The chemically inert nature of fully saturated hydrocarbon backbones endows vinyl polymers with desirable durability, but it also leads to their significant environmental persistence. Enhancing the sustainability of these materials requires a pivotal yet challenging shift: transforming the inert backbone into one that is degradable. Here, we present a versatile platform for mechanochemically editing the fully saturated backbone of vinyl polymers towards degradable polymer chains by integrating cyclobutene-fused succinimide (CBS) units along backbone through photo-iniferter reversible addition-fragmentation chain-transfer (RAFT) copolymerization. Significantly, the evenly insertion of CBS units does not compromise thermal or chemical stability but rather offers a means to adjust the properties of polymethylacrylate (PMA). Meanwhile, reactive acyclic imide units can be selectively introduced to the backbone through mechanochemical activation (pulse ultrasonication or ball-milling grinding) when required. Subsequent hydrolysis of the acyclic imide groups enables efficient degradation, yielding telechelic oligomers. This approach holds promise for inspiring the design and modification of more environmentally friendly vinyl polymers through backbone editing.
BACKGROUND: Direct-acting Antiviral Agents (DAAs) influence serum lipids of patients with Hepatitis C virus (HCV). This paper presents an analysis of the relevant literature to investigate the effects of DAAs in treating hepatitis C to achieve a sustained viral response (SVR) on lipid parameters. METHODS: PubMed,Web of science, Embase and Central databases were searched, with a deadline of September 2023. Studies on the effects of sustained viral response on lipid parameters after DAAs treatment for hepatitis C were selected. The required information was extracted from the included studies, and then the Stata 12.0 was used to analyze the data quantitatively. RESULTS: Of 32 studies, the results showed that total cholesterol (TC) levels increased from the end of treatment (WMD = 20.144, 95%CI = 3.404, 36.884,P = 0.018) to one year after treatment (WMD = 24.900, 95%CI = 13.669, 36.131, P < 0.001). From the end of treatment (WMD = 17.728, 95%CI = 4.375, 31.082, P = 0.009) to one year after treatment (WMD = 18.528, 95%CI = 7.622, 29.433, P < 0.001), the levels of low-density lipoprotein (LDL) were also increased. High-density lipoprotein (HDL) levels were elevated from 4 weeks after treatment (WMD = 6.665, 95%CI = 3.906, 9.424, P < 0.001) to 24 weeks after treatment (WMD = 3.159,95% CI = 0.176, 6.142, P = 0.038). Triglyceride (TG) levels showed no significant change after the treatment. CONCLUSIONS: Hepatitis C patients who achieved SVR on DAAs showed the increase of lipid levels and the improvement of hepatic inflammation indicators AST and ALT. This may provide evidence-based medical evidence for the follow-up and monitoring of blood lipids and hyperlipidemia treatment. REGISTRATION: PROSPERO CRD42020180793.
Hepatitis C, Chronic , Hepatitis C , Humans , Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Lipids
Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.
Carbon dioxide (CO2) has long been recognized as an ideal C1 feedstock comonomer for producing sustainable materials because it is renewable, abundant, and cost-effective. However, activating CO2 presents a significant challenge because it is highly oxidized and stable. A CO2/butadiene-derived δ-valerolactone (EVP), generated via palladium-catalyzed telomerization between CO2 and butadiene, has emerged as an attractive intermediate for producing sustainable copolymers from CO2 and butadiene. Owing to the presence of two active carbon-carbon double bonds and a lactone unit, EVP serves as a versatile intermediate for creating sustainable copolymers with a CO2 content of up to 29 wt % (33 mol %). In this Review, advances in the synthesis of copolymers from CO2 and butadiene with divergent structures through various polymerization protocols have been summarized. Achievements made in homo- and copolymerization of EVP or its derivatives are comprehensively reviewed, while the postmodification of the obtained copolymers to access new polymers are also discussed. Meanwhile, potential applications of the obtained copolymers are also discussed. The literature references were sorted into sections based on polymerization strategies and mechanisms, facilitating readers in gaining a comprehensive view of the present chemistry landscape and inspiring innovative approaches to synthesizing novel CO2-derived copolymers.
