Palmatine ameliorates N-methyl-N'-nitrosoguanidine-induced chronic atrophic gastritis through the STAT1/CXCL10 axis.

Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti-inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N-methyl-N'-nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose-dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA-seq and western blot revealed that PAL significantly improved IL-17, TNF, and NF-kappa B inflammation-related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL-17, TNF-α, and p-p65 expression. In conclusion, PAL was proposed to mitigate MNNG-induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.

Circular RNAs in tumor immunity and immunotherapy.

Circular RNAs (circRNAs) are unique noncoding RNAs that have a closed and stable loop structure generated through backsplicing. Due to their conservation, stability and tissue specificity, circRNAs can potentially be used as diagnostic indicators and therapeutic targets for certain tumors. Many studies have shown that circRNAs can act as microRNA (miRNA) sponges, and engage in interactions with proteins and translation templates to regulate gene expression and signal transduction, thereby participating in the occurrence and development of a variety of malignant tumors. Immunotherapy has revolutionized the treatment of cancer. Early researches have indicated that circRNAs are involved in regulating tumor immune microenvironment and antitumor immunity. CircRNAs may have the potential to be important targets for increasing sensitivity to immunotherapy and expanding the population of patients who benefit from cancer immunotherapy. However, few studies have investigated the correlation between circRNAs and tumor immunity. In this review, we summarize the current researches on circRNAs involved in antitumor immune regulation through different mechanisms and their potential value in increasing immunotherapy efficacy with the goal of providing new targets for cancer immunotherapy.

Albumin-Based Microneedles for Spatiotemporal Delivery of Temozolomide and Niclosamide to Resistant Glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard therapy includes maximal surgical resection, radiotherapy, and adjuvant temozolomide (TMZ) administration. However, the rapid development of TMZ resistance and the impermeability of the blood-brain barrier (BBB) significantly hinder the therapeutic efficacy. Herein, we developed spatiotemporally controlled microneedle patches (BMNs) loaded with TMZ and niclosamide (NIC) to overcome GBM resistance. We found that hyaluronic acid (HA) increased the viscosity of bovine serum albumin (BSA) and evidenced that concentrations of BSA/HA exert an impact degradation rates exposure to high-temperature treatment, showing that the higher BSA/HA concentrations result in slower drug release. To optimize drug release rates and ensure synergistic antitumor effects, a 15% BSA/HA solution constituting the bottoms of BMNs was chosen to load TMZ, showing sustained drug release for over 28 days, guaranteeing long-term DNA damage in TMZ-resistant cells (U251-TR). Needle tips made from 10% BSA/HA solution loaded with NIC released the drug within 14 days, enhancing TMZ's efficacy by inhibiting the activity of O6-methylguanine-DNA methyltransferase (MGMT). BMNs exhibit superior mechanical properties, bypass the BBB, and gradually release the drug into the tumor periphery, thus significantly inhibiting tumor proliferation and expanding median survival in mice. The on-demand delivery of BMNs patches shows a strong translational potential for clinical applications, particularly in synergistic GBM treatment.

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.

Most human Transcription factors (TFs) genes encode multiple protein isoforms differing in DNA binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators", both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.

Appropriately Reduced Nitrogen and Increased Phosphorus in Ratooning Rice Increased the Yield and Reduced the Greenhouse Gas Emissions in Southeast China.

