Mixed probiotics reduce the severity of stress-induced depressive-like behaviors.

In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.

GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.

BACKGROUND: Research has indicated that long-term sleep deprivation can lead to immune dysfunction and participate in the occurance and progression of tumors. However, the relationship between sleep deprivation and colon cancer remains unclear. This study explored the specific mechanism through which sleep deprivation promotes the proliferation and migration of colon cancer, with a focus on the neurotransmitter GABA. METHODS: Chronic sleep deprivation mice model were used to investigate the effect of sleep disorder on tumors. We detected neurotransmitter levels in the peripheral blood of mice using ELISA. CCK-8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the effect of GABA on colon cancer cells, while immunofluorescence showed the distribution of macrophages in lung metastatic tissues. We isolated exosomes from a GABA-induced culture medium to explore the effects of GABA-induced colon cancer cells on macrophages. Gain- and loss-of-function experiments, luciferase report analysis, immunohistochemistry, and cytokine detection were performed to reveal the crosstalk between colon cancer cells and macrophages. RESULTS: Sleep deprivation promote peripheral blood GABA level and colon cancer cell proliferation and migration. Immunofluorescence analysis revealed that GABA-induced colon cancer metastasis is associated with enhanced recruitment of macrophages in the lungs. The co-culture results showed that GABA intensified M2 polarization of macrophage induced by colon cancer cells. This effect is due to the activation of the macrophage MAPK pathway by tumor-derived exosomal miR-223-3p. Furthermore, M2-like macrophages promote tumor proliferation and migration by secreting IL-17. We also identified an endogenous miR-223-3p downregulation of the E3 ligase CBLB, which enhances the stability of cMYC protein and augments colon cancer cells proliferation and migration ability. Notably, cMYC acts as a transcription factor and can also regulate the expression of miR-223-3p. CONCLUSION: Our results suggest that sleep deprivation can promote the expression of miR-223-3p in colon cancer cells through GABA, leading to downregulation of the E3 ligase CBLB and inhibition of cMYC ubiquitination. Simultaneously, extracellular miR-223-3p promotes M2-like macrophage polarization, which leads to the secretion of IL-17, further enhancing the proliferation and migration of colon cancer cells.

Machine learning methods for accurately predicting survival and guiding treatment in stage I and II hepatocellular carcinoma.

Accurately predicting survival in patients with early hepatocellular carcinoma (HCC) is essential for making informed decisions about treatment and prognosis. Herein, we have developed a machine learning (ML) model that can predict patient survival and guide treatment decisions. We obtained patient demographic information, tumor characteristics, and treatment details from the SEER database. To analyze the data, we employed a Cox proportional hazards (CoxPH) model as well as 3 ML algorithms: neural network multitask logistic regression (N-MLTR), DeepSurv, and random survival forest (RSF). Our evaluation relied on the concordance index (C-index) and Integrated Brier Score (IBS). Additionally, we provided personalized treatment recommendations regarding surgery and chemotherapy choices and validated models' efficacy. A total of 1136 patients with early-stage (I, II) hepatocellular carcinoma (HCC) who underwent liver resection or transplantation were randomly divided into training and validation cohorts at a ratio of 3:7. Feature selection was conducted using Cox regression analyses. The ML models (NMLTR: C-index = 0.6793; DeepSurv: C-index = 0.7028; RSF: C-index = 0.6890) showed better discrimination in predicting survival than the standard CoxPH model (C-index = 0.6696). Patients who received recommended treatments had higher survival rates than those who received unrecommended treatments. ML-based surgery treatment recommendations yielded higher hazard ratios (HRs): NMTLR HR = 0.36 (95% CI: 0.25-0.51, P < .001), DeepSurv HR = 0.34 (95% CI: 0.24-0.49, P < .001), and RSF HR = 0.37 (95% CI: 0.26-0.52, P = <.001). Chemotherapy treatment recommendations were associated with significantly improved survival for DeepSurv (HR: 0.57; 95% CI: 0.4-0.82, P = .002) and RSF (HR: 0.66; 95% CI: 0.46-0.94, P = .020). The ML survival model has the potential to benefit prognostic evaluation and treatment of HCC. This novel analytical approach could provide reliable information on individual survival and treatment recommendations.

Modelling methane emissions and grain yields for a double-rice system in Southern China with DAYCENT and DNDC models.

