Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases.

The endoplasmic reticulum, a key cellular organelle, regulates a wide variety of cellular activities. Endoplasmic reticulum autophagy, one of the quality control systems of the endoplasmic reticulum, plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover, remodeling, and proteostasis. In this review, we briefly describe the endoplasmic reticulum quality control system, and subsequently focus on the role of endoplasmic reticulum autophagy, emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements. We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases. In summary, this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders. This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Cooperative Rh/Achiral Phosphoric Acid-Enabled [3+3] Cycloannulation of Carbonyl Ylides with Quinone Monoimines: Synthesis of Benzofused Dioxabicyclo[3.2.1]octane Scaffolds.

A cooperative Rh/achiral phosphoric acid-enabled [3+3] cycloaddition of in situ-generated carbonyl ylides with quinone monoimines has been developed. With the ability to build up the molecular complexity rapidly and efficiently, this method furnishes highly functionalized oxa-bridged benzofused dioxabicyclo[3.2.1]octane scaffolds bearing two quaternary centers in good to excellent yields under mild conditions. Moreover, the utility of the current method was demonstrated by gram-scale synthesis and elaboration of the products into various functionalized oxa-bridged heterocycles.

F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/ß-Catenin pathway.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. METHODS: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. RESULTS: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein ß-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate ß-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. CONCLUSION: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/ß-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

The IMPDH cytoophidium couples metabolism and fetal development in mice.

The cytoophidium is an evolutionarily conserved subcellular structure formed by filamentous polymers of metabolic enzymes. In vertebrates, inosine monophosphate dehydrogenase (IMPDH), which catalyses the rate-limiting step in guanosine triphosphate (GTP) biosynthesis, is one of the best-known cytoophidium-forming enzymes. Formation of the cytoophidium has been proposed to alleviate the inhibition of IMPDH, thereby facilitating GTP production to support the rapid proliferation of certain cell types such as lymphocytes, cancer cells and pluripotent stem cells (PSCs). However, past studies lacked appropriate models to elucidate the significance of IMPDH cytoophidium under normal physiological conditions. In this study, we demonstrate that the presence of IMPDH cytoophidium in mouse PSCs correlates with their metabolic status rather than pluripotency. By introducing IMPDH2 Y12C point mutation through genome editing, we established mouse embryonic stem cell (ESC) lines incapable of forming IMPDH polymers and the cytoophidium. Our data indicate an important role of IMPDH cytoophidium in sustaining a positive feedback loop that couples nucleotide biosynthesis with upstream metabolic pathways. Additionally, we find that IMPDH2 Y12C mutation leads to decreased cell proliferation and increased DNA damage in teratomas, as well as impaired embryo development following blastocoel injection. Further analysis shows that IMPDH cytoophidium assembly in mouse embryonic development begins after implantation and gradually increases throughout fetal development. These findings provide insights into the regulation of IMPDH polymerisation in embryogenesis and its significance in coordinating cell metabolism and development.

The functions and mechanisms of RNA modification in prostate: Current status and future perspectives.

The increasing incidence and mortality of prostate cancer worldwide significantly impact the life span of male patients, emphasizing the urgency of understanding its pathogenic mechanism and associated molecular changes that regulate tumor progression for effective prevention and treatment. RNA modification, an important post-transcriptional regulatory process, profoundly influences tumor cell growth and metabolism, shaping cell fate. Over 170 RNA modification methods are known, with prominent research focusing on N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, 5-methylcytidine, pseudouridine, and N4-acetylcytidine modifications. These alterations intricately regulate coding and non-coding RNA post-transcriptionally, affecting the stability of RNA and protein expression levels. This article delves into the latest advancements and challenges associated with various RNA modifications in prostate cancer tumor cells, tumor microenvironment, and core signaling molecule androgen receptors. It aims to provide new research targets and avenues for molecular diagnosis, treatment strategies, and improvement of the prognosis in prostate cancer.

Dual Channel H2O2 Photosynthesis in Pure Water over S-Scheme Heterojunction Cs3PMo12/CC Boosted by Proton and Electron Reservoirs.

