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1.
Plant J ; 119(1): 604-616, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38594953

ABSTRACT

Plant triacylglycerols (TAG) are used in food and various industrial feedstocks. LEAFY COTYLEDON 2 (LEC2), a master positive regulator of TAG biosynthesis, regulates a complex network of transcription factors (TFs) during seed development. Aside from WRINKLED1 (WRI1), the TFs regulated by LEC2 related to TAG biosynthesis have not yet been identified. Previously, we identified 25 seed-expressing TFs that were upregulated in Arabidopsis leaves that overexpressed senescence-induced LEC2. In this study, each of the 25 TFs was transiently expressed in the leaves of Nicotiana benthamiana to identify unknown TFs that regulate TAG biosynthesis. The TAG content of the transformed leaves was analyzed using thin layer chromatography and gas chromatography. We observed that five TFs, ARABIDOPSIS RESPONSIVE REGULATOR 21 (ARR21), AINTEGUMENTA-LIKE 6 (AIL6), APETALA2/ETHYLENE RESPONSIVE FACTOR 55 (ERF55), WRKY DNA-BINDING PROTEIN 8 (WRKY8), and ARABIDOPSIS NAC DOMAIN CONTAINING PROTEIN 38 (ANAC038) increased TAG synthesis in the leaves. Among these, the promoters of AIL6, ERF55, WRKY8, and ANAC038 contain RY motifs, which are LEC2-binding sites activated by LEC2. AIL6 overexpression in Arabidopsis increased the total fatty acid (FA) content in seeds and altered the FA composition, with increases in 16:0, 18:1, and 18:2 and decreases in 18:0, 18:3, and 20:1 compared with those in the wild type (WT). AIL6 overexpression activates several FA and TAG biosynthesis genes. Therefore, our study successfully identified several new TFs regulated by LEC2 in TAG biosynthesis and showed that AIL6 increased the TAG content in seeds.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Gene Expression Regulation, Plant , Plant Leaves , Transcription Factors , Triglycerides , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Triglycerides/biosynthesis , Triglycerides/metabolism , Plant Leaves/metabolism , Plant Leaves/genetics , Plants, Genetically Modified , Nicotiana/genetics , Nicotiana/metabolism , Seeds/metabolism , Seeds/genetics , Seeds/growth & development , Promoter Regions, Genetic
2.
Plants (Basel) ; 13(6)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38592766

ABSTRACT

α-Linolenic acid (ALA) is an important nutrient component in rapeseed oil, and rapeseed breeders want to either restrain or enhance the function of fatty acid desaturases (FADs) in the ALA biosynthesis pathway. To determine the reason for the upregulation of rapeseed BnFAD genes in two high-ALA accessions, R8Q10 and YH25005, we compared their transcriptome profiles in the seed at 24 days after pollination (DAP) with those of two low-ALA lines, A28 and SW. The expression levels of twenty-eight important genes in the seed samples at 20, 27, and 34 DAP were also investigated using an RT-qPCR. The expression levels of genes involved in flavonoid and proanthocyanidin synthesis, including BnCHS, BnCHI, BnDFR, BnFLS1, BnLDOX, BnBAN, BnTT10, and BnTT12 and genes encoding the transcription factors BnTT1, BnTT2, BnTT8, and BnTT16 were lower in R8Q10 and YH25005 than in A28 and SW. The expression levels of genes encoding master transcription factors in embryo development, such as BnLEC1, BnABI3, BnFUS3, BnL1L, BnAREB3, and BnbZIP67, were elevated significantly in the two high-ALA accessions. Combined with previous results in the Arabidopsis and rapeseed literature, we speculated that the yellow-seededness genes could elevate the activity of BnLEC1, BnABI3, BnFUS3, and BnbZIP67, etc., by reducing the expression levels of several transparent testa homologs, resulting in BnFAD3 and BnFAD7 upregulation and the acceleration of ALA synthesis. Yellow-seededness is a favorable factor to promote ALA synthesis in the two high-ALA accessions with the yellow-seeded trait. These findings provide initial insights into the transcriptomic differences between high-/low-ALA germplasms and a theoretic basis for seed quality breeding.