Gene expression during brain development or abnormal development is a biological process that is highly dynamic in spatio and temporal. Previous studies have mainly focused on individual brain regions or a certain developmental stage. Our motivation is to address this gap by incorporating spatio-temporal information to gain a more complete understanding of brain development or abnormal brain development, such as Alzheimer's disease (AD), and to identify potential determinants of response. In this study, we propose a novel two-step framework based on spatial-temporal information weighting and multi-step decision trees. This framework can effectively exploit the spatial similarity and temporal dependence between different stages and different brain regions, and facilitate differential gene analysis in brain regions with high heterogeneity. We focus on two datasets: the AD dataset, which includes gene expression data from early, middle and late stages, and the brain development dataset, spanning fetal development to adulthood. Our findings highlight the advantages of the proposed framework in discovering gene classes and elucidating their impact on brain development and AD progression across diverse brain regions and stages. These findings align with existing studies and provide insights into the processes of normal and abnormal brain development.
Alzheimer Disease , Brain , Humans , Alzheimer Disease/genetics , Gene Expression , Decision Trees
Carbon dioxide (CO2), as a renewable and nontoxic C1 feedstock, has been recognized as an ideal comonomer to prepare sustainable materials. In this regard, substantial focus has been dedicated to the ring-opening copolymerization of CO2 and epoxides, which results in the creation of aliphatic polycarbonates in most cases. Here, we report an unprecedented strategy to synthesize functional and degradable polyester-co-polyethers from CO2, butadiene, and epoxides via a CO2/butadiene-derived δ-valerolactone intermediate (EVP). Utilizing a chromium salen complex as the catalyst, the copolymerization of EVP and epoxides was successfully achieved to produce CO2/butadiene/epoxide terpolymers. The obtained polyester-co-polyethers with varied 39-93 mol % EVP content (equal to 18-28 wt % CO2 incorporation) show high thermal stability, tunable glass-transition temperatures, on-demand functionality, and good chemical degradability. This method extends the potential to access functional CO2-based polymers.
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC), and it is often associated with a high tumor grade, a younger age at diagnosis, and a low survival rate. Conventional endocrine and anti-HER-2 therapies are usually ineffective against TNBC, creating treatment challenges and resulting in a poor prognosis. Hence, new targets and treatment strategies for TNBC are urgently required. METHODS: The GSE102818 dataset was used to identify differentially expressed genes (DEGs) between primary BC and metastatic BC lesions. The Cancer Genome Atlas and the cBioPortal platform were employed to explore mutations in candidate genes. Utilizing the Tumor IMmune Estimation Resource (TIMER), the relationship between the expression of candidate genes and immune cell infiltration was assessed. Additionally, the cell-specific expression of the candidate genes was examined in the immune microenvironment of primary BC and metastatic BC lesions using the single-cell RNA sequencing (scRNA-seq) datasets GSE118389 and GSE202695. Finally, the protein expression of the candidate genes in clinical TNBC samples was evaluated. RESULTS: CD8A was identified as a hub gene in the DEG network and was found to be down-regulated in metastatic BC lesions. CD8A expression was highly correlated with the infiltration of CD8+ T cells, and elevated CD8A expression was correlated with improved survival. Interestingly, scRNA-seq data revealed that CD8A was down-regulated in CD8+ T cells in the immune microenvironment of metastatic BC lesions. Finally, the evaluation of clinical samples confirmed the down-regulation of CD8A in the immune microenvironment of BC lung metastases. CONCLUSIONS: In patients with metastatic TNBC, high levels of CD8A (especially in the immune microenvironment) are associated with a good prognosis.
