Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

Amygdalin ameliorates alopecia areata on C3H/HeJ mice by inhibiting inflammation through JAK2/STAT3 pathway.

BACKGROUND: Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. PURPOSE: Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. STUDY DESIGN: The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). METHODS: The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4+CD25+FOXP3+, CD4+ and CD8+ of skin tissue. And the levels of CD4+ and CD8+, p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. RESULTS: Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4+CD25+FOXP3+ and CD4+ cells, while inhibited the number of CD8+ positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. CONCLUSION: Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.

New Score Models for Predicting Bleeding and Ischemic of Ticagrelor Therapy in Patients with Diabetes Mellitus.

PURPOSE: Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. METHODS: We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. RESULTS: A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. CONCLUSION: The A4B score established in this study was better than the HAS-BLED score，and the same is true for the ABST score to the CHA2DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627).

Chinese surgical robot-assisted surgery for parotid tumor: a case report.

Robotic surgery is known as the "third technological revolution" in the field of surgery, and is an important milestone in the development of modern surgery. However, our country's innovative surgical robot industry is still in its early stages, and it is only being utilized in certain surgical fields. To explore the effectiveness of the application of domestic surgical robot in oral and maxillofacial surgery, the author successfully completed a case of benign parotid tumor resection with the assistance of a domestic autonomous robot. The operation was successful, facial nerve function was preserved, and postoperative wound healing was good.

Case report: Iatrogenic tattoos caused by skin marking pen in a postoperative patient.

In this report, a female patient suffering from pigment retention caused by a skin marking pen was elucidated. The patient underwent blepharoplasty 6 months ago and presented with blue-black linear marks at the upper eyelid incision 2 weeks after surgery. Under dermoscopy, scattered pigments were observed to accumulate in the epidermis of the upper eyelid. The patient was diagnosed with iatrogenic tattoo by a surgical marking pen. We chose surgical excision of the skin with the pigmentation. Previous studies have established that the risk of bacterial contamination, contact dermatitis, and allergies may increase with the surgical marking pens, while pigment retention has not yet been mentioned yet. Here, we present a case with a pigment retention in the incision. The selection of the surgical labelling methods and the management of the pigmentation were also addressed. According to our clinical findings, the risk of pigment retention by marking pens needs to be mentioned in the patient's informed consent. Therefore, the practitioner should ensure that the ink is cleaned by the end of each invasive procedure.

Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review.

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.

Cathepsin B as a key regulator of ferroptosis in microglia following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke marked by elevated mortality and disability rates. Recently, mounting evidence suggests a significant role of ferroptosis in the pathogenesis of ICH. Through a combination of bioinformatics analysis and basic experiments, our goal is to identify the primary cell types and key molecules implicated in ferroptosis post-ICH. This aims to propel the advancement of ferroptosis research, offering potential therapeutic targets for ICH treatment. Our study reveals pronounced ferroptosis in microglia and identifies the target gene, cathepsin B (Ctsb), by analyzing differentially expressed genes following ICH. Ctsb, a cysteine protease primarily located in lysosomes, becomes a focal point in our investigation. Utilizing in vitro and in vivo models, we explore the correlation between Ctsb and ferroptosis in microglia post-ICH. Results demonstrate that ICH and hemin-induced ferroptosis in microglia coincide with elevated levels and activity of Ctsb protein. Effective alleviation of ferroptosis in microglia after ICH is achieved through the inhibition of Ctsb protease activity and protein levels using inhibitors and shRNA. Additionally, a notable increase in m6A methylation levels of Ctsb mRNA post-ICH is observed, suggesting a pivotal role of m6A methylation in regulating Ctsb translation. These research insights deepen our comprehension of the molecular pathways involved in ferroptosis after ICH, underscoring the potential of Ctsb as a promising target for mitigating brain damage resulting from ICH.

High-Grade Ferronickel Concentrates Prepared from Laterite Nickel Ore by a Carbothermal Reduction and Magnetic Separation Method.