3.
New Phytol ; 242(3): 1098-1112, 2024 May.
Article in English | MEDLINE | ID: mdl-38515249

ABSTRACT

The potential for totipotency exists in all plant cells; however, the underlying mechanisms remain largely unknown. Earlier findings have revealed that the overexpression of LEAFY COTYLEDON 2 (LEC2) can directly trigger the formation of somatic embryos on the cotyledons of Arabidopsis. Furthermore, cotyledon cells that overexpress LEC2 accumulate significant lipid reserves typically found in seeds. The precise mechanisms and functions governing lipid accumulation in this process remain unexplored. In this study, we demonstrate that WRINKLED1 (WRI1), the key regulator of lipid biosynthesis, is essential for somatic embryo formation, suggesting that WRI1-mediated lipid biosynthesis plays a crucial role in the transition from vegetative to embryonic development. Our findings indicate a direct interaction between WRI1 and LEC2, which enhances the enrichment of LEC2 at downstream target genes and stimulates their induction. Besides, our data suggest that WRI1 forms a complex with LEC1, LEC2, and FUSCA3 (FUS3) to facilitate the accumulation of auxin and lipid for the somatic embryo induction, through strengthening the activation of YUCCA4 (YUC4) and OLEOSIN3 (OLE3) genes. Our results uncover a regulatory module controlled by WRI1, crucial for somatic embryogenesis. These findings provide valuable insights into our understanding of plant cell totipotency.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Indoleacetic Acids , Lipids , Seeds/genetics , Transcription Factors/metabolism
5.
Eur J Psychotraumatol ; 15(1): 2317055, 2024.
Article in English | MEDLINE | ID: mdl-38379510

ABSTRACT

Background: In attempts to elucidate PTSD, recent factor analytic studies resulted in complex models with a proliferating number of factors that lack psychometrical and clinical utility. Recently, suggestions have been made to optimize factor analytic practices to meet a refined set of statistical and psychometric criteria.Objective: This study aims to assess the factorial structure of the German version of the PCL-5, implementing recent methodological advancements to address the risk of overfitting models. In doing so we diverge from traditional factor analytical research on PTSD.Method: On a large-scale sample of the German general population (n = 1625), exploratory factor analyses were run to investigate the dimensionality found within the data. Subsequently, we validated and compared all model suggestions from our preliminary analyses plus all standard and common alternative PTSD factor models (including the ICD-11 model) from previous literature with confirmatory factor analyses. We not only consider model fit indices based on WLSMV estimation but also deploy criteria such as favouring less complex models with a parsimonious number of factors, sufficient items per factor, low inter-factor correlations and number of model misspecifications.Results: All tested models showed adequate to excellent fit in respect to traditional model fit indices; however, models with two or more factors increasingly failed to meet other statistical and psychometric criteria.Conclusion: Based on the results we favour a two-factor bifactor model with a strong general PTSD factor and two less dominant specific factors - one factor with trauma-related symptoms (re-experiencing and avoidance) and one factor with global psychological symptoms (describing the trauma's higher-order impact on mood, cognition, behaviour and arousal).From the perspective of clinical utility, we recommend the cut-off scoring method for the German version of the PCL-5. Basic psychometric properties and scale characteristics are provided.


We contribute new insights to the debate on the factor structure of the PTSD Checklist (PCL-5) based on a large German general population sample deploying the newest methodological developments in a revised factor-analytical approach.Combining theoretical, statistical and practical considerations, we favour a two-factor bifactor model with a strong general PTSD factor and two less dominant specific factors ­ one factor with trauma-related symptoms and one factor with global psychological symptoms.For clinical practitioners, we recommend using the cut-off scoring method.


