New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Isotoosendanin inhibits triple-negative breast cancer metastasis by reducing mitochondrial fission and lamellipodia formation regulated by the Smad2/3-GOT2-MYH9 signaling axis.

Triple-negative breast cancer (TNBC) is incurable and prone to widespread metastasis. Therefore, identification of key targets for TNBC progression is urgently needed. Our previous study revealed that isotoosendanin (ITSN) reduced TNBC metastasis by targeting TGFßR1. ITSN is currently used as an effective chemical probe to further discover the key molecules involved in TNBC metastasis downstream of TGFßR1. The results showed that GOT2 was the gene downstream of Smad2/3 and that ITSN decreased GOT2 expression by abrogating the activation of the TGF-ß-Smad2/3 signaling pathway through directly binding to TGFßR1. GOT2 was highly expressed in TNBC, and its knockdown decreased TNBC metastasis. However, GOT2 overexpression reversed the inhibitory effect of ITSN on TNBC metastasis both in vitro and in vivo. GOT2 interacted with MYH9 and hindered its binding to the E3 ubiquitin ligase STUB1, thereby reducing MYH9 ubiquitination and degradation. Moreover, GOT2 also enhanced the translocation of MYH9 to mitochondria and thus induced DRP1 phosphorylation, thereby promoting mitochondrial fission and lamellipodia formation in TNBC cells. ITSN-mediated inhibition of mitochondrial fission and lamellipodia formation was associated with reduced GOT2 expression. In conclusion, ITSN prevented MYH9-regulated mitochondrial fission and lamellipodia formation in TNBC cells by enhancing MYH9 protein degradation through a reduction in GOT2 expression, thus contributing to its inhibition of TNBC metastasis.

Effect of Thermal Treatment on Gelling and Emulsifying Properties of Soy ß-Conglycinin and Glycinin.

This study investigated the impact of different preheat treatments on the emulsifying and gel textural properties of soy protein with varying 11S/7S ratios. A mixture of 7S and 11S globulins, obtained from defatted soybean meal, was prepared at different ratios. The mixed proteins were subjected to preheating (75 °C, 85 °C, and 95 °C for 5 min) or non-preheating, followed by spray drying or non-spray drying. The solubility of protein mixtures rich in the 7S fraction tended to decrease significantly after heating at 85 °C, while protein mixtures rich in the 11S fraction showed a significant decrease after heating at 95 °C. Surprisingly, the emulsion stability index (ESI) of protein mixtures rich in the 7S fraction significantly improved twofold during processing at 75 °C. This study revealed a negative correlation between the emulsifying ability of soy protein and the 11S/7S ratio. For protein mixtures rich in either the 7S or the 11S fractions, gelling proprieties as well as emulsion activity index (EAI) and ESI showed no significant changes after spray drying; however, surface hydrophobicity was significantly enhanced following heating at 85 °C post-spray drying treatment. These findings provide insights into the alterations in gelling and emulsifying properties during various heating processes, offering great potential for producing soy protein ingredients with enhanced emulsifying ability and gelling property. They also contribute to establishing a theoretical basis for the standardized production of soy protein isolate with specific functional characteristics.

Lineage 1 PRRSVs infection induces hemorrhagic injury in intestines of piglets: Effects on complement and coagulation cascades.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly transmissible disease of significant concern in the pig industry. Previous studies have demonstrated that the XM-2020 strain (a lineage 1.8 PRRSV IA/2012/NADC30) can induce special hemorrhagic injury in the small intestines. However, the specific mechanism underlying this injurious effect remains incompletely understood. In this study, we examined the pathogenic properties of XM-2020 and YC-2020 strains (a lineage 1.5 PRRSV IA/2014/NADC34) in piglets. Animal pathogenic tests revealed that with either Lineage 1 PRRSVs strains XM-2020 or YC-2020 demonstrated pronounced intestinal hemorrhage and suppression of peripheral immunological organs, comparing to JXA1 infection. Transcriptome analysis of diseased small intestines unveiled that PRRSV infection stimulated oxidative and inflammatory reactions. Remarkably, we also observed activation of the complement system alongside a notable down-regulation of complement and coagulation cascade pathways in the Lineage 1 PRRSVs infection group. Based on these findings, we propose that the primary mechanism driving the hemorrhagic injury of the small intestine caused by Lineage 1 PRRSVs is the suppression of complement and coagulation cascades resulting from immunosuppression. This discovery deepens our understanding of the pathogenicity of PRRSV in the small intestine and provides promising ways out for the development of innovative strategies aimed at controlling PRRSV.

