ABSTRACT
The white adipose tissue-specific aptamer Adipo8 can specificity bindwith mature adipocytes or tissues and inhibit adipogenesis.In this research, we exploredthe effect of Adipo8 intervention on the transcriptome in the process of adipogenesis using mRNA-level sequencing,analyzed the mechanism ofAdipo8 ininhibiting adipogenesis. The results showed that Adipo8 can inhibit lipid formation and downregulate PPARγ and C/EBPα in differentiated 3 T3-L1 cells. Transcriptome mRNA sequencing of 3 T3-L1 cells after Adipo8 interventionrevealed that Adipo8 might inhibit the biological function of adipogenesis by downregulating Acsl1 and Plin1 to inhibit fatty acid metabolism and PPAR signaling pathways.After that, using Spacer18 to connect the optimized and truncated Adipo8, we constructed a bivalent aptamer Adipo8cBand compared the affinity, biological effects, and biological stability between the aptamers in differentiated and mature 3 T3-L1 cells. At the cellular level,the affinity, biological effects, and serum stability of Adipo8cB were verified to be superior to those of Adipo8in 3 T3-L1 cells.We then investigated the biological properties of Adipo8cB as a lipid-inhibiting drug invivo, using C57BL/6J mice with diet-induced obesity. The body weight, blood sugar, lipid levels, liver function, glucose tolerance, and other related indicators in each group of mice were observed and compared after intervention with the bivalent aptamers Adipo8cB and Adipo8. Both Adipo8cB and Adipo8 effectively prevented weight gain caused by fat accumulation in micewith diet induced obesity, while also reducing blood lipid levels, improving glucose tolerance, and protecting against liver steatosis, moreover, Adipo8cB has a better effect than Adipo8.
Subject(s)
3T3-L1 Cells , Adipose Tissue, White , Aptamers, Nucleotide , Mice, Inbred C57BL , Obesity , Animals , Mice , Obesity/metabolism , Adipose Tissue, White/metabolism , Adipose Tissue, White/drug effects , Aptamers, Nucleotide/pharmacology , Male , Adipogenesis/drug effects , Adipogenesis/physiology , Diet, High-Fat/adverse effectsABSTRACT
ADGRF5 (GPR116) has been identified as a facilitator of breast cancer cell migration and metastasis, yet the underlying mechanisms remain largely elusive. Our current study reveals that the absence of ADGRF5 in breast cancer cells impairs extracellular matrix (ECM)-associated cell motility and impedes in vivo tumor growth. This correlates with heightened expression of matrix metalloproteinase 8 (MMP8), a well-characterized antitumorigenic MMP, and a shift in the polarization of tumor-associated neutrophils (TANs) towards the antitumor N1 phenotype in the tumor microenvironment (TME). Mechanistically, ADGRF5 inhibits ERK1/2 activity by enhancing RhoA activation, leading to decreased phosphorylation of C/EBPß at Thr235, hindering its nuclear translocation and subsequent activation. Crucially, two C/EBPß binding motifs essential for MMP8 transcription are identified within its promoter region. Consequently, ADGRF5 silencing fosters MMP8 expression and CXCL8 secretion, attracting increased infiltration of TANs; simultaneously, MMP8 plays a role in decorin cleavage, which leads to trapped-inactivation of TGF-ß in the TME, thereby polarizing TANs towards the antitumor N1 neutrophil phenotype and mitigating TGF-ß-enhanced cell motility in breast cancer. Our findings reveal a novel connection between ADGRF5, an adhesion G protein-coupled receptor, and the orchestration of the TME, which dictates malignancy progression. Overall, the data underscore ADGRF5 as a promising therapeutic target for breast cancer intervention.
Subject(s)
Breast Neoplasms , Cell Movement , Matrix Metalloproteinase 8 , Receptors, G-Protein-Coupled , Animals , Female , Humans , Mice , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Disease Progression , Extracellular Matrix/metabolism , Gene Expression Regulation, Neoplastic , Interleukin-8/metabolism , Matrix Metalloproteinase 8/metabolism , Matrix Metalloproteinase 8/genetics , Mice, Nude , Neutrophils/metabolism , Receptors, G-Protein-Coupled/metabolism , rhoA GTP-Binding Protein/metabolism , Transforming Growth Factor beta/metabolism , Tumor MicroenvironmentABSTRACT
Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.