Subject(s)
Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Checklist/methods , Reproducibility of Results , Psychometrics , Factor Analysis, Statistical
6.
Prog Urol ; 33(14): 812-824, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37918981

ABSTRACT

Extracorporeal shock wave lithotripsy (ESWL) is a minimally invasive technique for the fragmentation of urinary tract stones using shock waves under fluoroscopic and/or ultrasound guidance. ESWL results depend on the indication (stone size/composition, clinical context) and also on how it is performed. The stone structure, nature and density (Hounsfield units; evaluated by CT without contrast agent) influence the fragmentation achieved by ESWL. The upper size limit of kidney stones has been lowered to 15mm (1.68cm3) due to the increased risk of steinstrasse with larger sizes and the potential need of anesthesia and ureteral stenting. Conversely, the development of endourological technologies allows a finer stone fragmentation and/or better elimination, thus reducing the risk of steinstrasse and decreasing the potential number of sessions or additional interventions. METHODOLOGY: These recommendations were developed using two methods: the Clinical Practice Recommendations method (CPR) and the ADAPTE method, depending on whether the question was considered in the European Association of Urology (EAU) recommendations (https://uroweb.org/guidelines/urolithiasis [EAU 2022]) and their adaptability to the French context.


Subject(s)
Kidney Calculi , Lithiasis , Lithotripsy , Urinary Calculi , Humans , Urinary Calculi/therapy , Kidney Calculi/therapy , Lithotripsy/methods , Ultrasonography , Treatment Outcome
7.
Cell Rep ; 42(11): 113317, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37897725

ABSTRACT

Why some of us remember events more clearly than others and why memory loses precision over time is a major focus in memory research. Here, we show that the recruitment of specific neuroanatomical pathways within the medial temporal lobe (MTL) of the brain defines the precision of the memory recalled over the lifespan. Using optogenetics, neuronal activity mapping, and studying recent to very remote memories, we report that the hippocampal subfield CA1 is necessary for retrieving the gist of events and receives maximal support from MTL cortical areas (MEC, LEC, PER, and POR) for recalling the most remote memories. In contrast, reduction of CA3's activity alone coincides with the loss of memory precision over time. We propose that a shift between specific MTL subnetworks over time might be a fundamental mechanism of memory consolidation.


Subject(s)
Hippocampus , Mental Recall , Hippocampus/metabolism , Mental Recall/physiology , Temporal Lobe/physiology , Memory, Long-Term , Neurons
8.
Int J Mol Sci ; 24(19)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37834366

ABSTRACT

Alzheimer's disease (AD) is the most common form of dementia, which disproportionately affects women. AD symptoms include progressive memory loss associated with amyloid-ß (Aß) plaques and dismantled synaptic mechanisms. Perineuronal nets (PNNs) are important components of the extracellular matrix with a critical role in synaptic stabilisation and have been shown to be influenced by microglia, which enter an activated state during AD. This study aimed to investigate whether sex differences affected the density of PNNs alongside the labelling of microglia and Aß plaques density.We performed neurochemistry experiments using acute brain slices from both sexes of the APPNL-F/NL-F mouse model of AD, aged-matched (2-5 and 12-16 months) to wild-type mice, combined with a weighted gene co-expression network analysis (WGCNA). The lateral entorhinal cortex (LEC) and hippocampal CA1, which are vulnerable during early AD pathology, were investigated and compared to the presubiculum (PRS), a region unscathed by AD pathology. The highest density of PNNs was found in the LEC and PRS regions of aged APPNL-F/NL-F mice with a region-specific sex differences. Analysis of the CA1 region using multiplex-fluorescent images from aged APPNL-F/NL-F mice showed regions of dense Aß plaques near clusters of CD68, indicative of activated microglia and PNNs. This was consistent with the results of WGCNA performed on normalised data on microglial cells isolated from age-matched, late-stage male and female wild-type and APP knock-in mice, which revealed one microglial module that showed differential expression associated with tissue, age, genotype, and sex, which showed enrichment for fc-receptor-mediated phagocytosis. Our data are consistent with the hypothesis that sex-related differences contribute to a disrupted interaction between PNNs and microglia in specific brain regions associated with AD pathogenesis.