Role of lingonberry press cake in producing stable herring protein isolates via pH-shift processing: A dose response study.

The effects of cross-processing lingonberry press cake (LPC) (2.5-30 %, dw/dw) with herring co-products on protein yield, oxidative stability and color of pH-shift-produced protein isolates were investigated. Even at 2.5 % LPC, the formation of volatile oxidation-derived aldehydes, including hexanal, (E)-2-hexenal, heptanal, octanal, and 2,4-heptadienal, were prevented during the actual protein isolate production. Adding 10 % LPC successfully prevented formation of all these aldehydes also during eight days ice storage which was explained by the partitioning of phenolics, especially ideain (1.09 mg/g dw) and procyanidin A1 (65.5 mg/g dw), into isolates. Although higher amounts of LPC (20-30 %) further prolonged the oxidation lag phase, it reduced total protein yield, increased the consumption of acid and base, and darkened protein isolates. Therefore, it is recommended to use 10 % LPC when pH-shift-processing sensitive fish raw materials as a route to mitigate lipid oxidation and at the same time promote industrial symbiosis and more circular food production.

Hematite Hollow-Sphere-Array Photoanodes for Efficient Photoelectrochemical Water Splitting.

Constructing 3D nanophotonic structures is regarded as an effective method to realize efficient solar-to-hydrogen conversion. These photonic structures can enhance the absorbance of photoelectrodes by the light trapping effect, promote the charge separation by designable charge transport pathway and provide a high specific surface area for catalytic reaction. However, most 3D structures reported so far mainly focused on the influence of light absorption and lacked a systematic investigation of the overall water splitting process. Herein, hematite hollow-sphere-array photoanodes are fabricated through a facile hydrothermal method with polystyrene templates. Validating by simulations and experiments, the hollow sphere array is proved to enhance the efficiency of light harvesting, charge separation and surface reaction at the same time. With an additional annealing treatment in oxygen, a photocurrent density of 2.26 mA cm-2 at 1.23 V versus reversible hydrogen electrode can be obtained, which is 3.70 times larger than that with a planar structure in otherwise the same system. This work gains an insight into the photoelectrochemical water splitting process, which is valuable for the further design of advancing solar driven water splitting devices.

Quercetin Alleviates Perimenopausal Depression Induced by Ovariectomy Combined with Chronic Unpredictable Mild Stress Through Regulating Serum Elements and Inhibiting Ferroptosis in Prefrontal Cortex of Rats.

This study investigated the effects of quercetin on the alterations of serum elements in perimenopausal depression rat model induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS) and possible mechanisms. According to the results of the sucrose preference test, the rats were randomly assigned to four groups: sham, OVX-CUMS, OVX-CUMS + 17ß-estradiol (17ß-estradiol: 0.27 mg/kg.bw), and OVX-CUMS + Quercetin (Quercetin: 50 mg/kg.bw). At the end of experiment, serum and prefrontal cortex of rats were collected. The inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co) and zinc (Zn) decreased, and levels of iron (Fe) and copper (Cu) increased in serum and prefrontal cortex of OVX-CUMS rats compared with sham group (p < 0.01). Meanwhile, the levels of the above elements in prefrontal cortex had correlation with behavioral characteristics in OVX-CUMS rats (p < 0.05 or p < 0.01). The abnormal elements in serum may cross blood-brain-barrier into the brain and induce oxidative stress, leading to ferroptosis. Furtherly, the expressions of ferroptosis-related protein including GPX4 and SLC7A11 were decreased in prefrontal cortex of OVX-CUMS rats (p < 0.01), which confirmed the above results. Quercetin treatment restored the above abnormal indicators (p < 0.05 or p < 0.01) induced by OVX-CUMS in rats. Our study suggested that quercetin regulated variation of elements in serum and prefrontal cortex, further inhibiting ferroptosis in prefrontal cortex through alleviating oxidative stress in OVX-CUMS rats.

