA). Human-derived monocyte-macrophage cell line (THP-1) or mouse bone marrow-derived macrophages (BMDMs) were primed with lipopolysaccharide (LPS) and stimulated by silicon dioxide (SiO2) to induce cell pyroptosis. Fibroblasts from patients with SSc were co-cultured with pyroptotic THP-1 cells, and the collagen production was assessed.
Pyroptotic/inflammatory proteins, including NLRP3, cleaved-Caspase (CASP)1, GSDMD-N terminal and IL-18 were increased in the serum, and ASC aggregation and GSDMD were elevated in macrophages in the skin of SSc patients. SSc mice showed increased pyroptosis markers, dermal thickness and collagen deposition in skins, which were alleviated by MCC950, Disulfiram and NSA. Pyroptosis of THP-1 cells and BMDMs was induced by LPS/SiO2, and it was reduced by the inhibitors of Cathepsin B, NLRP3, CASP1 and GSDMD. Co-culture with pyroptotic THP-1 cells increased the fibrotic proteins in fibroblasts, which were alleviated by pyroptosis inhibitors.
SSc patients and BLM-induced mouse model presented increased pyroptosis. LPS/SiO2-induced macrophage pyroptosis promoted fibrosis of SSc through Cathepsin B/NLRP3/GSDMD pathway.
•Macrophage pyroptosis was increased in SSc patients and BLM-induced SSc mouse model.•Inhibition of pyroptosis reduced inflammation and fibrosis of SSc mouse model.•Inhibiting NLRP3/GSDMD-mediated macrophage pyroptosis inactivates fibroblasts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to ...explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na
/K
transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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