Nickel is widely used in industrial processes and plays a crucial role in many applications. However, most of the nickel resource mainly exists as nickel oxide in laterite nickel ore with complex composition, resulting in difficulty in upgrading the nickel content using physical separation methods. In this study, high-grade ferronickel concentrates were obtained through a carbothermal reduction and magnetic separation using laterite nickel ore and anthracite as raw materials. The effects of different types of additives (CaF2, Na2SO4, and H3BO3), carbon ratio (the molar ratio of oxygen atoms in the laterite nickel ore to carbon atoms in anthracite), and grinding time on the recoveries and grades of ferronickel concentrates were experimentally investigated, along with the microstructure and chemical composition of the products. CaF2 was proved to be the primary active additive in the aggregation and growth of the ferronickel particles and the improvement of the grade of the product. Under the optimal conditions of CaF2 addition of 9.85 wt%, carbon ratio of 1.4, and grinding time of 240 s, high-grade magnetically separable ferronickel concentrate with nickel grade 8.93 wt% and iron grade 63.96 wt% was successfully prepared. This work presents a practical method for the highly efficient recovery and utilization of iron and nickel from low-grade laterite nickel ore, contributing to the development of strategies for the sustainable extraction and utilization of nickel resources.

Clinical Effect of Platelet-Rich Fibrin Combined with BIO-GENE Artificial Bone Meal in Bone Defects After Jaw Cyst Surgery.

Purpose: To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy. Patients and Methods: From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared. Results: After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06±13.38%, while group B had a rate of 92.87±5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P<0.05), t=-6.84.Group A and Group B showed a statistically significant difference. Conclusion: Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.

Nickel/Titanocene-Catalyzed Electrophilic Acylation Coupling of Styrene Oxides.

The cross-coupling of epoxides with acyl chlorides or anhydrides by a nickel/titanocene dual catalytic system is established. A variety of synthetically useful ß-hydroxy ketones were obtained in good to high yields by using modified pyridine-oxazoline ligand. The reaction proceeds via the cooperation of titanocene-catalyzed ring-opening of epoxides and nickel-catalyzed acylation of the benzylic radical intermediate.

Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug delivery.

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules. Using a squamous cell carcinoma model, we demonstrated that a pH-sensitive fusogenic peptide -modification of BMSC-EVs achieved targetability in the microenvironment of a hypoxic tumor to deliver anti-tumor drugs. Using EGFR+HER2- and EGFR-HER2+ breast cancer models, we demonstrated that anti-EGFR and anti-HER2 modifications of BMSC-EVs were able to specifically deliver drugs to EGFR+ and HER2+ tumors, respectively. Using a collagen-induced arthritis model, we confirmed that anti-IL12/IL23-modified BMSC-EVs specifically accumulated in the arthritic joint and alleviated inflammation. Administration of SA-overexpressing BMSC-EVs has limited immunogenicity and high safety in vivo, suggesting that BMSC-derived EVs are ideal drug delivery vehicle. These representative scenarios of targeting modification suggest that, using different biotinylated molecules, the SA-overexpressing BMSC-EVs could be endowed with different targetabilities, which allows BMSC-EVs to serve as a versatile platform for targeted drug delivery under various situations.

Elucidating the central anorexigenic mechanism of glucagon-like peptide 1 in Japanese quail (Coturnix japonica).

Glucagon-like peptide 1 (GLP-1) elicits a potent reduction in food intake, although the central mechanism mediating this appetite-suppressive effect is not fully understood in all species. To begin to elucidate the molecular mechanisms in quail, we administered GLP-1 via intracerebroventricular (ICV) injection to 7-day-old Japanese quail (Coturnix japonica) and determined effects on food and water intake, behavior, and brain nucleus activation. We observed a reduction in food and water intake, with the lowest effective dose being 0.01 nmol. Quail injected with GLP-1 displayed fewer steps, feeding pecks, exploratory pecks, and jumps, while time spent sitting increased. We quantified c-Fos immunoreactivity at 60 min post-injection in hypothalamic and brainstem nuclei that mediate food intake and determined that the hypothalamic paraventricular nucleus (PVN), and nucleus of the solitary tract and area postrema of the brainstem were activated in response to GLP-1. In conclusion, these results suggest that GLP-1 induces anorexigenic effects that are likely mediated at the level of the PVN and brainstem.

Identification, genetic diversity, and pathogenicity of Ralstonia pseudosolanacearum causing cigar tobacco bacterial wilt in China.