PIEZO1-mediated mechanosensing governs NK-cell killing efficiency and infiltration in three-dimensional matrices.

Natural killer (NK) cells play a vital role in eliminating tumorigenic cells. Efficient locating and killing of target cells in complex three-dimensional (3D) environments are critical for their functions under physiological conditions. However, the role of mechanosensing in regulating NK-cell killing efficiency in physiologically relevant scenarios is poorly understood. Here, we report that the responsiveness of NK cells is regulated by tumor cell stiffness. NK-cell killing efficiency in 3D is impaired against softened tumor cells, whereas it is enhanced against stiffened tumor cells. Notably, the durations required for NK-cell killing and detachment are significantly shortened for stiffened tumor cells. Furthermore, we have identified PIEZO1 as the predominantly expressed mechanosensitive ion channel among the examined candidates in NK cells. Perturbation of PIEZO1 abolishes stiffness-dependent NK-cell responsiveness, significantly impairs the killing efficiency of NK cells in 3D, and substantially reduces NK-cell infiltration into 3D collagen matrices. Conversely, PIEZO1 activation enhances NK killing efficiency as well as infiltration. In conclusion, our findings demonstrate that PIEZO1-mediated mechanosensing is crucial for NK killing functions, highlighting the role of mechanosensing in NK-cell killing efficiency under 3D physiological conditions and the influence of environmental physical cues on NK-cell functions.

Hemodynamics, anatomy, and outcomes of quadricuspid aortic valves: Multimodality imaging assessment.

BACKGROUND: Quadricuspid aortic valve (QAV) is a rare congenital heart disease with a limited body of literature. This retrospective cohort study investigates QAV morphology, function, and clinical outcomes. METHODS: Echocardiography was used to assess valvular function. Morphological characteristics such as phenotypes, raphe, regurgitant orifice area (ROA), and aortic dilation (diameter >40 â€‹mm) were assessed by cardiac CT. Patients were followed up for the combined event of all-cause death and aortic valve replacement (AVR). RESULTS: Ninety QAV patients (screened from 322385 CT scans) were included (mean age 55.2 â€‹± â€‹13.6 years, 61.1 â€‹% male). Isolated significant aortic regurgitation (AR) was present in 75.6 â€‹% of patients. The cohort was dominated by type I (four equal leaflets, 37.8 â€‹%) and type II (3 larger and 1 smaller leaflets, 42.2 â€‹%) QAV. Fused raphe was present in 26.7 â€‹% of patients. ROACT was correlated with AR severity and aortic dilation (41.1 â€‹%, n â€‹= â€‹37). Among patients without AVR at baseline (n â€‹= â€‹60), one died and 17 underwent AVR during a median follow-up of 35.0 months (IQR:17.3-62.8). ROACT was associated with an increasing risk of combined event (as a categorical variable with a cut-off of 21.4 â€‹mm2, HR â€‹= â€‹4.25, 95%CI 1.49-12.17, p â€‹= â€‹0.007; as a continuous variable (per mm2 increment), HR â€‹= â€‹1.04, 95%CI 1.01-1.07, p â€‹= â€‹0.003). Additionally, ROACT had incremental prognostic value when added to the AR severity model (area under the receiver-operating characteristic curve increased from 86.8 to 88.4, p â€‹= â€‹0.004). CONCLUSION: QAV is characterized by variable anatomy, progressive AR, concomitant cusp fusion and aortic enlargement. ROACT may be a potential ancillary prognostic marker in patients with QAV.

Edwardsiella tarda Causing Septicemia in a Wild Crested Ibis (Nipponia nippon).

An adult Crested Ibis (Nipponia nippon) was found moribund in the Qinling area of China. Postmortem examination and histopathological analysis revealed lung inflammation and multi-organ hemorrhage. Bacterial isolation and whole-genome sequencing confirmed Edwardsiella tarda infection.

Ameliorative effect of anisodamine (654-1/654-2) against myocardial dysfunction induced by septic shock via the NF-κB/NLRP-3 or the PI3K-AKT/NF-κB pathway.