Subject(s)
Antigens, CD7 , Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Antigens, CD7/immunology , Receptors, Chimeric Antigen/immunology , Male , Tissue Donors , T-Lymphocytes/immunology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Treatment Outcome , AdultABSTRACT
Here, the influence and potential mechanism by which cellulose nanocrystals (CNC) collaborated with Ca2+ enhancing the heat-induced gelation of pea protein isolate (PPI) were investigated. It was found that the combination of 0.45% CNC and 15 mM Ca2+ synergistically increased the gel strength (from 14.18 to 65.42 g) and viscoelasticity of PPI while decreased the water holding capacity. The improved particle size, turbidity, and thermostability as well as the reduced solubility, crystallinity, and gel porosity were observed in CNC/CaCl2 composite system. CNC fragments bind to specific amino acids in 11S legumin and 7S vicilin mainly through hydrogen bonding and van der Waals forces. Moreover, changes in the protein secondary structure and enhancement of the molecular interaction induced by CNC and Ca2+ could favor the robust gel network. The results will provide a new perspective on the functional regulation of pea protein and the creation of pea protein gel-based food.
Subject(s)
Nanoparticles , Pea Proteins , Cellulose/chemistry , Calcium , Gels/chemistry , Water/chemistry , Nanoparticles/chemistrySubject(s)
Anemia, Aplastic , Hematopoietic Stem Cell Transplantation , Registries , Transplantation, Homologous , Humans , Hematopoietic Stem Cell Transplantation/methods , Anemia, Aplastic/therapy , Anemia, Aplastic/mortality , Anemia, Aplastic/diagnosis , Aged , Male , Female , Middle Aged , Treatment Outcome , China/epidemiology , East Asian PeopleABSTRACT
Background: Hyaluronic acid (HA), the main component of the extracellular matrix, has the ability to promote tissue repair and regulate inflammation. It is used in otolaryngology as an adjuvant treatment to alleviate postoperative nasal symptoms. However, there is currently insufficient evidence demonstrating the therapeutic efficacy of HA for patients with nasal inflammatory diseases (NIDs). Therefore, this study aimed to evaluate the efficacy and safety of topical HA in the treatment of NID patients without receiving surgery. Methods: In this meta-analysis, comprehensive searches were conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science. Keywords searched included "hyaluronic acid," "sinusitis," "allergic rhinitis," "rhinitis," and "randomized controlled trials (RCTs)." The Cochrane Collaboration's "Risk of Bias Assessment" tool was used to assess the quality of the included trials, and the meta-analysis was performed using the RevMan 5.3 and STATA 15 statistical software. Results: A total of 11 articles and 825 participants were enrolled. For the primary outcomes, the pooled results revealed that HA significantly improves nasal obstruction (SMD, -0.53; 95% CI, -0.92 to -0.14; p = 0.008; and I2 = 79%) and rhinorrhea (SMD, -0.71; 95% CI, -1.27 to -0.15; p = 0.01; and I2 = 90%) in patients with NIDs. As for the secondary outcomes, the pooled results demonstrated that when compared with the control group, HA could significantly improve nasal endoscopic scores (p < 0.05), rhinitis scores (p < 0.05), rhinomanometry (p < 0.05), nasal neutrophils (p < 0.05), and mucociliary clearance (p < 0.05). However, no significant differences were observed between the two groups regarding nasal itching, sneezing, hyposmia, quality-of-life scores, and nasal eosinophils. For the risk of bias, 54.5% and 45.5% of trials had a low risk of bias in the randomization process and deviation of the intended intervention, respectively. Conclusion: In the present study, the results reveal that HA might ameliorate symptoms of patients with NIDs. However, more clinical trials with larger participant cohorts are required to confirm this result. Systematic review registration number: clinicaltrials.gov, identifier CRD42023414539.
