Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.

Cancer­associated fibroblasts under therapy­induced senescence in the tumor microenvironment (Review).

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

The antiferroptotic effect of indigo on ulcerative colitis.

The protective effect of indigo on intestinal epithelial cells remains unclear. Yokote Akihito et al. preliminarily investigated the anti-ferroptosis effect of indigo in inflammatory bowel disease. Here, we further discuss and evaluate the role of indigo based on the results.

Patients' perspectives on irritable bowel syndrome: a qualitative analysis based on social media in China.

AIM: To explore the perspectives, experience, and concerns of patients with irritable bowel syndrome (IBS) in China. METHODS: We used data mining to investigate posts shared in Baidu Tieba concerned with IBS; we collected the data through the crawler code, and mined the cleaned data's themes based on Latent Dirichlet allocation (LDA) and the Grounded theory. RESULTS: We found 5746 network posts related to IBS. LDA analysis generated 20 topics, and grounded theory analysis established eight topics. Combining the two methods, we finally arranged the topics according to five concepts: difficulty in obtaining disease information; serious psychosocial problems; dissatisfied with the treatment; lack of social support; and low quality of life. CONCLUSION: Social media research improved patient-centric understanding of patients' experiences and perceptions. Our study may facilitate doctor-patient communication and assist in the formulation of medical policies.

Patients' perspectives on, experience with and concerns about crohn's disease: insights from Chinese social media.

AIM: The aim of this study was to explore the experience and perceptions of patients with Crohn's disease in China. METHODS: Data mining was used to investigate posts in Crohn's disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning. RESULTS: In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition. CONCLUSION: Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.

Caizhixuan hair tonic regulates both apoptosis and the PI3K/Akt pathway to treat androgenetic alopecia.

PURPOSE: Caizhixuan hair tonic (CZX) is a topical traditional Chinese medicine (TCM) preparation for the treatment of androgenetic alopecia (AGA). However, its active compounds and underlying mechanism for treating AGA are still unclear. The purpose of this study was to observe the effects of CZX on hair growth promotion in AGA mice and to explore the active components and mechanism. METHODS: Testosterone propionate was administered subcutaneously to mice to establish an AGA mouse model. The therapeutic effects of CZX on AGA were evaluated by observing skin colour changes, hair growth time, and average hair length; calculating the hair growth score; and performing skin histopathological analysis. Following that, CZX chemical components were analysed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Network pharmacology was used to predict the major effects and possible mechanisms of CZX for the treatment of AGA. Furthermore, RT-qPCR and Western blotting were performed to assess the expression of key genes and proteins involved in PI3K/Akt and apoptosis pathways in order to validate CZX's predicted mechanism in AGA. RESULTS: CZX promoted hair growth and improved the pathological morphology of hair follicles in the skin. In UPLC-Q-TOF/MS analysis, 69 components from CZX were isolated. Based on network pharmacology, CZX alleviated AGA by regulating PI3K/Akt and apoptosis pathways. According to RT-qPCR and Western blotting, CZX upregulated the expressions of PI3K, Akt, and Bcl-2, while downregulating that of Bax and caspase-3. CONCLUSIONS: CZX promotes hair growth to treat AGA by regulating the PI3K/Akt and apoptosis pathways.

Involvement of kynurenine pathway between inflammation and glutamate in the underlying etiopathology of CUMS-induced depression mouse model.