BACKGROUND: Septic shock, an extremely dangerous condition that causes impairment of organ function, always largely contributes to mortality in intensive care units. The impact of septic shock-induced organ damage on morbidity and mortality is substantially influenced by myocardial dysfunction. However, it remains unclear whether and in what manner anisodamine (654-1/654-2) ameliorates myocardial dysfunction caused by septic shock. PURPOSE: This study is the pioneering investigation and validation about the protective efficacy of anisodamine (654-1/654-2) against LPS-induced myocardial dysfunction in septic shock rats. It also aims to explore the differences in the underlying molecular mechanisms of both drugs. METHODS: A septic shock model was established in SD rats by after tail vein administration of LPS. 64 rats were distributed into eight groups, such as LPS group, control group, LPS+654-1 group (1.25, 2.5, and 5 mg/kg), and LPS+654-2 group (1.25, 2.5, and 5 mg/kg). The hemodynamics, echocardiography, immunohistochemical analysis, TEM, TUNEL assay, and H&E staining were utilized to assess the septic shock model and myocardial function. Lactic acid, inflammatory markers (IL-1ß, IL-6, and TNF-α), endothelial injure markers (SDC-1, HS and TM) and myocardial injury markers (CK, c-TNT and NT-pro BNP) were assessed using ELISA or biochemical kits. Additionally, the mechanisms of 654-1/654-2 were analyzed using RNA-seq and bioinformatics, and validated using western blotting and RT-PCR. RESULTS: Administration of 654-1/654-2 significantly restored hemodynamics and improved myocardial and endothelial glycocalyx injury in septic shock rats. Furthermore, 654-1/654-2 dose-dependently reduced plasma levels of lactic acid, inflammatory cytokines, and markers of endothelial and myocardial injury. Analyses using RNA-seq, WB and RT-PCR techniques indicated that 654-1/654-2 could mitigate myocardial and endothelial injury by inhibiting the NF-κB and NLRP-3 pathways, and activating the PI3K-AKT pathway. CONCLUSIONS: These findings demonstrated that 654-1/654-2 could alleviate myocardial damage in septic shock rats. Specifically, 654-1 inhibited the NF-κB/NLRP-3 pathway, whereas 654-2 promoted the PI3K-AKT pathway and inhibited the NF-κB pathway, effectively mitigating the inflammatory response and cell apoptosis.

Andrographolide attenuated MCT-induced HSOS via regulating NRF2-initiated mitochondrial biogenesis and antioxidant response.

Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1.

Targeting endothelial cells with golden spice curcumin: A promising therapy for cardiometabolic multimorbidity.

Cardiometabolic multimorbidity (CMM) is an increasingly significant global public health concern. It encompasses the coexistence of multiple cardiometabolic diseases, including hypertension, stroke, heart disease, atherosclerosis, and T2DM. A crucial component to the development of CMM is the disruption of endothelial homeostasis. Therefore, therapies targeting endothelial cells through multi-targeted and multi-pathway approaches hold promise for preventing and treatment of CMM. Curcumin, a widely used dietary supplement derived from the golden spice Carcuma longa, has demonstrated remarkable potential in treatment of CMM through its interaction with endothelial cells. Numerous studies have identified various molecular targets of curcumin (such as NF-κB/PI3K/AKT, MAPK/NF-κB/IL-1ß, HO-1, NOs, VEGF, ICAM-1 and ROS). These findings highlight the efficacy of curcumin as a therapeutic agent against CMM through the regulation of endothelial function. It is worth noting that there is a close relationship between the progression of CMM and endothelial damage, characterized by oxidative stress, inflammation, abnormal NO bioavailability and cell adhesion. This paper provides a comprehensive review of curcumin, including its availability, pharmacokinetics, pharmaceutics, and therapeutic application in treatment of CMM, as well as the challenges and future prospects for its clinical translation. In summary, curcumin shows promise as a potential treatment option for CMM, particularly due to its ability to target endothelial cells. It represents a novel and natural lead compound that may offer significant therapeutic benefits in the management of CMM.

Alpinia katsumadai Hayata Volatile Oil Is Effective in Treating 5-Fluorouracil-Induced Mucositis by Regulating Gut Microbiota and Modulating the GC/GR Pathway and the mPGES-1/PGE2/EP4 Pathways.