Subject(s)
Alzheimer Disease , Female , Male , Mice , Humans , Animals , Aged , Alzheimer Disease/metabolism , Sex Characteristics , Mice, Transgenic , Amyloid beta-Peptides/metabolism , Brain/metabolism , Plaque, Amyloid/metabolism , Disease Models, Animal , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism
9.
PeerJ ; 11: e15931, 2023.
Article in English | MEDLINE | ID: mdl-37663301

ABSTRACT

Air quality has emerged as a critical concern in recent years, with the concentration of PM2.5 recognized as a vital index for assessing it. The accuracy of predicting PM2.5 concentrations holds significant value for effective air quality monitoring and management. In response to this, a combined model comprising CEEMDAN-RLMD-BiLSTM-LEC has been introduced, analyzed, and compared against various other models. The combined decomposition method effectively underlines the fundamental characteristics of the data compared to individual decomposition techniques. Additionally, local error correction (LEC) efficiently addresses the issue of prediction errors induced by excessive disturbances. The empirical results of nine steps indicate that the combined CEEMDAN-RLMD-BiLSTM-LEC model outperforms single prediction models such as RLMD and CEEMDAN, reducing MAE, RMSE, and SAMPE by 36.16%, 28.63%, 45.27% and 16.31%, 6.15%, 37.76%, respectively. Moreover, the inclusion of LEC in the model further diminishes MAE, RMSE, and SMAPE by 20.69%, 7.15%, and 44.65%, respectively, exhibiting commendable performance in generalization experiments. These findings demonstrate that the combined CEEMDAN-RLMD-BiLSTM-LEC model offers high predictive accuracy and robustness, effectively handling noisy data predictions and severe local variations. With its wide applicability, this model emerges as a potent tool for addressing various related challenges in the field.


Subject(s)
Generalization, Psychological , Manipulation, Osteopathic , Particulate Matter/adverse effects
10.
Asian J Psychiatr ; 89: 103772, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37748229

ABSTRACT

This cross-sectional study aimed to validate the Life Events Checklist for DSM-5 (LEC-5) among Malaysian undergraduates (N = 500; mean age = 21.66 ± 1.57), of which 90.4% had ever experienced a lifetime traumatic event. Cronbach's alpha of .87 (95% CI [.86, .89]) and McDonald's omega of .89 (95% CI [.89, .93]) indicated good reliability. Confirmatory factor analysis based on a six-factor structure showed the best fit. The measurement invariance showed that the six-factor structure was similar across sexes. Therefore, the Malay LEC-5 is a valid and reliable instrument to screen for traumatic events among Malaysian undergraduates.


Subject(s)
Asian People , Checklist , Life Change Events , Students , Humans , Young Adult , Cross-Sectional Studies , Malaysia , Reproducibility of Results , Universities
11.
ACS Appl Mater Interfaces ; 15(35): 41680-41687, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37615302

ABSTRACT

Distinct doping propagation characteristics between p-doping and n-doping in light-emitting electrochemical cells (LECs) have been highlighted by intensive reports. Typically, there are significant differences in the doping speeds between p-doping and n-doping, with the former exhibiting a sawtooth frontier and the latter displaying a more uniform frontier profile. In addition, experimental observations demonstrate a uniform motion instead of the theoretically suggested accelerated electrochemical doping frontier propagation. Therefore, there is an urgent need to establish a quantitative model that delves into the underlying mechanisms responsible for doping propagation in LECs. In this study, four variables were selected to investigate the detailed mechanism of electrochemical doping propagation: temperature, voltage, and concentrations of salt and solid electrolyte. Fluorescence imaging revealed that the n-doping and p-doping propagations behaved contrarily with increasing temperature and voltage. By numerically fitting the doping propagation frontier, equations were derived to describe the relationship between the speed of electrochemical doping propagation and temperature/voltage. The underlying mechanisms were elucidated, indicating that anions undergo motion through the cooperative effects of electric field drift and concentration diffusion, while cation transport strongly relies on poly(ethylene oxide) (PEO) segmental motions. In other words, the movement of anions within the electrolyte is characterized by a greater degree of freedom, whereas the motion of cations is significantly dependent on the segmental motions of PEO. The resulting equations were well-fitted with experimental data, providing a solid foundation for further theoretical investigations into electrochemical doping in various devices.