Ralstonia pseudosolanacearum, previously known as R. solanacearum species complex (RSSC) phylotypes I and III, is a plant pathogenic bacterium causing significant yield losses in economical crops. In the May of 2020 and 2021, cigar tobacco bacterial wilt was first observed in fields in Danzhou, Hainan Province, China. A total of eight bacterial isolates were isolated and identified as R. pseudosolanacearum with race 1, biovar III by 16S rRNA gene sequencing, Biolog, and host identification. The amino acid sequence showed that Hainan strains and 15 R. pseudosolanacearum reference strains from flue-cured tobacco in Shandong and Guizhou Provinces, all belonged to RS1000 type containing the avrA gene, only Guizhou strains also had the popP1 gene. On the basis of phylotype-specific multiplex PCR amplification, mismatch repair gene and endoglucanase gene-base tree, Hainan strains were identified as phylotype I sequevar 70, and showed stronger pathogenic capabilities on three different varieties than those reference strains. This is the first report of cigar tobacco bacterial wilt caused by R. pseudosolanacearum sequevar 70. The results revealed the diversity of RSSC in Nicotiana tabacum in China and provided useful information regarding the epidemiology of cigar tobacco wilt disease, as well as the breeding for disease resistance in local cigar tobacco.

Oestrogen ameliorates blood-brain barrier damage after experimental subarachnoid haemorrhage via the SHH pathway in male rats.

BACKGROUND: Sex differences affect the occurrence, progression and regression of subarachnoid haemorrhage (SAH). Oestrogen plays a protective role in alleviating the vasospasm and neuronal apoptosis induced by SAH. However, whether oestrogen affects blood‒brain barrier (BBB) integrity has not been fully studied. Oestrogen has been found to regulate the sonic hedgehog (SHH) signalling pathway through the oestrogen receptor in gastric cancer and adrenal glands, and the SHH signalling pathway has an important role in maintaining the BBB by upregulating the expression of tight junction proteins. In this study, we investigated the relationship between oestrogen and the SHH signalling pathway using clinical data and established an experimental SAH model to explore whether oestrogen could ameliorate BBB damage after SAH through the SHH pathway. METHODS: Correlations between oestrogen and the SHH pathway were analysed by patients' cerebrospinal fluid (CSF) samples and the Genotype-Tissue Expression database (GTEx). Then, an experimental rat SAH model was established using the endovascular perforation method and treated with oestrogen, oestrogen inhibitors and SHH signalling pathway inhibitors. Then, the effects of oestrogen on BBB damage were analysed by western blot, immunofluorescence and neurobehavioural experiments. RESULTS: ESLIA detection and correlation analysis showed that oestrogen levels in patients' CSF were positively correlated with the SHH pathway, which was further verified by GTEx gene-correlation analysis. SHH was found to be mainly expressed in neurons and astrocytes in rats under physiological conditions and was upregulated by oestrogen pretreatment. In the SAH model, oestrogen pretreatment was found to reverse SAH-induced decreases in the SHH pathway, which were counteracted by oestrogen receptor inhibitors. Furthermore, oestrogen pretreatment reduced SAH-induced BBB damage, brain oedema and neurological dysfunction, which were eliminated by SHH pathway inhibitors. CONCLUSION: In conclusion, we demonstrate here that oestrogen pretreatment ameliorates brain injury after SAH, at least in part through SHH pathway-mediated BBB protection.

Association between nut consumption and cancer risk: a meta-analysis.

This study aims to conduct a meta-analysis and dose-response analysis of the relationship between nut intake and cancer risk and mortality. Electronic databases were searched. A meta-analysis was conducted to calculate the pooled effect sizes (ESs) with the corresponding 95% CIs, and a dose-response analysis was performed. A random-effects model was used in the statistical analysis. Two independent reviewers completed the full-text screening, data extraction, and quality assessment. We included 17 articles in the present meta-analysis. Total nuts intake was revealed to be significantly associated with reduced cancer risk (ES: 0.9; 95% CI: 0.86-0.95; P < 0.001) and cancer mortality (ES: 0.88; 95% CI: 0.85-0.92, P < 0.001), especially lung cancer risk (ES: 0.86; 95% CI: 0.81-0.91, P < 0.001) and gastric cancer risk (ES: 0.79; 95% CI: 0.68-0.91, P = 0.001). Moreover, a 10 g/d increment of tree nuts consumption was associated with a 20% cancer mortality reduction (ES: 0.80; 95% CI: 0.71-0.89; P < 0.0001). Nuts intake is significantly associated with the reduction of cancer risk and mortality. Especially, nuts intake is significantly associated with reduced lung cancer risk and gastric cancer risk. Noticeably, a 10 g/d increase in tree nuts intake is related to a 20% reduction in overall cancer mortality.

Loss of the placental iron exporter ferroportin 1 causes embryonic demise in late-gestation mouse pregnancy.

