Gas6-Axl signal promotes indoor VOCs exposure-induced pulmonary fibrosis via pulmonary microvascular endothelial cells-fibroblasts cross-talk.

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure.

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

Interior decorative volatile organic compounds exposure induces sleep disorders through aberrant branched chain amino acid transaminase 2 mediated glutamatergic signaling resulting from a neuroinflammatory cascade.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

The interactions of subcellular organelles in pulmonary fibrosis induced by carbon black nanoparticles: a comprehensive review.

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.

Impact of sex and age on the lateralisation of the tibial tubercle in normal paediatric and adolescent populations.

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.

ZMYND8 protects breast cancer stem cells against oxidative stress and ferroptosis through activation of NRF2.

Breast cancer stem cells (BCSCs) mitigate oxidative stress to maintain their viability and plasticity. However, the regulatory mechanism of oxidative stress in BCSCs remains unclear. We recently found that the histone reader ZMYND8 was upregulated in BCSCs. Here, we showed that ZMYND8 reduced ROS and iron to inhibit ferroptosis in aldehyde dehydrogenase-high (ALDHhi) BCSCs, leading to BCSC expansion and tumor initiation in mice. The underlying mechanism involved a two-fold posttranslational regulation of nuclear factor erythroid 2-related factor 2 (NRF2). ZMYND8 increased stability of NRF2 protein through KEAP1 silencing. On the other hand, ZMYND8 interacted with and recruited NRF2 to the promoters of antioxidant genes to enhance gene transcription in mammospheres. NRF2 phenocopied ZMYND8 to enhance BCSC stemness and tumor initiation by inhibiting ROS and ferroptosis. Loss of NRF2 counteracted ZMYND8's effects on antioxidant genes and ROS in mammospheres. Interestingly, ZMYND8 expression was directly controlled by NRF2 in mammospheres. Collectively, these findings uncover a positive feedback loop that amplifies the antioxidant defense mechanism sustaining BCSC survival and stemness.

Exposure to micron-grade silica particles triggers pulmonary fibrosis through cell-to-cell delivery of exosomal miR-107.

Long-term exposure to inhalable silica particles may lead to severe systemic pulmonary disease, such as silicosis. Exosomes have been demonstrated to dominate the pathogenesis of silicosis, but the underlying mechanisms remain unclear. Therefore, this study aimed to explore the roles of exosomes by transmitting miR-107, which has been linked to the toxic pulmonary effects of silica particles. We found that miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in exosomes extracted from the serum of patients with silicosis. Notably, an increase in miR-107 in serum exosomes and lung tissue was observed in the experimental silicosis mouse model, while the inhibition of miR-107 reduced pulmonary fibrosis. Moreover, exosomes helped the migration of miR-107 from macrophages to lung fibroblasts, triggering the transdifferentiation of cell phenotypes. Further experiments demonstrated that miR-107 targets CDK6 and suppresses the expression of retinoblastoma protein phosphorylation and E2F1, resulting in cell-cycle arrest. Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets.

Investigation of Anticancer Therapy Using pH-Sensitive Carbon Dots-Functionalized Doxorubicin in Cubosomes.

