Identification of the role of DAB2 and CXCL8 in uterine spiral artery remodeling in early-onset preeclampsia.

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.

Pepsin-mediated inflammation in laryngopharyngeal reflux via the ROS/NLRP3/IL-1ß signaling pathway.

BACKGROUND: Laryngopharyngeal reflux (LPR) is one of the most common disorders in otorhinolaryngology, affecting up to 10% of outpatients visiting otolaryngology departments. In addition, 50% of hoarseness cases are related to LPR. Pepsin reflux-induced aseptic inflammation is a major trigger of LPR; however, the underlying mechanisms are unclear. The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has become an important bridge between stimulation and sterile inflammation and is activated by intracellular reactive oxygen species (ROS) in response to danger signals, leading to an inflammatory cascade. In this study, we aimed to determine whether pepsin causes LPR-associated inflammatory injury via mediating inflammasome activation and explore the potential mechanism. METHODS: We evaluated NLRP3 inflammasome expression and ROS in the laryngeal mucosa using immunofluorescence and immunohistochemistry. Laryngeal epithelial cells were exposed to pepsin and analyzed using flow cytometry, western blotting, and real-time quantitative PCR to determine ROS, NLRP3, and pro-inflammatorycytokine levels. RESULTS: Pepsin expression was positively correlated with ROS as well as caspase-1 and IL-1ß levels in laryngeal tissues. Intracellular ROS levels were elevated by increased pepsin concentrations, which were attenuated by apocynin (APO)-a ROS inhibitor-in vitro. Furthermore, pepsin significantly induced the mRNA and protein expression of thioredoxin-interacting protein, NLRP3, caspase-1, and IL-1ß in a dose-dependent manner. APO and the NLRP3 inhibitor, MCC950, inhibited NLRP3 inflammasome formation and suppressed laryngeal epithelial cell damage. CONCLUSION: Our findings verified that pepsin could regulate the NLRP3/IL-1ß signaling pathway through ROS activation and further induce inflammatory injury in LPR. Targeting the ROS/NLRP3 inflammasome signaling pathway may help treat patients with LPR disease.

Intracorporeal versus extracorporeal anastomosis in laparoscopic right hemicolectomy for overweight colon cancer patients: a case-control study.

INTRODUCTION: Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. METHODS: Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. RESULTS: The incidence of postoperative complications was 20.8% (10/48) in the EA group and 14.6% (7/48) in the IA group respectively, with no statistical difference. Compared to the EA group, patients in the IA group revealed faster gas (40.2 + 7.8 h vs. 45.6 + 7.9 h, P = 0.001) and stool discharge (4.0 + 1.2 d vs. 4.5 + 1.1 d, P = 0.040), shorter assisted incision (5.3 + 1.3 cm vs. 7.5 + 1.2 cm, P = 0.000), and less analgesic used (3.3 + 1.3 d vs. 4.0 + 1.3 d, P = 0.012). There were no significant differences in operation time, blood loss, or postoperative hospital stays. In the IA group, the first one third of cases presented longer operation time (228.4 + 29.3 min) compared to the middle (191.0 + 35.0 min, P = 0.003) and the last one third of patients (182.2 + 20.7 min, P = 0.000). CONCLUSION: LRH with IA is feasible and safe for overweight RCC, with faster bowel function recovery and less pain. Accumulation of certain cases of LRH with IA will facilitate surgical procedures and reduce operation time.

Calreticulin regulates the expression of MMP14 and ADAR1 through EIF2AK2 signaling to promote the proliferation and progression of malignant melanoma cells.

It has been demonstrated that calreticulin (CALR) is expressed abnormally in various tumors and is involved in the occurrence and development of tumors. In this study, CALR and EIF2AK2 expression was measured in the clinical specimens of 39 patients with melanoma. Then, we constructed knockdown and overexpression cell models of CALR and EIF2AK2 and used wound healing and Transwell assays to observe cell migration and invasion. Apoptosis, EDU, and ROS assays were used to measure cell apoptosis and proliferation, as well as ROS levels. The effect of CALR on endoplasmic reticulum stress was detected using endoplasmic reticulum fluorescent probes. Western blotting was used to detect protein levels of CALR, EIF2AK2, ADAR1, and MMP14. The results indicated that CALR and EIF2AK2 expression levels were significantly higher in human melanoma tissues than in adjacent non-tumor tissue. In addition, we found a correlation between CALR and the expression of EIF2AK2 and MMP14, and the experimental results indicated that overexpression of CALR significantly upregulated the expression of EIF2AK2, MMP14, and ADAR1, while knockdown of CALR inhibited their expression. Notably, the knockdown of EIF2AK2 in the CALR overexpression group blocked the upregulation of MMP14 and ADAR1 expression by CALR, and the knockdown of both CALR and EIF2AK2 significantly inhibited MMP14 and ADAR1 expression. In conclusion, CALR and EIF2AK2 play a promoting role in melanoma progression, and knockdown of CALR and EIF2AK2 may be an effective anti-tumor target, and its mechanism may be through MMP14, ADAR1 signaling.

Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis.

Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1ß, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 µM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.

Two Undescribed Coumarins from Notopterygium incisum with Anti-inflammatory Activity.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.

Microplastics supply contaminants in food chain: non-negligible threat to health safety.

The occurrence of microplastics (MPs) and organic pollutants (OPs) residues is commonly observed in diverse environmental settings, where their interactions can potentially alter the behavior, availability, and toxicity of OPs, thereby posing risks to ecosystems. Herein, we particularly emphasize the potential for bioaccumulation and the biomagnification effect of MPs in the presence of OPs within the food chain. Despite the ongoing influx of novel information, there exists a dearth of data concerning the destiny and consequences of MPs in the context of food pollution. Further endeavors are imperative to unravel the destiny and repercussions of MPs/OPs within food ecosystems and processing procedures, aiming to gain a deeper understanding of the joint effect on human health and food quality. Nevertheless, the adsorption and desorption behavior of coexisting pollutants can be significantly influenced by MPs forming biofilms within real-world environments, including temperature, pH, and food constituents. A considerable portion of MPs tend to accumulate in the epidermis of vegetables and fruits, thus necessitating further research to comprehend the potential ramifications of MPs on the infiltration behavior of OPs on agricultural product surfaces.

Tai Chi Improves Cognitive Function of Dementia Patients: A Systematic Review and Meta-analysis.

Background: Studies show that Tai Chi, a traditional Chinese mind-body exercise, has the potential to improve cognitive and physical function among the elderly. However, debates continue about its effectiveness among persons with dementia (PWD). Primary study objective: This study assessed the effectiveness of Tai Chi in improving cognitive, physical, and emotional function among PWDs. Methods: We conducted a systematic review of research on online databases (MEDLINE, EMBASE, Pubmed, and Cochrane Library) published up to April 2021. Relevant randomized clinical trials (RCTs) were reviewed and analyzed. A random-effect model was used to evaluate the pooled mean difference values. Intervention: The individuals in the intervention group practiced Tai Chi exercises in addition to their regular care, while the individuals in the control group continued their usual care. Primary Outcome Measures: We focus on three outcome measures: the Mini-mental State Examination (MMSE), Timed Up and Go (TUG), and Geriatric Depression Scale (GDS) scores. Results: Seven studies (N = 616) were included in the meta-analysis. Our results show that Tai Chi can improve cognitive function in PWDs (P = .007, SMD = 0.27; 95% CI, 0.08 to 0.47). However, Tai Chi might not improve the TUG (P = .25, SMD = -0.64; 95% CI, -1.74 to 0.46) and GDS (P = .61; SMD = -0.36; 95% CI -2.00 to 1.17) functions. Conclusions: The results suggest that Tai Chi can help improve cognitive function among PWDs, but it has no physical and emotional benefits as assessed using the TUG and GDS scales, respectively.

The status of low anterior resection syndrome: data from a single-center in China.

AIM: The incidence and risk factors of low anterior resection syndrome (LARS) largely variate in different studies. In addition, there is lack of study on how patients evaluate the therapeutic effect of LARS. This single-center retrospective study aims to investigate the status of LARS in Chinese patients undergoing laparoscopic low anterior resection (LAR). METHODS: Consequent patients undergoing laparoscopic LAR and free from disease recurrence from January 2015 to May 2021 were issued with both LARS questionnaire and satisfaction survey. Related data were collected and analyzed. RESULTS: Both LARS questionnaires and self-made satisfaction survey were received from 261 eligible patients. The overall incidence of LARS was 47.1% (minor in 19.5%, major in 27.6%), decreased with the passage of postoperative time (64.7% within 12 months, and 41.7% within 12-36 months), and became stable 36 months later (39.7%). The most common symptoms were defecation clustering (n = 107/261, 41.0%) and defecation urgency (n = 101/261, 38.7%). According to the multivariable regression analysis, risk factors of major LARS were: 1 year increase in age (OR 1.035, 95% CI 1.004-1.068), protective stoma (OR 2.656, 95% CI 1.233-5.724) and T3 - 4 stage (OR 2.449, 95% CI 1.137-5.273). Most patients complained defecation disorder (87.3%) to doctors and 84.5% got suggestions or treatments for it. However, only 36.8% patients thought the treatments worked for them. CONCLUSIONS: LARS frequently occurs after laparoscopic LAR, while the therapeutic effect is not satisfying. Elder, advanced T-stage and protective stoma were risk factors for postoperative major LARS.

Two previously undescribed phthalides from Talaromyces amestolkiae, a symbiotic fungus of Syngnathus acus.

Amestolkins A (1) and B (2), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3H)-one were isolated from Talaromyces amestolkiae. Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 µM.

Isolation, Purification, and Application of Protoplasts and Transient Expression Systems in Plants.

Protoplasts, derived from plant cells, exhibit remarkable totipotency and hold significant value across a wide spectrum of biological and biotechnological applications. These versatile applications encompass protein subcellular localization and interaction analysis, gene expression regulation, functional characterization, gene editing techniques, and single-cell sequencing. Protoplasts' usability stems from their inherent accessibility and their ability to efficiently incorporate exogenous genes. In this review, we provide a comprehensive overview, including details on isolation procedures and influencing factors, purification and viability assessment methodologies, and the utilization of the protoplast transient expression system. The aim is to provide a comprehensive overview of current applications and offer valuable insights into protoplast isolation and the establishment of transient expression systems in a diverse range of plant species, thereby serving as a valuable resource for the plant science community.

Lumbar facet joint osteoarthritis as the underlying reason for persistent low back pain after minimally invasive discectomy.

INTRODUCTION: A post-hoc subgroup analysis of prospective collected data in a randomized controlled trial (RCT) of minimally invasive discectomy was conducted, to find out the possible underlying reasons for patients with persistent low back pain (LBP) following surgery. MATERIALS AND METHODS: Patients who were diagnosed with lumbar disc herniation (LDH) and underwent either percutaneous transforaminal endoscopic discectomy or microendoscopic discectomy in our RCT were analyzed. Patients with persistent LBP in 2-year follow-up were compared with the non-LBP patients to determine the underlying reasons. Then, the demographic characteristics, clinical outcomes and radiological parameters of patients with preoperative lumbar facet joint osteoarthritis (LFJOA) were assessed and compared with the non-LFJOA subgroup. RESULTS: 18 patients (8.1%) were reported to have persistent LBP in 2-year follow-up. Significantly higher proportion of preoperative LFJOA were found in the persistent LBP subgroup and was considered to be a risk factor using multivariate analysis. The prevalence of LFJOA is strongly associated with older age, female, high BMI and heavy labor in the LDH population. All of the clinical outcomes including ODI, SF36-PF, SF36-BP, EQ-5D, VAS-back and VAS-leg were worse in LFJOA subgroup in 2-year follow-up. LFJOA subgroup was associated with more adjacent segment degeneration and more lateral recess stenosis. CONCLUSIONS: LFJOA is a possible underlying reason for patients with persistent LBP after minimally invasive discectomy. Surgeons should carefully review the preoperative radiological images to find out whether there is LFJOA in the LDH segment, and kindly diminish the expectation of back pain relief for those patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov at November 14, 2013, registration number NCT01997086. ( https://clinicaltrials.gov/ct2/show/NCT01997086 ).

Work immersion and perceived stress among clinical nurses: a latent profile analysis and moderated mediation analysis.

BACKGROUND: Exploration of the relationship between individual work immersion and perceived stress is critical for clinical nurses' effective psychological interventions and human resource management, as well as to alleviate nursing staff shortages. In order to further dissect the influencing factors of perceived stress among nursing staff, our study introduces the concepts of perfectionism and social connectedness to analyze the specific pathways that influence perceived stress in terms of an individual's intrinsic and external personality traits. This study provides relevant recommendations for the development of stress management measures for nursing staff. METHODS: This was a cross-sectional survey. 993 registered clinical nurses were included from four hospitals in Guangzhou through a convenience sampling method. Clinical nurses' work immersion, perceived stress, perfectionism, and social connectedness were investigated using questionnaires based on latent profile analysis. The relationships between variables were analyzed using t-tests, analysis of variance, Pearson's correlation analysis, latent profile analysis, and moderated mediation analysis. RESULTS: The results showed that (1) general influences on nurses' perceived stress included only child, labor relationship, labor allowance, and family support; (2) nurses' work immersion contained four subgroups: lowest (12.6%), medium-low (39.8%), medium-high (39.9%), and highest (7.7%); (3) positive and negative perfectionism played a mediating role between the association of work immersion and perceived stress; (4) social connectedness played a moderating role in the mediation model of perceived stress. CONCLUSIONS: Work immersion, perfectionism, and social connectedness have an important impact on clinical nurses' perceived stress. Nursing managers or leaders should pay attention to the differences of individual work immersion status, adopt reasonable stress management strategies, accurately identify positive perfectionist groups and strengthen the relationship between groups, so as to ensure the quality of nursing care, and reduce nursing turnover and alleviate the problem of staff shortage.

Summary of best evidence for prevention and control of pressure ulcer on support surfaces.

The aim of this study was to summarise the best evidence for the prevention and control of pressure ulcer at the support surface based on the site and stage of the pressure ulcer in order to reduce the incidence of pressure ulcer and improve the quality of care. In accordance with the top-down principle of the 6 S model of evidence-based resources, evidence from domestic and international databases and websites on the prevention and control of pressure ulcer on support surfaces, including randomised controlled trials, systematic reviews, evidence-based guidelines, and evidence summaries, was systematically searched for the period from January 2000 to July 2022. Evidence grading based on the Joanna Briggs Institute Evidence-Based Health Care Centre Evidence Pre-grading System (2014 version), Australia. The outcomes mainly embraced 12 papers, including three randomised controlled trials, three systematic reviews, three evidence-based guidelines, and three evidence summaries. The best evidence summarised included a total of 19 recommendations in three areas: type of support surface selection assessment, use of support surfaces, and team management and quality control.

The AP2/ERF transcription factor ORA59 regulates ethylene-induced phytoalexin synthesis through modulation of an acyltransferase gene expression.

The gaseous ethylene (ET) and the oxylipin-derived jasmonic acid (JA) in plants jointly regulate an arsenal of pathogen responsive genes involved in defending against necrotrophic pathogens. The APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factor ORA59 is a major positive regulator of the ET/JA-mediated defense pathway in Arabidopsis thaliana. The Arabidopsis agmatine coumaroyltransferase (AtACT) catalyzes the formation of hydroxycinnamic acid amides (HCAAs) which are effective toxic antimicrobial substances known as phytoalexins and play an important role in plant defense response. However, induction and regulation of AtACT gene expression and HCAAs synthesis in plants remain less understood. Through gene coexpression network analysis, we identified a list of GCC-box cis-element containing genes that were coexpressed with ORA59 under diverse biotic stress conditions and might be potential downstream targets of this AP2/ERF-domain transcription factor. Particularly, ORA59 directly binds to AtACT gene promoter via the GCC-boxes and activates AtACT gene expression. The ET precursor 1-aminocyclopropane-1-carboxylic acid (ACC)-treatment significantly induces AtACT gene expression. Both ORA59 and members of the class II TGA transcription factors are indispensable for ACC-induced AtACT expression. Interestingly, the expression of AtACT is also subject to the signaling crosstalk of the salicylic acid- and ET/JA-mediated defense response pathways. In addition, we found that genes of the phenylpropanoid metabolism pathway were specifically induced by Botrytis cinerea. Taking together, these evidence suggest that the ET/JA signaling pathway activate the expression of AtACT to increase antimicrobial HCAAs production through the transcription factor ORA59 in response to the infection of necrotrophic plant pathogens.

The α-tubulin of Laodelphax striatellus mediates the passage of rice stripe virus (RSV) and enhances horizontal transmission.

Rice stripe virus (RSV, genus Tenuivirus, family Phenuiviridae) is the causal agent of rice stripe disease transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a persistent propagative manner. The midgut and salivary glands of SBPH are the first and last barriers to the viral circulation and transmission processes, respectively; however, the precise mechanisms used by RSV to cross these organs and transmit to rice plants have not been fully elucidated. We obtained the full-length cDNA sequence of L. striatellus α-tubulin 2 (LsTUB) and found that RSV infection increased the level of LsTUB in vivo. Furthermore, LsTUB was shown to co-localize with RSV nonstructural protein 3 (NS3) in vivo and bound NS3 at positions 74-76 and 80-82 in vitro. Transient gene silencing of LsTUB expression caused a significant reduction in detectable RSV loads and viral NS3 expression levels, but had no effect on NS3 silencing suppressor activity and viral replication in insect cells. However, suppression of LsTUB attenuated viral spread in the bodies of SBPHs and decreased RSV transmission rates to rice plants. Electrical penetration graphs (EPG) showed that LsTUB knockdown by RNAi did not impact SBPH feeding; therefore, the reduction in RSV transmission rates was likely caused by a decrease in viral loads inside the planthopper. These findings suggest that LsTUB mediates the passage of RSV through midgut and salivary glands and leads to successful horizontal transmission.

Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis.

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K (1-11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1-11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of the NF-κB and MAPK signaling pathways.

Three previously undescribed polyketides [proliferatin A-C (1-3)] with anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 attenuated the production of inflammatory signal messengers including nitric oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß), as well as the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 involved in the nuclear factor kappa-B (NF-κB) and mitogen activated protein kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels revealed that 1-3 can inhibit the phosphorylation of IκB kinase (IKK), the degradation of NF-κB Inhibitor-α (IκBα), the phosphorylation of nuclear factor-κB (NF-κB) and can reduce NF-κB transportation to the nucleus. Interestingly, 1-3 decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may lead to inhibition of NF-κB and MAPK signaling pathways, which was confirmed in vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute potential therapeutic candidates for the treatment of inflammation-associated diseases.

Association between the second-stage duration of labor and perinatal outcomes in women with a prior cesarean delivery.

BACKGROUND: The cesarean delivery (CD) rate has been increasing globally. Trial of labor after cesarean delivery (TOLAC) has been used as a key method for the reduction of the CD rate. Little is known, however, about the association between the second-stage duration of TOLAC and adverse maternal and neonatal outcomes. This study evaluated the association between perinatal outcomes and the duration of second-stage labor in women undergoing TOLAC. METHODS: A 10-year retrospective cohort study was performed at the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2010 and January 2020. Women undergoing TOLAC who reached the second stage of labor were included in this study. Duration of the second stage of labor was examined as a categorical variable (group I: <0.5 h, group II: 0.5-2 h and group III: ≥2 h) and as a continuous variable to evaluate the association with adverse perinatal outcomes by using multivariable regression models and a Cox proportional hazards regression model adjusting for potential confounders. RESULTS: Of the 1,174 women who met the inclusion criteria, the median (interquartile range) length of the second stage was 0.5 h (0.3-0.9 h). Among them, 1,143 (97.4%) delivered vaginally and 31 underwent an unplanned CD. As the second-stage duration increased, operative vaginal delivery (OVD), CD, and postpartum hemorrhage (PPH) rates increased. Women in group III had higher risks of OVD (aOR = 11.34; 95% CI [5.06-25.41]), CD (aOR = 4.22; 95% CI [1.32-13.43]), and PPH (aOR = 2.43; 95% CI [1.31-4.50]) compared with group I. Correspondingly, blood loss and the oxytocin used to treat PPH increased significantly, while the postpartum hemoglobin reduced significantly in group III compared with group I. The incidence of uterine rupture, uterine atony, cervical laceration, red blood cell transfusion, and intensive care unit admission were similar in all three groups. Neonatal outcomes were not affected by the second-stage duration. CONCLUSIONS: Women undergoing TOLAC with second-stage duration of ≥2 h have higher odds of OVD, unplanned intrapartum CD, and PPH.