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Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice

Journal of Environmental Sciences 2024年第3期137卷 553-566页

作者： Xingpei Fan Xiaoyan Li Jiaxin Li Yuxia Zhang Xiangjuan Wei Hailong Hu Boya Zhang Haining Du Meimei Zhao Ruijiao Zhu Daqian Yang Yuri Oh Ning Gu School of Life Science and Technology Harbin Institute of TechnologyHarbin 150001China State Key Laboratory of Urban Water Resource and Environment Harbin Institute of TechnologyHarbin 150006China Department of Medicine Renal Electrolyte and Hypertension DivisionDepartment of GeneticsPerelman School of MedicineUniversity of PennsylvaniaPhiladelphia 19104USA Faculty of Education Wakayama UniversityWakayama 640-8441Japan

Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.

关键词： Nanoplastics Resveratrol hyperglycemia Lipid metabolism Infammatory response Reactive oxygen species(ROS)

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High glucose microenvironment and human mesenchymal stem cell behavior

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World Journal of Stem Cells 2024年第3期16卷 237-244页

作者： Muhammad Abdul Mateen Nouralsalhin Alaagib Khawaja Husnain Haider Basic Sciences Sulaiman AlRajhi UniversityAlQaseem 52736Saudi Arabia Cellular and Molecular Pharmacology Sulaiman AlRajhi Medical SchoolAl Bukairiyah 51941Saudi Arabia

High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our body.It interferes with diverse signaling pathways,i.***.mammalian target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis rates.While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP production.This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities.Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG.Some previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial homeostasis.The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce ATP.These are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy.Therefore,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment proliferation.As hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.

关键词： Adipose tissue Apoptosis Bioenergetics Cell survival Cell therapy hyperglycemia Mitochondria Mesenchymal stem cells Stem cells

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Chiglitazar and Thiazolidinedione in patients with type 2 diabetes:Which is better?

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World Journal of Diabetes 2024年第3期15卷 565-567页

作者： Kotha Sugunakar Reddy Archana Gaur Sakthivadivel Varatharajan Arvind Kumar Morya Department of General Medicine All India Institute of Medical SciencesHyderabad 508126TelanganaIndia Department of Physiology All India Institute of Medical SciencesHyderabad 508126TelanganaIndia Department of Medicine All India Institute of Medical SciencesHyderabad 508126TelanganaIndia Department of Ophthalmology All India Institute of Medical SciencesHyderabad 508126TelanganaIndia

This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and ... 详细信息

关键词： Type-Ⅱdiabetes mellitus Glucose intolerance hyperglycemia Research methodology

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Nutrition interventions and clinical outcomes of pregnant women with gestational diabetes mellitus: More than meets the eye

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World Journal of Diabetes 2024年第1期15卷 126-128页

作者： Sony Sinha Prateek Nishant Ranjeet Kumar Sinha Arvind Kumar Morya Ripunjay Prasad Department of Ophthalmology-Vitreo-Retina Neuro-Ophthalmology and OculoplastyAll India Institute of Medical SciencesPatnaPatna 801507BiharIndia Department of Ophthalmology ESIC Medical CollegePatnaPatna 801103BiharIndia Department of Community Medicine Patna Medical CollegePatna 800004BiharIndia Department of Ophthalmology All India Institute of Medical SciencesHyderabad 508126TelanganaIndia Department of Ophthalmology RP Eye InstituteDelhi 110001DelhiIndia

In the retrospective study by Luo et al regarding clinical outcomes in gestational diabetes mellitus(GDM),the results are statistically significant in favour of the benefits of individualized nutrition interventions enumerated therein.The study has provided important evidence to improve maternal and child health in the Asian population.The methods,however,appear to have considerable limi-tations,wherein the time point of diagnosis of GDM,severity of GDM,selection bias,compliance to therapy,important maternal covariates,observable microvascular abnormalities and the confounding effect of added insulin have not been considered.We have provided suggestions to improve the external validity of the study,including the use of Equator Network reporting guidelines and inclusion of overweight and obese patients in future studies.

关键词： Glucose intolerance hyperglycemia Obesity Pregnancy Research methodology

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hyperglycemia in acute ischemic stroke: physiopathological and therapeutic complexity

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Neural Regeneration Research 2022年第2期17卷 292-299页

作者： Federica Ferrari Antonio Moretti Roberto Federico Villa Department of Biology and Biotechnology Laboratory of Pharmacology and Molecular Medicine of Central Nervous SystemUniversity of PaviaVia FerrataPaviaItaly

Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.