12.
Int J Mol Sci ; 24(14)2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37511166

ABSTRACT

Giant arachnoid granulations (GAGs) are poorly investigated. Here, we document clinical findings associated with five new GAGs and illustrate the anatomical composition of these structures as well as diagnostic considerations in three symptomatic adults. The GAGs ranged from 1.1 to 3.6 cm (mean, 2.2 cm) in maximum dimension and manifested in middle-aged individuals who presented with long-standing brain mass and/or chronic headache. On imaging examinations, the tissues appeared as irregular parasagittal and/or perisinus structures that demonstrated heterogeneous internal elements. The GAGs abutted dura, extended through calvarial marrow spaces, and impinged on dural venous sinuses, causing their stenosis. The histologic workup of two GAG specimens resected from separate individuals revealed central collagen with pronounced internal vascular proliferation. One specimen additionally exhibited reactive changes within the lesion, including venous thrombosis, hemorrhage, and conspicuous inflammation. The salient immune component consisted of a foam cell-rich infiltrate that obstructed subcapsular and internal sinusoidal GAG spaces. Within this specimen, meningothelial hyperplasia was also appreciated. Notably, proliferated lymphatic vascular elements were additionally observed within the structure, extending into deep central collagen regions and engulfing many extravasated erythrocytes in the subcapsular space. In both surgically treated patients, symptoms resolved completely following resection. This report is the first to definitively depict reactive vascular and immunological changes within GAGs that were clinically associated with headache. The frequency of reactive changes within these meningeal structures is unclear in the literature, as GAGs are rarely sampled and investigated. Further systematic analyses are warranted to elucidate the causes and consequences of GAG genesis and their roles in physiology and disease states.


Subject(s)
Arachnoid , Vascular Diseases , Middle Aged , Adult , Humans , Arachnoid/pathology , Dura Mater , Cranial Sinuses/pathology , Headache/etiology , Headache/pathology , Vascular Diseases/pathology
13.
Peptides ; 168: 171045, 2023 10.
Article in English | MEDLINE | ID: mdl-37507091

ABSTRACT

Secondary lymphedema often occurs after filariasis, trauma, lymph node dissection and radiation therapy, which is manifested by infiltration of inflammatory cells and fibrosis formation in pathologically. Substance P is a widely used neuropeptide in the field of tissue repair, while the regenerative potential of the substance P has not been proven in the secondary lymphedema. In this study, animal model of secondary lymphedema was constructed by excising the skin and subcutaneous lymphatic network in the tail of mice, and the degree of swelling in the tail of mice was evaluated after 6 weeks under the treatment with substance P. Immunofluorescence staining was also performed to assess immune cell infiltration, subcutaneous fibrosis and lymphangiogenesis. The results revealed that substance P significantly alleviated post-surgical lymphedema in mice. Furthermore, we found that substance P promoted macrophages M2 polarization, a process associated with downregulation of the NF-kB/NLRP3 pathway. After application of disodium clodronate (macrophage scavenger, CLO), the positive effect of substance P in lymphedema is significantly inhibited. In vitro experiments, we further demonstrated the polarizing effect of substance P on bone marrow-derived macrophages (BMDMs), while substance P inhibited the activation of the NF-kB/NLRP3 pathway in BMDMs after the treatment of lipopolysaccharide (LPS). In addition, polarized macrophages were demonstrated to promote the proliferation, tube-forming and migratory functions of human lymphatic endothelial cells (hLEC). In conclusion, our study provides preliminary evidence that substance P alleviates secondary lymphedema by promoting macrophage M2 polarization, and this therapeutic effect may be associated with downregulation of the NF-kB/NLRP3 pathway.


Subject(s)
Lymphedema , NF-kappa B , Mice , Humans , Animals , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Substance P/metabolism , Endothelial Cells/metabolism , Signal Transduction , Macrophages/metabolism , Fibrosis , Lymphedema/drug therapy , Lymphedema/metabolism
14.
Nano Lett ; 23(12): 5822-5827, 2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37310291

ABSTRACT

We demonstrate an alternating current (AC) driven light emitting capacitor in which the color of the emission spectra can be changed via an applied AC frequency. The device has a simple metal-oxide-semiconductor (MOS) capacitor structure with an organic emissive layer, enabling facile fabrication processing. The organic emissive layer comprises a thin, submonolayer low energy dye layer underneath a thick host matrix (∼30 nm) with higher energy emitting dyes. The emission of the lower energy dyes dominates at low frequency, while the higher energy emission of the host matrix dominates at high frequency. This simple color tunable device could be used for full-color displays and lighting in the future.