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Background: Antihypertensive therapy is crucial for preventing stroke in hypertensive patients. However, the efficacy of antihypertensive therapy varies across individuals, partially due to therapy-related genetic variations among individuals. We investigated the association of antihypertensive drug-related gene polymorphism with stroke in patients with hypertension. Methods: Demographic information, medication, and outcome data were obtained from a hypertensive patient management system, and a PCR fluorescence probe technique was used to detect 7 gene polymorphic loci (CYP2D6∗10, ADRB1, CYP2C9∗3, AGTR1, ACE, CYP3A5∗3, and NPPA), and these loci were compared between patients with and without stroke. Logistic regression was performed to analyze the association of these genetic variations with stroke risk in hypertensive patients while controlling for potential factors. Results: The prevalence of stroke in the hypertensive population in Changsha County of Hunan Province was 2.75%. The mutation frequencies of ADRB1 (1165G > C), CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), NPPA (2238T > C), and CYP3A5∗3 were 74.43%, 57.23%, 4.26%, 5.71%, 31.62%, 1.17%, and 69.58%, respectively. Univariate analysis revealed that ADRB1 polymorphism was associated with stroke (χ2 = 8.659, P < 0.05), with a higher stroke risk in the CC group than in the GC and GG groups (GC + GG). Multivariate unconditional logistic regression analysis showed that the CC genotype in ADRB1 (vs. the GC + GG genotype) was associated with an increased risk of stroke [odds ratio (OR) = 1.184, P<0.05] in hypertensive patients. No association was observed between CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), CYP3A5∗3, and NPPA (2238T > C) polymorphisms and stroke. Conclusions: ADRB1 (1165G > C) gene polymorphism is associated with the risk of stroke in Chinese hypertensive patients. The CC genotype is correlated with a higher risk of stroke than the GC + GG genotype.
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BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.
Subject(s)
Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Smoking , Tuberculosis , Humans , Case-Control Studies , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Smoking/adverse effects , Smoking/genetics , Tuberculosis/epidemiology , Tuberculosis/geneticsABSTRACT
In the context of the connotative development of higher education, the match between what college graduates have learned and what they have used and its causes has aroused the attention of society. Human capital and family capital are two important research perspectives when analyzing what graduates learn and what they use. The study selects professional ability, general ability and allocation ability to measure graduates' human capital and analyzes their family capital from three levels: economic, cultural and social. The study verified that human capital plays a mediating role in the influence of family capital on graduates' learning-application matching. Among the factors of human capital, professional ability and allocation ability have a significant positive influence on graduates' learning-application matching while general ability has a negative influence on graduates' learning-application matching. Family economic capital and family cultural capital have a significant positive influence on graduates' learning-application matching. Based on the findings of the empirical study, we propose countermeasures for universities to improve and enhance graduates' learning-application matching.
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INTRODUCTION: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. OBJECTIVES: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. METHODS: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. RESULTS: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. CONCLUSION: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.
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OBJECTIVE: Doxorubicin (DOX) is commonly used for chemotherapy; however, its clinical value is extremely dampened because of the fatal cardiotoxicity. Leucine zipper protein 1 (LUZP1) plays critical roles in cardiovascular development, and this study is designed for determining its function and mechanism in DOX-induced cardiotoxicity. METHODS: Cardiac-specific Luzp1 knockout (cKO) and transgenic (cTG) mice received a single or repeated DOX injections to establish acute and chronic cardiotoxicity. Biomarkers of inflammation, oxidative damage and cell apoptosis were evaluated. Transcriptome and co-immunoprecipitation analysis were used to screen the underlying molecular pathways. Meanwhile, primary cardiomyocytes were applied to confirm the beneficial effects of LUZP1 in depth. RESULTS: LUZP1 was upregulated in DOX-injured hearts and cardiomyocytes. Cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated DOX-associated inflammation, oxidative damage, cell apoptosis and acute cardiac injury. Mechanistic studies revealed that LUZP1 ameliorated DOX-induced cardiotoxicity through activating 5'-AMP-activated protein kinase (AMPK) pathway, and AMPK deficiency abolished the cardioprotection of LUZP1. Further findings suggested that LUZP1 interacted with protein phosphatase 1 to activate AMPK pathway. Moreover, we determined that cardiac-specific LUZP1 overexpression could also attenuate DOX-associated chronic cardiac injury in mice. CONCLUSION: LUZP1 attenuates DOX-induced inflammation, oxidative damage, cell apoptosis and ventricular impairment through regulating AMPK pathway, and gene therapy targeting LUZP1 may provide novel therapeutic approached to treat DOX-induced cardiotoxicity.