Lung Neoplasms , Triple Negative Breast Neoplasms , Humans , Down-Regulation , Gene Expression , Oncogenes , Triple Negative Breast Neoplasms/genetics , Tumor Microenvironment/genetics
Introduction: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality. ACLF has been increasingly studied in recent years; however, a bibliometric analysis of the entire ACLF field has not been conducted. This study assesses current global trends and hotspots in ACLF research. Materials and methods: The core Web of Science database was searched for all ACLF-related publications conducted during 2012-2022. The data included information on the author, country, author keywords, publication year, citation frequency, and references. Microsoft Excel was used to collate the data and calculate percentages. VOSviewer software was used for citation and density visualization analysis. Histogram rendering was performed using GraphPad Prism Version 8.0 and R software was used to supplement the analysis. Result: A total of 1609 ACLF-related articles from 67 different countries were identified. China contributed the most literature, followed by the United States. However, Chinese literature only had the 4th highest number of citations, indicating that cooperation with other countries needs to be strengthened. The Journal of Hepatology had the highest number of ACLF-related citations. Prognosis was one of the most common author keywords, which may highlight current research hotspots. Bacterial infection was a common keyword and was closely related to prognosis. Conclusion: This bibliometric analysis suggests that future research hotspots will focus on the interplay among bacterial infection, organ failure, and prognosis.
With the increasing public attention to the health benefit of polyunsaturated fatty acids (PUFAs) and demand for linolenic acid (C18:3), it is of great significance to increase the C18:3 content in our meal. As an oil crop with high content of C18:3, Camelina sativa has three homologous copies of FAD2 and three homologous copies FAD3. In this study, we seed-specifically overexpressed two Camelina sativa fatty acid desaturase genes, CsFAD2 and CsFAD3, in rapeseed cultivar Zhongshuang 9. The results show that C18:3 content in CsFAD2 and CsFAD3 overexpressed seeds is increased from 8.62% in wild-type (WT) to 10.62-12.95% and 14.54-26.16%, respectively. We crossed CsFAD2 and CsFAD3 overexpression lines, and stable homozygous digenic crossed lines were obtained. The C18:3 content was increased from 8.62% in WT to 28.46-53.57% in crossed overexpression lines. In addition, we found that the overexpression of CsFAD2 and CsFAD3 had no effect on rapeseed growth, development, and other agronomic traits. In conclusion, we successfully generated rapeseed germplasms with high C18:3 content by simultaneously overexpressing CsFAD2 and CsFAD3, which provides a feasible way for breeding high C18:3 rapeseed cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01445-0.
Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.
Peptides , Proteins , Proteins/chemistry , Peptides/chemistry , Amino Acids/chemistry , Chemistry Techniques, Synthetic/methods , Peptide Hydrolases , Endopeptidases
BACKGROUND: Based on the Maillard reaction principle of red ginseng, this study innovatively synthesized a new amino acid derivative by combining arginine with lactose through simulated synthesis and was separated and purified through repeated silica gel and polyacrylamide gel (Bio-gel P-II) column chromatography. PURPOSE: The work was aimed at elucidating the synthesis of a novel amino acid derivative and investigating the intestinal protective activity of the novel amino acid derivative and possible molecular mechanism by establishing the intestinal injury model induced by cisplatin in mice. METHODS: The purity and molecular weight of the amino acid derivatives were determined to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by establishing cisplatin (20 mg/kg)-induced intestinal injury in vivo for 10 days and IEC-6 cell model. The biochemical indexes and histopathological analysis were used to evaluate the oxidative stress and inflammatory and pathological changes of intestinal tissue in mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB), cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C, phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified through immunofluorescence staining and western blot analysis. RESULTS: The new amino acid derivatives of chemical structure were identified to be 1- (arginine-Nαgroup)-1-deoxy-4-O-(ß-D-galactopyranosyl)-D-fructose, named Argininylfructosyl- galactose (AFGA, C18H34N4O12). The results showed that pretreatment with a single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury, and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells (p<0.05, p<0.01) and could effectively reduce the secretion of TNF-α and IL-1ß in serum and the expression level of NF-κB protein in intestinal tissues (p<0.01). Meantime, AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also suggested a better binding ability with the above-mentioned related target proteins. CONCLUSION: The results clearly revealed AFGA as a potential multifunctional therapeutic agent with a clear protective effect against cisplatin-induced intestinal injury may be related to the PI3K/Akt signaling pathway.