Reducing greenhouse gas emissions while improving productivity is the core of sustainable agriculture development. In recent years, rice ratooning has developed rapidly in China and other Asian countries, becoming an effective measure to increase rice production and reduce greenhouse gas emissions in these regions. However, the lower yield of ratooning rice caused by the application of a single nitrogen fertilizer in the ratooning season has become one of the main reasons limiting the further development of rice ratooning. The combined application of nitrogen and phosphorus plays a crucial role in increasing crop yield and reducing greenhouse gas emissions. The effects of combined nitrogen and phosphorus application on ratooning rice remain unclear. Therefore, this paper aimed to investigate the effect of combined nitrogen and phosphorus application on ratooning rice. Two hybrid rice varieties, 'Luyou 1831' and 'Yongyou 1540', were used as experimental materials. A control treatment of nitrogen-only fertilization (187.50 kg·ha-1 N) was set, and six treatments were established by reducing nitrogen fertilizer by 10% (N1) and 20% (N2), and applying three levels of phosphorus fertilizer: N1P1 (168.75 kg·ha-1 N; 13.50 kg·ha-1 P), N1P2 (168.75 kg·ha-1 N; 27.00 kg·ha-1 P), N1P3 (168.75 kg·ha-1 N; 40.50 kg·ha-1 P), N2P1 (150.00 kg·ha-1 N; 13.50 kg·ha-1 P), N2P2 (150.00 kg·ha-1 N; 27.00 kg·ha-1 P), and N2P3 (150.00 kg·ha-1 N; 40.50 kg·ha-1 P). The effects of reduced nitrogen and increased phosphorus treatments in ratooning rice on the yield, the greenhouse gas emissions, and the community structure of rhizosphere soil microbes were examined. The results showed that the yield of ratooning rice in different treatments followed the sequence N1P2 > N1P1 > N1P3 > N2P3 > N2P2 > N2P1 > N. Specifically, under the N1P2 treatment, the average two-year yields of 'Luyou 1831' and 'Yongyou 1540' reached 8520.55 kg·ha-1 and 9184.90 kg·ha-1, respectively, representing increases of 74.30% and 25.79% compared to the N treatment. Different nitrogen and phosphorus application combinations also reduced methane emissions during the ratooning season. Appropriately combined nitrogen and phosphorus application reduced the relative contribution of stochastic processes in microbial community assembly, broadened the niche breadth of microbial communities, enhanced the abundance of functional genes related to methane-oxidizing bacteria and soil ammonia-oxidizing bacteria in the rhizosphere, and decreased the abundance of functional genes related to methanogenic and denitrifying bacteria, thereby reducing greenhouse gas emissions in the ratooning season. The carbon footprint of ratooning rice for 'Luyou 1831' and 'Yongyou 1540' decreased by 25.82% and 38.99%, respectively, under the N1P2 treatment compared to the N treatment. This study offered a new fertilization pattern for the green sustainable development of rice ratooning.

Microneedle Patch Delivery of PLCG1-siRNA Efficient Enhanced Temozolomide Therapy for Glioblastoma.

The blood-brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through in situ implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.

CRISPR-Cas12a based target recognition initiated duplex-specific nuclease enhanced fluorescence and colorimetric analysis of cell-free DNA (cfDNA).

The significant role of cell-free DNA (cfDNA) for disease diagnosis, including cancer, has garnered a lot of attention. The challenges of creating target-specific primers and the possibility of false-positive signals make amplification-based detection methods problematic. Fluorescent biosensors based on CRISPR-Cas have been widely established, however they still require an amplification step before they can be used for detection. To detect cfDNA, researchers have created a CRISPR-Cas12a-based nucleic acid amplification-free fluorescent biosensor that uses a combination of fluorescence and colorimetric signaling improved by duplex-specific nuclease (DSN). DSN-assisted signal recycling is initiated in H1@MBs when the target cfDNA activates the CRISPR-Cas12a complex, leading to the degradation of single-strand DNA (ssDNA) sequences. This method has an extremely high detection limit for the BRCA-1 breast cancer gene. In addition to measuring viral DNA in a field-deployable and point-of-care testing (POCT) platform, this fast and highly selective sensor can be used to evaluate additional nucleic acid biomarkers.

Integrating transcriptomics and network pharmacology to reveal the mechanisms of total Rhizoma Coptidis alkaloids against nonalcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY: This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS: The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS: TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS: TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.

Role of bioactive peptides derived from food proteins in programmed cell death to treat inflammatory diseases and cancer.