Inflammation and glutamate (GLU) are widely thought to participate in the pathogenesis of depression, and current evidence suggests that the development of depression is associated with the activation of the kynurenine pathway (KP). However, the exact mechanism of KP among the inflammation, GLU and depression remain poorly understood. In this study, we examined the involvement of KP, inflammation and GLU in depressive phenotype induced by chronic unpredictable mild stress (CUMS) in C57B/6 J mice. Our results showed that CUMS caused depressive like-behavior in the sucrose preference test, tail suspension test and forced swimming test. From a molecular perspective, CUMS upregulated the peripheral and central inflammatory response and activated indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of KP, which converts tryptophan (TRP) into kynurenine (KYN). KYN is a precursor for QA in microglia, which could activate the N-methyl-D-aspartate receptor (NMDAR), increasing the GLU release, mirrored by increased IDO activity, quinolinic acid and GLU levels in the hippocampus, prefrontal cortex and serum. However, intervention with IDO inhibitor 1-methyl-DL-tryptophan (50 mg/kg/s.c.) and 1-methyl-L-tryptophan (15 mg/kg/i.p.) reversed the depressive-like behaviors and adjusted central and peripheral KP's metabolisms levels as well as GLU content, but the inflammation levels were not completely affected. These results provide certain evidence that KP may be a vital pathway mediated by IDO linking inflammation and glutamate, contributing to depression.

Endoscopic submucosal dissection for early signet ring cell gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The use of endoscopic submucosal dissection (ESD) for treating early signet ring cell carcinoma (SRC) is controversial due to the risk of lymph node metastasis. AIM: To carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer. METHODS: The PubMed, Web of Science, Cochrane Library, and EMBASE databases were used to search for relevant studies evaluating the therapeutic efficacy and safety of ESD in SRC. The rates of recurrence, complete resection, incomplete resection, curative resection, en bloc resection, and adverse events were extracted and analyzed. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated by the Egger's test. Institutional review board approval and written consent were not needed for this report. RESULTS: This meta-analysis enrolled seven studies with 653 participants undergoing ESD treatment for early SRC. The overall recurrence rate was 0.010 [95% confidence interval (CI): 0.000-0.040, Z = 1.422, P = 0.155]. The total lymphovascular invasion rate was 0.038 (95%CI: 0.007-0.088, Z = 3.026, P = 0.002). The total en bloc resection rate was estimated at 0.984 (95%CI: 0.925-1.000, Z = 19.463, P = 0.000). The total complete and incomplete resection rates were estimated at 0.785 (95%CI: 0.596-0.928, Z = 9.789, P = 0.000) and 0.188 (95%CI: 0.016-0.468, Z = 2.531, P = 0.011), respectively. The total procedure-associated gastric hemorrhage and perforation rates were estimated at 0.026 (95%CI: 0.005-0.061, Z = 3.006 P = 0.003) and 0.004 (95%CI: 0.000-0.028, Z = 0.938, P = 0.348), respectively. The curative resection, vertical margin invasion, and lateral margin invasion rates were 72.1% (145/341), 2.3% (8/348), and 34.45% (41/119), respectively. CONCLUSION: ESD constitutes a promising therapeutic approach for early undifferentiated SRC gastric cancer. However, further improvements are required for increasing its treatment efficacy and reducing adverse outcomes.

Identification of AKIRIN2 as a potential biomarker and correlation with immunotherapy in gastric adenocarcinoma by integrated bioinformatics analysis.

Gastric adenocarcinoma is major type of gastric cancer that endangers human health. AKIRIN2 has been shown to be associated with cholangiocarcinoma promoting invasion and angiogenesis. In this study, AKIRIN2 is highly expressed in Gastric adenocarcinoma through bioinformatics analysis based on Stomach adenocarcinoma samples data from The Cancer Genome Atlas. Correlation analysis showed that the high-expression of AKIRIN2 was associated with poor survival rate compared to the low-expression group. Univariate and multivariate Cox regression analyses determined the correlation between clinical characteristics and overall survival. Next, the correlation between AKIRIN2 and immune infiltration was evaluated. The distribution of 24 immune cells and their correlation with the expression of AKIRIN2 were explored using the immune cell database. In addition, three Immune cell methods were used to verify the positive correlation between immune cells and AKIRIN2. Also, Genomics of Drug Sensitivity in Cancer database was utilized to verify the correlation between AKIRIN2 expression level and the efficacy of chemotherapy and immunotherapy. The results showed that AKIRIN2 is an effective biomarker of Gastric adenocarcinoma prognosis, which can guide chemotherapy and immunotherapy and clarify the progress of Gastric adenocarcinoma promoted by immune microenvironment.