Glutamate is a neurotransmitter that can cause excitatory neurotoxicity when its extracellular concentration is too high, leading to disrupted calcium balance and increased production of reactive oxygen species (ROS). Cordycepin, a nucleoside adenosine derivative, has been shown to protect against excitatory neurotoxicity induced by glutamate. To investigate its potential neuroprotective effects, the present study employed fluorescence detection and spectrophotometry techniques to analyze primary hippocampal-cultured neurons. The results showed that glutamate toxicity reduced hippocampal neuron viability, increased ROS production, and increased intracellular calcium levels. Additionally, glutamate-induced cytotoxicity activated acetylcholinesterase and decreased glutathione levels. However, cordycepin inhibited glutamate-induced cell death, improved cell viability, reduced ROS production, and lowered Ca2+ levels. It also inhibited acetylcholinesterase activation and increased glutathione levels. This study suggests that cordycepin can protect against glutamate-induced neuronal injury in cell models, and this effect was inhibited by adenosine A1 receptor blockers, indicating that its neuroprotective effect is achieved through activation of the adenosine A1 receptor.
Neuroprotective Agents , Neuroprotective Agents/pharmacology , Glutamic Acid/toxicity , Glutamic Acid/metabolism , Acetylcholinesterase/metabolism , Acetylcholinesterase/pharmacology , Reactive Oxygen Species/metabolism , Calcium/metabolism , Apoptosis , Deoxyadenosines/pharmacology , Deoxyadenosines/metabolism , Hippocampus/metabolism , Neurons/metabolism , Glutathione/metabolism
Brown fat adipose tissue (BAT) is a therapeutic potential target to improve obesity, diabetes and cold acclimation in mammals. During the long-term cold exposure, the hyperplastic sympathetic network is crucial for BAT the maintain the highly thermogenic status. It has been proved that the sympathetic nervous drives the thermogenic activity of BAT via the release of norepinephrine. However, it is still unclear that how the thermogenic BAT affects the remodeling of the hyperplastic sympathetic network, especially during the long-term cold exposure. Here, we showed that following long-term cold exposure, SCD1-mediated monounsaturated fatty acid biosynthesis pathway was enriched, and the ratios of monounsaturated/saturated fatty acids were significantly up-regulated in BAT. And SCD1-deficiency in BAT decreased the capacity of cold acclimation, and suppressed long-term cold mediated BAT thermogenic activation. Furthermore, by using thermoneutral exposure and sympathetic nerve excision models, we disclosed that SCD1-deficiency in BAT affected the thermogenic activity, depended on sympathetic nerve. In mechanism, SCD1-deficiency resulted in the unbalanced ratio of palmitic acid (PA)/palmitoleic acid (PO), with obviously higher level of PA and lower level of PO. And PO supplement efficiently reversed the inhibitory role of SCD1-deficiency on BAT thermogenesis and the hyperplastic sympathetic network. Thus, our data provided insight into the role of SCD1-mediated monounsaturated fatty acids metabolism to the interaction between thermogenic activity BAT and hyperplastic sympathetic networks, and illustrated the critical role of monounsaturated fatty acids biosynthetic pathway in cold acclimation during the long-term cold exposure.
