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1.
BMC Pediatr ; 24(1): 338, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755601

BACKGROUND: Transient symptomatic zinc deficiency (TSZD), an acquired type of zinc deficiency, is a rare, but probably underrecognized disease, extremely in breastfed premature with low birthweight infants. Its clinical manefestations are similar to Acrodermatitis enteropathica (AE), which is a genetic zinc absorption disorder caused by SLC39A4 gene mutations. This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. TSZD is often misdiagnosed as AE because of their extremely similar manefestations, characterized by a typical rash. Therefore, the differention between them is still a clinical challenging. CASE PRESENTATION: Here, we present a case of TSZD in a 4 month and 23 days female Chinese Yi-ethnic premature with AE-like skin lesions, mainly presenting periorificial, perianal and perineal crusted, eroded, erythemato-squamous eruption. Laboratory examination showed the patient's blood zinc level was significantly decreased. Further sequencing of the SLC39A4 gene showed no mutation in the infant and her parents. Skin lesions significantly improved after 6 days of initial zinc supplementation (3 mg/kg/d), and maintenance treatment with 1 mg/kg/day of zinc was discontinued after 8 months without recurrence. CONCLUSIONS: The clinical manifestations of TSZD and AE are extremely similar, leading to a high rate of clinical misdiagnosis. While genetic analysis of the SLC39A4 gene is a reliable method for differentiating TSZD from AE. It is recommended that SLC39A4 gene test should be performed as far as possible in children with AE-like rash.


Acrodermatitis , Zinc , Humans , Zinc/deficiency , Zinc/blood , Acrodermatitis/diagnosis , Acrodermatitis/genetics , Acrodermatitis/etiology , Female , Infant , Diagnosis, Differential , China , Cation Transport Proteins/genetics , Infant, Premature , Infant, Newborn , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/genetics , Infant, Premature, Diseases/blood , East Asian People
2.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167170, 2024 Jun.
Article En | MEDLINE | ID: mdl-38631407

Intimal hyperplasia (IH) is a common pathological feature of vascular proliferative diseases, such as atherosclerosis and restenosis after angioplasty. Urotensin II (UII) and its receptor (UTR) are widely expressed in cardiovascular tissues. However, it remains unclear whether the UII/UTR system is involved in IH. Right unilateral common carotid artery ligation was performed and maintained for 21 days to induce IH in UTR knockout (UTR-/-) and wild-type (WT) mice. Histological analysis revealed that compared with WT mice, UTR-deficient mice exhibited a decreased neointimal area, angiostenosis and intima-media ratio. Immunostaining revealed fewer smooth muscle cells (SMCs), endothelial cells and macrophages in the lesions of UTR-/- mice than in those of WT mice. Protein interaction analysis suggested that the UTR may affect cell proliferation by regulating YAP and its downstream target genes. In vitro experiments revealed that UII can promote the proliferation and migration of SMCs, and western blotting also revealed that UII increased the protein expression of RhoA, CTGF, Cyclin D1 and PCNA and downregulated p-YAP protein expression, while these effects could be partly reversed by urantide. To evaluate the translational value of UTRs in IH management, WT mice were also treated with two doses of urantide, a UTR antagonist, to confirm the benefit of UTR blockade in IH progression. A high dose of urantide (600 µg/kg/day), rather than a low dose (60 µg/kg/day), successfully improved ligation-induced IH compared with that in mice receiving vehicle. The results of the present study suggested that the UII/UTR system may regulate IH partly through the RhoA-YAP signaling pathway.


Adaptor Proteins, Signal Transducing , Cell Proliferation , Hyperplasia , Mice, Knockout , Receptors, G-Protein-Coupled , Signal Transduction , YAP-Signaling Proteins , rhoA GTP-Binding Protein , Animals , YAP-Signaling Proteins/metabolism , rhoA GTP-Binding Protein/metabolism , rhoA GTP-Binding Protein/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Mice , Hyperplasia/metabolism , Hyperplasia/pathology , Ligation , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Male , Tunica Intima/pathology , Tunica Intima/metabolism , Urotensins/metabolism , Urotensins/genetics , Urotensins/pharmacology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Mice, Inbred C57BL , Cell Movement , Neointima/metabolism , Neointima/pathology , Neointima/genetics
3.
Nat Commun ; 15(1): 3282, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627380

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary gland alterations.


