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1.
Radiology ; 311(2): e232178, 2024 May.
Article in English | MEDLINE | ID: mdl-38742970

ABSTRACT

Background Accurate characterization of suspicious small renal masses is crucial for optimized management. Deep learning (DL) algorithms may assist with this effort. Purpose To develop and validate a DL algorithm for identifying benign small renal masses at contrast-enhanced multiphase CT. Materials and Methods Surgically resected renal masses measuring 3 cm or less in diameter at contrast-enhanced CT were included. The DL algorithm was developed by using retrospective data from one hospital between 2009 and 2021, with patients randomly allocated in a training and internal test set ratio of 8:2. Between 2013 and 2021, external testing was performed on data from five independent hospitals. A prospective test set was obtained between 2021 and 2022 from one hospital. Algorithm performance was evaluated by using the area under the receiver operating characteristic curve (AUC) and compared with the results of seven clinicians using the DeLong test. Results A total of 1703 patients (mean age, 56 years ± 12 [SD]; 619 female) with a single renal mass per patient were evaluated. The retrospective data set included 1063 lesions (874 in training set, 189 internal test set); the multicenter external test set included 537 lesions (12.3%, 66 benign) with 89 subcentimeter (≤1 cm) lesions (16.6%); and the prospective test set included 103 lesions (13.6%, 14 benign) with 20 (19.4%) subcentimeter lesions. The DL algorithm performance was comparable with that of urological radiologists: for the external test set, AUC was 0.80 (95% CI: 0.75, 0.85) versus 0.84 (95% CI: 0.78, 0.88) (P = .61); for the prospective test set, AUC was 0.87 (95% CI: 0.79, 0.93) versus 0.92 (95% CI: 0.86, 0.96) (P = .70). For subcentimeter lesions in the external test set, the algorithm and urological radiologists had similar AUC of 0.74 (95% CI: 0.63, 0.83) and 0.81 (95% CI: 0.68, 0.92) (P = .78), respectively. Conclusion The multiphase CT-based DL algorithm showed comparable performance with that of radiologists for identifying benign small renal masses, including lesions of 1 cm or less. Published under a CC BY 4.0 license. Supplemental material is available for this article.


Subject(s)
Contrast Media , Deep Learning , Kidney Neoplasms , Tomography, X-Ray Computed , Humans , Female , Male , Middle Aged , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Retrospective Studies , Tomography, X-Ray Computed/methods , Prospective Studies , Radiographic Image Interpretation, Computer-Assisted/methods , Aged , Algorithms , Kidney/diagnostic imaging , Adult
2.
Exp Ther Med ; 27(5): 202, 2024 May.
Article in English | MEDLINE | ID: mdl-38590576

ABSTRACT

Dixon surgery for rectal cancer can lead to severe intestinal narrowing and blockage that is difficult to treat with open surgery or colonoscopy. The aim of the present study was to develop a minimally invasive approach for treating rectal anastomotic atresia based on three cases that were managed with transurethral prostate resection instrumentation. Preoperative imaging determined the distance from the anastomotic closure to the anal margin, the length of the anastomotic closure and the degree of proximal intestinal dilation for all cases. During the procedure, the anastomotic site was visualized, and a circular electrode was used to excavate and open the blockage. Membrane-like closures were directly incised to achieve satisfactory results, with an anastomotic diameter >20 mm. Those cases with tubular atresia required an initial incision using the prostate resectoscope to relieve the obstruction, followed by radial incisions until achieving an anastomotic diameter >20 mm. At 3-6 months post-dilation, two of the patients with anastomotic atresia >20 mm had satisfactory bowel movements, whereas the remaining patient experienced tumor recurrence at the anastomotic site and discontinued treatment. This case series demonstrates the potential of transurethral prostate resection instrumentation as a safe and effective minimally invasive approach for rectal anastomotic atresia. Given that prostate resection instrumentation is readily available in hospitals in China, this approach is widely accessible to most patients. Furthermore, the technique leverages existing surgical technology and practices, requiring only a shift in the surgical site.