Adipose Tissue, Brown , Thermogenesis , Animals , Adipose Tissue, Brown/metabolism , Thermogenesis/physiology , Sympathetic Nervous System , Obesity/metabolism , Fatty Acids, Monounsaturated/metabolism , Cold Temperature , Mammals
D-peptide ligands can be screened for therapeutic potency and enzymatic stability using synthetic mirror-image proteins (D-proteins), but efficient acquisition of these D-proteins can be hampered by the need to accomplish their in vitro folding, which often requires the formation of correctly linked disulfide bonds. Here, we report the finding that temporary installation of natural O-linked-ß-N-acetyl-D-glucosamine (O-GlcNAc) groups onto selected D-serine or D-threonine residues of the synthetic disulfide-bonded D-proteins can facilitate their folding in vitro, and that the natural glycosyl groups can be completely removed from the folded D-proteins to afford the desired chirally inverted D-protein targets using naturally occurring O-GlcNAcase. This approach enabled the efficient chemical syntheses of several important but difficult-to-fold D-proteins incorporating disulfide bonds including the mirror-image tumor necrosis factor alpha (D-TNFα) homotrimer and the mirror-image receptor-binding domain of the Omicron spike protein (D-RBD). Our work establishes the use of O-GlcNAc to facilitate D-protein synthesis and folding and proves that D-proteins bearing O-GlcNAc can be good substrates for naturally occurring O-GlcNAcase.
Acetylglucosaminidase , Proteins , Peptides , Polysaccharides , Glucosamine
Converting CO2 to olefins is an ideal route to achieve carbon neutrality. However, selective hydrogenation to light olefins, especially single-component olefin, while reducing CH4 formation remains a great challenge. Herein, we developed ZnZrOx /SSZ-13 tandem catalyst for the highly selective hydrogenation of CO2 to light olefins. This catalyst shows C2 = -C4 = and propylene selectivity up to 89.4 % and 52 %, respectively, while CH4 is suppressed down to 2 %, and there is no obvious deactivation. It is demonstrated that the isolated moderate Brønsted acid sites (BAS) of SSZ-13 promotes the rapid conversion of intermediate species derived from ZnZrOx , thereby enhancing the kinetic coupling of the reactions and inhibit the formation of alkanes and improve the light olefins selectivity. Besides, the weaker BAS of SSZ-13 promote the conversion of intermediates into aromatics with 4-6 methyl groups, which is conducive to the aromatics cycle. Accordingly, more propene can be obtained by elevating the Si/Al ratio of SSZ-13. This provides an efficient strategy for CO2 hydrogenation to light olefins with high selectivity.
Emerging CRISPR-Cas9 technology permits synthetic lethality (SL) screening of large number of gene pairs from gene combination double knockout (CDKO) experiments. However, the poor integration and annotation of CDKO SL data in current SL databases limit their utility, and diverse methods of calculating SL scores prohibit their comparison. To overcome these shortcomings, we have developed SL knowledge base (SLKB) that incorporates data of 11 CDKO experiments in 22 cell lines, 16,059 SL gene pairs and 264,424 non-SL gene pairs. Additionally, within SLKB, we have implemented five SL calculation methods: median score with and without background control normalization (Median-B/NB), sgRNA-derived score (sgRNA-B/NB), Horlbeck score, GEMINI score and MAGeCK score. The five scores have demonstrated a mere 1.21% overlap among their top 10% SL gene pairs, reflecting high diversity. Users can browse SL networks and assess the impact of scoring methods using Venn diagrams. The SL network generated from all data in SLKB shows a greater likelihood of SL gene pair connectivity with other SL gene pairs than non-SL pairs. Comparison of SL networks between two cell lines demonstrated greater likelihood to share SL hub genes than SL gene pairs. SLKB website and pipeline can be freely accessed at https://slkb.osubmi.org and https://slkb.docs.osubmi.org/, respectively.
Knowledge Bases , Synthetic Lethal Mutations , Humans , RNA, Guide, CRISPR-Cas Systems , Internet Use
Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.
