-
Medical Science Monitor : International... Jul 2024BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important...
BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.
Topics: Humans; Insulin Resistance; Child; Male; Female; Body Mass Index; Triglycerides; Pediatric Obesity; Overweight; Adolescent; Retrospective Studies; Blood Glucose; Obesity; Anthropometry; Waist Circumference; Cholesterol, HDL; ROC Curve; Biomarkers; Fatty Liver; Non-alcoholic Fatty Liver Disease
PubMed: 38956840
DOI: 10.12659/MSM.943375 -
Journal of Economic Entomology Jul 2024Hylurgus ligniperda invaded Shandong, China, through imported forest timber, posing a threat to China's forest health. Exotic insects with broad environmental tolerance,...
Hylurgus ligniperda invaded Shandong, China, through imported forest timber, posing a threat to China's forest health. Exotic insects with broad environmental tolerance, including low temperatures, may have a better chance of surviving the winters and becoming invasive. Understanding the cold-tolerance strategies of H. ligniperda may help to design sustainable pest management approaches. In this study, we aim to investigate the cold-tolerance ability and relevant physiological indicators in overwintering H. ligniperda adults to determine any possible overwintering strategies. Supercooling points (SCPs) for adults H. ligniperda differed significantly across months and reached the lowest level in the mid- and post-overwintering period, the minimum SCPs -6.45 ± 0.18 °C. As the cold exposure temperature decreased, the survival rate of adults gradually decreased, and no adult survived more than 1 day at -15 °C, and the LLT50 for 1 day was -7.1 °C. Since H. ligniperda adults can survive internal ice formation, they are freeze-tolerant insects. Throughout the overwintering period, the SCPs and the water, protein, sorbitol, and glycerol content in adults decreased initially and then increased. We reported significant correlations between total protein, sorbitol, trehalose, and glycerol content in the beetles and SCPs. Glycogen, lipid, protein, trehalose, and sorbitol content in adult beetles may directly affect their cold-tolerance capacity and survival during winter. This study provides a physiological and biochemical basis for further study of metabolism and cold-tolerance strategies in H. ligniperda adults, which may help predict population dynamics and distribution potential of pests.
PubMed: 38956822
DOI: 10.1093/jee/toae137 -
Brain and Behavior Jul 2024High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor...
The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.
BACKGROUND
High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.
OBJECTIVE
The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model.
METHODS
Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.
RESULTS
We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.
CONCLUSIONS
Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.
Topics: Animals; Transcranial Magnetic Stimulation; Mice; Male; Disease Models, Animal; Probenecid; Parkinsonian Disorders; Mice, Inbred C57BL; Brain-Derived Neurotrophic Factor; Motor Cortex; Dopaminergic Neurons; Dopamine Plasma Membrane Transport Proteins; Interleukin-1beta; Substantia Nigra; Corpus Striatum; Vesicular Monoamine Transport Proteins; MPTP Poisoning; Motor Activity; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
PubMed: 38956819
DOI: 10.1002/brb3.3605 -
Physiologia Plantarum 2024This study explores the impact of juglone on cucumber (Cucumis sativus cv. Beith Alpha), scrutinizing its effects on seed germination, growth, and the polyphenol oxidase...
This study explores the impact of juglone on cucumber (Cucumis sativus cv. Beith Alpha), scrutinizing its effects on seed germination, growth, and the polyphenol oxidase (PPO) enzyme's activity and gene expression. Employing concentrations ranging from 0.01 to 0.5 mM, we found juglone's effects to be concentration-dependent. At lower concentrations (0.01 and 0.1 mM), juglone promoted root and shoot growth along with germination, whereas higher concentrations (0.25 and 0.5 mM) exerted inhibitory effects, delineating a threshold for its allelopathic influence. Notably, PPO activity surged, especially at 0.5 mM in roots, hinting at oxidative stress involvement. Real-time PCR unveiled that juglone modulates PPO gene expression in cotyledons, peaking at 0.1 mM and diminishing at elevated levels. Correlation analyses elucidated a positive link between juglone-induced root growth and cotyledon PPO gene expression but a negative correlation with heightened root enzyme activity. Additionally, germination percentage inversely correlated with root PPO activity, while PPO activities positively associated with dopa and catechol substrates in both roots and cotyledons. Molecular docking studies revealed juglone's selective interactions with PPO's B chain, suggesting regulatory impacts. Protein interaction assessments highlighted juglone's influence on amino acid metabolism, and molecular dynamics indicated juglone's stronger, more stable binding to PPO, inferring potential alterations in enzyme function and stability. Conclusively, our findings elucidate juglone's dose-dependent physiological and biochemical shifts in cucumber plants, offering insights into its role in plant growth, stress response, and metabolic modulation.
Topics: Catechol Oxidase; Cucumis sativus; Naphthoquinones; Molecular Docking Simulation; Germination; Plant Roots; Gene Expression Regulation, Plant; Plant Proteins; Cotyledon
PubMed: 38956780
DOI: 10.1111/ppl.14420 -
Stem Cell Research & Therapy Jul 2024Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in...