Dual channel photo-driven H2O2 production in pure water on small-scale on-site setups is a promising strategy to provide low-concentrated H2O2 whenever needed. This process suffers, however, strongly from the fast recombination of photo-generated charge carriers and the sluggish oxidation process. Here, insoluble Keggin-type cesium phosphomolybdate Cs3PMo12O40 (abbreviated to Cs3PMo12) is introduced to carbonized cellulose (CC) to construct S-scheme heterojunction Cs3PMo12/CC. Dual channel H2O2 photosynthesis from both H2O oxidation and O2 reduction in pure water has been thus achieved with the production rate of 20.1 mmol L-1 gcat. -1 h-1, apparent quantum yield (AQY) of 2.1% and solar-to-chemical conversion (SCC) efficiency of 0.050%. H2O2 accumulative concentration reaches 4.9 mmol L-1. This high photocatalytic activity is guaranteed by unique features of Cs3PMo12/CC, namely, S-scheme heterojunction, electron reservoir, and proton reservoir. The former two enhance the separation of photo-generated charge carriers, while the latter speeds up the torpid oxidation process. In situ experiments reveal that H2O2 is formed via successive single-electron transfer in both channels. In real practice, exposing the reaction system under natural sunlight outdoors successfully results in 0.24 mmol L-1 H2O2. This work provides a key practical strategy for designing photocatalysts in modulating redox half-reactions in photosynthesis.

New initiation of opioids, benzodiazepines and antipsychotics following hospitalization for COVID-19.

BACKGROUND: Patients newly initiated on opioids (OP), benzodiazepines (BZD), and antipsychotics (AP) during hospitalization are often prescribed these on discharge. Implications of this practice on outcomes remains unexplored. OBJECTIVE: To explore the prevalence and risk factors of new initiation of select OP, BZD and AP among patients requiring in-patient stays. Test the hypothesis that new prescriptions are associated with higher odds of readmission or death within 28 days of discharge. DESIGN: Single center retrospective cohort study. SETTING AND PARTICIPANTS: Patients admitted to a tertiary-level medical center with either a primary diagnosis of RT-PCR positive for COVID-19 or high index of clinical suspicion thereof. INTERVENTION: None. MAIN OUTCOME AND MEASURES: Exposure was the new initiation of select common OP, BZD, and AP which were continued on hospital discharge. Outcome was a composite of 28-day readmission or death following index admission. Multivariable logistic regression was used to assess patient mortality or readmission within 28 days of discharge associated with new prescriptions at discharge. RESULTS: One thousand three hundred and nineteen patients were included in the analysis. 11.3% (149/1319) were discharged with a new prescription of select OP, BZD, or AP either alone or in combination. OP (110/149) were most prescribed followed by BZD (41/149) and AP (22/149). After adjusting for unbalanced confounders, new prescriptions (adjusted odds ratio: 2.44, 95% confidence interval: 1.42-4.12; p = .001) were associated with readmission or death within 28 days of discharge. One in nine patients admitted with a diagnosis of COVID-19 or high clinical suspicion thereof were discharged with a new prescription of either OP, BZD or AP. New prescriptions were associated with higher odds of 28-day readmission or death. Strengthening medication reconciliation processes focused on these classes may reduce avoidable harm.

Origin and Function of Monocytes in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (Mφs) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease's progression. On the other hand, their differentiated offsprings, namely moMφs and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes' origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD's course. Through this lens, we aspire to furnish novel perspectives into IBD's etiology and potential therapeutic strategies.

SIRT1 restores mitochondrial structure and function in rats by activating SIRT3 after cerebral ischemia/reperfusion injury.