Bioactive peptides are specific peptide which usually contains 2-20 amino acid residues and actively exerts various functions and biological activities and ultimately affect health. Programmed cell deaths are some styles of cell death discovered in recent years, which is the key to tissue development and balance, eliminating excess, damaged or aging cells. More importantly, programmed cell death is a potential way to treat inflammatory diseases and cancer. In this review, through screening references from 2015 to present, we introduce the effect of bioactive peptides derived from food proteins on inflammatory diseases or cancer through regulating programmed cell deaths, including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis. And this review also introduces the targets of these bioactive peptides to regulate programmed cell death. The purpose of this review is to help to expand the prospective applications of bioactive peptides in the field of inflammatory disease and cancer to provide some guidance.

Helicobacter pylori promotes inflammatory factor secretion and lung injury through VacA exotoxin-mediated activation of NF-κB signaling.

Previous reports have shown that Helicobacter pylori (H. pylori) infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major H. pylori exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to H. pylori infection and VacA. Mice were treated with H. pylori and VacA, and histopathological analysis of lung tissues was performed using hematoxylin-eosin, Masson's trichrome, and periodic acid Schiff staining. The secretion of inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay. The expression of VacA, nuclear factor-kappa B (NF-κB), and p65 NF-κB was analyzed by Western blotting and immunofluorescence. Cell proliferation and apoptosis were assessed using the MTS assay and flow cytometry, respectively. In mice, H. pylori infection and VacA treatment promoted the secretion of the inflammatory factors interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), IL-6, and IL-8, increased p65 NF-κB protein phosphorylation, and induced lung injury. Furthermore, H. pylori infection promoted VacA production. In an in vitro cell model, VacA treatment significantly suppressed the proliferation of WI-38 and BEAS-2B cells, promoted apoptosis, induced TNF-α, IL-1ß, IL-6, and IL-8 secretion, and promoted p65 NF-κB protein phosphorylation and NF-κB nuclear transfer. The NF-κB inhibitor BAY11-7082 alleviated VacA-induced inflammation and apoptosis and increased cell viability. In conclusion, VacA promotes the secretion of inflammatory factors and induces lung injury through NF-κB signaling.

Residual based attention-Unet combing DAC and RMP modules for automatic liver tumor segmentation in CT.

Purpose: Due to the complex distribution of liver tumors in the abdomen, the accuracy of liver tumor segmentation cannot meet the needs of clinical assistance yet. This paper aims to propose a new end-to-end network to improve the segmentation accuracy of liver tumors from CT. Method: We proposed a hybrid network, leveraging the residual block, the context encoder (CE), and the Attention-Unet, called ResCEAttUnet. The CE comprises a dense atrous convolution (DAC) module and a residual multi-kernel pooling (RMP) module. The DAC module ensures the network derives high-level semantic information and minimizes detailed information loss. The RMP module improves the ability of the network to extract multi-scale features. Moreover, a hybrid loss function based on cross-entropy and Tversky loss function is employed to distribute the weights of the two-loss parts through training iterations. Results: We evaluated the proposed method in LiTS17 and 3DIRCADb databases. It significantly improved the segmentation accuracy compared to state-of-the-art methods. Conclusions: Experimental results demonstrate the satisfying effects of the proposed method through both quantitative and qualitative analyses, thus proving a promising tool in liver tumor segmentation.

Phospholipase Cγ1 (PLCG1) overexpression is associated with tumor growth and poor survival in IDH wild-type lower-grade gliomas in adult patients.

