Dectin-1, a key innate immune receptor, plays a critical role in cellular responses and is implicated in chronic inflammation and metabolic syndromes. This study addresses a pivotal gap in elucidating the regulatory mechanism governing Dectin-1 expressionin obesity and diabetes, hypothesizing that hyperglycemia and TNF-α synergistically upregulate Dectin-1 in adipose tissue (AT), thereby exacerbating inflammatory responses and contributing to metabolic dysfunction.

This study aimed to explore the effect of LIM domain and actin binding 1 (LIMA1) on bladder cancer (BCa) cells and to investigate its underlying molecular mechanisms.

Integration of immune checkpoint inhibitors (ICIs) with non-immune therapies relies on identifying combinatorial biomarkers, which are essential for patient stratification and personalized treatment.

Sympathetic overactivity is closely associated with vascular remodeling. Sympathetic fibers dominantly innervate the adventitia of arteries rather than tunica media. Vascular adventitial fibroblasts (VAFs) play crucial roles in vascular remodeling. However, the link between sympathetic overactivity and VAF proliferation and migration is unknown.

Soil salinization poses a significant challenge for rice farming, affecting approximately 20% of irrigated land worldwide. It leads to osmotic stress, ionic toxicity, and oxidative damage, severely hindering growth and yield. This study investigates the potential of lignin-containing cellulose nanofiber (LCNF)-selenium nanoparticle (SeNPs) hybrids to enhance salt tolerance in rice, focusing on two rice genotypes with contrasting responses to salt stress. LCNF-SeNP hybrids were synthesized using a microwave-assisted green synthesis method and characterized through FTIR, X-ray diffraction, SEM, TEM, and TGA. The effects of LCNF/SeNPs on seed germination, physiological responses, and gene expression were evaluated under varying levels of NaCl-induced salt stress. Results indicated that LCNF/SeNPs significantly enhanced the salt tolerance of the salt-sensitive genotype IR29, as evidenced by increased germination rates, reduced salt injury scores, and higher chlorophyll content. For the salt-tolerant genotype TCCP, LCNF/SeNPs improved shoot lengths and maintained elevated chlorophyll levels under salt stress. Furthermore, LCNF/SeNPs improved ion homeostasis in both genotypes by reducing the Na+/K+ ratio, which is crucial for maintaining cellular function under salt stress. Gene expression analysis revealed upregulation of key salt stress-responsive genes, suggesting enhanced stress tolerance due to the application of LCNF/SeNPs in both genotypes. This study underscores the potential of LCNF/SeNPs as a sustainable strategy for improving crop performance in saline environments.

Cervical cancer (CC) remains a leading cause of cancer-related deaths worldwide and still requires effective interventions to improve patient outcomes. Angiopoietin-like 4 (ANGPTL4) is a multifaceted glycoprotein that plays crucial roles in lipid metabolism and tumor progression. ANGPTL4 exhibits both tumor-promoting and tumor-suppressing effects and has been proposed as a promising target for cancer therapy. This study investigated the role and potential of ANGPTL4 in enhancing therapeutic efficacy in CC using cell line models in vitro. Our analysis revealed a decreased expression of ANGPTL4 in CC samples from the GSE dataset and in the CC cell lines examined. Functional assays demonstrated that ANGPTL4 overexpression suppressed CC cell proliferation, migration, and invasion. Notably, overexpression of ANGPTL4 resulted in decreased cell viability and increased levels of apoptosis, cleaved caspase-3, and cleaved PARP under cisplatin treatment. Furthermore, these analyses were also conducted in ANGPTL4-knockdown cells, and results supporting the tumor-suppressive roles of ANGPTL4 were observed. Taken together, our study elucidates the critical role of ANGPTL4 in modulating progression and chemosensitivity of CC cells, suggesting ANGPTL4 as a potential target for CC treatment.