Subject(s)
Cardiotoxicity , Heart Injuries , Mice , Animals , Cardiotoxicity/etiology , Cardiotoxicity/metabolism , AMP-Activated Protein Kinases/metabolism , Leucine Zippers , Doxorubicin/adverse effects , Myocytes, Cardiac/metabolism , Oxidative Stress , Apoptosis , Inflammation/metabolism , DNA-Binding Proteins/metabolismABSTRACT
BACKGROUND: Atherosclerosis and thrombosis play important roles in the pathophysiology of acute coronary syndrome, with platelet activation and inflammation as the key and initiative factors. Recently mean platelet volume-to-lymphocyte ratio (MPVLR) and monocyte to high-density lipoprotein cholesterol ratio (MHR) have emerged as new prognostic indicators of cardiovascular diseases. However, the predicting effect of the combination of MPVLR and MHR in myocardial infarction has not been reported. OBJECTIVE: The aim of this study was to investigate the usefulness of combination of MPVLR and MHR in predicting patients with AMI. METHODS: 375 patients who had chest pain or stuffiness were retrospectively enrolled in this study. According to the results of coronary angiography and cardiac troponin, patients were divided into AMI group (n = 284) and control group (n = 91). MPVLR, MHR, Gensini score and Grace score were calculated. RESULTS: MPVLR and MHR were significantly higher in AMI group than that in control group (6.47 (4.70-9.58) VS 4.88 (3.82-6.44), 13.56 (8.44-19.01) VS 9.14 (7.00-10.86), P < 0.001, respectively). Meanwhile, both were positively correlated with Gensini score and Grace score. Patients with a high level of MPVLR or MHR had an increased risk for AMI (odds ratio (OR) = 1.2, 95% confidence interval (CI) 1.1-1.4, OR = 1.2, 95% CI 1.2-1.3). Combination of MPVLR and MHR identified a greater ROC area than its individual parameters (P < 0.001). CONCLUSION: Both MPVLR and MHR are independent predictors of AMI. Combination of MPVLR and MHR had higher predicting value in AMI, and thus appears to be a new risk factor and biomarker in the evaluation of risk and severity of atherosclerosis in AMI.
Subject(s)
Atherosclerosis , Myocardial Infarction , Humans , Mean Platelet Volume , Monocytes , Cholesterol, HDL , Retrospective Studies , Myocardial Infarction/diagnosis , Lymphocytes , Atherosclerosis/diagnosisABSTRACT
This work focused on the pathways by which NCC regulated the digestibility of corn starch. The addition of NCC changed the viscosity of the starch during pasting, improved the rheological properties and short-range order of the starch gel, and finally formed a compact, ordered, and stable gel structure. In this respect, NCC affected the digestion process by changing the properties of the substrate, which reduced the degree and rate of starch digestion. Moreover, NCC induced changes in the intrinsic fluorescence, secondary conformation, and hydrophobicity of α-amylase, which lowered its activity. Molecular simulation analyses suggested that NCC bonded with amino acid residues (Trp 58, Trp 59, and Tyr 62) at the active site entrance via hydrogen bonding and van der Waals forces. In conclusion, NCC decreased CS digestibility by modifying the gelatinization and structural properties of starch and inhibiting α-amylase activity. This study provides new insights into the mechanisms by which NCC regulates starch digestibility, which could be beneficial for the development of functional foods to tackle type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Starch , Starch/chemistry , Cellulose/chemistry , Zea mays/chemistry , Digestion , alpha-AmylasesABSTRACT