Helicobacter pylori eradication: Exploring its impacts on the gastric mucosa.

Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.

Insect group II chitinase OfChtII promotes chitin degradation during larva-pupa molting.

The insect group II chitinase (ChtII, also known as Cht10) is a unique chitinase with multiple catalytic and chitin-binding domains. It has been proven genetically to be an essential chitinase for molting. However, ChtII's role in chitin degradation during insect development remains poorly understood. Obtaining this knowledge is the key to fully understanding the chitin degradation system in insects. Here, we investigated the role of OfChtII during the molting of Ostrinia furnacalis, a model lepidopteran pest insect. OfChtII was expressed earlier than OfChtI (OfCht5) and OfChi-h, at both the gene and protein levels during larva-pupa molting as evidenced by quantitative polymerase chain reaction and western blot analyses. A truncated OfChtII, OfChtII-B4C1, was recombinantly expressed in Pichia pastoris cells and purified to homogeneity. The recombinant OfChtII-B4C1 loosened compacted chitin particles and produced holes in the cuticle surface as evidenced by scanning electron microscopy. It synergized with OfChtI and OfChi-h when hydrolyzing insoluble α-chitin. These findings suggested an important role for ChtII during insect molting and also provided a strategy for the coordinated degradation of cuticular chitin during insect molting by ChtII, ChtI and Chi-h.

miR-325-3p Overexpression Inhibits Proliferation and Metastasis of Bladder Cancer Cells by Regulating MT3.

BACKGROUND miRNAs have been widely used in cancer treatment. Our study was designed to explore the effects of miR-325-3p in bladder cancer cells. MATERIAL AND METHODS Levels ofd miR-325-3p and MT3 in bladder cancer tissues and cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). miR-325-3p mimics were transfected into bladder cancer T24 cells, and cell migration and invasion rates and cell proliferation were assessed by transwell assay and Cell Counting Kit-8 (CCK-8). The target mRNA for miR-325-3p was predicted by Targetscan7.2 and confirmed by dual-luciferase reporter assay. More experiments were performed to confirm the effects of miR-325-3p and MT3 in T24 cells. Additionally, the levels of TIMP-2, MMP9, and E-cadherin were assessed by Western blotting to identify the effects of miR-325-3p and MT3 on epithelial-mesenchymal transition (EMT). RESULTS miR-325-3p expression was reduced and MT3 was increased in bladder cancer tissues and bladder cancer cells. miR-325-3p mimics suppressed cell proliferation ability and invasion and migration rates of T24 cells. Moreover, miR-325-3p was confirmed to target MT3. Further experiments showed that the effects of increased cell proliferation, invasion, migration, and EMT promoted by MT3 overexpression were abolished by miR-325-3p mimics, proving that miR-325-3p is a tumor suppressor through targeting MT3 in bladder cancer cells. CONCLUSIONS Downregulation of miR-325-3p in bladder cancer regulates cell proliferation, migration, invasion, and EMT by targeting MT3. Furthermore, miR-325-3p is a potential therapeutic target in treating bladder cancer.

Identification of potential hub-lncRNAs in ischemic stroke based on Subpathway-LNCE method.