关键词： acute ischemic stroke diabetes mellitus DPP-4 inhibitor glucose-like peptide-1 receptor agonist hyperglycemia hypoglycemia insulin physiopathology sodium glucose cotransporter 2 inhibitor

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A Potential Role for GLUT4 in Predicting Sepsis in Critically Ill Children

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Open Journal of Internal Medicine 2024年第1期14卷 1-15页

作者： Yanna Zhou Guangming Liu Xiaohui Wu Aidi Kuang Cuiping Zhu Qiuyan Peng Department of Pediatric Emergency Medicine Guangzhou Women and Children’s Medical Center Guangzhou Medical University Guangzhou China

Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.

关键词： Children Critical Illness Glucose Transporter Type 4 hyperglycemia Insulin Resistance

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Artificial intelligence powered glucose monitoring and controlling system:Pumping module

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World Journal of Experimental Medicine 2024年第1期14卷 100-112页

作者： Sravani Medanki Nikhil Dommati Hema Harshitha Bodapati Venkata Naga Sai Kowsik Katru Gollapalli Moses Abhishek Komaraju Nanda Sai Donepudi Dhanya Yalamanchili Jasti Sateesh Pratap Turimerla Department of Electronics and Communication Engineering Velagapudi Ramakrishna Siddhartha Engineering CollegeVijayawada 520007Andhra PradeshIndia Department of General Medicine Siddhartha Government Medical CollegeVijayawada 520008Andhra PradeshIndia

BACKGROUND Diabetes,a globally escalating health concern,necessitates innovative solutions for efficient detection and management.Blood glucose control is an essential aspect of managing diabetes and finding the most effective ways to control it.The latest findings suggest that a basal insulin administration rate and a single,highconcentration injection before a meal may not be sufficient to maintain healthy blood glucose levels.While the basal insulin rate treatment can stabilize blood glucose levels over the long term,it may not be enough to bring the levels below the post-meal limit after 60 min.The short-term impacts of meals can be greatly reduced by high-concentration injections,which can help stabilize blood glucose levels.Unfortunately,they cannot provide long-term stability to satisfy the postmeal or pre-meal restrictions.However,proportional-integral-derivative(PID)control with basal dose maintains the blood glucose levels within the range for a longer period.AIM To develop a closed-loop electronic system to pump required insulin into the patient's body automatically in synchronization with glucose sensor readings.METHODS The proposed system integrates a glucose sensor,decision unit,and pumping module to specifically address the pumping of insulin and enhance system effectiveness.Serving as the intelligence hub,the decision unit analyzes data from the glucose sensor to determine the optimal insulin dosage,guided by a pre-existing glucose and insulin level table.The artificial intelligence detection block processes this information,providing decision instructions to the pumping module.Equipped with communication antennas,the glucose sensor and micropump operate in a feedback loop,creating a closed-loop system that eliminates the need for manual intervention.RESULTS The incorporation of a PID controller to assess and regulate blood glucose and insulin levels in individuals with diabetes introduces a sophisticated and dynamic element to diabetes management.The simulation not only allows visualization of ho

关键词： Diabetes hyperglycemia Insulin Micropump Closed loop systems Artificial intelligence automation

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hyperglycemia in COVID-19 infection without diabetes mellitus:Association with inflammatory markers

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World Journal of Clinical Cases 2023年第6期11卷 1287-1298页

作者： Harinivaas Shanmugavel Geetha Garima Singh Abinesh Sekar Maya Gogtay Yuvaraj Singh George MAbraham Nitin Trivedi Department of Internal Medicine Saint Vincent HospitalWorcesterMA 01608United States Department of Hospice and Palliative Medicine University of Texas HealthSan AntonioTX 78229United States Department of Internal Medicine University of Massachusetts Chan Medical SchoolWorcesterMA 01655United States

BACKGROUND New onset hyperglycemia is common in patients with severe coronavirus disease 2019(COVID-19)infection.Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia,but factors like direct severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced pancreaticβ-cell failure have also been postulated to play a role.AIM We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia,particularly the rationale of the cytokine-induced hyperglycemia hypothesis,by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection.METHODS We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection.The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected.hyperglycemia was defined as glucose levels≥140 mg/dL.C-Reactive protein(CRP)≥100 mg/L,ferritin≥530 ng/mL,lactate dehydrogenase(LDH)≥590 U/L,and D-dimer≥0.5 mg/L were considered elevated.We used theχ2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia.RESULTS Of the 520 patients screened,248 met the inclusion criteria.Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic.Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows:CRP(58.1%vs 65.6%,P=0.29),ferritin(48.4%vs 34.9%,P=0.14),D-dimer(37.1%vs 37.1%,P=0.76)and LDH(19.4%vs 11.8%,P=0.02).Logistic regression analysis showed LDH odds ratio(OR)=1.623(P=0.256).We observed significantly higher mortality(24.2%vs 9.1%,P=0.001;OR=2.528,P=0.024)and length of stay(8.89 vs 6.69,P=0.026)in patients with hyperglycemia.CONCLUSION Our study showed no association between CRP,ferritin,LDH,D-dimer levels,and new-onset hyperglycemia in non-diabetic patients with COVID-19 i