BACKGROUND
Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in ophthalmology, can readily impact a dog's working capacity and lead to economic losses. Although there are several medications available for this disease, all of them only improve the symptoms on the surface of the eye, and they are irritating and not easy to use for long periods of time. Adipose-derived mesenchymal stem cells (ADMSC) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of ADMSC. Here, we aimed to use ADMSC overexpressing Secreted Protein Acidic and Rich in Cysteine (SPARC) to treat 0.25% benzalkonium chloride-treated dogs with dry eye to verify its efficacy. For in vitro validation, we induced corneal epithelial cell (HCECs) damage using 1 µg/mL benzalkonium chloride.
METHODS
Fifteen male crossbred dogs were randomly divided into five groups: normal, dry eye self-healing control, cyclosporine-treated, ADMSC-CMV-treated and ADMSC-OESPARC-treated. HCECs were divided into four groups: normal control group, untreated model group, ADMSC-CMV supernatant culture group and ADMSC-OESRARC supernatant culture group.
RESULTS
SPARC-modified ADMSC had the most significant effect on canine ocular surface inflammation, corneal injury, and tear recovery, and the addition of ADMSC-OESPARC cell supernatant also had a salvage effect on HCECs cellular damage, such as cell viability and cell proliferation ability. Moreover, analysis of the co-transcriptome sequencing data showed that SPARC could promote corneal epithelial cell repair by enhancing the in vitro viability, migration and proliferation and immunosuppression of ADMSC.
CONCLUSION
The in vitro cell test and in vivo model totally suggest that the combination of SPARC and ADMSC has a promising future in novel dry eye therapy.
Topics: Animals; Dogs; Benzalkonium Compounds; Mesenchymal Stem Cells; Dry Eye Syndromes; Osteonectin; Male; Disease Models, Animal; Adipose Tissue; Mesenchymal Stem Cell Transplantation
PubMed: 38956738
DOI: 10.1186/s13287-024-03815-z -
Critical Care (London, England) Jul 2024Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency,... (Review)
Review
BACKGROUND
Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach.
METHODS
In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation.
RESULTS
A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes.
CONCLUSIONS
Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation.
IMPACT RESEARCH
To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.
Topics: Humans; Critical Illness; Vitamin K; Vitamin K Deficiency; Intensive Care Units
PubMed: 38956732
DOI: 10.1186/s13054-024-05001-2 -
Stem Cell Research & Therapy Jul 2024Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for...
BACKGROUND
Inherited retinal dystrophies (IRD) are one of the main causes of incurable blindness worldwide. IRD are caused by mutations in genes that encode essential proteins for the retina, leading to photoreceptor degeneration and loss of visual function. IRD generates an enormous global financial burden due to the lack of understanding of a significant part of its pathophysiology, molecular diagnosis, and the near absence of non-palliative treatment options. Patient-derived induced pluripotent stem cells (iPSC) for IRD seem to be an excellent option for addressing these questions, serving as exceptional tools for in-depth studies of IRD pathophysiology and testing new therapeutic approaches.
METHODS
From a cohort of 8 patients with PROM1-related IRD, we identified 3 patients carrying the same variant (c.1354dupT) but expressing three different IRD phenotypes: Cone and rod dystrophy (CORD), Retinitis pigmentosa (RP), and Stargardt disease type 4 (STGD4). These three target patients, along with one healthy relative from each, underwent comprehensive ophthalmic examinations and their genetic panel study was expanded through clinical exome sequencing (CES). Subsequently, non-integrative patient-derived iPSC were generated and fully characterized. Correction of the c.1354dupT mutation was performed using CRISPR/Cas9, and the genetic restoration of the PROM1 gene was confirmed through flow cytometry and western blotting in the patient-derived iPSC lines.
RESULTS
CES revealed that 2 target patients with the c.1354dupT mutation presented monoallelic variants in genes associated with the complement system or photoreceptor differentiation and peroxisome biogenesis disorders, respectively. The pluripotency and functionality of the patient-derived iPSC lines were confirmed, and the correction of the target mutation fully restored the capability of encoding Prominin-1 (CD133) in the genetically repaired patient-derived iPSC lines.
CONCLUSIONS
The c.1354dupT mutation in the PROM1 gene is associated to three distinct AR phenotypes of IRD. This pleotropic effect might be related to the influence of monoallelic variants in other genes associated with retinal dystrophies. However, further evidence needs to be provided. Future experiments should include gene-edited patient-derived iPSC due to its potential as disease modelling tools to elucidate this matter in question.
Topics: Humans; Induced Pluripotent Stem Cells; AC133 Antigen; Male; Female; Phenotype; Targeted Gene Repair; Retinal Dystrophies; Adult; Mutation; Exome Sequencing; Exome
PubMed: 38956727
DOI: 10.1186/s13287-024-03804-2 -
Stem Cell Research & Therapy Jul 2024The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate...