Mitochondrial dysfunction contributes to cerebral ischemia-reperfusion (CI/R) injury, which can be ameliorated by Sirtuin-3 (SIRT3). Under stress conditions, the SIRT3-promoted mitochondrial functional recovery depends on both its activity and expression. However, the approach to enhance SIRT3 activity after CI/R injury remains unelucidated. In this study, Sprague-Dawley (SD) rats were intracranially injected with either adeno-associated viral Sirtuin-1 (AAV-SIRT1) or AAV-sh_SIRT1 before undergoing transient middle cerebral artery occlusion (tMCAO). Primary cortical neurons were cultured and transfected with lentiviral SIRT1 (LV-SIRT1) and LV-sh_SIRT1 respectively before oxygen-glucose deprivation/reoxygenation (OGD/R). Afterwards, rats and neurons were respectively treated with a selective SIRT3 inhibitor, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). The expression, function, and related mechanism of SIRT1 were investigated by Western Blot, flow cytometry, immunofluorescence staining, etc. After CI/R injury, SIRT1 expression decreased in vivo and in vitro. The simulation and immune-analyses reported strong interaction between SIRT1 and SIRT3 in the cerebral mitochondria before and after CI/R. SIRT1 overexpression enhanced SIRT3 activity by increasing the deacetylation of SIRT3, which ameliorated CI/R-induced cerebral infarction, neuronal apoptosis, oxidative stress, neurological and motor dysfunction, and mitochondrial respiratory chain dysfunction, promoted mitochondrial biogenesis, and retained mitochondrial integrity and mitochondrial morphology. Meanwhile, SIRT1 overexpression alleviated OGD/R-induced neuronal death and mitochondrial bioenergetic deficits. These effects were reversed by AAV-sh_SIRT1 and the neuroprotective effects of SIRT1 were partially offset by 3-TYP. These results suggest that SIRT1 restores the structure and function of mitochondria by activating SIRT3, offering neuroprotection against CI/R injury, which signifies a potential approach for the clinical management of cerebral ischemia.

Co-localization and analysis of miR477b with fiber length quantitative trait loci in cotton.

Cotton is an important cash crop for the textile industry. However, the understanding of natural genetic variation of fiber elongation in relation to miRNA is lacking. A miRNA gene (miR477b) was found to co-localize with a previously mapped fiber length (FL) quantitative trait locus (QTL). The miR477b was differentially expressed during fiber elongation between two backcross inbred lines (BILs) differing in FL and its precursor sequences. Bioinformatics and qRT-PCR analysis were further used to analyse the miRNA genes, which could produce mature miR477b. Cotton plants with virus-induced gene silencing (VIGS) constructs to over-express the allele of miR477b from the BIL with longer fibers had significantly longer fibers as compared with negative control plants, while the VIGS plants with suppressed miRNA expression had significantly shorter fibers. The expression level of the target gene (DELLA) and related genes (RDL1 and EXPA1 for DELLA through HOX3 protein) in the two BILs and/or the VIGS plants were generally congruent, as expected. This report represents one of the first comprehensive studies to integrate QTL linkage mapping and physical mapping of small RNAs with both small and mRNA transcriptome analysis, followed by VIGS, to identify candidate small RNA genes affecting the natural variation of fiber elongation in cotton.

Development of a contrast-enhanced ultrasound guided high intensity focused ultrasound system for coagulation of liver parenchyma.

BACKGROUND: The liver is the most common organ injured in blunt abdominal trauma and makes up roughly 5% of all trauma admissions. Current treatments are invasive and resource-intensive, which may delay care. We aim to develop and validate a contrast-enhanced ultrasound (CEUS)guided noninvasive tool to treat liver lacerations at the bedside. METHODS: Two 1.8 MHz high-intensity focused ultrasound (HIFU) elements were coupled to a C1-6 diagnostic ultrasound probe and a Logiq E10 scanner (GE HealthCare) utilizing a custom enclosure for co-registered imaging and ablation. A phantom was created from polyacrylamide gel combined with thermochromic ink whose color changes above biological ablative temperatures (60 °C). The HIFU wave was focused approximately 0.5 cm below the surface utilizing a 50% duty cycle generating 11.9 MPa for 20, 30, 40, 50, and 60s. Experiments were repeated on ex vivo chicken livers in a water bath. Finally, the livers of 4 live swine underwent up to 6 CEUS-guided treatments using parameters optimized from in vitro work. RESULTS: Treatment of the phantom between 20-60s, produced ablation sizes from 0.016 to 0.4 cm 3 . The relationship between time and size was exponential (R 2 = 0.992). Ablation areas were also well visualized on with ultrasound imaging. The ex vivo liver ablation size at 20s was 0.37 cm 3 , at 30s was 0.66 cm 3 , and at 100 s was 5.0 cm 3 . For the in-vivo swine experiments, the average ablation area measured 2.0x0.75 cm with a maximum of 3.5x1.5 cm. CEUS was utilized with the contrast agent Definity (Lantheus) for identification of lacerations as well as immediate post operative evaluation of therapy. CONCLUSION: These experiments demonstrate the feasibility of CEUS guided transdermal HIFU ablation and the time-dependent size of ablation. This work warrants future investigations into using ultrasound to detect active bleeding and HIFU to coagulate grade III and IV liver laceration. STUDY TYPE: Therapeutic/care management.