SABATH gene family in plants participates in metabolic processes such as methylation of various hormones and plays an essential role in plant response to abiotic stress. In this study, we identified and sequenced 28 SABATH genes in soybean and divided them into three groups. Genome mapping annotation suggested that tandem repeat was the cause of SABATH gene amplification in soybean. Phylogenetic and homology analyses show that the three groups may have originated from different ancestors. Transcriptome analysis was performed in six soybean tissues using data from public transcriptome. In addition, transcriptome and gene expression analyses revealed their expression patterns under different soybean varieties and various abiotic stresses. These results reveal the differential expression of GmSABATHs gene under these stresses, indicating their potential role in the mechanism of soybean adapting to environmental challenges. These results provide reference information for the evolutionary study of the SABATH family and the potential role of GmSABATHs in soybean resistance to abiotic stress.

Glioblastoma remains an incurable tumour (median survival: ~ 15 months) and little clinical progress has been made over the past decades. Therefore, identification of novel biomarkers and therapeutic targets is imperative. Targeting the somatostatin/cortistatin-system is considered a successful avenue for treating different tumour pathologies. Thus, we comprehensively characterized (clinically and molecularly) the expression of the somatostatin/cortistatin-system components [ligands and receptors (SSTRs)] using five cohorts of patients and tested the in-vitro therapeutic response of different SSTR-agonists and somatostatin analogs (SSAs) in primary patient-derived glioblastoma cells. A clear downregulation of the whole somatostatin/cortistatin-system (except for SSTR5) in glioblastoma vs. non-tumour brain samples was demonstrated, with high discriminatory capacity. Moreover, poor overall-survival and critical aggressiveness-parameters (i.e., recurrence, IDH1-wildtype and G-CIMP status, classical and mesenchymal GBM-subtypes, EGFR-amplification) were robustly associated with SSTR1/SSTR2 downregulation. Notably, octreotide, pasireotide, and SSTR1/2/5-agonists treatments significantly reduced cell-proliferation in primary patient-derived GBM-cells. Molecularly, antitumour effects of octreotide/pasireotide were exerted through key signalling-factors related to glioblastoma-aggressiveness (i.e., CDKN1A-B/JAK-STAT/NF-κB/TGF-β-pathways). Altogether, this study demonstrated that somatostatin/cortistatin-system is drastically altered in GBM representing a useful prognostic tool, and that SSTR-modulators might represent a potential therapeutic strategy to treat specific subsets of patients with GBM.

Exogenous hormones can regulate bud dormancy release, particularly in cases where inadequate winter chill accumulation due to global warming affects perennial plants. Gibberellin (GA) is recognized as a critical signal for dormancy release in woody perennials. This study explores the influence of GA and its signaling components on the dormancy release in sweet cherry. The external application of GA4 + 7 significantly promoted the bud break rate and dormancy release. Notably, there was a substantial accumulation of GA3, GA4, and GA7 in the buds, accompanied by a reduced concentration of abscisic acid (ABA) following GA treatment. RNA-Seq identified 8,610 differentially expressed transcripts in GA-treated buds compared to the Mock group. Transcriptome sequencing revealed differential expressions of PavGID1s, the GA receptor GID1, in sweet cherry flower buds after GA treatment. These findings were further verified across different seasons in sweet cherry. In both PavGID1b and PavGID1c, the open reading frame (ORF) is 1,032 bases long and encodes 344 amino acids. Overexpression of PavGID1b and PavGID1c resulted in early flowering and higher plants in Arabidopsis. However, these genes have opposing roles in seed germination in Arabidopsis. Furthermore, PavWRKY31 may regulate the stabilization and release of dormancy by modulating the transcriptional level of PavGID1c. PavGA20ox-2 and PavGID2 may also influence sweet cherry dormancy release by interacting with GID1s and affecting DELLA protein stability. These results provide a theoretical basis for understanding the regulatory effect of gibberellin on the bud dormancy of plants.