3.
Cancer Control ; 30: 10732748231197511, 2023.
Article in English | MEDLINE | ID: mdl-37673428

ABSTRACT

OBJECTIVE: We aimed to retrospectively investigate whether the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR) can predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib or sorafenib. METHODS: We retrospectively identified 210 patients with mRCC treated with sunitinib or sorafenib from 2007 to 2017 at Fudan University- and Hexi University-affiliated hospitals. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Multivariate regression analysis was used to evaluate predictors of PFS and OS. RESULTS: Low NLR (<2.85) and MLR (<.30) were strongly associated with increased PFS and OS. Multivariable analyses verified that the NLR and MLR were both independent prognostic factors. Additionally, the NLR was negatively correlated with CD8+ and CD4+ T-cell infiltration in tumors. CONCLUSION: In patients with mRCC treated with sunitinib and sorafenib, an NLR <2.85 and MLR <.30 was associated with superior PFS and OS, which may be related to the reduced lymphocytic infiltration of tumors.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Sunitinib/therapeutic use , Sorafenib/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Retrospective Studies , Biomarkers , Prognosis , Lymphocytes/pathology
4.
Int J Gen Med ; 16: 2493-2501, 2023.
Article in English | MEDLINE | ID: mdl-37342406

ABSTRACT

Purpose: Observe uninterrupted thrombolytic therapy via indwelling catheter for lower limb deep vein thrombosis. Methods: We retrospectively studied data from 32 patients with lower extremity deep vein thrombosis who received comprehensive treatment, consisting of general treatment, inferior vena cava filter implantation, interventional thrombolysis, angioplasty, stenting, and post-operative monitoring. Results: The efficacy and safety of the comprehensive treatment were observed for a follow-up period of 6-12 months. The treatment was 100% effective; patient results indicated no serious bleeding, acute pulmonary embolism, or death after surgery. Conclusion: The combination of intravenous and healthy side femoral vein puncture and directed thrombolysis to treat acute lower limb deep vein thrombosis is safe, effective, and minimally invasive while still achieving a good therapeutic effect.

5.
Medicine (Baltimore) ; 102(19): e33799, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37171313

ABSTRACT

BACKGROUND: Anastomotic stenosis is a common complication of colorectal surgery with anastomosis. To explore a minimally invasive novel approach surgical method for the treatment of rectal anastomotic strictures using transurethral prostate resection instrumentation. METHODS: From 2012 to 2022, 18 patients for the treatment of rectal anastomotic strictures using transurethral prostate resection instrumentation. The transurethral prostate resection instrumentation enters the rectum through the anus to incise the narrow anastomotic orifice in a 4-point radial manner under the resectoscope. RESULTS: The surgery was successfully completed in 18 patients, and there were no postoperative complications. Postoperatively, 12 patients achieved satisfactory improvement in defecation after 1 incision, and 4 patients underwent another incision 3 months later. Two patients underwent incisions thrice, and the ease of defecation improved in a short period; however, they later underwent permanent colostomy due to repeated stenosis and pain. CONCLUSION: The transanal 4-point radial incision of the prostate using transurethral prostate resection instrumentation is a minimally invasive, safe, effective, and simple surgical method for the treatment of rectal anastomotic stenosis supplemented by postoperative dilatation, and is worthy of clinical application.