Mammary Glands, Animal , Urinary Tract Infections , Animals , Female , Mice , Collagen , Extracellular Matrix/physiology , Homeostasis
4.
Parasit Vectors ; 17(1): 190, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643149

BACKGROUND: Cystic echinococcosis (CE) is a widespread zoonosis caused by the infection with Echinococcus granulosus sensu lato (E. granulosus s.l.). CE cysts mainly develop in the liver of intermediate hosts, characterized by the fibrotic tissue that separates host organ from parasite. However, precise mechanism underlying the formation of fibrotic tissue in CE remains unclear. METHODS: To investigate the potential impact of ubiquitin-conjugating enzymes on liver fibrosis formation in CE, two members of ubiquitin-conjugating (UBC) enzyme of Echinococcus granulosus (EgE2D2 and EgE2N) were recombinantly expressed in Escherichia coli and analyzed for bioinformatics, immunogenicity, localization, and enzyme activity. In addition, the secretory pathway and their effects on the formation of liver fibrosis were also explored. RESULTS: Both rEgE2D2 and rEgE2N possess intact UBC domains and active sites, exhibiting classical ubiquitin binding activity and strong immunoreactivity. Additionally, EgE2D2 and EgE2N were widely distributed in protoscoleces and germinal layer, with differences observed in their distribution in 25-day strobilated worms. Further, these two enzymes were secreted to the hydatid fluid and CE-infected sheep liver tissues via a non-classical secretory pathway. Notably, TGFß1-induced LX-2 cells exposed to rEgE2D2 and rEgE2N resulted in increasing expression of fibrosis-related genes, enhancing cell proliferation, and facilitating cell migration. CONCLUSIONS: Our findings suggest that EgE2D2 and EgE2N could secrete into the liver and may interact with hepatic stellate cells, thereby promoting the formation of liver fibrosis.


Echinococcosis , Echinococcus granulosus , Sheep Diseases , Animals , Sheep , Echinococcus granulosus/genetics , Ubiquitin-Conjugating Enzymes/genetics , Echinococcosis/parasitology , Liver Cirrhosis , Ubiquitins/genetics , Genotype , Sheep Diseases/parasitology
5.
J Integr Plant Biol ; 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38656698

Leaf senescence is an essential physiological process related to grain yield potential and nutritional quality. Green leaf duration (GLD) after anthesis directly reflects the leaf senescence process and exhibits large genotypic differences in common wheat; however, the underlying gene regulatory mechanism is still lacking. Here, we identified TaNAM-A1 as the causal gene of the major loci qGLD-6A for GLD during grain filling by map-based cloning. Transgenic assays and TILLING mutant analyses demonstrated that TaNAM-A1 played a critical role in regulating leaf senescence, and also affected spike length and grain size. Furthermore, the functional divergences among the three haplotypes of TaNAM-A1 were systematically evaluated. Wheat varieties with TaNAM-A1d (containing two mutations in the coding DNA sequence of TaNAM-A1) exhibited a longer GLD and superior yield-related traits compared to those with the wild type TaNAM-A1a. All three haplotypes were functional in activating the expression of genes involved in macromolecule degradation and mineral nutrient remobilization, with TaNAM-A1a showing the strongest activity and TaNAM-A1d the weakest. TaNAM-A1 also modulated the expression of the senescence-related transcription factors TaNAC-S-7A and TaNAC016-3A. TaNAC016-3A enhanced the transcriptional activation ability of TaNAM-A1a by protein-protein interaction, thereby promoting the senescence process. Our study offers new insights into the fine-tuning of the leaf functional period and grain yield formation for wheat breeding under various geographical climatic conditions.

6.
Psychol Res Behav Manag ; 17: 1573-1585, 2024.
Article En | MEDLINE | ID: mdl-38617578

Background: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD. Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively. Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p<0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p<0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047). Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 577-582, 2024 Apr.
Article Zh | MEDLINE | ID: mdl-38660869