Fetal development relies on adequate iron supply by the placenta. The placental syncytiotrophoblasts (SCTB) express high levels of iron transporters, including ferroportin1 (Fpn1). Whether they are essential in the placenta has not been tested directly, mainly due to the lack of gene manipulation tools in SCTB. Here, we aimed to generate a SCTB-specific Cre mouse and use it to determine the role of placental Fpn1. Using CRISPR/Cas9 technology, we created a syncytin b (Synb) Cre line (SynbCre) targeting the fetal-facing SCTB layer in mouse placental labyrinth. SynbCre deleted Fpn1 in late gestation mouse placentas reliably with high efficiency. Embryos without placental Fpn1 were pale and runted, and died before birth. Fpn1 null placentas had reduced transferrin receptor expression, increased oxidative stress and detoxification responses, and accumulated ferritin in the SCTB instead of the fetal endothelium. In summary, we demonstrate that SynbCre is an effective and specific tool to investigate placental gene function in vivo. The loss of Fpn1 in late gestation mouse placenta is embryonically lethal, providing direct evidence for an essential role of Fpn1 in placental iron transport.

Feasibility of same-day discharge following endoscopic submucosal dissection for esophageal or gastric early cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an established technique for the treatment of early gastrointestinal neoplasia. Generally, multi-day (M-D) admission is required for patients undergoing ESD due to potential complications. AIM: To evaluate the feasibility of a same-day (S-D) discharge strategy for ESD of the esophagus or stomach. METHODS: The data of patients who underwent esophageal or gastric ESD were retrospectively collected from January 2018 to December 2021 at Peking University Cancer Hospital. The propensity score matching (PSM) method was applied to balance the unevenly distributed patient baseline characteristics between the S-D and M-D groups. Intraoperative and postoperative parameters were compared between the matched groups. RESULTS: Among the 479 patients reviewed, 470 patients, including 91 in the S-D group and 379 in the M-D group, fulfilled the inclusion and exclusion criteria. Following PSM, 78 patients in each group were paired using the 1:1 nearest available score match algorithm. No significant difference was found between groups with respect to intraoperative and postprocedural major adverse events (AEs). Tumor size, complete resection rate, and procedural duration were comparable between the groups. The S-D group demonstrated a significantly shorter length of hospital stay (P < 0.001) and lower overall medical expenses (P < 0.001) compared with the M-D group. CONCLUSION: The S-D discharge strategy may be feasible and effective for esophagogastric ESD, and the procedural-related AEs can be managed successfully.

Advances in Hyaluronic Acid for Biomedical Applications.

Hyaluronic acid (HA) is a large non-sulfated glycosaminoglycan that is the main component of the extracellular matrix (ECM). Because of its strong and diversified functions applied in broad fields, HA has been widely studied and reported previously. The molecular properties of HA and its derivatives, including a wide range of molecular weights but distinct effects on cells, moisture retention and anti-aging, and CD44 targeting, promised its role as a popular participant in tissue engineering, wound healing, cancer treatment, ophthalmology, and cosmetics. In recent years, HA and its derivatives have played an increasingly important role in the aforementioned biomedical fields in the formulation of coatings, nanoparticles, and hydrogels. This article highlights recent efforts in converting HA to smart formulation, such as multifunctional coatings, targeted nanoparticles, or injectable hydrogels, which are used in advanced biomedical application.

Forkhead Box q1 promotes invasion and metastasis in colorectal cancer by activating the epidermal growth factor receptor pathway.

BACKGROUND: Colorectal cancer (CRC) is an extremely malignant tumor with a high mortality rate. Little is known about the mechanism by which forkhead Box q1 (FOXQ1) causes CRC invasion and metastasis through the epidermal growth factor receptor (EGFR) pathway. AIM: To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor (HB-EGF)/EGFR pathway. METHODS: We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis (GEPIA) website (http://gepia.cancer-pku.cn/index.html). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues, and we constructed a stable low-expressing FOXQ1 cell line and verified it with the above method. The expression changes of membrane-bound HB-EGF (proHB-EGF) and soluble HB-EGF (sHB-EGF) in the low-expressing FOXQ1 cell line were detected by flow cytometry and ELISA. Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells. Proliferation experiments, transwell migration experiments, and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF, and then to evaluate the clinical relevance of FOXQ1 and HB-EGF. RESULTS: GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate. PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways. Knockdown of FOXQ1 suppressed the expression of HB-EGF, and led to a decrease in EGFR and its downstream genes AKT, RAF, KRAS expression levels. After knockdown of FOXQ1 in CRC cell lines, cell proliferation, migration and invasion were attenuated. Adding HB-EGF restored the migration and invasion ability of CRC, but not the cell proliferation ability. Kaplan-Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival. CONCLUSION: Based on these collective data, we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.