Subject(s)
Rectal Neoplasms , Transurethral Resection of Prostate , Male , Humans , Rectal Neoplasms/surgery , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Transurethral Resection of Prostate/adverse effects , Rectum/surgery , Anastomosis, Surgical/adverse effects
6.
Exp Ther Med ; 25(5): 210, 2023 May.
Article in English | MEDLINE | ID: mdl-37090076

ABSTRACT

The present study aimed to explore the clinical efficacy of laparoscopic partial splenectomy in the treatment of benign lesions of the spleen and partial splenic rupture. The clinical value of laparoscopic partial splenectomies performed between March 2015 and May 2022 was retrospectively analyzed. Cases considered included the following: 14 spleen cysts, five spleen hemangiomas, one spleen hamartoma and two splenic ruptures. Lesion diameters of cases ranged from 5.0-11.3 cm. Results indicated that all 22 patients had an uneventful surgery, including 11 cases with lesions located in the upper pole of the spleen, nine in the lower pole of the spleen, one in the upper middle pole and one in the middle and lower pole. Operation time ranged from 75-180 min (mean: 120±17 min) and intraoperative bleeding ranged from 80-300 ml (mean: 178±70 ml). The average duration of postoperative hospitalization was 6±2 days, with all patients followed up for 10-12 months. Patients reported no symptoms of discomfort and had platelet levels within normal range. In conclusion, laparoscopic partial splenectomy allows for lesion resection while retaining normal splenic function and may be effectively used for treating benign spleen tumors and partial splenic rupture. However, the operation is difficult and surgeons must be able to perform minimally invasive techniques and strictly screen cases.

7.
Int J Biol Markers ; 38(2): 124-132, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36883235

ABSTRACT

INTRODUCTION: Complement C5a is an important component of the innate immune system. An increasing number of reports have revealed the relevance of C5a in tumor progression; however, its exact role in metastatic renal cell carcinoma (mRCC) remains unknown. METHODS: We evaluated C5a expression in tumor tissue microarrays of 231 mRCC patients and analyzed the relationship between C5a levels and clinical outcomes, and the expression of epithelial-mesenchymal transition (EMT)-related proteins, programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). In-vitro functional experiments using exogenous C5a stimulation and C5a silencing in renal cell carcinoma cells were used to validate the tissue findings. RESULTS: High C5a expression was associated with poor therapeutic responses, poor overall and progression-free survival, and high expression of EMT-related proteins and PD-1/PD-L1 in mRCC patients. Exogenous C5a promoted proliferation, migration, and invasion of renal cell carcinoma cells, and induced the expression of EMT-related proteins and PD-1/PD-L1. Conversely, C5a silencing inhibited migration and invasion of renal cell carcinoma cells and decreased the expression of EMT-related proteins and PD-1/PD-L1. CONCLUSIONS: Our findings indicate that elevated C5a expression is associated with poor outcomes in patients with mRCC, and this effect may be partly attributed to the ability of C5a to promote EMT and PD-1/PD-L1 expression. C5a may be a potential novel target for the treatment of mRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Programmed Cell Death 1 Receptor , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , B7-H1 Antigen/metabolism , Complement C5a/genetics , Complement C5a/pharmacology , Complement C5a/therapeutic use , Epithelial-Mesenchymal Transition/genetics
8.
Cancer Control ; 29: 10732748221134398, 2022.
Article in English | MEDLINE | ID: mdl-36346167

ABSTRACT

OBJECTIVE: This study aimed to evaluate the expression levels of Shh, Gli1, and Cyr61 proteins in gastric cancer tissues and analyze the relationship between these three proteins and the clinicopathological factors and prognosis of patients. METHODS: This was a retrospective study. Four hundred gastric cancer tissue specimens from patients who underwent radical gastrectomy in Zhangye People's Hospital affiliated to Hexi University between February 2013 and February 2021 underwent immunohistochemical analysis. RESULTS: The positive expression rates of Shh, Gli1, and Cyr61 in gastric cancer tissues were 55.5%, 56.5%, and 64.5%, respectively. The expressions of Shh, Gli1, and Cyr61 in gastric cancer tissues were significantly correlated with tumor size, depth of invasion, and degree of differentiation (P < .05). The expression of Shh protein was positively correlated with the expression of Gli1 protein (P < .01), and the expression of Gli1 protein was positively correlated with the expression of Cyr61 protein (P < .01). Univariate and multivariate analyses showed that the expression of Shh, Gli1, and Cyr61 could predict the prognosis of patients (P < .05). Receiver operating characteristic curve analysis combined with TNM staging could better predict the three-year overall survival of patients (P < .05). CONCLUSION: Shh, Gli1, and Cyr61 proteins are significantly expressed in gastric cancer tissues and are risk factors for the prognosis of patients with gastric cancer.