Polyethylene Terephthalates , Hydrolases/chemistry , Peptide Fragments , Peptides/chemistry , Polyethylene Terephthalates/chemistry
BACKGROUND: The diagnosis of Wilson's disease (WD) remains a challenging endeavor in clinical practice. Serum sphingolipids play a significant role in the development of liver disease. In this study, we examined the serum sphingolipid profile in patients with WD and explored the potential diagnostic utility of serum sphingolipid metabolites. These metabolites may aid in distinguishing WD patients from healthy controls and identifying those with a risk of cirrhosis. METHODS: This study consecutively enrolled 26 WD patients and 88 healthy controls. We utilized high-performance liquid chromatography-tandem mass spectrometry to analyze a panel of 88 serum sphingolipid metabolites. The data were analyzed by multivariate statistical methods. RESULTS: Among the 88 sphingolipids metabolites analyzed, 17 sphingolipids were observed significant differences between WD and HC groups (all P < 0.05). Notably, five sphingolipids, namely S1P (d18:1), Cer (d18:2/21:0), SM41:2, sph(d18:1), and Cer (d18:2/22:0), each with an AUC exceeding 0.9, emerged as potential biomarkers for WD. Additionally, in the comparison between WD patients with and without cirrhosis, 24 sphingolipid metabolites exhibited significant differences (all P < 0.05). We identified Cer(d18:1/20:0), Cer(d18:2/22:0), Cer(d18:2/24:0), Cer(d18:2/20:0), and Cer(d18:2/18:0), each with an AUC exceeding 0.9, as potential serological markers for WD patients with cirrhosis. CONCLUSION: For enhanced clinical applicability, we propose considering Cer (d18:2/22:0) as a predictive marker applicable to both WD patients and their susceptibility to cirrhosis. This particular ceramide has exhibited strong diagnostic and predictive performance. These findings have the potential to facilitate non-invasive WD diagnosis.
Hepatolenticular Degeneration , Sphingolipids , Humans , Hepatolenticular Degeneration/diagnosis , Ceramides , Biomarkers , Liver Cirrhosis/diagnosis
Membrane lipidomes are dynamic and their changes generate lipid mediators affecting various biological processes. Phosphatidic acid (PA) has emerged as an important class of lipid mediators involved in a wide range of cellular and physiological responses in plants, animals, and microbes. The regulatory functions of PA have been studied primarily outside the nuclei, but an increasing number of recent studies indicates that some of the PA effects result from its action in nuclei. PA levels in nuclei are dynamic in response to stimuli. Changes in nuclear PA levels can result from activities of enzymes associated with nuclei and/or from movements of PA generated extranuclearly. PA has also been found to interact with proteins involved in nuclear functions, such as transcription factors and proteins undergoing nuclear translocation in response to stimuli. The nuclear action of PA affects various aspects of plant growth, development, and response to stress and environmental changes.
Phosphatidic Acids , Signal Transduction , Animals , Phosphatidic Acids/metabolism , Signal Transduction/physiology , Plants/metabolism
Albumin and prealbumin serve as vital markers reflecting hepatic synthesis activity and overall body nutrient status. Hypoproteinemia can result from various etiological factors, with reduced blood inflow into the liver due to portal vein thrombosis being one such cause. However, literature addressing this specific association remains limited. This report presents an atypical case of malnutrition involving a patient who experienced prolonged hypoproteinemia attributable to a gradual decline in hepatic blood perfusion caused by progressive portal thrombosis and cavernous transformation of the portal vein (CTPV). The case encompasses an in-depth analysis of the factors contributing to undernutrition, the etiology and diagnosis of hypoproteinemia, and its clinical implications. Vigilance for the presence of hypoproteinemia is essential in the management of patients afflicted by progressive portal vein thrombosis complicated by CTPV. Timely and effective interventions aimed at rectifying hypoproteinemia can significantly enhance clinical outcomes. Moreover, reduced hepatic blood flow should be considered a plausible underlying cause in cases of unexplained hypoproteinemia, warranting thorough evaluation. This case underscores the importance of recognizing the intricate interplay between hepatic vascular pathology and protein homeostasis in clinical practice.