Cotton transposon-related variome reveals roles of transposon-related variations in modern cotton cultivation.

INTRODUCTION: Transposon plays a vital role in cotton genome evolution, contributing to the expansion and divergence of genomes within the Gossypium genus. However, knowledge of transposon activity in modern cotton cultivation is limited. OBJECTIVES: In this study, we aimed to construct transposon-related variome within Gossypium genus and reveal role of transposon-related variations during cotton cultivation. In addition, we try to identify valuable transposon-related variations for cotton breeding. METHODS: We utilized graphical genome construction to build up the graphical transposon-related variome. Based on the graphical variome, we integrated t-test, eQTL analysis and Mendelian Randomization (MR) to identify valuable transposon activities and elite genes. In addition, a convolutional neural network (CNN) model was constructed to evaluate epigenomic effects of transposon-related variations. RESULTS: We identified 35,980 transposon activities among 10 cotton genomes, and the diversity of genomic and epigenomic features was observed among 21 transposon categories. The graphical cotton transposon-related variome was constructed, and 9,614 transposon-related variations with plasticity in the modern cotton cohort were used for eQTL, phenotypic t-test and Mendelian Randomization. 128 genes were identified as gene resources improving fiber length and strength simultaneously. 4 genes were selected from 128 genes to construct the elite gene panel whose utility has been validated in a natural cotton cohort and 2 accessions with phenotypic divergence. Based on the eQTL analysis results, we identified transposon-related variations involved in cotton's environmental adaption and human domestication, providing evidence of their role in cotton's adaption-domestication cooperation. CONCLUSIONS: The cotton transposon-related variome revealed the role of transposon-related variations in modern cotton cultivation, providing genomic resources for cotton molecular breeding.

Prognostic significance of systemic immune inflammatory index in NSCLC: a meta-analysis.

Aim: The aim of this meta-analysis was to investigate the relationship between the baseline systemic immune inflammatory index (SII) and prognosis in patients with NSCLC. Materials & methods: The relation between pretreatment SII and overall survival, disease-free survival, cancer-specific survival, progression-free survival and recurrence-free survival in NSCLC patients was analyzed combined with hazard ratio and 95% CI. Results: The results showed that high SII was significantly correlated with overall survival and progression-free survival of NSCLC patients, but not with disease-free survival, cancer-specific survival and recurrence-free survival. Conclusion: The study suggests that a higher SII has association with worse prognosis in NSCLC patients. PROSPERO registration number: CRD42022336270.

Development of Novel ß-Carboline/Furylmalononitrile Hybrids as Type I/II Photosensitizers with Chemo-Photodynamic Therapy and Minimal Toxicity.

Chemo-photodynamic therapy is a treatment method that combines chemotherapy and photodynamic therapy and has demonstrated significant potential in cancer treatment. However, the development of chemo-photodynamic therapeutic agents with fewer side effects still poses a challenge. Herein, we designed and synthesized a novel series of ß-carboline/furylmalononitrile hybrids 10a-i and evaluated their chemo-photodynamic therapeutic effects. Most of the compounds were photodynamically active and exhibited cytotoxic effects in four cancer cells. In particular, 10f possessed type-I/II photodynamic characteristics, and its 1O2 quantum yield increased by 3-fold from pH 7.4 to 4.5. Most interestingly, 10f exhibited robust antiproliferative effects by tumor-selective cytotoxicities and hypoxic-overcoming phototoxicities. In addition, 10f generated intracellular ROS and induced hepatocellular apoptosis, mitochondrial damage, and autophagy. Finally, 10f demonstrated extremely low acute toxicity (LD50 = 1415 mg/kg) and a high tumor-inhibitory rate of 80.5% through chemo-photodynamic dual therapy. Our findings may provide a promising framework for the design of new photosensitizers for chemo-photodynamic therapy.

Discovery of a Biocontrol Strain Trichaptum laricinum: Its Metabolites and Antifungal Activity against Pathogenic Fungus Colletotrichum anthrisci.