Subject(s)
Stomach Neoplasms , Humans , Hedgehog Proteins/analysis , Hedgehog Proteins/metabolism , Prognosis , Retrospective Studies , Stomach Neoplasms/surgery , Zinc Finger Protein GLI1
9.
Exp Ther Med ; 24(5): 645, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36277162

ABSTRACT

Vesicovaginal fistula is one of the most common types of female genitourinary fistulas encountered in clinical practice, and its treatment is determined by the disease characteristics and at the discretion of the attending physician. The present study describes a unique conservative approach to the management of vesicovaginal fistulas. A 56-year-old woman developed a vesicovaginal fistula after laparoscopic hysterectomy. A bilateral ureteral single-J tube drainage through suprapubic bladder puncture with indwelling catheterization was performed. Thus, urine diversion and bladder emptying were achieved. In addition, the healing of the vesicovaginal fistula was promoted and the trauma of open or laparoscopic surgery was avoided. This minimally invasive method is simple and convenient, has few complications, and may be used as an alternative method for treating vesicovaginal fistulas.

10.
Exp Ther Med ; 24(5): 661, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36168424

ABSTRACT

Vaginal leiomyomas are rare and only a small number of cases have been reported in the literature. Due to the rarity of the disease and complexity of the vaginal anatomy, definitive diagnosis and treatment are challenging. A 48-year-old female patient presented with a vaginal mass and urinary incontinence. Magnetic resonance imaging (MRI) revealed a clear tumor measuring 65x46 mm in diameter at the anterior vaginal wall. Intraoperatively, frozen-section analysis was performed to confirm that the tumor was benign. The tumor was resected using the transvaginal approach. The patient recovered well without any complications. The pathological diagnosis was leiomyoma. The present case suggests that intraoperative frozen-section analysis should be performed in all patients with vaginal wall tumors with MRI findings suggestive of malignancy, and surgical treatment should be performed once the diagnosis is confirmed to prevent misdiagnosis and incorrect treatment.

11.
Oncol Lett ; 24(3): 314, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35949617

ABSTRACT

Liposarcoma is a rare malignant tumor type and surgical resection is the gold standard treatment. The present study reported on the case of a 51-year-old woman who presented with a mass in the left upper abdomen. Computed tomography revealed a 32-cm giant retroperitoneal liposarcoma. Complete tumor resection was performed without the removal of other organs. Postoperative pathological examination indicated retroperitoneal well-differentiated liposarcoma and immunohistochemistry revealed S-100(-), MDM2(+), vimentin(+), CDK4(+), p16(+) and STAT6(+) results. The patient recovered well after the surgery. Complete tumor resection during the first surgery is key to cure liposarcoma. The present case report will be helpful for clinical oncologists to fully understand giant retroperitoneal liposarcoma and treat it accordingly.

12.
Exp Ther Med ; 24(2): 535, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35837049

ABSTRACT

Giant bladder stones are rare in younger patients. Herein, we report a case of acute renal failure in a 31-year-old male with a giant bladder stone. The patient presented with lower urinary tract symptoms and urinary retention with milky-white urine. An emergency suprapubic cystotomy was performed and an 11-cm oval, solid stone was removed. Post-operative creatinine levels progressively decreased to normal and the patient exhibited smooth urination and good recovery at follow-up. A comprehensive physical examination and thorough investigation of the patient's medical history are required during clinical evaluation, diagnosis and treatment, thus preventing misdiagnoses and ensuring prompt treatment.