OBJECTIVE: To explore the optimal storage condition and time of umbilical cord blood from collection to preparation. METHODS: Collect cord blood samples from 30 healthy newborns, with each new born's umbilical cord blood was divided into two parts on average. One part was stored in cold storage (4 ℃) and the other was stored at room temperature (20-24 ℃). Samples were taken at 24, 36, 48, 60 and 72 h, respectively, total nucleated cells (TNC) count and TNC viability was analyzed. Flow cytometry was used to detect the ratio of viable CD34+ cells to viable CD45+ cells and viability of CD34+ cells, and colony-forming unit-granulocyte-macrophage (CFU-GM) count was performed by hematopoietic progenitor cell colony culture. The change trend of each index over time was observed, and the differences in each index was compared between cold storage and room temperature storage under the same storage time. RESULTS: The TNC count (r 4 ℃=-0.9588, r 20-24 ℃=-0.9790), TNC viability (r 4 ℃=-0.9941, r 20-24 ℃=-0.9970), CD34+ cells viability (r 4 ℃=-0.9932, r 20-24 ℃=-0.9828) of cord blood stored in cold storage (4 ℃) and room temperature storage (20-24 ℃) showed a consistent downward trend with the prolongation of storage time. The percentage of viable CD34+ cells (r 4 ℃=0.9169, r 20-24 ℃=0.7470) and CFU-GM count (r 4 ℃=-0.2537, r 20-24 ℃=-0.8098) did not show consistent trends. When the storage time was the same, the TNC count, TNC viability, CD34+ cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature. Under the same storage time (24, 36, 48, 60 or 72 h), TNC viability in room temperature storage was significantly lower than that in cold storage (P <0.001), but TNC count, percentage of viable CD34+ cells and CFU-GM count were not significantly different between room temperature storage and cold storage. When stored at room temperature for 24 h and 36 h, the viability of CD34+ cells was significantly lower than that in cold storage (P <0.001, P <0.01), when the storage time for 48, 60 and 72 h, there was no significant difference in the CD34+ cells viability between room temperature storage and cold storage. CONCLUSION: It is recommended that cord blood be stored in cold storage (4 ℃) from collection to preparation, and processed as soon as possible.


Antigens, CD34 , Blood Preservation , Fetal Blood , Humans , Fetal Blood/cytology , Infant, Newborn , Time Factors , Flow Cytometry , Hematopoietic Stem Cells/cytology , Cell Survival , Temperature , Blood Specimen Collection
8.
Toxicol Appl Pharmacol ; 486: 116914, 2024 May.
Article En | MEDLINE | ID: mdl-38522585

Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.


Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Coenzyme A Ligases , Ferroptosis , Hepatocytes , Mice, Inbred C57BL , Organophosphorus Compounds , Reactive Oxygen Species , Up-Regulation , Animals , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Up-Regulation/drug effects , Hep G2 Cells , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/genetics , Mice , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/metabolism , Ferroptosis/drug effects , Carbon Tetrachloride/toxicity , Reactive Oxygen Species/metabolism , Male , Organophosphorus Compounds/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Antioxidants/pharmacology , Lipid Peroxidation/drug effects
9.
Am J Chin Med ; 52(2): 541-563, 2024.
Article En | MEDLINE | ID: mdl-38490807

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.


Melanoma , Humans , Melanoma/drug therapy , Quercetin/pharmacology , Quercetin/therapeutic use , Tumor Escape , CD47 Antigen/genetics , RNA, Messenger , Tumor Microenvironment
10.
Plast Reconstr Surg Glob Open ; 12(3): e5619, 2024 Mar.
Article En | MEDLINE | ID: mdl-38463704

Background: With the popularity of liposuction surgery, more awareness should be obtained regarding complications. Liposuction has been thought of as a safe procedure with a very low incidence of major complications. However, life-threatening risks of liposuction have rarely been reported. Methods: We present a case of a 36-year-old woman who developed cardiac arrest during a liposuction procedure, and we present a literature review. Results: She was previously healthy and had no risk factors for pulmonary embolism. The diagnosis was made based on clinical presentation and the presence of an electrolyte disorder and a positive sign on computed tomography pulmonary angiogram (CTPA). Mild hypothermia treatment, symptomatic treatment, and supportive therapy were applied. As the respiratory and circulation were smooth, she was discharged to a rehabilitation hospital. Seven months after discharge, the patient was still in a coma with eye opening. Conclusions: Spinal anesthesia, pulmonary embolism, and hyperkalemia are the most probable contributors to the cardiac arrest observed during the liposuction procedure in this specific case. There is a heightened imperative to vigilantly monitor for critical incidents during these operations and to meticulously identify associated risk factors during liposuction.