Finding safe and environmentally friendly fungicides is one of the important strategies in modern pesticide research and development. In this work, the antipathogenic effects of the fungus Trichaptum laricinum against the anthracnose pathogen Colletotrichum anthrisci were studied. The EtOAc extract of T. laricinum showed remarkable antifungal activity against C. anthrisci with an inhibition rate of 50% at 256 µg/mL. Bioguided isolation of the cultural broth of T. laricinum produced four new drimane sesquiterpenes, trichalarins A-D (1-4), and six other metabolites (5-10). Their structures were established by extensive spectroscopic methods, quantum chemical calculations, and single-crystal X-ray diffraction. All compounds exhibited antifungal activity against C. anthrisci with minimum inhibitory concentrations (MICs) of 8-64 µg/mL in vitro. Further in vivo assay suggested that compounds 2, 6, and 9 could significantly inhibit C. anthrisci growth in avocado fruit with inhibition rates close to 80% at the concentration of 256 µg/mL, while compounds 2 and 6 had an inhibition rate over 90% at the concentration of 512 µg/mL. The EtOAc extract of T. laricinum had no inhibitory effect on Pinus massoniana seed germination and growth at the concentration of 2 mg/mL, showing good environmental friendliness. Thus, the fungus T. laricinum could be considered as an ideal biocontrol strain, and its metabolites provided a diverse material basis for the antibiotic agents.

Dynamic Arabidopsis P5CS filament facilitates substrate channelling.

In plants, the rapid accumulation of proline is a common response to combat abiotic stress1-7. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline8. Here we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS1 (AtP5CS1) and P5CS2 (AtP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of AtP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveal that filament-based substrate channelling is essential for maintaining the high catalytic efficiency of AtP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of AtP5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response.

Investigation of autophagy­related genes and immune infiltration in calcific aortic valve disease: A bioinformatics analysis and experimental validation.

The present study aimed to elucidate the role of autophagy-related genes (ARGs) in calcific aortic valve disease (CAVD) and their potential interactions with immune infiltration via experimental verification and bioinformatics analysis. A total of three microarray datasets (GSE12644, GSE51472 and GSE77287) were obtained from the Gene Expression Omnibus database, and gene set enrichment analysis was performed to identify the relationship between autophagy and CAVD. After differentially expressed genes and differentially expressed ARGs (DEARGs) were identified using CAVD samples and normal aortic valve samples, a functional analysis was performed, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, protein-protein interaction network construction, hub gene identification and validation, immune infiltration and drug prediction. The results of the present study indicated a significant relationship between autophagy and CAVD. A total of 46 DEARGs were identified. GO and pathway enrichment analyses revealed the complex roles of DEARGs in regulating CAVD, including multiple gene functions and pathways. A total of 10 hub genes were identified, with three (SPP1, CXCL12 and CXCR4) consistently upregulated in CAVD samples compared with normal aortic valve samples in multiple datasets and experimental validation. Immune infiltration analyses demonstrated significant differences in immune cell proportions between CAVD samples and normal aortic valve samples, thus showing the crucial role of immune infiltration in CAVD development. Furthermore, therapeutic drugs were predicted that could target the identified hub genes, including bisphenol A, resveratrol, progesterone and estradiol. In summary, the present study illuminated the crucial role of autophagy in CAVD development and identified key ARGs as potential therapeutic targets. In addition, the observed immune cell infiltration and predicted autophagy-related drugs suggest promising avenues for future research and novel CAVD treatments.

Carpesabrolide A, a novel meroterpenoid with anti-inflammatory activity from Carpesium abrotanoides.

Carpesabrolide A (1), featuring an unprecedented fumaric acid-guaiane sesquiterpenoid hybrid, has been isolated from the folk medicinal plant Carpesium abrotanoides. The structure with absolute configuration has been established by spectroscopic methods and single crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1 is proposed. Compound 1 shows significant anti-inflammatory activity by inhibiting NO production with an IC50 value of 2.7 µM.

How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation.

Mesenchymal stem cells (MSCs) are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts, chondrocytes and adipocytes. The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes, in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes. Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis. However, the mechanism underlying the adipogenic differentiation of MSCs is not fully understood. Here, the current knowledge of adipogenic differentiation in MSCs is reviewed, focusing on signaling pathways, noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation. Finally, the relationship between maladipogenic differentiation and diseases is briefly discussed. We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.