15.
BMC Plant Biol ; 23(1): 268, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37208597

ABSTRACT

BACKGROUND: Based on our previous studied on different provenances of Pistacia chinensis, some accessions with high quality and quantity of seed oils has emerged as novel source of biodiesel. To better develop P. chinensis seed oils as woody biodiesel, a concurrent exploration of oil content, FA profile, biodiesel yield, and fuel properties was conducted on the seeds from 5 plus germplasms to determine superior genotype for ideal biodiesel production. Another vital challenge is to unravel mechanism that govern the differences in oil content and FA profile of P. chinensis seeds across different accessions. FA biosynthesis and oil accumulation of oil plants are known to be highly controlled by the transcription factors. An integrated analysis of our recent transcriptome data, qRT-PCR detection and functional identification was performed as an attempt to highlight LEC1/WRI1-mediated transcription regulatory mechanism for high-quality oil accumulation in P. chinensis seeds. RESULTS: To select ideal germplasm and unravel high oil accumulative mechanism for developing P. chinensis seed oils as biodiesel, five plus trees (accession PC-BJ/PC-AH/PC-SX/PC-HN/PC-HB) with high-yield seeds were selected to assess the variabilities in weight, oil content, FA profile, biodiesel yield and fuel property, revealing a variation in the levels of seed oil (50.76-60.88%), monounsaturated FA (42.80-70.72%) and polyunsaturated FA (18.78-43.35%), and biodiesel yield (84.98-98.15%) across different accessions. PC-HN had a maximum values of seed weight (26.23 mg), oil (60.88%) and biodiesel yield (98.15%), and ideal proportions of C18:1 (69.94%), C18:2 (17.65%) and C18:3 (1.13%), implying that seed oils of accession PC-HN was the most suitable for ideal biodiesel production. To highlight molecular mechanism that govern such differences in oil content and FA profile of different accessions, a combination of our recent transcriptome data, qRT-PCR detection and protein interaction analysis was performed to identify a pivotal role of LEC1/WRI1-mediated transcription regulatory network in high oil accumulation of P. chinensis seeds from different accessions. Notably, overexpression of PcWRI1 or PcLEC1 from P. chinensis seeds in Arabidopsis could facilitate seed development and upregulate several genes relevant for carbon flux allocation (plastidic glycolysis and acetyl-CoA generation), FA synthesis, TAG assembly and oil storage, causing an increase in seed oil content and monounsaturated FA level, destined for biodiesel fuel property improvement. Our findings may present strategies for better developing P. chinensis seed oils as biodiesel feedstock and bioengineering its high oil accumulation. CONCLUSIONS: This is the first report on the cross-accessions assessments of P. chinensis seed oils to determine ideal accession for high-quality biodiesel production, and an effective combination of PcWRI1 or PcLEC1 overexpression, morphological assay, oil accumulation and qRT-PCR detection was applied to unravel a role of LEC1/WRI1-mediated regulatory network for oil accumulation in P. chinensis seeds, and to highlight the potential application of PcWRI1 or PcLEC1 for increasing oil production. Our finding may provide new strategies for developing biodiesel resource and molecular breeding.