BACKGROUND
The human induced pluripotent stem cells (hiPSCs) can generate all the cells composing the human body, theoretically. Therefore, hiPSCs are thought to be a candidate source of stem cells for regenerative medicine. The major challenge of allogeneic hiPSC-derived cell products is their immunogenicity. The hypoimmunogenic cell strategy is allogenic cell therapy without using immune suppressants. Advances in gene engineering technology now permit the generation of hypoimmunogenic cells to avoid allogeneic immune rejection. In this study, we generated a hypoimmunogenic hiPSC (HyPSC) clone that had diminished expression of human leukocyte antigen (HLA) class Ia and class II and expressed immune checkpoint molecules and a safety switch.
METHODS
First, we generated HLA class Ia and class II double knockout (HLA class Ia/II DKO) hiPSCs. Then, a HyPSC clone was generated by introducing exogenous β-2-microglobulin (B2M), HLA-G, PD-L1, and PD-L2 genes, and the Rapamycin-activated Caspase 9 (RapaCasp9)-based suicide gene as a safety switch into the HLA class Ia/II DKO hiPSCs. The characteristics and immunogenicity of the HyPSCs and their derivatives were analyzed.
RESULTS
We found that the expression of HLA-G on the cell surface can be enhanced by introducing the exogenous HLA-G gene along with B2M gene into HLA class Ia/II DKO hiPSCs. The HyPSCs retained a normal karyotype and had the characteristics of pluripotent stem cells. Moreover, the HyPSCs could differentiate into cells of all three germ layer lineages including CD45 hematopoietic progenitor cells (HPCs), functional endothelial cells, and hepatocytes. The HyPSCs-derived HPCs exhibited the ability to evade innate and adaptive immunity. Further, we demonstrated that RapaCasp9 could be used as a safety switch in vitro and in vivo.
CONCLUSION
The HLA class Ia/II DKO hiPSCs armed with HLA-G, PD-L1, PD-L2, and RapaCasp9 molecules are a potential source of stem cells for allogeneic transplantation.
Topics: Humans; Induced Pluripotent Stem Cells; B7-H1 Antigen; Adaptive Immunity; Immunity, Innate; HLA-G Antigens; Programmed Cell Death 1 Ligand 2 Protein; Animals; Mice
PubMed: 38956724
DOI: 10.1186/s13287-024-03810-4 -
Stem Cell Research & Therapy Jul 2024Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to...
BACKGROUND
Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis.
METHODS
The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair.
RESULTS
The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects.
CONCLUSION
NGF/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.
Topics: Animals; Nerve Growth Factor; Mesenchymal Stem Cells; Rats; Tissue Scaffolds; Rats, Sprague-Dawley; Osteogenesis; Bone Regeneration; Allografts; Male; Tissue Engineering; Pyroptosis; Sulfonamides; Cell Differentiation; Mesenchymal Stem Cell Transplantation; Bone Transplantation
PubMed: 38956719
DOI: 10.1186/s13287-024-03807-z -
Hereditas Jul 2024Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa with a high incidence rate all over the world. Methyltransferase-like 14...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa with a high incidence rate all over the world. Methyltransferase-like 14 (METTL14) is a major RNA N6-adenosine methyltransferase implicated in tumor progression by regulating RNA function. This study is designed to explore the biological function and mechanism of METTL14 in NPC.
METHODS
METTL14 and Amine oxidase copper containing 1 (AOC1) expression were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of METTL14, AOC1, Cyclin D1, B-cell lymphoma-2 (Bcl-2), and N-cadherin were measured using western blot. Cell proliferation, cycle progression, apoptosis, migration, and invasion were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, wound scratch, and transwell assays. The interaction between METTL14 and AOC1 was verified using RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation (MeRIP), and dual-luciferase reporter assays. The biological role of METTL14 on NPC tumor growth was examined by the xenograft tumor model in vivo.
RESULTS
METTL14 and AOC1 were highly expressed in NPC tissues and cells. Moreover, METTL14 knockdown might block NPC cell proliferation, migration, invasion, and induce cell apoptosis in vitro. In mechanism, METTL14 might enhance the stability of AOC1 mRNA via m6A methylation. METTL14 silencing might repress NPC tumor growth in vivo.
CONCLUSION
METTL14 might boosted the development of NPC cells partly by regulating the stability of AOC1 mRNA, which provided a promising therapeutic target for NPC treatment.
Topics: Humans; Nasopharyngeal Carcinoma; Methyltransferases; Cell Line, Tumor; Cell Proliferation; Animals; RNA Stability; Gene Expression Regulation, Neoplastic; Nasopharyngeal Neoplasms; RNA, Messenger; Apoptosis; Mice; Cell Movement; Disease Progression; Male; Female
PubMed: 38956710
DOI: 10.1186/s41065-024-00317-z