11.
Math Biosci Eng ; 21(2): 1884-1898, 2024 Jan 04.
Article En | MEDLINE | ID: mdl-38454666

Here, we formulated a delayed mosquito population suppression model including two switching sub-equations, in which we assumed that the growth of the wild mosquito population obeys the Ricker-type density-dependent survival function and the release period of sterile males equals the maturation period of wild mosquitoes. For the time-switched delay model, to tackle with the difficulties brought by the non-monotonicity of its growth term to its dynamical analysis, we employed an essential transformation, derived an auxiliary function and obtained some expected analytical results. Finally, we proved that under certain conditions, the number of periodic solutions and their global attractivities for the delay model mirror that of the corresponding delay-free model. The findings can boost a better understanding of the impact of the time delay on the creation/suppression of oscillations harbored by the mosquito population dynamics and enhance the success of real-world mosquito control programs.


Aedes , Models, Biological , Male , Animals , Mosquito Vectors , Mosquito Control/methods , Probability , Population Dynamics
12.
PLoS One ; 19(3): e0299273, 2024.
Article En | MEDLINE | ID: mdl-38452128

PURPOSE: This study aims to evaluate the efficacy and satisfaction of using a multi-angle laser device (MLD) for C-arm fluoroscopy to assist novice learners during lumbar spine surgery. METHODS: Forty novice learners were randomly assigned to Group A using an MLD-equipped C-arm or Group B using a traditional C-arm. Both groups performed X-ray fluoroscopy on a lumbar spine model in supine and rotated positions. Time, number of shots, and deviation from the target were compared. A questionnaire was used to assess the learning experience. RESULTS: Group A required less time (13.66 vs. 25.63 min), and fewer shots (15.05 vs. 32.50), and had a smaller deviation (22.9% vs. 61.5%) than Group B (all p<0.05). The questionnaire revealed higher scores in Group A for comfort, efficiency, and knowledge mastery (all p<0.05). CONCLUSION: The MLD significantly improves novice learning of C-arm fluoroscopy during lumbar spine surgery.


Lumbar Vertebrae , Surgery, Computer-Assisted , Fluoroscopy , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Surveys and Questionnaires , Humans
13.
Neurosci Lett ; 826: 137712, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38447888

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.


Benzamides , Glaucoma , Naphthols , Ocular Hypertension , Mice , Animals , Resveratrol/pharmacology , Resveratrol/therapeutic use , NF-kappa B/metabolism , Sirtuin 1/metabolism , bcl-2-Associated X Protein , Interleukin-6 , Mice, Inbred C57BL , Ocular Hypertension/drug therapy , Glaucoma/drug therapy
15.
Pharmacogenomics J ; 24(2): 8, 2024 Mar 14.
Article En | MEDLINE | ID: mdl-38485921

BACKGROUND: Tibetan medicine Gaoyuan'an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease. METHODS: The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment. RESULTS: We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models. CONCLUSIONS: The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What's more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.


Drugs, Chinese Herbal , Interleukin-6 , Humans , Molecular Docking Simulation , Luteolin , Network Pharmacology , Hypoxia/drug therapy , Hypoxia/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
16.
Cancer Cell ; 42(3): 474-486.e12, 2024 Mar 11.
Article En | MEDLINE | ID: mdl-38402610

Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.


Extracellular Traps , Lung Neoplasms , Humans , Animals , Mice , Neutrophils/pathology , Lung Neoplasms/pathology , Lung/pathology , Tumor Microenvironment
17.
New Phytol ; 242(2): 641-657, 2024 Apr.
Article En | MEDLINE | ID: mdl-38379453

Nitrate is the main source of nitrogen (N) available to plants and also is a signal that triggers complex regulation of transcriptional networks to modulate a wide variety of physiological and developmental responses in plants. How plants adapt to soil nitrate fluctuations is a complex process involving a fine-tuned response to nitrate provision and N starvation, the molecular mechanisms of which remain largely uncharted. Here, we report that the wheat transcription factor TaLBD41 interacts with the nitrate-inducible transcription factor TaNAC2 and is repressed by nitrate provision. Electrophoretic mobility shift assay and dual-luciferase system show that the TaLBD41-NAC2 interaction confers homeostatic coordination of nitrate uptake, reduction, and assimilation by competitively binding to TaNRT2.1, TaNR1.2, and TaNADH-GOGAT. Knockdown of TaLBD41 expression enhances N uptake and assimilation, increases spike number, grain yield, and nitrogen harvest index under different N supply conditions. We also identified an elite haplotype of TaLBD41-2B associated with increased spike number and grain yield. Our study uncovers a novel mechanism underlying the interaction between two transcription factors in mediating wheat adaptation to nitrate availability by antagonistically regulating nitrate uptake and assimilation, providing a potential target for designing varieties with efficient N use in wheat (Triticum aestivum).