Subject(s)
Biofuels , Pistacia , Plant Oils , Arabidopsis/metabolism , Fatty Acids/metabolism , Pistacia/genetics , Pistacia/metabolism , Plant Oils/metabolism , Seeds
16.
Front Pharmacol ; 14: 1152314, 2023.
Article in English | MEDLINE | ID: mdl-37188266

ABSTRACT

Introduction: Surgery and radiotherapy are key cancer treatments and the leading causes of damage to the lymphatics, a vascular network critical to fluid homeostasis and immunity. The clinical manifestation of this damage constitutes a devastating side-effect of cancer treatment, known as lymphoedema. Lymphoedema is a chronic condition evolving from the accumulation of interstitial fluid due to impaired drainage via the lymphatics and is recognised to contribute significant morbidity to patients who survive their cancer. Nevertheless, the molecular mechanisms underlying the damage inflicted on lymphatic vessels, and particularly the lymphatic endothelial cells (LEC) that constitute them, by these treatment modalities, remain poorly understood. Methods: We used a combination of cell based assays, biochemistry and animal models of lymphatic injury to examine the molecular mechanisms behind LEC injury and the subsequent effects on lymphatic vessels, particularly the role of the VEGF-C/VEGF-D/VEGFR-3 lymphangiogenic signalling pathway, in lymphatic injury underpinning the development of lymphoedema. Results: We demonstrate that radiotherapy selectively impairs key LEC functions needed for new lymphatic vessel growth (lymphangiogenesis). This effect is mediated by attenuation of VEGFR-3 signalling and downstream signalling cascades. VEGFR-3 protein levels were downregulated in LEC that were exposed to radiation, and LEC were therefore selectively less responsive to VEGF-C and VEGF-D. These findings were validated in our animal models of radiation and surgical injury. Discussion: Our data provide mechanistic insight into injury sustained by LEC and lymphatics during surgical and radiotherapy cancer treatments and underscore the need for alternative non-VEGF-C/VEGFR-3-based therapies to treat lymphoedema.

17.
Aging (Albany NY) ; 15(5): 1652-1667, 2023 03 13.
Article in English | MEDLINE | ID: mdl-36917086

ABSTRACT

Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressive disease and lymph node metastasis. ANGPTL2 enhanced VEGF-A-dependent lymphatic endothelial cell (LEC) tube formation and migration. Integrin α5ß1, p38 and nuclear factor (NF)-κB signaling mediated ANGPTL2-regulated lymphangiogenesis. Importantly, overexpression ANGPTL2 facilitated tumor growth and lymphangiogenesis in vivo. Thus, ANGPTL2 is a promising therapeutic object for treating lung cancer.


Subject(s)
Lung Neoplasms , Lymphangiogenesis , Humans , Angiopoietin-Like Protein 2 , Vascular Endothelial Growth Factor A , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Signal Transduction , NF-kappa B/metabolism , Cell Line, Tumor
18.
Acta Oncol ; 62(3): 231-236, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36951901

ABSTRACT

BACKGROUND: Salivary gland tumors are assumed to be predominantly malignant in the Greenlandic Inuit population, but there is limited literature on the subject. We conducted a retrospective cohort study using national registers to describe the histological tumor types, location, incidence, and survival of benign and malignant salivary gland tumors. METHODS: We analyzed data on all Greenlandic Inuit with an epithelial-derived salivary gland tumor from 1990 to 2019. We extracted data from the Central Personal Registry and crossmatched it with the Danish Pathology Data Bank. All specimens were reviewed by a specialized pathologist. We noted patient and histological characteristics, calculated crude and age-adjusted incidence rates, overall survival, and excess mortality. RESULTS: Our study found that 76% of salivary gland tumors in the Greenlandic Inuit population were benign, with pleomorphic adenoma being the most common. Malignant tumors accounted for 24% of cases, with lymphoepithelial carcinoma being the most common type. The most common place of origin for malignant tumors was the parotid gland (71%) and the submandibular gland (15%). The median age of onset for malignant tumors was 47 years. Age-adjusted incidence rates of malignant tumors for men and women were 3.00 and 4.12 per 100,000 person-years, respectively. CONCLUSION: Our findings suggest that the proportion of malignant salivary gland tumors in the Greenlandic Inuit population is similar to other nonendemic populations. Our incidence rates are higher than previously reported, likely due to differences in methodology and definitions of the Inuit population. This study provides valuable insights into the epidemiology of salivary gland tumors in the Greenlandic Inuit population and may have implications for other Inuit populations as well.