Ischemic stroke is a devastating condition with a high burden of neurological disability and death. The aim of this study was to explore the potential long noncoding RNA (lncRNA) biomarkers underlying the mechanism of stroke. The Subpathway-LNCE method, which was specifically designed to identify lncRNAs competitively regulated functions in diseases, was applied in ischemic stroke dataset to identify ischemic-stroke-associated dysfunctional subpathway that regulated by lncRNAs. At first, based on the shared microRNA (miRNA) between miRNA-messenger RNA (mRNA) and lncRNA-miRNA interactions, lncRNA-mRNA interactions were constructed. Then, the transcription profiling of 18 631 genes was downloaded from Array Express database and was preprocessed, including normalization and gene expression difference (DEG) analysis, to identify candidate differential pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Next, the pathway-lncRNA-mRNA networks were constructed by linking lncRNAs to candidate differential pathways. At last, there were 11 lncRNAs were identified in the top three subpathways as hub-lncRNAs totally, including LINC00240, LINC00472, LINC00265, LINC00473, MIR497HG, NEXN-AS1, HCG17, MEG8, EPB41L4A-AS1, SNHG7, and BCYRN1, five of which were validated to be very effective stroke biomarker by RT-PCR. In conclusion, we applied Subpathway-LNCE method and experimental verification to identify five lncRNAs, including LINC00265, LINC00473, NEXN-AS1, HCG17, and MEG8, which were considered as important lncRNAs biomarkers in ischemic stroke.

Induction of mitochondrial-dependent apoptosis in T24 cells by a selenium (Se)-containing polysaccharide from Ginkgo biloba L. leaves.

In the present study, a selenium (Se)-containing polysaccharide (Se-GBLP) was isolated and purified from the leaves of Ginkgo biloba L. Se-GBLP was further evaluated for its antitumor activity against human bladder cancer T24 cells together with the possible mechanism of action. Our results showed that treatment of T24 cells with Se-GBLP (50, 100 and 200µg/ml) for 48h significantly inhibited cell viability and induced apoptosis in a dose- dependent manner. This Se-GBLP-induced apoptosis is associated with an increased protein expression of pro-apoptotic Bax, decreased expression of anti-apoptotic Bcl-2, loss of mitochondrial membrane potential, and cleavage of caspase-9, caspase-3 and PARP, suggesting that Se-GBLP-induced apoptosis occurs through the mitochondria-dependent pathway. Se-GBLP therefore merits further investigation as a promising preventive and/or therapeutic agent against human bladder cancer.

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO-cGMP pathway.

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid II. This study investigates the effects of icarisid II on diabetic rats with ED and its potential mechanism via the assessment of advanced glycosylation end products (AGEs), autophagy, mTOR and the NO-cGMP pathway. Icarisid II was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid II group, rats were administered icarisid II intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure (ICP/MAP). AGE concentrations, nitric oxide synthase (NOS) activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 localisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid II increased ICP/MAP values, the smooth muscle cell (SMC) growth curve, S phase and SMC/collagen fibril (SMC/CF) proportions and decreased Beclin 1 (P<0.05). Icarisid II significantly increased the proliferative index and p-p70S6K(Thr389) levels and decreased the numbers of autophagosomes and the levels of LC3-II (P<0.01). Icarisid II decreased AGE concentrations and increased cGMP concentration, NOS activity (P<0.05) and cNOS levels (P<0.01) in the diabetic ED group. Therefore, Icarisid II constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

[Comparison of clinical efficacy between Huorongbushen and indomethacin in patients with oligospermia or asthenospermia].

OBJECTIVE: To compare the clinical efficacy and safety between Huorongbushen and indomethacin in patients with oligospermia or asthenospermia. METHODS: 86 patients with oligoasthenospermia were received at our clinic of andrology. They were randomly divided into group A and B. The patients in group A received Huorongbushen 48 g daily for 3 months, and the other patients in group B were given indomethacin 50 mg daily for 3 months. The sperm parameters of the patients were analyzed by computer-assisted sperm analysis system before and after treatment. RESULTS: Patients of group A were significantly improved in sperm concentration, forward sperm motility, total sperm motility, straight line velocity and average path velocity. Patients of group B remained unimproved in sperm concentration and were significantly improved in other sperm parameters. The patients in group A reported a significantly higher sperm concentration than that in group B. There was no significant difference between group A and B in other sperm parameters. CONCLUSION: Compared with indomethacin, Huorongbushen is efficacious for oligoasthenospermia with lower side effects.