This study was aimed to investigate the therapeutic effect and mechanism of AKHO on 5-fluorouracil (5-FU)-induced intestinal mucositis in mice. Mouse body weight, diarrhea score, and H&E staining were applied to judge the therapeutic effect of AKHO. 16S rDNA and nontargeted metabolomics have been used to study the mechanism. WB, ELISA, and immunohistochemistry were adopted to validate possible mechanisms. The results demonstrated that AKHO significantly reduced diarrhea scores and intestinal damage induced by 5-FU in mice. AKHO lowered the serum levels of LD and DAO, and upregulated the expressions of ZO-1 and occludin in the ileum. Also, AKHO upregulated the abundance of Lactobacillus in the gut and suppressed KEGG pathways such as cortisol synthesis and secretion and arachidonic acid metabolism. Further validation studies indicated that AKHO downregulated the expressions of prostaglandin E2 (PGE2), microsomal prostaglandin E synthase-1 (mPGES-1), and PGE2 receptor EP4, as well as upregulated the expression of glucocorticoid (GC) receptor (GR), leading to improved intestinal epithelial barrier function. Taken together, AKHO elicited protective effects against 5-FU-induced mucositis by regulating the expressions of tight junction proteins via modulation of GC/GR and mPGES-1/PGE2/EP4 pathway, providing novel insights into the utilization and development of this pharmaceutical/food resource.

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells.

Triple-negative breast cancer (TNBC) is heterogeneous and aggressive, with high vascularity and frequent metastasis. We have already found natural flavonoid scutellarin (SC) suppressed spontaneous TNBC metastasis via normalizing tumor vasculature in vivo. In this study, supernatant from tumor necrosis factorα (TNFα)-treated human mammary microvascular endothelial cell (HMMEC) promoted cell migration and pseudopod formation in TNBC cells, but these phenomena were disappeared in SC-co-treated HMMEC. TNFα enhanced the expression of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in both HMMEC and human umbilical vein endothelial cell (HUVEC). G-CSF promoted TNBC migration and invasion in vitro, while G-CSF neutralization antibody and SC both inhibited TNBC metastasis in Balb/c mice. SC had no inhibition on the G-CSF-induced TNBC cell migration, but reduced G-CSF content in TNBC tumor tissues and TNFα-stimulated endothelial cells (ECs). SC restricted the nuclear translocation of runt-related transcription factor 1 (RUNX1) in TNBC tumor vessels and TNFα-treated ECs. RUNX1 was found to directly bind to the promoter of G-CSF in TNBC tumor vessels and regulated G-CSF expression. TNF receptor 2 (TNFR2) was crucial for regulating the TNFα-induced RUNX1 activation and G-CSF expression. Notably, SC hindered the interaction between TNFα and TNFR2 via binding to TNFR2. This work demonstrated that SC reduced TNBC metastasis by targeting TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated ECs.

GAS5-inhibited hepatocyte pyroptosis contributes to hepatic stellate cell inactivation via microRNA-684 and AHR.

Hepatocyte pyroptosis has been shown to be involved in liver damage progression. Previously, we found that growth arrest-specific 5 (GAS5) is a regulator of hepatic stellate cell (HSC) activation. However, whether GAS5 plays a role in hepatocyte pyroptosis remains unclear. In this study, reduced GAS5 was shown in CCl4-treated mice and restoration of GAS5-inhibited liver fibrosis in vivo. Hepatocyte pyroptosis participated in the effects of GAS5-inhibited liver fibrosis, associated with reduced caspase-1, NLRP3, and IL-1ß (hepatocyte pyroptosis markers). Notably, AHR expression, a suppressor of NLRP3, was enhanced by GAS5. Silencing AHR inhibited GAS5-mediated hepatocyte pyroptosis. GAS5 and AHR were targets of microRNA-684 (miR-684). In addition, the effects of GAS5 on hepatocyte pyroptosis could be inhibited by miR-684. Interestingly, GAS5-mediated hepatocyte pyroptosis contributed to HSC inactivation. In conclusion, we demonstrate that GAS5 inhibits hepatocyte pyroptosis and HSC activation, at least in part, via regulation of miR-684 and AHR.

Nutrient Inadequacy in Korean Young Adults with Depression: A Case Control Study.