Methane (CH4) is an important greenhouse gas that contributes to climate change and one of its major sources is rice cultivation. The main aim of this paper was to compare two well-established biogeochemical models, namely Daily Century (DAYCENT) and DeNitrification-DeComposition (DNDC) for estimating CH4 emissions and grain yields for a double-rice cropping system with tillage practice and/or stubble incorporation in the winter fallow season in Southern China. Both models were calibrated and validated using field measured data from November 2008 to November 2014. The calibrated models performed effectively in estimating the daily CH4 emission pattern (correlation coefficient, r = 0.58-0.63, p < 0.001), but model efficiency (EF) values were higher in stubble incorporation treatments, with and without winter tillage (treatments S and WS) (EF = 0.22-0.28) than that in winter tillage without stubble incorporation treatment (W) (EF = -0.06-0.08). We recommend that algorithms for the impacts of tillage practice on CH4 emission should be improved for both models. DAYCENT and DNDC also estimated rice yields for all treatments without a significant bias. Our results showed that tillage practice in the winter fallow season (treatments WS and W) significantly decreased annual CH4 emissions, by 13-37 % (p < 0.05) for measured values, 15-20 % (p < 0.05) for DAYCENT-simulated values, and 12-32 % (p < 0.05) for DNDC-simulated values, respectively, compared to no-till practice (treatments S), but had no significant impact on grain yields.

From Medical Herb to Functional Food: Development of a Fermented Milk Containing Silybin and Protein from Milk Thistle.

Milk thistle is a traditional medicinal herb. Silybin is a medicinal component found in the seed coat of milk thistle, which has liver-protective and anti-cancer properties. Conventional studies have focused on the extraction of silybin with organic reagents, which was inapplicable to the food industry. This study aims to develop a fermented milk containing silybin and protein from the milk thistle seeds. A three step procedure was developed, comprising homogenization of milk thistle seeds, NaHCO3 heat treatment, and microbial fermentation. The silybin was characterized by high performance liquid chromatography, and the protein was quantified and electrophorized. It was found that the homogenization step was essential for the preparation of protein, and the NaHCO3 heat treatment was the crucial step in obtaining silybin. The optimal NaHCO3 treatment settings were 1% NaHCO3, 60°C, and 3 h, and the optimal strains for microbial fermentation were L131 (Rummeliibacillus stabekisii) and RS72 (Lactobacillus plantarum). The silybin yield in the fermented milk reached 11.24-12.14 mg/g seeds, accounting for 72.6-78.4% of the total silybin in the milk thistle seeds, and the protein yield reached 121.8-129.6 mg/g seeds. The fermented milk had a slightly sweet yoghurt-like flavor and could be used as a dietary supplement for silybin and protein.

Increasing rate of hospitalization for severe peptic ulcer in digestive disease emergencies after the pandemic.

Since December 2019, the novel coronavirus has spread worldwide, affecting more than 510 million people, with more than 6 million deaths. However, some of the potential effects of the pandemic have not been thoroughly studied. We collected data from 2 regional emergency centers from May to November for the years 2015 to 2019, before the pandemic, and from May to November 2020, after the pandemic. We evaluated the incidence of each major type of digestive disease before and after the pandemic in adults at the 2 hospitals, which experienced coronavirus disease 2019 outbreaks with varying severity. A total of 11,394 patients were enrolled in the study Affiliated Hospital of Putian University (PUTIAN, n = 5503) Union Hospital, Tongji Medical college, Huazhong University of Science and Technology (UNION, n = 5891), and the proportion of male patients was approximately the same at both hospitals, with 3360 (61.1%) and 3680 (62.5%), respectively. The average ages of the patients were 55.8 ±â€…18.4 years PUTIAN and 54.3 ±â€…15.8 years UNION. The numbers of patients at the 2 hospitals increased steadily, but in 2020, the number of patients at UNION declined. The baseline characteristics of the 2 groups at the 2 hospitals showed significant differences for age before and after the pandemic but not for sex. The constituent ratios of diseases in each year in the 2 hospitals differed. The number of patients with peptic ulcers in 2020 was significantly different from those in each year from 2015 to 2019 (PUTIAN 2015-2020, 15.0%, 18.2%, 14.9%, 16.9%, 19.5%, 34.9%; UNION 2015-2020, 29.2%, 32.5%, 29.3%, 29.4%, 29.7%, 41.3%, respectively). The rates of peptic ulcer increased dramatically in both hospitals in 2020. An increase in the incidence of severe peptic ulcer was observed after the pandemic compared to the same period before the pandemic. Therefore, these factors should be considered in the formulation of public health strategies and the allocation of medical resources in the post pandemic era.

Can an incomplete ERAS protocol reduce postoperative complications compared with conventional care in laparoscopic radical resection of colorectal cancer? A multicenter observational cohort and propensity score-matched analysis.