13.
Exp Ther Med ; 24(2): 491, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35837074

ABSTRACT

Radical cystectomy is the gold standard treatment for muscular invasive bladder cancer. Bricker surgery is the most common technique used for urinary diversion; however, troublesome complications such as postoperative anastomotic stenosis or fistula may occur. The case of a patient who had a urinary fistula after Bricker surgery performed at our hospital, is described. The patient was successfully treated with continuous double-cannula negative-pressure drainage and avoided a second surgery. The patient recovered well and is on regular follow-up. This case highlights the importance of timely and relevant treatment for patients with postoperative urinary fistula to avoid more invasive surgery.

14.
Cancer Manag Res ; 14: 1987-1994, 2022.
Article in English | MEDLINE | ID: mdl-35733511

ABSTRACT

Purpose: To determine an accurate method of inspecting low anastomotic leakages and application of transurethral prostate resection instrumentation for treating low rectal anastomotic leakage. Patients and Methods: Clinical data of eight patients treated for anastomotic leakage after rectal cancer surgery at Zhangye People's Hospital (affiliated to Hexi University), from August 2019 to November 2021, were retrospectively analyzed. Transanal prostate resection instrumentation was used to assess the leakage and surrounding conditions. Using prostate resection instrumentation, the presacral and perirectal residual cavities were washed and removed, and indwelling suprapubic presacral, transanal presacral, and rectal drainage tubes were placed. Continuous presacral saline irrigation and drainage and open negative-pressure suction in the rectal cavity were performed until the patients' fistula healed. Results: Of the eight patients with anastomotic leakages, one had grade B and seven had grade C International Study Group of Rectal Cancer anastomotic leakage classifications following Dixon operation. Transanal prostate resection instrumentation showed that the leakage of the one patient with grade B was less than a third of the circumference of the anastomosis. Among the seven patients with grade C, one leakage was less than a third of the anastomotic circumference. One patient had complete separation of the anastomosis and one distal colon necrosis, which necessitated immediate descending colostomy. Conservative treatment was successful in six patients; the conservative overall cure rate was 75%, and the median healing time was 43 (21-68) days. Conclusion: Transanal examination of rectal anastomotic leakage using prostate resection instrumentation is comprehensive, easy to perform, provides clear visualization, accurately guides catheter placement, and can be combined with continuous open negative-pressure drainage, which is a safe, convenient, and effective method for treating low rectal leakage.

15.
Front Genet ; 13: 904536, 2022.
Article in English | MEDLINE | ID: mdl-35769986

ABSTRACT

Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures. Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC. Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen. Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.

16.
J Cancer ; 13(5): 1679-1684, 2022.
Article in English | MEDLINE | ID: mdl-35371320

ABSTRACT

Purpose: To explore a minimally invasive emergency solution for acute obstruction caused by rectal cancer in patients in whom rectal stents or drainage tubes cannot be placed under the guidance of conventional colonoscopy or digital subtraction angiography (DSA). Patients and Methods: Without anesthesia, analgesia, or sedation, the prostate resection endoscopy was inserted into the rectum through the anus, and the rectal space in which the tumor caused obstruction was searched with a certain flushing pressure until it crossed the area of obstruction to reach the proximal intestinal cavity. The drainage catheter or rectal stent was inserted through the sheath of the endoscope to relieve the acute obstruction and permit further cancer treatment. Results: In 31 patients in whom a drainage catheter or rectal stent could not be inserted using conventional colonoscopy or DSA guidance, placement of the catheter or stent into the proximal intestinal cavity was achieved in 28 patients, including drainage tube placement in 21 patients and rectal stent placement in seven patients. Three patients could not undergo placement because of their advanced age and poor general condition. The operative time ranged 15-40 min. Among the 28 patients whose obstruction was relieved, 23 patients underwent radical resection rectal cancer after 10-14 days, and five patients were discharged with stents because they were unwilling to receive further treatment. There were no postoperative complications. Conclusion: Transanal resection is a minimally invasive, effective, safe, and feasible emergency treatment for rectal cancer-associated obstruction.