Gliomas are the most common and recalcitrant intracranial tumors, approximately a quarter of which are classified as lower-grade gliomas (WHO II-III). Although the prognosis of lower-grade gliomas (LGGs) is significantly better than that of higher-grade gliomas, as a highly heterogeneous tumor type, the prognosis of LGGs varies greatly based on the molecular diagnosis. IDH wild-type used to be regarded as a dismal prognostic biomarker in LGGs; however, several studies revealed that IDH wild-type LGGs might not always be equivalent to glioblastoma (WHO IV). Hence, we hypothesize that underlying biological events in LGGs can result in different prognosis. In our study, transcriptome profiling was performed in 24 samples of LGG, and the results showed that the expression of phospholipase Cγ1 (PLCG1) was significantly correlated with IDH1/2 status and patients' clinical outcome. Furthermore, the cancer genome atlas (TCGA) and the Chinese glioma genome atlas (CGGA) databases verified that elevated PLCG1 expression was associated with tumor progression and poor survival in LGG patients. Moreover, PLCG1-targeted siRNA dramatically affected the growth, migration and invasiveness of IDH wild-type LGG cell lines. In in vitro and in vivo experiments, the PLC-targeted drug significantly suppressed the tumor growth of IDH wild-type LGG cell lines in vitro and tumors in mouse models. Taken together, our results demonstrated that higher PLCG1 expression was associated with tumor growth and worse prognosis in IDH wild-type LGGs and PLCG1 could serve as a potential therapeutic target for IDH wild-type LGG patients.

Potency of miR-144-3p in promoting abdominal aortic aneurysm progression in mice correlates with apoptosis of smooth muscle cells.

Abdominal aortic aneurysm (AAA), a life-threatening disease, is commonly diagnosed among people with risk factors, including increasing age, male gender, and smoking. The apoptosis of smooth muscle cells (SMCs) has been reported to disrupt the vascular structural integrity, which causes AAA. Thus, we sought to characterize the potential role of microRNA (miR)-144-3p in SMC apoptosis, and to outline the molecular mechanisms involved in this pathway. We collected pathological abdominal aortic tissues and adjacent normal aortic biopsy specimens from 18 patients undergoing AAA repair surgery. The relationship between miR-144-3p expression and SMC proliferation was assessed by transfecting mimic/inhibitor of miR-144-3p in human aortic smooth muscle cells (HASMCs). Anti-growth effect of miR-144-3p and related genes was evaluated in a murine AAA model. Dual luciferase reporter gene assay was adopted to validate the targeting relationship between miR-144-3p and enhancer of zeste homolog 2 (EZH2), and the enrichment of EZH2 in the p21 promoter region was determined by chromatin immunoprecipitation assay. MiR-144-3p was highly expressed in AAA tissues. Enhanced miR-144-3p diminished SMC proliferation by binding to the EZH2 3'-untranslated region and thereby inhibiting EZH2 expression. In addition, EZH2 was highly enriched in the promoter region of p21, and knockdown of p21 expression could rescue the effect of miR-144-3p on SMC proliferation and apoptosis. miR-144-3p serves as a promoter for the apoptosis of SMCs, which contributes to the occurrence and progression of AAA. This observation will serve as the basis for further investigations into potential p21-based therapies for AAA treatment.

Silk Microneedle Patch Capable of On-Demand Multidrug Delivery to the Brain for Glioblastoma Treatment.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Surgery followed by chemotherapy and radiotherapy remains the standard treatment strategy for GBM patients. However, challenges still exist when surgery is difficult or impossible to remove the tumor completely. Herein, the design, fabrication and application of a heterogenous silk fibroin microneedle (SMN) patch is reported for circumventing the blood-brain barrier and releasing multiple drugs directly to the tumor site for drug combination treatment. The biocompatible and biodegradable SMN patch can dissolve slowly over time, allowing the sustained release of multiple drugs at different doses. Furthermore, it can be triggered remotely to induce rapid drug delivery at a designated stage after implantation. In the GBM mouse models, two clinically relevant chemotherapeutic agents (thrombin and temozolomide) and targeted drug (bevacizumab) are loaded into the SMN patch with individually controlled release profiles. The drugs are spatiotemporally and sequentially delivered for hemostasis, anti-angiogenesis, and apoptosis of tumor cells. Device application is non-toxic and results in decreased tumor volume and increased survival rate in mice. The SMN patch with on-demand multidrug delivery has potential applications for the combined administration of therapeutic drugs for the clinical treatment of brain tumors when other methods are insufficient.