Cancer remains a highly lethal disease due to its elusive early detection, rapid spread, and significant side effects. Nanomedicine has emerged as a promising platform for drug delivery, diagnosis, and treatment monitoring. In particular, carbon dots (CDs), a type of fluorescent nanomaterial, offer excellent fluorescence properties and the ability to carry multiple drugs simultaneously through covalent bonding. In this work, CDs with carbonyl groups on the surface were prepared by aldol condensation and reacted with amine groups in the structure of doxorubicin (DOX) through Schiff base reaction to generate pH-responsive CDs-DOX. On the other hand, cubosomes with three-dimensional lattice structures formed by lipid bilayers have advantageous capabilities of encapsulating various hydrophilic, amphiphilic, and hydrophobic substances. The pH-responsive CDs-DOX are subsequently loaded into cubosomes to form an anticancer therapeutic nanosystem, CDs-DOX@cubosome. Leveraging the unique properties of CDs-DOX and cubosomes, our CDs-DOX@cubosome can enter tumor tissue through the enhanced permeation and retention effect first and conduct membrane fusion with tumor cells to intracellularly release CDs-DOX. Then, the imine bond in CDs-DOX breaks under acidic conditions within human cancer cell lines (HeLa and HepG-2 cells), releasing DOX and achieving enhanced treatment of tumors. Additionally, fluorescent CDs can synchronously achieve real-time in situ diagnosis of tumor tissue. We demonstrate that our CDs-DOX@cubosome works as an excellent drug delivery system with therapeutic efficiency enhancement to the tumor and reduced side effects.

Fibrous dysplasia with aneurysmal bone cyst-like change occurring in pediatric orbit: case report and literature review.

PURPOSE: We report a case of fibrous dysplasia (FD) with aneurysmal bone cyst (ABC)-like change in a child with orbital involvement, review the related cases, and discuss clinical features, therapy, and prognosis of this disease. CASE PRESENTATION: A 10-year-old girl had right proptosis (degree of exophthalmos: OD 16 mm, OS 13 mm) and limited vision (visual acuity: OD 1.0, OS 0.8) without trauma. Preoperative CT showed a 5.0*4.3 cm right-sided crania-orbital communicating tumor. MRI indicated a well-defined multicystic mass with scattered fluid levels and soap bubble-like alterations. The child underwent total tumor resection and orbital parietal titanium mesh reconstruction. At 20 months of follow-up, the child has recovered from ocular problems, and the tumor has not recurred. CONCLUSION: FD combined with ABC rarely occurs in orbit and generally begins with ocular symptoms. The etiology is uncertain. Early diagnosis and surgery are essential. Complete resection is suggested whenever possible because residual lesions may recur.

Roles, underlying mechanisms and clinical significances of LINC01503 in human cancers.

Long intergenic non-coding RNA 01503 (LINC01503) is a long non-coding RNA (lncRNA) located on human chromosome 9q34.11. There is compelling evidence indicating that LINC01503 is upregulated in multiple types of tumors and functions as a tumor stimulator. The upregulation of LINC01503 was significantly associated with the risk of 12 tumors and showed a strong correlation with clinicopathological characteristics and poor prognosis in 9 tumors. The expression of LINC01503 is regulated by transcription factors such as TP63, EGR1, c-MYC, GATA1 and AR. The downstream regulatory mechanisms of LINC01503 are complex and multifaceted. LINC01503, as a competing endogenous RNA (ceRNA), regulates gene expression by competitively inhibiting miRNA. LINC01503 may also regulate gene expression via interacting with biomolecules or recruiting chromatin-modifying complexes. In addition, LINC01503 can abnormally activate the ERK/MAPK, PI3K/AKT and Wnt/ß-catenin signaling pathways to enhance tumor progression. Here, this review presents an overview of the latest research progress of LINC01503 in the field of oncology, summarizes its comprehensive network involved in multiple cancer molecular mechanisms, and explores its potential applications in cancer diagnosis, prognosis, and treatment.

Integrated RNA expression and alternative polyadenylation analysis identified CPSF1-CCDC137 oncogenic axis in lung adenocarcinoma.