The role of diet is gaining attention among the modifiable factors associated with depression; thus, this case-control study examined the association between nutrition and depression in young Korean adults. Dietary surveys in individuals with depression (n = 39) and age- and gender-matched controls (n = 76) were conducted using food records and food frequency questionnaires. Men with depression consumed less mushrooms and meat, while women consumed significantly less grains (p < 0.05). Overall, the depression group consumed less energy and nutrients, and the difference was more pronounced in men. The male depression group had lower nutrient adequacy ratio (NAR) for energy, protein, vitamin A, thiamine, niacin, folate, and phosphorus, whereas the female depression group had lower NARs for energy, protein, niacin, and vitamin B12. The depression group had a significantly lower mean adequacy ratio in both genders. Furthermore, the proportion of inappropriate nutrient intake was higher in both genders of the depression group, exhibiting significant differences in energy, protein, niacin, folate, and zinc in men and energy, riboflavin, folate, and vitamin C in women. Hence, both men and women in the depression group had poor nutrient intake and high rates of nutrient inadequacy and improper consumption. This suggests that the quantity and quality of meals should be improved for individuals with depressive symptoms.

Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11.

BACKGROUND: Sustained liver fibrosis may lead to cirrhosis. Activated hepatic stellate cells (HSCs) are crucial for liver fibrosis development. Ferroptosis, a newly iron-dependent regulated cell death, has been demonstrated to be involved in HSC inactivation. PURPOSE: Ginsenoside Rh2 (GRh2), a natural bioactive product derived from ginseng, has been shown to promote HSC inactivation. However, the effect of GRh2 on HSC ferroptosis remains unclear. METHODS: We explored the effects of GRh2 on liver fibrosis in vivo and in vitro. RNA-sequence analysis was performed in HSCs after GRh2 treatment. The crosstalk between ferroptotic HSCs and macrophages was also explored. RESULTS: GRh2 alleviated liver fibrosis in vivo. In vitro, GRh2 reduced HSC proliferation and activation via ferroptosis, with increased intracellular iron, reactive oxygen species, malondialdehyde and glutathione depletion. The expression of SLC7A11, a negative regulator of ferroptosis, was obviously reduced by GRh2. Interestingly, interferon regulatory factor 1 (IRF1), a transcription factor, was predicted to bind the promoter region of SCL7A11. The interaction between IRF1 and SCL7A11 was further confirmed by the results of chromatin immunoprecipitation and luciferase reporter assays. Furthermore, loss of IRF1 led to an increase in SCL7A11, which contributed to the suppression of HSC ferroptosis and the enhancement of HSC activation in GRh2-treated HSCs. Further studies revealed that GRh2-induced HSC ferroptosis contributed to the inhibition of macrophage recruitment via regulation of inflammation-related genes. Moreover, GRh2 caused a reduction in liver inflammation in vivo. CONCLUSION: Collectively, GRh2 up-regulates IRF1 expression, resulting in the suppression of SLC7A11, which contributes to HSC ferroptosis and inactivation. GRh2 ameliorates liver fibrosis through enhancing HSC ferroptosis and inhibiting liver inflammation. GRh2 may be a promising drug for treating liver fibrosis.

Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-ß-induced epithelial-mesenchymal transition via directly targeting TGFßR1.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-ß-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-ß receptor type-1 (TGFßR1) and abrogated the kinase activity of TGFßR1, thereby blocking the TGF-ß-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFßR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFßR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFßR1 were found to be crucial for the interaction of ITSN with TGFßR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-ß-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFßR1 in TNBC metastasis, but also provide a leading compound targeting TGFßR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFßR1 inhibitor.

A stochastic block Ising model for multi-layer networks with inter-layer dependence.

Community detection has attracted tremendous interests in network analysis, which aims at finding group of nodes with similar characteristics. Various detection methods have been developed to detect homogeneous communities in multi-layer networks, where inter-layer dependence is a widely acknowledged but severely under-investigated issue. In this paper, we propose a novel stochastic block Ising model (SBIM) to incorporate the inter-layer dependence to help with community detection in multi-layer networks. The community structure is modeled by the stochastic block model (SBM) and the inter-layer dependence is incorporated via the popular Ising model. Furthermore, we develop an efficient variational EM algorithm to tackle the resultant optimization task and establish the asymptotic consistency of the proposed method. Extensive simulated examples and a real example on gene co-expression multi-layer network data are also provided to demonstrate the advantage of the proposed method.