关键词： COVID-19 Inflammatory markers hyperglycemia C-reactive protein Mortality Severity Mechanisms Diabetes mellitus

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Dark red tongue color formation caused by hyperglycemia is attributed to decreased blood flow of tongue tissue partially due to nuclear factor-kappa B pathway activation

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Journal of Traditional Chinese Medicine 2023年第6期43卷 1118-1125页

作者： JIN Shenyi LIU Yahua HAN Xu CAI Mengjie XU Jiatuo LU Hao CHEN Qingguang Department of Endocrinology Diabetes InstituteShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Basic Medical College Shanghai University of Traditional Chinese MedicineShanghai 201203China

OBJECTIVE:To investigate the potential mechanisms underlying the dark red tongue color formation induced by hyperglycemia.METHODS:A high-fat diet and intraperitoneal injection of streptozotocin were used to establish a diabetes model.The color and blood flow of tongues were analyzed by the Tongue Diagnosis Analysis System and laser Doppler flowmetry,respectively.Inflammatory factors and adhesion factors were measured in the circulation and tongue tissue by an enzyme-linked immunosorbent assay.Western blotting was employed to evaluate nuclear factor-kappa B(NF-κB)p50 and inhibitor of kappa B kinase protein expression levels in the tongue.Then,the NF-κB inhibitor,pyrrolidine dithiocarbamic acid ammonium salt was utilized to repress NF-κB pathway activation to validate that the NF-κB pathway plays a key role in blood flow and dark red tongue color formation.RESULTS:The diabetic rats displayed a dark red tongue color that was accompanied by NF-κB pathway activation and decreased blood flow in the tongue.These effects could be reversed by the NF-κB inhibitor.CONCLUSIONS:Our investigation demonstrated that hyperglycemia led to dark red tongue color formation by decreasing blood flow in the tongue,which was partly due to NF-κB pathway activation.

关键词： tongue diagnosis type 2 diabetes mellitus hyperglycemia NF-kappa B blood circulation

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Intrauterine hyperglycemia impairs endometrial receptivity via up-regulating SGK1 in diabetes

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Science China(Life Sciences) 2022年第8期65卷 1578-1589页

作者： Haiyan Xu Jingyi Li Luyang Jin Dan Zhang Bin Chen Xinmei Liu Xianhua Lin Yiting Huang Zhanghong Ke Juan Liu Lin Gao Jianzhong Sheng Hefeng Huang Reproductive Medicine Center Ningbo First HospitalNingbo 315100China Key Laboratory of Reproductive Genetics Ministry of Education(Zhejiang University)Hangzhou 310058China Department of Reproductive Endocrinology Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Department of Pathology&Pathophysiology Zhejiang University School of MedicineHangzhou 310058China Shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China

Diabetes is a complex metabolic disorder which can adversely affect reproductive function. SGK1 is found to be up-regulated in multiple tissues of diabetic patients. However, the effects of diabetes on endometrial SGK1 expression and endometrial receptivity remain unknown. In this study, we established a streptozotocin-induced diabetic mouse model and observed reduced implantation sites, retarded development of pinopodes, increased SGK1, and aberrant expression of LIF and MUC1 in the endometrial epithelium. We injected the uterine lumen of normal mice with high-glucose solution and cultured endometrial cells in high-glucose medium to mimic intrauterine hyperglycemia. Both studies provided compelling evidence that hyperglycemia could lead to diminished embryo implantation and dysregulated SGK1, LIF and MUC1. Additionally, through over-expression of SGK1 in vivo and in vitro, we found that enhanced SGK1 also decreased LIF expression, increased MUC1 expression, and attenuated embryo implantation rate. We further identified that hyperglycemia-activated SMAD2/3 might be responsible for the enhancement of SGK1 and verified directly the interaction between SMAD3 and corresponding SMAD binding elements within SGK1 promoter. Taken together, our study confirmed the association between diabetes-related hyperglycemia and endometrial receptivity defects. hyperglycemia-induced SGK1 has a tremendous role in this pathological process, rendering it as an attractive therapeutic target for diabetes-related reproductive disorders.

关键词： diabetes endometrial receptivity hyperglycemia serum/glucocorticoid-regulated kinase

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