17.
Medicine (Baltimore) ; 101(1): e28344, 2022 Jan 07.
Article in English | MEDLINE | ID: mdl-35029880

ABSTRACT

RATIONALE: Omental liposarcoma is extremely rare, and only a few reports have been published in the literature. Due to the rarity of the disease, establishing a clear diagnosis and formulating a treatment plan may be challenging for clinicians. PATIENT CONCERNS: The patient was a 51-year-old woman who presented with a protruding mass and pain in the lower abdomen. DIAGNOSIS: Magnetic resonance imaging revealed a tumor measuring 15 cm in diameter in the pelvis. Ovarian cancer was suspected based on pre-operative imaging findings. INTERVENTIONS: An exploratory laparotomy was performed. Intra-operative analysis of the frozen section suggested a benign tumor. OUTCOMES: Postoperative histopathological analysis confirmed the diagnosis of omental liposarcoma. The patient recovered well after surgery. LESSON: This case report helps clinical oncologists to develop a comprehensive understanding of this disease and treat it accordingly.


Subject(s)
Liposarcoma/diagnostic imaging , Omentum/diagnostic imaging , Female , Humans , Laparotomy , Liposarcoma/pathology , Liposarcoma/surgery , Magnetic Resonance Imaging , Middle Aged , Omentum/surgery , Tomography, X-Ray Computed
18.
Front Endocrinol (Lausanne) ; 12: 665912, 2021.
Article in English | MEDLINE | ID: mdl-33986730

ABSTRACT

Thousands of papers on primary aldosteronism (PA) have been published in the last two decades. This study aimed to evaluate the research hotspots and future trends in PA research using bibliometric analysis. A total of 2,365 PA research papers between 2000 and 2020 were included. The dominant position of the United States in global PA research throughout this 20-year period was evident, and it was also the country most frequently involved in international cooperation. The University of Padua was the most productive institution and a leader in research collaboration. The Journal of Clinical Endocrinology & Metabolism was the most productive journal in terms of the number of publications on PA. Further, Mulatero P, Reincke M, Beuschlein F and Wu VC all made significant contributions to PA research. Five hotspots have been identified: (1) metabolic syndrome associated with PA; (2) molecular mechanisms of PA; (3) adrenal adenoma and adrenal cortex; (4) hypertension associated with PA; and (5) clinical monitoring parameters and diagnosis in patients with PA. Our results suggest that the molecular mechanisms of PA will remain research hotspots in the future. International collaboration is also expected to widen and deepen in the field of PA research.


Subject(s)
Bibliometrics , Biomedical Research/trends , Hyperaldosteronism/diagnosis , Hyperaldosteronism/therapy , Publications/statistics & numerical data , Humans , Time Factors
19.
Gut Microbes ; 13(1): 1-16, 2021.
Article in English | MEDLINE | ID: mdl-33535879

ABSTRACT

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to "leak" into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.


Subject(s)
Brain-Gut Axis/physiology , Gastrointestinal Microbiome/physiology , Kynurenine/metabolism , Animals , Bacteroidetes/physiology , Brain/metabolism , Depression/etiology , Depression/metabolism , Depression/microbiology , Depression/therapy , Dysbiosis/etiology , Dysbiosis/microbiology , Dysbiosis/therapy , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Intestines/metabolism , Intestines/pathology , Male , Mice , Neurotransmitter Agents/metabolism , Probiotics , Restraint, Physical/adverse effects , Restraint, Physical/psychology , Tryptophan/metabolism
20.
Front Cell Dev Biol ; 9: 822315, 2021.
Article in English | MEDLINE | ID: mdl-35127731

ABSTRACT

Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

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