Subject(s)
Adenoma, Pleomorphic , Carcinoma, Squamous Cell , Salivary Gland Neoplasms , Male , Humans , Female , Middle Aged , Retrospective Studies , Inuit , Salivary Gland Neoplasms/epidemiology , Salivary Gland Neoplasms/pathology , Adenoma, Pleomorphic/epidemiology , Adenoma, Pleomorphic/pathology
19.
Langenbecks Arch Surg ; 408(1): 82, 2023 Feb 11.
Article in English | MEDLINE | ID: mdl-36773118

ABSTRACT

BACKGROUND: Differentiation of cystic pancreatic neoplasms remains a challenging task for radiologists regarding the main aim of identifying malignant and premalignant lesions. PURPOSE: The study aimed to compare the radiological features of lymphoepithelial cysts (LEC) with other cystic pancreatic lesions, which could help to differentiate them in order to avoid unnecessary resection. MATERIAL AND METHODS: We retrospectively reviewed 10 cases of resected and histopathologically confirmed LECs during a 12-year period with available imaging studies; 20 patients with mucinous cystic neoplasms (MCN), 20 patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), and 20 patients with serous cystic neoplasms (SCN) were selected to serve as control groups. Imaging findings as well as clinical data were analyzed. RESULTS: The following imaging morphology of LEC was identified: simple cystic appearance (20%) and mixed cystic-solid appearance (80%) with either a diffuse subsolid component (30%) or mural nodule(s) (50%). All lesions revealed exophytic location with a strong male predominance (9:1). MCNs occurred exclusively in middle-aged women, IPMN in both sexes showed slight male predominance (13:7), and SCN showed female predominance (5:15). Median patient age in LEC (48.5, IQR 47-54.5) was significantly younger compared to IPMN (p < 0.001) and SCN (p = 0.02). Unenhanced CT attenuation of LEC was higher than MCNs (p = 0.025) and IPMNs (p = 0.021), showing no significant difference to SCN (p = 0.343). CONCLUSION: The present study provides key radiological features of LEC for the differentiation from other cystic pancreatic lesions such as increased CT attenuation in the unenhanced phase, absence of a connection to the main pancreatic duct (MPD), and exophytic location. In addition to these imaging features, clinical data, such as male predominance in LEC, must be considered for the differentiation of cystic pancreatic lesions.


Subject(s)
Carcinoma, Pancreatic Ductal , Neoplasms, Cystic, Mucinous, and Serous , Pancreatic Cyst , Pancreatic Intraductal Neoplasms , Pancreatic Neoplasms , Middle Aged , Humans , Male , Female , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/surgery , Pancreatic Cyst/pathology , Retrospective Studies , Pancreas , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/pathology
20.
Graefes Arch Clin Exp Ophthalmol ; 261(6): 1505-1514, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36380123

ABSTRACT

PURPOSE: Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) represent two distinct conditions which have been associated with several ocular and systemic comorbidities. The main aim of this systematic review and meta-analysis is to explore the available literature to estimate the prevalence rate of LEC and FES in obstructive sleep apnea (OSA). METHODS: The protocol of this systematic review and meta-analysis has been registered in PROSPERO. Four electronic databases (PubMed/MEDLINE, Google Scholar, Cochrane Library, Web of Science) were searched from inception to December 24, 2021. A random intercept logistic regression model was carried out for the analysis of overall proportions. Odds ratio and mean difference were reported as measures of the effect size in the presence of binary and continuous outcomes, respectively. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random-effects model and the corresponding Benjafield et al.'s population prospect. RESULTS: We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6-53.1%) and of 22.4% (95%CI: 13.8-34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95%CI: 2.2-5.2) and a 3.0 (95%CI: 1.7-5.5) increased risk of developing LEC and FES than the healthy counterpart. CONCLUSION: Prevalence of LEC and FES is higher in OSA-affected patients compared to controls. More studies are warranted to investigate the mechanisms leading to the development of LEC and/or FES in OSA patients, as well as the feasibility of the adoption of these clinical findings as screening tools for OSA.


Subject(s)
Eyelid Diseases , Sleep Apnea, Obstructive , Humans , Prevalence , Syndrome , Eyelid Diseases/diagnosis , Eyelid Diseases/epidemiology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Eyelids
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