Brain metastasis (BM) is a serious complication of increasing incidence in patients with advanced breast cancer, which is characterized by swift deterioration in quality of life with few efficient therapy strategies. There is an urgent clinical requirement to devise potent therapeutic strategies for the prevention and management of brain metastases. Here, we report isoliquiritigenin (ISL), a key bioactive substance extracted from licorice root, which effectively inhibited triple-negative breast cancer (TNBC) brain metastasis (BM) by downregulation of circNAV3. CircRNAs expression analyses and functional studies, coupled with clinical significance investigations identified circNAV3 as a key molecule promoting TNBC BM. Functionally, circNAV3 could promote proliferation, migration, invasion, angiogenesis and capacity to penetrate the blood-brain barrier of TNBC cells. Mechanistically, circNAV3 could competitively bind with miR-4262, hence intercepting the suppressive effect of miR-4262 on ST6GALNAC5. Subsequently, this interplay enhanced EGFR sialylation and activation, initiating the PI3K/Akt pathway and ultimately fostering the development of TNBC brain metastases. In conclusion, our research establishes that ISL impede the initiation and advancement of TNBC brain metastasis by modulation of circNAV3/miR-4262/ST6GALNAC5/EGFR axis, laying a theoretical groundwork for the therapeutic use of ISL in this scenario.

This study investigated the regulatory mechanisms of cuproptosis-related genes (CRGs) in spinal cord injury (SCI) and explored the therapeutic potential of neurotrophin-3 (NT3)-loaded chitosan in promoting functional recovery.

This study investigates the molecular mechanisms by which selenide-modified hyaluronic acid hydrogel (Se-HA gel) promotes scleral remodeling during the recovery phase of form-deprivation myopia (FDM). The Se-HA gel was synthesized and characterized, exhibiting an average hydrodynamic diameter of 191.72 nm, a polydispersity index (PDI) of 0.19, and a zeta potential of -7.96 mV, indicating a monodisperse state in PBS. Both in vitro experiments and the FDM mouse model confirmed its therapeutic efficacy. At a concentration of 250 μg/mL, Se-HA gel significantly promoted fibroblast proliferation, inhibited apoptosis, and prevented transdifferentiation. A 200 mg/kg subtenon injection improved key ocular biometric parameters in FDM mice. Single-cell and transcriptomic sequencing analyses revealed that Se-HA gel facilitated scleral remodeling by downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α) expression and regulating inflammation-related gene expression. Notably, HIF-1α overexpression reversed the beneficial effects of Se-HA gel, reinforcing its pivotal role in mediating these therapeutic outcomes. This study introduces a novel biomaterial-based strategy and identifies new molecular targets for myopia treatment. Furthermore, it addresses a critical gap in understanding how Se-HA gel promotes scleral remodeling through HIF-1α-mediated signaling pathways, with important scientific and translational potential in the field of myopia management.

Trehalose promotes polysaccharide synthesis in edible mushrooms, yet its effect on the antioxidant activity and structure of Lentinula edodes mycelium polysaccharides is still unknown. We investigated the effect of trehalose on the antioxidant activity of L. edodes polysaccharides and expression of genes related to L. edodes polysaccharide metabolism. Five g/L trehalose increased the biomass and polysaccharide content of L. edodes mycelium by over 50 % compared to the control. Trehalose increased the superoxide anion radical scavenging rate of L. edodes polysaccharides up to 80.9 %. Compared to the control, the molecular weight of polysaccharides was lower, and their glucuronic acid content was higher in the trehalose treatment. RNA-seq analysis revealed 1045 differentially expressed genes in the trehalose treatment compared to the control. Genes related to glycolysis/gluconeogenesis pathway, starch and sucrose metabolic pathway, and the pentose and glucuronate interconversions pathway were differentially expressed, possibly accounting for the increased polysaccharide synthesis. In summary, exogenous trehalose has potential to increase the biosynthesis and biological activity of L. edodes polysaccharides.

Buprofezin (BPFN), a pesticide used to control crop pests and diseases, causes potential harm to aquatic animals and the environment by leaching into aquatic ecosystems. However, there are limited studies on the toxicity of BPFN to aquatic organisms. Using zebrafish embryos, we integrated flow cytometry, qRT-PCR, RNA-seq and other techniques to assess BPFN's developmental toxicity. Additionally, IBRv2 index and Mantel test correlation were applied to comprehensively evaluate the developmental toxicity of BPFN. The results showed that BPFN induced cytotoxicity, including increased reactive oxygen species levels, mitochondrial membrane potential depolarization, and apoptosis, which further resulted in developmental toxicity of zebrafish embryos such as delayed hatching, reduced survival rate, and severe morphological deformities. BPFN also affected the number and distribution of immune cells, resulting in immunotoxicity, and disrupted the endogenous antioxidant system by altering the activities of catalase, superoxide dismutase, and glutathione S-transferase and contents of malondialdehyde and glutathione. Gene expression analysis revealed that BPFN induced changes in the expression of genes associated with oxidative stress, apoptosis, inflammation, swim bladder development, and eye development. In the comprehensive evaluation, BPFN showed the strongest developmental toxic effect in the 20 μM BPFN-treated group at 48 hpf, and there was the significant correlation between embryonic development, oxidative stress, apoptosis, and inflammatory response. The rescue experiment confirmed that astaxanthin can alleviate the embryonic developmental toxicity caused by BPFN to a certain extent. In summary, BPFN induced early developmental toxicity in zebrafish embryos, which might be associated with mitochondria-mediated apoptosis pathway induced by oxidative stress.

Cancer-causing aberrations recurrently target the chromatic-regulatory factors, leading to epigenetic dysregulation. Almost all patients with synovial sarcoma (SS) carry a characteristic gene fusion, SS18::SSX, which produces a disease-specific oncoprotein that is incorporated into the switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complexes and profoundly alters their functionalities. Targeting epigenetic dependency in cancers holds promise for improving current treatment. Leveraging on cancer cell dependency dataset, pharmacological tools, and genomic profiling, we find WDR5, a factor critical for depositing histone H3 lysine 4 (H3K4) methylation, to be an unexplored vulnerability in SS. Mechanistically, WDR5 and SS18::SSX interact and colocalize at oncogenes where WDR5 promotes H3K4 methylation and the chromatin association of SS18::SSX-containing chromatin-remodeling complexes. WDR5 degradation by proteolysis-targeting chimera (PROTAC) not only suppresses the SS18::SSX-related oncogenic programs but additionally causes the ribosomal protein deregulations leading to p53 activation. WDR5-targeted PROTAC suppresses SS growth in vitro and in vivo, providing a promising strategy for the SS treatment.

Preconditioning with volatile anesthetics, such as isoflurane and sevoflurane, can protect the myocardium against ischemia/reperfusion injury (IRI). Syntaxin1A (Stx1A) is cardioprotective and regulated by volatile anesthetics. However, is the mechanism by which sevoflurane preconditioning (SPC) induces Stx1A to exert myocardial protection remains unclear. The study investigates whether SPC induces upregulation of Stx1A through the thymoma viral proto-oncogene (AKT)/Glycogen synthase kinase 3 β (GSK3β) signaling pathway. Myocardial IRI model in mice was established by surgically ligating the left anterior descending coronary followed by loosening of the occlusion. Regulation of signaling pathway by intraperitoneal administration of the phosphatidylinositol 3-kinase (PI3K) inhibitor, Ly294002 (30 mg/kg), and GSK3β inhibitor, TWS119 (30 mg/kg). The triphenyl tetrazolium chloride (TTC) staining method was used to measure the myocardial infarction area. Serum creatine kinase MB (CK-MB) and lactic dehydrogenase (LDH) concentration were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to examine AKT/GSK3β pathway activity, as well as expressions of Stx1A, small ubiquitin-like modifier 1 (SUMO1), growth hormone-releasing hormone (GHRH), or calcitonin gene-related peptide (CGRP), and brain natriuretic peptide (BNP). Both IRI and SPC induced upregulation of Stx1A in mice. However, the upregulation was abolished by treatment with Ly294002, while TWS119 further increased its expression (p < 0.05). Myocardial infarct area, serum CK-MB, and LDH were elevated in the IRI group but were inhibited by SPC-induced (p < 0.05); however, this inhibition by SPC was eliminated by Ly294002 (p < 0.05). TWS119 causes the opposite effect (p < 0.05). These findings demonstrated that SPC activated the AKT/GSK3β signaling pathway to upregulate Stx1A expression and provide protection to the myocardium.

Cisplatin-based chemotherapy resistance is a common issue for cancer clinical efficacy. Metformin is being studied for its possible anticancer effect. The present study aimed to investigate whether metformin affects the chemosensitivity of gastric cancer to cisplatin and reveal the molecular mechanism. In this study, the effects of combination therapy with metformin and cisplatin on cell viability, cell apoptosis, malondialdehyde, superoxide dismutase, reactive oxygen species level, glucose uptake, lactate production, protein level, and xenograft tumor formation were analyzed in gastric cancer cells. Immunohistochemical staining was performed to detect Ki67 expression in matched tumor samples. The results showed that NCI-N87 and SNU-16 cells were most resistant and sensitive to cisplatin, respectively. Metformin treatment increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Furthermore, overexpression of nuclear factor erythroid 2-related factor 2 (Nrf2) reversed the effects of metformin in the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Metformin activated p53 and AMPK pathways in cisplatin-induced NCI-N87 cells, which were reversed by upregulating Nrf2. BAY-3827 (AMPK inhibitor) or p-nitro-Pifithrin-α (p53 inhibitor) treatments also reversed the effects of metformin increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. These results suggest that metformin significantly increases chemosensitivity of gastric cancer to cisplatin by inhibiting Nrf2 expression and metabolic reprogramming and activating oxidative stress and the pathway of p53 and AMPK.

BRAF activating mutations occur in approximately 10% of metastatic colorectal cancer (CRCs) and are associated with worse prognosis in part due to an inferior response to standard chemotherapy. Standard of care for patients with refractory metastatic BRAFV600E CRC is treatment with BRAF and EGFR inhibitors and recent FDA approval was given to use these inhibitors in combination with chemotherapy for patients with treatment naïve metastatic BRAFV600E CRC. Lineage plasticity to neuroendocrine cancer is an emerging mechanism of targeted therapy resistance in several cancer types. Enteroendocrine cells (EECs), the neuroendocrine cell of the intestine, are uniquely present in BRAF mutant CRC as compared to BRAF wildtype CRC.

Ethylnitrosourea (ENU) is a potent mutagen that induces gliomas in experimental models. Understanding the molecular mechanisms underlying ENU-induced gliomagenesis can provide insights into glioma pathogenesis and potential therapeutic targets.

Jaboticaba peel extract (JPE) has demonstrated chemopreventive effects on the development of prostatic lesions in experimental systems, including the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP). However, its influence over castration-resistant prostate cancer (CRPC) and the androgenic dependence of its actions in this model remain unknown. Therefore, we aimed to evaluate JPE effects on TRAMP mice tumorigenesis under different androgen reliance settings. Mice were submitted to short- or long-term JPE administration, associated or not with androgen deprivation therapy (ADT) by surgical and chemical castration. Prostate, periaortic lymph nodes and lung samples were harvested to determine the incidence of primary and metastatic lesions. Protein expression of proliferative, hormonal and angiogenesis markers was evaluated. Results showed that JPE administration in a hormone naive setting restricted poorly-differentiated tumors to the ventral prostate. Additionally, treatment extension improved the proportion of tumor-free individuals and the timeline for the development of palpable tumors. These results were paralleled by significant increment on VE-Cadherin expression. Furthermore, JPE-treated groups demonstrated significantly lower incidences of lymphatic metastasis. Conversely, JPE plus ADT resulted in poor outcomes, especially upon the extension of this association. In this setting, decreased survival, lower tumor-free mice proportion and increment of proliferative epithelial areas were registered. Altogether, such effects were attributed to a time-dependent up- (VEGF, latent TGF-β2 and TGFβ-RI) or downregulation (VEGFR-2 and VE-Cadherin) of angiogenic mediators expression. Therefore, we conclude that long-term ADT in TRAMP mice drives the prostatic microenvironment dynamics towards a proangiogenic state, which negatively impacts or even abolishes the otherwise beneficial effects of JPE.