Comparison of ultrasound-guided high-intensity focused ultrasound ablation and hysteroscopic myomectomy for submucosal fibroids: a retrospective study.

OBJECTIVE: To compare the safety, reintervention and pregnancy outcomes between ultrasound-guided high intensity focused ultrasound (USgHIFU) and hysteroscopic myomectomy (HM) for submucosal fibroids. MATERIALS AND METHODS: A total of 215 patients with a solitary submucosal fibroid treated by USgHIFU or HM at the third Xiangya Hospital were retrospectively reviewed. Among them, 58 treated with USgHIFU, 157 treated with HM. RESULTS: A significant difference was observed in size, location and type of the fibroids, effective rate, and cumulative reintervention rate between the two groups (p < .05). The size of the fibroids was 57.9 ± 1.9 mm in the USgHIFU group, while it was 32.6 ± 1.2 mm in the HM group. The number of the fibroids at horn or fundus/uterine cavity was 16/42 in the USgHIFU group, while it was 21/136 in the HM group. The number of type I/II/2-5 was 16/17/25 in the USgHIFU group, while it was 133/24/0 in the HM group. In the USgHIFU group, the effective rate was 100% and the cumulative reintervention rate at 50 (17-97) months was 19.0%, while in the HM group, it was 94.3% and 7.6%, respectively. During the follow-up period, the pregnancy rate was 22.4% (13/58) and the reintervention rate due to invalid and recurrence was 15.5% (9/58) in the USgHIFU group, while they were 18.5% (29/157) and 7.0% (11/157) in the HM group. No significant difference was observed between the two groups (p > .05). Furthermore, the reintervention rate was positively correlated with age, treatment methods and parity and fertility requirements. No other significant difference was observed between the two groups. CONCLUSIONS: Both USgHIFU and HM are safe and effective in treating submucosal fibroids. Compared with the HM group, the USgHIFU group had lower postoperative complications, but higher reintervention rate, with similar recurrence rate, pregnancy rate and reintervention rate due to invalid and recurrence. Reintervention was related to age, treatment methods, parity and fertility requirements.

Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery.

Systemic inflammatory response after cardiovascular surgery is associated with poor prognosis, to which gut barrier impairment is related. To investigate whether perioperative changes of the gut microbiome are associated with systemic and intestinal inflammatory response, we examined changes of the gut microbiome, intestinal homeostasis, and systemic inflammatory response in cardiovascular patients before (Pre) surgery and on the first defecation day [postoperative time 1 (Po1)] or a week [postoperative time 2 (Po2)] postsurgery. Markedly, the enhanced systemic inflammatory response was observed in Po1 and Po2 compared with that in Pre. In line with inflammatory response, impaired gut barrier and elevated gut local inflammation were observed in Po1 and Po2. Microbiome analysis showed a remarkable and steady decline of alpha diversity perioperatively. In addition, microbial composition in the postoperation period was characterized by significant expansion of Enterococcus along with a decrease in anaerobes (Blautia, Faecalibacterium, Bifidobacterium, Roseburia, Gemmiger, [Ruminococcus], and Coprococcus), which were typically health-associated bacteria. Spearman correlation analysis showed microbiome disorder was associated with enhanced systemic inflammatory response and intestinal dysbiosis. These results suggest that microbiome disorder was related to disturbed gut homeostatic and subsequently elevates plasma endotoxin and systemic inflammatory response after cardiovascular surgery. This study not only highlights gut microbiome would be considered in future clinical practice but also proposes a promising perspective of potential diagnostic and therapeutic options for perioperative management of cardiovascular surgery patients.

Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor.