Nitrates , Nitrogen , Nitrates/metabolism , Nitrogen/metabolism , Biological Transport , Edible Grain/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
18.
J Affect Disord ; 351: 683-693, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38316259

OBJECTIVE: This study aimed to examine the bidirectional associations between dietary diversity and clinical depressive symptoms in adult women, and influencing factors of clinical depressive symptoms. METHODS: This longitudinal study included a total of 22,385 participants, each of whom underwent at least two data collections. We used convenience sampling to recruit women from a health management center of a general hospital in southern China from April 2015 to December 2021. They completed an online self-reported health questionnaire, which included demographic characteristics, lifestyle information, the Dietary Diversity Scale (DDS), and the Patient Health Questionnaire-9. RESULTS: New-onset depressive symptoms and low dietary diversity were observed in this study among 1285 and 3223 participants, respectively. Negative associations were observed between baseline low dietary diversity and new-onset depressive symptoms (P < 0.05) and between baseline depressive symptoms and low dietary diversity (P < 0.001). Cross-lagged panel analysis indicated that dietary diversity negatively and prospectively predicted depressive symptoms, but vice versa (P < 0.05). Strong evidence of a nonlinear association between DDS scores and incident depressive symptoms was found (P nonlinear < 0.05) regardless of whether the variables were adjusted. Besides, age, menarche age, physical activity, sleep duration, longer sedentary behavior and other lifestyle factors were influencing factors of depressive symptoms (P < 0.05). CONCLUSIONS: The present study identified bidirectional associations between dietary diversity and depressive symptoms, and the associations were found to have a non-linear pattern. Adherence to dietary diversity and a healthy lifestyle could be effective non-pharmacological preventive measures to reduce the incidence of depressive symptoms.


Depression , Diet , Adult , Humans , Female , Longitudinal Studies , Depression/epidemiology , Depression/etiology , Retrospective Studies , Surveys and Questionnaires
19.
Obes Surg ; 34(2): 534-541, 2024 Feb.
Article En | MEDLINE | ID: mdl-38191965

PURPOSE: Ectopic fat accumulation plays a significant role in obesity-related metabolic dysfunction, and few studies have reported an association between ectopic gastric fat and metabolic risk factors. We aim to fulfill this need by assessing the degree of gastric submucosal fat accumulation in pathologic sections of 190 sleeve gastrectomy specimens. METHODS: Study patients were divided into two groups (D1 and D2) based on whether fat accumulation exceeded 1/3 of the submucosa of the stomach. Demographic and metabolic risk factors were compared between the two groups. Metabolic risk variables that might be associated with the degree of fat accumulation were screened in the original cohort. After balancing for possible confounders, the robustness of the correlations was assessed using binary and conditional logistic regression analyses. RESULTS: All study patients had fat accumulation in the submucosa of the stomach. C-reactive protein (CRP), body mass index (BMI), visceral fat area (VFA), and insulin resistance (IR) were higher in the D2 group than in the D1 group in the original cohort (P < 0.05). Logistic regression analysis showed that BMI and IR may be associated with increased fat accumulation. After balancing variables other than obesity indicators and IR using propensity score matching, BMI and IR remained significantly different between the two groups (P < 0.05). Further analysis of the matched cohort using two logistic regression analyses showed that IR was an independent risk factor for increased fat accumulation. CONCLUSION: This study indicated that gastric submucosal fat accumulation was prevalent in patients with obesity and was associated with IR.


Insulin Resistance , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Obesity/complications , Obesity/surgery , Stomach , Risk Factors , Intra-Abdominal Fat , Body Mass Index
20.
BMC Med Educ ; 24(1): 32, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38183036

BACKGROUND: Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students' clinical judgment ability and understanding of nursing students' experiences of the combined simulation. METHODS: A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data. RESULTS: Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students' clinical judgment ability. CONCLUSIONS: The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students' self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.


Education, Nursing, Baccalaureate , Students, Nursing , Humans , Judgment , China , Clinical Reasoning
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