Atmospheric dryness events are bound to have a broad and profound impact on the functions and structures of grassland ecosystems. Current research has confirmed that atmospheric dryness is a key moisture constraint that inhibits grassland productivity, yet the risk threshold for atmospheric dryness to initiate ecosystem productivity loss has not been explored. Based on this, we used four terrestrial ecosystem models to simulate gross primary productivity (GPP) data, analyzed the role of vapor pressure deficit (VPD) in regulating interannual variability in Chinese grasslands by focusing on the dependence structure of VPD and GPP, and then constructed a bivariate linkage function to calculate the conditional probability of ecosystem GPP loss under atmospheric dryness, and further analyzed the risk threshold of ecosystem GPP loss triggered by atmospheric dryness. The main results are as follows: we found that (1) the observed and modeled VPD of Chinese grasslands increases rapidly in both historical and future periods. VPD has a strongly negative regulation on ecosystem GPP, and atmospheric dryness is an important moisture constraint that causes deficit and even death to ecosystem GPP. (2) The probability of the enhanced atmospheric dryness that induced GPP decline in Chinese grasslands in the future period increases significantly. (3) When the VPD is higher than 40.07 and 27.65 percentile of the past and future time series, respectively, the risk threshold of slight ecosystem GPP loss can be easily initiated by atmospheric dryness. (4) When the VPD is higher than 82.57 and 65.09 percentile, respectively, the threshold of moderate ecosystem GPP loss can be exceeded by the benchmark probability. (5) The risk threshold of severe ecosystem GPP loss is not initiated by atmospheric dryness in the historical period, and the threshold of severe ecosystem GPP loss can be initiated when the future VPD is higher than 91.92 percentile. In total, a slight atmospheric dryness event is required to initiate a slight ecosystem GPP loss threshold, and a stronger atmospheric dryness event is required to initiate a severe ecosystem GPP loss. Our study enhances the understandings of past and future atmospheric dryness on grassland ecosystems, and strongly suggests that more attention be invested in improving next-generation models of vegetation dynamics processes with respect to the response of mechanisms of ecosystem to atmospheric dryness.
Subject(s)
Ecosystem , Grassland , Carbon Cycle , China , ProbabilityABSTRACT
As the first line of defense against risk factors, the nasal epithelial barrier maintains homeostasis in nasal mucosa. The composition of the epithelial barrier contains physical, chemical, immune, and microbiological barriers. Together, these barriers form the nasal defense against irritations. Risk factors from both internal and external environments can disrupt them. External risk factors contain allergens containing proteases, bacteria, virus, particulate matter, diesel exhaust particles, and cigarette smoke. In the meantime, inflammatory cytokines also increase the load on the barrier. Taking into account the role of the epithelial barrier in the nasal mucosa, some studies focus on the treatment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) by restoring the epithelial barrier, and some progress has been made. Among the therapeutic approaches, histone deacetylase (HDAC) inhibitor and steroid corticosteroids are considered two of the more studied categories, and their roles in repairing barriers have been demonstrated in AR and CRS. The underlying mechanism of HDAC inhibitor may be related to the transcription factor p63. And the protection of corticosteroids may be associated with the allergic disease susceptibility gene, protocadherin-1. Notably, manipulation of the microbiological barrier also has a positive effect on AR and CRS. Lactococcus and probiotics are two categories that are worth being explored continuously. We here review and discuss the compositions and risk factors of the nasal epithelial barrier. Furthermore, some novel and promising approaches to restore the defective barrier in nasal allergic diseases were mentioned.
Subject(s)
Rhinitis, Allergic , Sinusitis , Humans , Nasal Mucosa , Allergens , Chronic Disease , Vehicle EmissionsABSTRACT
AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.