In this work, we discovered a new fermentation broth that can prevent and regulate alcoholic liver disease (ALD) and intestinal flora, which fermented the mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1. The contents of polyphenols, puerarin, total isoflavones, and amino acids were significantly increased. Animal experiments showed that the fermentation broth could improve the liver indexes of ALD mice model, increase the activity of superoxide dismutase and glutathione in liver tissue, and reduce the level of malondialdehyde (MDA). Furthermore, the fermentation broth can reduce the levels of serum lipopolysaccharide (LPS), inflammatory factors interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Importantly, intestinal flora analysis showed that the fermentation broth could increase the abundance of Lactobacillales and reduce the production of Gram-negative bacteria, thereby reducing the abnormal increase in bacterial diversity caused by alcohol. In conclusion, we may have discovered a new functional food raw material with great application potential. The above findings indicate that the fermentation broth can actively regulate the intestinal flora and improve liver inflammation. The underlying mechanism might be that the fermentation broth could enhance intestinal permeability and reduce the inflammatory signals and LPS transmitted through the gut-liver axis, thereby reducing the oxidative stress and inflammation of the liver caused by alcohol.

Gly-Pro-Ala peptide and FGSHF3 exert protective effects in DON-induced toxicity and intestinal damage via decreasing oxidative stress.

Deoxynivalenol (DON), a common mycotoxin, usually induces oxidative stress and intestinal injury of humans and animals. This study aims to investigate the protective effect of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate fraction 3 (FGSHF3), on alleviating the toxicity and oxidative stress induced by DON in the mice and IPEC-J2 cells. DON treatment decreases average daily gain and feeds intake, which causes enlargement of the liver and spleen. FGSHF3 (200 mg/kg) and GPA (200 mg/kg) treatment significantly increase average daily gain and inhibits enlargement of the liver and spleen. Furthermore, FGSHF3 and GPA treatment significantly alleviates intestinal injury and maintains tight junction in mice and IPEC-J2 cells. FGSHF3 and GPA treatment significantly inhibits ROS and MDA production and enhances antioxidant enzyme activity, such as CAT, SOD-1, GCLM, GCLC, and GSH-PX. Furthermore, FGSHF3 and GPA treatment promote Nrf2 migration from the cytoplasm to the nucleus, resulting in exerting antioxidant effects. And its effects are abolished after Nrf2 is knockdown by siRNA. Overall, our results suggest GPA peptide may be a promising candidate for the alleviation of DON-induced toxicity in humans and animals.

Karyotyping of circulating tumor cells for predicting chemotherapeutic sensitivity and efficacy in patients with esophageal cancer.

BACKGROUND: Aneuploidy of chromosome 8 in circulating tumor cells (CTCs) has been reported correlates with therapeutic efficacy and prognosis in patients with advanced gastric cancer. However, it is not clear whether it is also appropriate for other cancer. Therefore, in this study, we evaluate the clinical application aneuploidy of CTCs for esophageal cancer. METHODS: Peripheral blood were collected for karyotyping analysis before and after first 4-cycles chemotherapy from seventy nine patients with newly diagnosed esophageal cancer. Karyotyping of chromosome 8 in CTCs detected by SET-iFISH (Subtraction Enrichment-Immunostaining fluorescence in situ hybridizatio) in those patients were grouped into two categories according to CTC number: triploid group and non-triploid group. Pearson Chi-Square were used to compare the association between different aneuploidy type and chemotherapeutic sensitivity and efficacy. RESULTS: Among the 16 patients with triploid of chromosome 8, 4 patients benefit, and of the 63 patients with non-triploid, 54 patients benefit. Chi-square test analysis found that clinical benefit of non-triploid patients was significantly higher than triploid patients, suggesting non-triploid patients were more sensitive to chemotherapy than triploid patients. After 4-cycles chemotherapy, it is found that chemotherapeutic efficacy was positively correlated with non-triploid proportion. These results suggest that non-triploid proportion could be used as a candidate maker for assessing chemotherapeutic efficacy. CONCLUSIONS: Monitoring aneuploidy of chromosome 8 in CTCs before and after chemotherapy may help predict sensitivity and efficacy of chemotherapy in patients with esophageal cancer.