This study aims to analyze the RNA expression and alternative polyadenylation (APA) events and identify APA tuned genes with prognostic significance in lung adenocarcinoma (LUAD). Genome-wide RNA expression profile and APA events were acquired in LUAD cancer and normal samples in GSE197346. Comparative analysis screened common deregulated genes and transcripts. All 11 and 19 transcripts were up and down expressed and polyadenylated in cancer samples, respectively. Clinical analysis found eight genes with prognostic significance, such as coiled-coil domain containing 137 (CCDC137). Role of CCDC137 in LUAD was first reported in this study. The cellular and animal experiments indicated that downregulated CCDC137 suppressed the malignant tumor phenotype and tumor growth in LUAD. Then, to identify APA regulators for elevated CCDC137, we analyzed the expression of 26 APA regulators in GSE197346 and The Cancer Genome Atlas (TCGA), and found 4 differential regulators: CPSF1, CELF2, NUDT21, and ELAVL1. At last, the correlation of eight genes with four differential APA regulators was analyzed, and CPSF1 showed a strong positive correlation with CCDC137. Based on the above results, we propose an oncogenic axis of CPSF1-CCDC137 in LUAD. This study first constructed a polyadenylation tuned RNA expression map in LUAD, and the proposed oncogenic axis of CPSF1-CCDC137 would shed light on the pathogenesis of LUAD.

DBU-catalyzed diastereoselective 1,3-dipolar [3+2] cycloaddition of trifluoroethyl amine-derived isatin ketimines with chalcones: synthesis of 5'-CF3-substituted 3,2'-pyrrolidinyl spirooxindoles.

A diastereoselective 1,3-dipolar cycloaddition reaction between trifluoroethyl amine-derived isatin ketimines and chalcones was successfully achieved in the presence of DBU. A series of 5'-CF3-substituted 3,2'-pyrrolidinyl spirooxindoles were efficiently synthesized with high yields and excellent diastereoselectivities (up to 89% yield, and >99 : 1 dr). The in vitro anticancer activities of these highly functionalized spiro[pyrrolidin-3,2'-oxindole] derivatives were evaluated.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. METHODS: This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. RESULTS: Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. CONCLUSION: Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

Multi-scale molecular simulation of random peptide phase separation and its extended-to-compact structure transition driven by hydrophobic interactions.

Intrinsically disordered proteins (IDPs) often undergo liquid-liquid phase separation (LLPS) and form membraneless organelles or protein condensates. One of the core problems is how do electrostatic repulsion and hydrophobic interactions in peptides regulate the phase separation process? To answer this question, this study uses random peptides composed of positively charged arginine (Arg, R) and hydrophobic isoleucine (Ile, I) as the model systems, and conduct large-scale simulations using all atom and coarse-grained model multi-scale simulation methods. In this article, we investigate the phase separation of different sequences using a coarse-grained model. It is found that the stronger the electrostatic repulsion in the system, the more extended the single-chain structure, and the more likely the system forms a low-density homogeneous phase. In contrast, the stronger the hydrophobic effect of the system, the more compact the single-chain structure, the easier phase separation, and the higher the critical temperature of phase separation. Overall, by taking the random polypeptides composed of two types of amino acid residues as model systems, this study discusses the relationship between the protein sequence and phase behaviour, and provides theoretical insights into the interactions within or between proteins. It is expected to provide essential physical information for the sequence design of functional IDPs, as well as data to support the diagnosis and treatment of the LLPS-associated diseases.

SAP30 promotes breast tumor progression by bridging the transcriptional corepressor SIN3 complex and MLL1.

SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30's tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer.

Antibacterial and anticancer activities of green-synthesized silver nanoparticles using Photinia glabra fruit extract.

Aims: We prepared Photinia glabra (PG) aqueous fruit extract, utilized it to synthesize silver nanoparticles (PG-Ag NPs) and evaluated the antibacterial and anticancer activities of the nanoparticles (NPs). Materials & methods: Silver nitrate aqueous solution was reduced to PG-Ag NPs using aqueous PG fruit extract. NP shape, size, composition and functionalization were determined using transmission electron microscopy, x-ray photoelectron spectroscopy, Fourier transform infrared and x-ray diffraction. Results & conclusions: PG-Ag NPs were spherical, approximately 39-77 nm-sized, functionalized surfaces with notable antibacterial activity against both Escherichia coli and Staphylococcus aureus, with an MIC <30 ug/ml and cytotoxicity toward esophageal cancer cells, with IC50 values less than 20 ug/ml. PG-Ag@rt NPs have been shown to be a potent antibacterial and anticancer agent, and their enriched particle surfaces can be conjugated with other compounds for multibiomedical applications.