Subject(s)
Diabetes, Gestational , Child , Pregnancy , Humans , Female , Diabetes, Gestational/epidemiology , Iron/adverse effects , Pregnancy Trimester, First , Case-Control Studies , FerritinsABSTRACT
The primary function of regulatory T cells (Tregs) is blocking the pathogenic immunological response mediated by autoreactive cells, establishing and maintaining immune homeostasis in tissues. Kidney diseases are often caused by Immune imbalance, including alloimmune graft damage after renal transplantation, direct immune-mediated kidney diseases like membranous nephropathy (MN) and anti-glomerular basement membrane (anti-GBM) glomerulonephritis, as well as indirect immune-mediated ones like Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAVs), IgA nephropathy (IgAN) and lupus nephritis (LN). Treg cells are deficient numerically and/or functionally in those kidney diseases. Targeted-Treg therapies, including adoptive Tregs transfer therapy and low-dose IL-2 therapy, have begun to thrive in treating autoimmune diseases in recent years. However, the clinical use of targeted Treg-therapies is rarely mentioned in those kidney diseases above except for kidney transplantation. This article mainly discusses the newest progressions of targeted-Treg therapies in those specific examples of immune-mediated kidney diseases. Meanwhile, we also reviewed the main factors that affect Treg development and differentiation, hoping to inspire new strategies to develop target Tregs-therapies. Lastly, we emphasize the significant impediments and prospects to the clinical translation of target-Treg therapy. We advocate for more preclinical and clinical studies on target Tregs-therapies to decipher Tregs in those diseases.
Subject(s)
Glomerulonephritis, IGA , Glomerulonephritis , Lupus Nephritis , Humans , T-Lymphocytes, Regulatory , Kidney Glomerulus , Lupus Nephritis/pathologyABSTRACT
The desertification reversal is a process of revegetation and natural restoration in fragile dryland areas due to human activities and climate change mediation. Understanding the impact of desertification reversion on terrestrial ecosystems, including vegetation greenness and photosynthetic capacity, is crucial for land policy-making and carbon-cycle model improvement. However, the phenomenon of desertification reversal is rarely mentioned in previous studies, which dramatically limits the understanding of vegetation dynamics in the arid area. Therefore, it is of great necessity to investigate the status of desertification reversal on the ecosystem in arid areas. In this study, we first reported the phenomenon of desertification reversion over the southern edge of the Gurbantunggut Desert through the Moderate-resolution Imaging Spectroradiometer classification map year by year. We discussed the consequences, ways, and causes of desertification reversion. Our results showed that the desertification reversal significantly increased vegetation greenness and photosynthetic capacity, which largely offset the negative impact of desertification on the ecosystem productivity; cropland expansion and grassland's natural restoration were the two main ways of desertification reversal; the improvement of soil-water condition was an essential environmental factor leading to the phenomenon of reverse desertification. This finding highlights the importance of desertification reversal in the carbon cycle of dryland ecosystems and prove that desertification reversal is an integral part of global and dryland vegetation greening.
Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Fluorescence , Desert Climate , Chlorophyll , ChinaABSTRACT
Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease caused by pathogenic mutations in the APOE gene. Collagen type III glomerulopathy (CG) is a sporadic condition in adults characterized by abnormal accumulation of type III collagen in the subendothelial space and mesangium of the glomerulus. We report the first case of both LPG and CG in a 21-year-old male. A search of the literature found no confirmed reports of these two concomitant nephropathies. The patient presented with hypertension, proteinuria, hematuria and hyperlipidemia. Renal pathology showed lipid vacuoles in the enlarged glomerular capillary loops and type III collagen in the segmental mesangial area and on the inner side of the glomerular basement membrane by electron microscopy. Whole-exome sequencing revealed a heterozygous mutation (c.127C>T; p. Arg43Cys) in exon 3 of the APOE gene, known as the APOE-Kyoto of LPG. In addition, two heterozygous COL4A4 mutations (c.4715C>T in exon 47 and c.5065 T>C in exon 48) were observed, the first one was suspected pathogenic and the other one was uncertain significant. There is no special treatment for these diseases. The patient was treated with lipid-lowering agents, renin-angiotensin-aldosterone system inhibition and tripterygium glycosides. The patient received double-filtration plasmapheresis and immunoadsorption therapy when renal function deteriorated dramatically. Immunoadsorption was beneficial for this patient.
Subject(s)
Collagen Type III , Kidney Diseases , Male , Adult , Humans , Young Adult , Collagen Type III/genetics , Kidney Diseases/pathology , Kidney/pathology , Kidney Glomerulus/pathologyABSTRACT
Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction. Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients. Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy. Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease.