Triterpenes from Ganoderma lucidum inhibit hepatocellular carcinoma by regulating enhancer-associated lncRNA in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. AIM OF THE STUDY: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. MATERIALS AND METHODS: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. RESULTS: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. CONCLUSIONS: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.

GATA-4 overexpressing BMSC-derived exosomes suppress H/R-induced cardiomyocyte ferroptosis.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes overexpressing GATA-4 (Exosoe-GATA-4) can protect cardiac function. Mitochondrial permeability transition pore (mPTP) has a crucial role in ferroptosis. This study aimed to assess the mechanism of Exosoe-GATA-4 in myocardial ischemia/reperfusion (I/R) injury. Exos were successfully excreted, and 185 differential expression miRNAs were obtained using bioinformatics. The Exosoe-GATA-4 effectively suppressed hypoxia/reoxygenation (H/R)-induced cardiomyocytes' ferroptosis, while the effects were reversed by miR-330-3p inhibitor. miR-330-3p targeted negative regulated BAP1. The effects of miR-330-3p inhibitor were reversed by knock-down BAP1. Also, BAP1 reversed the effects of Exosoe-GATA-4 on H/R-induced cardiomyocytes' ferroptosis by downregulating SLC7A11. Mechanistically, BAP1 interacted with IP3R and increased cardiomyocytes' Ca2+ level, causing mPTP opening and mitochondrial dysfunction, promoting H/R-induced cardiomyocytes' ferroptosis. Moreover, hydrogen sulfide (H2S) content was increased and regulated the keap1/Nrf2 signaling pathway by Exosoe-GATA-4 treated. Exosoe-GATA-4 effectively suppresses H/R-induced cardiomyocytes' ferroptosis by upregulating miR-330-3p, which regulates the BAP1/SLC7A11/IP3R axis and inhibits mPTP opening.

Impact of Demographics on Early-Stage vs. Stage IV Diagnosis in Amelanotic Melanoma: An Analysis of the National Cancer Database.

Introduction Amelanotic melanoma (AM) is a rare form of melanoma that lacks pigment. Although curable when diagnosed early, it is often missed or mistaken for other benign conditions. There has not been a study investigating the impact of demographic features on the diagnosis of stage 0-I (early-stage) versus stage IV AM. Objective This study addresses a gap in knowledge regarding demographic factors that influence the odds of early-stage vs. stage IV diagnosis of AM. Methods This study identified 684 patients from the National Cancer Database who were diagnosed with early-stage AM or stage IV AM from 2004 to 2020 and compared them based on age, sex, race, insurance, income, education, insurance status, rurality, facility type, geographic region, and Charleson-Deyo score. Socioeconomic and demographic features of patients with early-stage and stage IV were compared using the chi-squared test, the independent t-test, and multivariate logistic regression. Statistical significance was set at α = 0.05. Results Most cases analyzed were White (98.5%), male (57.7%), and lived in a metropolitan setting (86.7%). Males made up most of the early-stage and stage IV groups (55.0% vs. 45% and 66.5% vs. 33.5%, respectively, p < 0.05). Younger age is associated with decreased odds of stage IV disease (OR = 0.973, 95% CI = 0.952-0.993, p < 0.05). In addition, the female sex is associated with decreased odds of stage IV disease (OR = 0.584, 95% CI = 0.381-0.897, p < 0.05). Conclusions Age and sex are two variables that influence the odds of stage IV diagnosis in patients with AM, which is strongly associated with worse survival outcomes.

Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.

Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS. Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424). Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2=94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49). Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice.

Effects of seaweed fertilizer application on crops' yield and quality in field conditions in China-A meta-analysis.

Seaweed fertilizer, formulated primarily with seaweed extract as its main ingredient, has been extensively studied and found to significantly improve nutrient use efficiency, increase crop yield and quality, and enhance soil properties under field conditions. This growing body of evidence shows that seaweed fertilizer is a suitable option for sustainable agriculture in China. However, a comprehensive and quantitative analysis of the overall effects of seaweed fertilizer application in China is lacking. To address this gap, we conducted a meta-analysis of relevant studies on the effects of seaweed fertilizers under field conditions in China with MetaWin and SPSS software. Our analysis examined the effects of seaweed fertilizers on crop yield, quality, and growth under different preparation methods, application techniques, and regions. Our results showed that the application of seaweed fertilizer led to a significant average increase in crop yield of 15.17% compared with the control treatments. Root & tuber crops exhibited the most pronounced response, with a yield boost of 21.19%. Moreover, seaweed fertilizer application significantly improved crop quality, with elevations in the sugar-acid ratio (38.32%) vitamin C (18.07%), starch (19.65%), and protein (11.45%). In addition, plant growth parameters such as height, stem thickness, root weight, and leaf area showed significant enhancement with seaweed fertilizer use. The yield-increasing effect of seaweed fertilizers varied depending on their preparation and use method, climate, and soil of application location. Our study provides fundamental reference data for the efficient and scientific application of seaweed fertilizers in agricultural practices.

Copper-Catalyzed Vicinal Thiocyanosulfonylation of Alkenes and Alkynes.

Efficient copper-catalyzed radical thiocyanosulfonylation of alkenes and alkynes with potassium thiocyanate and sodium phenylsulfinate is described. The reactions provide general and convenient methods toward the synthesis of ß-thiocyanoalkyl sulfones and ß-thiocyanoalkenyl sulfones, respectively, in satisfactory yields. Based on conducted mechanistic experiments, a mechanism involving oxidative generation of sulfonyl radicals and subsequent addition to alkenes followed by Cu-assisted thiocyanation is proposed. Moreover, the practicability of the reaction is successfully demonstrated by its successful application on a gram scale.

Innovative insights into organic nitrogen degradation through protein family domains analysis in chicken and pig manure composting using metagenomic sequencing.

The nitrogen loss in composting is primarily driven by the transformation of organic nitrogen, yet the mechanisms underlying the degradation process remain incompletely understood. This study employed protein family domains (Pfams) analysis based on metagenomic sequencing to investigate the functional characteristics, key microorganisms, and environmental parameters influencing organic nitrogen degradation in chicken manure and pig manure composting. 154 Pfams associated with ammonification function were identified. Predominant Pfams: proteolytic peptidase, followed by chitin/cell wall degraders, least involved in nucleic acid degradation. Ammonifying microbial diversity was basically consistent among compost types, particularly in the thermophilic stage with the peak of abundance of dominant ammonifying microorganisms. Viruses played an important role in ammonification process, especially Uroviricota. 26 key ammonifying genera were identified by the microbial network. pH dominated the metabolic activity of ammonifying microorganisms in various manure compost types, primarily consisting of protein-degrading bacteria with stable community structures.

tRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner.

It has been demonstrated that tRNA-derived small RNAs (tsRNAs) perform essential functions in the pathophysiology of cancer. In this study, we focused on the possible mechanisms of tRF-33-P4R8YP9LON4VDP (tRF-33) underlying the development of gastric malignancy. In total, 454 tissue samples with different gastric mucosal lesions were collected. The tRF-33 expression level in different cohorts was determined, and its value for diagnostic efficiency and prognosis evaluation were assessed. Cell proliferation assays, Transwell assay, flow cytometry, and xenotransplantation model were used to evaluate its effect on gastric cancer cells. The molecular mechanism was verified by fluorescence in situ hybridization, dual luciferase assay, Western blot, and RNA binding protein immunoprecipitation. The results showed that the expression of tRF-33 exhibited a gradual modification from normal control samples to gastritis tissues, early and latent stage of gastric cancer tissues. Consequently, tRF-33 holds significant potential as a predictive and diagnostic biomarker for gastric malignancy. Over-expression of tRF-33 inhibited gastric cancer cell progression and metastatic viability, and induced cell apoptosis. Tumorigenicity in nude mice showed the suppressive characteristics of tRF-33. Mechanistic investigation revealed that tRF-33 exerted silencing on STAT3 mRNA via binding to AGO2. In conclusion, tRF-33 exhibited values in diagnosing gastric cancer and evaluating its prognosis, and suppressed tumor cell viability by inhibiting STAT3 signaling pathway. The schematic mechanisms underlying tRF-33 regulating gastric cancer occurrence. tRF-33 binds to AGO2 proteins and then negatively regulates STAT3 expression through targeting its 3'UTR. The downregulated expression of STAT3 results in the decrease of STAT3 and p-STAT3 and further blocks the transcription of the downstream genes and finally inhibits the gastric cancer occurrence. MMP-9, matrix metalloproteinase-9; Bcl-2, B-cell lymphoma-2; STAT3, signal transducer and activator of transcription 3; UTR, untranslated region.

Exploring the role of autophagy in psoriasis pathogenesis: Insights into sustained inflammation and dysfunctional keratinocyte differentiation.

Psoriasis is a common and prevalent chronic papulosquamous cutaneous disorder characterized by sustained inflammation, uncontrolled keratinocyte proliferation, dysfunctional differentiation, and angiogenesis. Autophagy, an intracellular catabolic process, can be induced in response to nutrient stress. It entails the degradation of cellular constituents through the lysosomal machinery, and its association with psoriasis has been well-documented. Nevertheless, there remains a notable dearth of research concerning the involvement of autophagy in the pathogenesis of psoriasis within human skin. This review provides a comprehensive overview of autophagy in psoriasis pathogenesis, focusing on its involvement in two key pathological manifestations: sustained inflammation and uncontrolled keratinocyte proliferation and differentiation. Additionally, it discusses potential avenues for disease management.

Visible-Light-Promoted [4π + 2σ] Annulation of Dienes and Alkylamines via Dual Inert C(sp3)-H Bond Activation.

Herein, visible-light-promoted [4π + 2σ] annulation of dienes and alkylamines was achieved via dual C(sp3)-H bond functionalization of alkylamines. The elusive enamine precursors are generated under mild conditions by photoredox catalysis, efficiently annulated by the diene, and simultaneously functionalized with two aliphatic C(sp3)-H bonds, resulting in the productive synthesis of new aromatic rings. The aromatic ring construction provides direct access to 2-hydroxybenzophenone derivatives in high yields (up to 90%). This [4π + 2σ] annulation reaction demonstrates mild reaction conditions, high reaction efficiency, and broad functional group tolerance, and this synthetic protocol has been made available for the late-stage transformation of natural products and commercial drugs.

Innovative Percutaneous 3-Stitch Suture Technique for Site Closure in Venoarterial Extracorporeal Membrane Oxygenation Decannulation Without Direct Artery Repair: A Case Series.

No previous studies have reported the use of a percutaneous suture technique performed by bedside intensivists for site closure during decannulation without direct artery repair in venoarterial extracorporeal membrane oxygenation (VA-ECMO) cases. Thus, the objective of this study was to evaluate the safety and effectiveness of this alternative approach. This retrospective study included 26 consecutive patients who underwent percutaneous VA-ECMO decannulation at Maoming People's Hospital. Bedside percutaneous suture technique performed by intensivists facilitated cannula site closure. Primary outcome was successful closure without additional interventions. Secondary outcomes included procedural time, surgical conversion rate, complications (bleeding, vascular/wound complications, neuropathy, lymphocele), procedure-related death. Follow-up ultrasound were conducted within 6 months after discharge. All patients achieved successful site hemostasis with a median procedural time of 28 minutes. Procedure-related complications included minor bleeding (7.7%), acute lower limb ischemia (15.4%), venous thrombus (11.5%), minor arterial stenosis (7.7%), wound infection (4.2%), delayed healing (15.4%), and wound secondary suturing (6.3%). No procedure-related deaths occurred. Follow-up vascular ultrasound revealed two cases (7.7%) of minor arterial stenosis. The perivascular suture technique may offer intensivists a safe and effective alternative method for access site closure without direct artery suture during ECMO decannulation.

Coalescence-Induced Self-Propelled Particle Transport with Asymmetry Arrangement.

We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching ∼2.1 mm, ∼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.

RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14.

Colorectal cancer (CRC) is a deadly and aggressive type of cancer that has a high fatality rate. The expression levels of replication factor C subunit 3 (RFC3) and kinesin family member 14 (KIF14) have been reported to be increased in CRC. The current study aimed to explore the effects of RFC3 on the malignant behaviors of CRC cells and its possible underlying mechanism involving KIF14. RFC3 and KIF14 expression levels in CRC tissues were analyzed using TNMplot database and Gene Expression Profiling Interactive Analysis database bioinformatics tools. RFC3 and KIF14 levels in CRC cells were examined using reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to assess cell proliferation. Cell apoptosis was determined using flow cytometric analysis. Wound healing and Transwell assays were adopted for the evaluation of cell migration and invasion. Tube formation assay in human umbilical vein endothelial cells was used to measure angiogenesis. Western blotting analysis was performed to determine the expression of apoptosis-, migration- and angiogenesis-associated proteins. Additionally, bioinformatics tools predicted the co-expression and interaction of RFC3 and KIF14, which was verified by a co-immunoprecipitation assay. RFC3 displayed elevated expression in CRC tissues and cells, and depletion of RFC3 halted the proliferation, migration, invasion and angiogenesis, while increasing the apoptosis of CRC cells; this was accompanied by changes in the expression levels of related proteins. In addition, RFC3 bound to KIF14 and interference with RFC3 reduced KIF14 expression. Moreover, KIF14 upregulation reversed the effects of RFC3 depletion on the aggressive cellular behaviors in CRC. In conclusion, RFC3 might interact with KIF14 to function as a contributor to the malignant development of CRC.

Evaluation of pathogen spread risk from excavated landfill.

Landfill is a huge pathogen reservoir and needs special attention. Herein, the distribution and spread risk of pathogen were assessed in excavated landfill scenario. The results show that landfill excavation will greatly increase the risk of environmental microbial contamination. The highest total concentration of culturable bacteria among landfill refuse, topsoil and plant leaves was found to be as high as 1010 CFU g-1. Total coliforms, Hemolytic bacteria, Staphylococcus aureus, Salmonella, Enterococci, and Fecal coliforms were detected in the landfill surrounding environment. Notably, pathogens were more likely to adhere to plant leaves, making it an important source of secondary pathogens. The culturable bacteria concentration in the air samples differed with the landfill zone with different operation status, and the highest culturable bacteria concentration was found in the excavated area of the landfill (3.3 × 104 CFU m-3), which was the main source of bioaerosol release. The distribution of bioaerosols in the downwind outside of the landfill showed a tendency of increasing and then decreasing, and the highest concentration of bioaerosols outside of the landfill (6.56 × 104 CFU m-3) was significantly higher than that in the excavated area of the landfill. The risk of respiratory inhalation was the main pathway leading to infection, whereas the HQin (population inhalation hazardous quotient) at 500 m downwind the excavation landfill was still higher than 1, indicating that the neighboring residents were exposed to airborne microbial pollutants. The results of the study provide evidence for bioaerosols control protective measures taken to reduce health risk from the excavated landfill.

Z-selective radical difunctionalization of aromatic alkynes: synthesis of multi-substituted triarylethenes.

An efficient method for the radical difunctionalization of aromatic alkynes has been developed, resulting in the synthesis of a range of valuable triarylethenes. This approach utilizes strategically designed aryldiazonium salts with tertiary alcohol substitution as bifunctional reagents, along with cost-effective cuprous chloride as a catalyst. The method demonstrates remarkable Z-selectivity and is capable of gram-scale preparation. Additionally, a novel spin-trapping reagent has been developed based on the synthesized product.

Organo-Photocatalytic Anti-Markovnikov Hydroamidation of Alkenes with Sulfonyl Azides: A Combined Experimental and Computational Study.

The construction of C(sp3)-N bonds via direct N-centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo-photocatalytic approach to achieve anti-Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition-metal-free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet-triplet energy transfer manner to achieve photosensitization by the organo-photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4-H bond, which triggers a straightforward H-atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p-toluenethiol could proceed to afford the desired anti-Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs.

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis.

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results' stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs' viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared with normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.

Accurate network pharmacology and novel ingredients formula of herbal targeting estrogen signaling for psoriasis intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: As a common chronic inflammatory skin disease, psoriasis is incompletely understood and brings a lot of distress to patients. The estrogen signaling pathway has been implicated in its pathogenesis, making it a potential therapeutic target. Si Cao Formula (SCF) has demonstrated promise in treating psoriasis clinically. However, its molecular mechanisms concerning psoriasis remain largely unexplored. AIM OF THE STUDY: To elucidate the underlying mechanisms of the action of SCF on psoriasis. MATERIALS AND METHODS: Active ingredients were identified by LC-MS/MS. After the treatment with SCF, the exploration of differentially expressed proteins (DEPs) were conducted using tandem mass tag (TMT)-based quantitative proteomics analysis. By GO/KEGG, WikiPathways and network pharmacology, core signaling pathway and protein targets were explored. Consequently, major signaling pathway and protein targets were validated by RT-qPCR, immunoblotting and immunofluorescence. Based on Lipinski's Rule of Five rules and molecular docking, 8 active compounds were identified that acted on the core targets. RESULTS: 41 compounds of SCF and 848 specific targets of these compounds were identified. There were 570 DEPs between IMQ (Imiquimod) and IMQ + SCF group, including 279 up-regulated and 304 down-regulated proteins. GO/KEGG, WikiPathways and network pharmacology revealed estrogen signaling pathway as the paramount pathways, through which SCF functioned on psoriasis. We further show novel ingredients formula of SCF contributes to estrogen signaling intervention, including liquiritin, parvisoflavone B, glycycoumarin, 8-prenylluteone, licochalcone A, licochalcone B, oxymatrine, and 13-Hydroxylupanine, where targeting MAP2K1, ILK, HDAC1 and PRKACA, respectively. Molecular docking proves that they have good binding properties. CONCLUSION: Our results provide an in-depth view of psoriasis pathogenesis and herbal intervention, which expands our understanding of the systemic pharmacology to reveal the multiple ingredients and multiple targets of SCF and focus on one pathway (estrogen signaling pathway) may be a novel therapeutic strategy for psoriasis treatment of herbal medicine.