The present study reports for the first time the preparation of Photinia glabra (PG) aqueous fruit extract and its use for the synthesis of smaller silver particles (PG-Ag NPs) from bulk aqueous silver nitrate solution (AgNO₃). The preparation followed the reduction ability of PG fruit extract phytochemical under different preparation conditions: at room temperature (PG-Ag@rt), at 70°C (PG-Ag@70) and in the presence of cerium oxide at 70°C (PG-Ag+CeO₂@70). The prepared smaller particles were found using transmission electron microscopy to be spherical in shape with sizes 39, 77 and 44 nm for PG-Ag@rt, PG-Ag@70 and PG-Ag+CeO₂@70, respectively. The NPs contained different functional groups on their surfaces due to the capping ability of PG fruit extract components. Among all, PG-Ag@rt NPs showed strongest antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC 7.0 µg/ml and 28.0 µg/ml, respectively, and commendable anticancer activity toward Eca-109 cancer cells with IC₅₀ less than 20 ug/ml.

Targeting LSD1 in tumor immunotherapy: rationale, challenges and potential.

Lysine-specific demethylase 1 (LSD1) is an enzyme that removes lysine methylation marks from nucleosome histone tails and plays an important role in cancer initiation, progression, metastasis, and recurrence. Recent research shows that LSD1 regulates tumor cells and immune cells through multiple upstream and downstream pathways, enabling tumor cells to adapt to the tumor microenvironment (TME). As a potential anti-tumor treatment strategy, immunotherapy has developed rapidly in the past few years. However, most patients have a low response rate to available immune checkpoint inhibitors (ICIs), including anti-PD-(L)1 therapy and CAR-T cell therapy, due to a broad array of immunosuppressive mechanisms. Notably, inhibition of LSD1 turns "cold tumors" into "hot tumors" and subsequently enhances tumor cell sensitivity to ICIs. This review focuses on recent advances in LSD1 and tumor immunity and discusses a potential therapeutic strategy for combining LSD1 inhibition with immunotherapy.

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent long-term disease in the world. Liquiritigenin (LQ) is protective against a variety of hepatotoxins. Herein, we report the potential mechanism of LQ on a high-fat diet (HFD) induced NAFLD. NAFLD mice model was established by HFD for 12 weeks, and LQ treatment for 1 week. Commercially available assay kits measure liver triglycerides (TG) and total cholesterol (TC) levels. Plasm TC, TG, high-density-lipoprotein (HDL-C), and low-density-lipoprotein cholesterol (LDL-C) levels were also monitored by biochemistry. Enzyme linked immunosorbent assay (ELISA) kits were performed to analyze the pro-inflammatory factors, and intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and serum insulin were also determined. GO and KEGG pathway enrichment analysis was employed to analyze the overlapping genes of LQ targets and NAFLD development-related targets. Western blot was performed on key proteins of the enriched signaling pathway. HFD mice showed significant increases in hepatic TG and TC, and plasm TC, TG, and LDL-C in blood lipids, while HDL-C significantly decreased, and LQ treatment reversed their levels (p < 0.05). LQ also alleviated HFD-induced elevated levels of IPGTT, IPITT, and homeostasis model assessment of insulin resistance (HOMA-IR). And serum levels of the pro-inflammatory factor were also suppressed by LQ. PI3K/AKT pathway was enriched by KEGG pathway enrichment, and its key proteins p-PI3K and p-AKT were elevated after LQ treatment (p < 0.05). We found for the first time that LQ improves lipid accumulation, alleviates insulin resistance, and suppresses inflammatory responses in NAFLD mice, which might be associated with the activation of the PI3K/AKT pathway.