Background: The patients undergoing laparoscopic radical colorectomy in many Chinese hospitals do not achieve high compliance with the ERAS (enhanced recovery programs after surgery) protocol. Methods: The clinical data from 1,258 patients were collected and divided into the non-ERAS and incomplete ERAS groups. Results: A total of 1,169 patients were screened for inclusion. After propensity score-matched analysis (PSM), 464 pairs of well-matched patients were generated for comparative study. Incomplete ERAS reduced the incidence of postoperative complications (p = 0.002), both mild (6.7% vs. 10.8%, p = 0.008) and severe (3.2% vs. 6.0%, p = 0.008). Statistically, incomplete ERAS reduced indirect surgical complications (27,5.8% vs. 59, 12.7) but not local complications (19,4.1% vs. 19, 4.1%). The subgroup analysis of postoperative complications revealed that all patients benefited from the incomplete ERAS protocol regardless of sex (male, p = 0.037, 11.9% vs. 17.9%; female, p = 0.010, 5.9% vs. 14.8%) or whether neoadjuvant chemotherapy was administered (neoadjuvant chemotherapy, p = 0.015, 7.4% vs. 24.5%; no neoadjuvant chemotherapy, p = 0.018, 10.2% vs. 15.8%). Younger patients (<60 year, p = 0.002, 7.6% vs. 17.5%) with a low BMI (<22.84, 9.4% vs. 21.1%, p < 0.001), smaller tumor size (<4.0 cm, 8.1% vs. 18.1%, p = 0.004), no fundamental diseases (8.8% vs. 17.0%, p = 0.007), a low ASA score (1/2, 9.7% vs. 16.3%, p = 0.004), proximal colon tumors (ascending/transverse colon, 12.2% vs. 24.3%, p = 0.027), poor (6.1% vs. 23.7%, p = 0.012)/moderate (10.3% vs. 15.3%, p = 0.034) tumor differentiation and no preoperative neoadjuvant radiotherapy (10.3% vs. 16.9%, p = 0.004) received more benefit from the incomplete ERAS protocol. Conclusion: The incomplete ERAS protocol decreased the incidence of postoperative complications, especially among younger patients (<60 year) with a low BMI (<22.84), smaller tumor size (<4.0 cm), no fundamental diseases, low ASA score (1/2), proximal colon tumors (ascending/transverse colon), poor/moderate differentiation and no preoperative neoadjuvant radiotherapy. ERAS should be recommended to as many patients as possible, although some will not exhibit high compliance. In the future, the core elements of ERAS need to be identified to improve the protocol.

Lactobacillus Ameliorates SD-Induced Stress Responses and Gut Dysbiosis by Increasing the Absorption of Gut-Derived GABA in Rhesus Monkeys.

Sleep deprivation (SD) has become a health problem in the modern society. Although probiotics supplementation has been proven to improve SD-induced gut dysbiosis, the potential neuroendocrine mechanisms remain elusive. In this study, thirty rhesus monkeys (RMs) were recruited. Paradoxical sleep, bright light, and noise were used to build an RM SD model. We examined the plasma γ-aminobutyric acid (GABA), stress hormones, and inflammatory cytokines using ELISAs. 16S ribosomal DNA sequencing and untargeted metabolomics sequencing were employed to detect gut microbial community and metabolites, respectively. The results of our study showed that RMs subjected to SD had elevated plasma stress hormones (such as cortisol and norepinephrine) and proinflammatory cytokines (such as TNF-α, IL-6, and IL-8), and a decreased anti-inflammatory cytokine IL-10 level. Additionally, SD could give rise to a significant change in gut microbiota and metabolites. The differential gut microbiota and metabolites caused by SD were enriched in the signaling pathways related to GABA metabolism. Pearson correlation analysis revealed that there is a significant correlation between plasma GABA and SD-induced stress responses and gut dysbiosis. The supplementation of GABA-producing probiotics could significantly increase the relative abundance of Lactobacillus and plasma GABA levels, and reverse SD-induced stress responses and gut dysbiosis. Therefore, we speculated that SD-induced stress response and gut dysbiosis might be an outcome of reduced gut-derived GABA absorption. The supplementation of GABA-producing Lactobacillus might be beneficial for the treatment of SD-induced intestinal dysfunction.

Stress-induced epinephrine promotes epithelial-to-mesenchymal transition and stemness of CRC through the CEBPB/TRIM2/P53 axis.

BACKGROUND: Previous studies have indicated that chronic emotional stressors likely participate in the occurrence of cancers. However, direct evidence connecting stress and colorectal cancer development remains almost completely unexplored. METHODS: Chronic stress mouse model was used to investigate the influence of stress on tumorigenesis. Several major agonists and antagonists of adrenergic receptors were applied to investigate the effects of ß-adrenergic signaling on the development of CRC. Chromatin immunoprecipitation assays (CHIP) were used to investigate the binding of p53 and CEBPB to TRIM2 promoter. Mammosphere cultures, Cell Counting Kit-8 (CCK-8) assay, colony-formation assay, scratch wound healing assays, qPCR, immunofluorescence, coimmunoprecipitation and western blotting were used to explore the effect of stress-induced epinephrine on the CEBPB/TRIM2/P53 axis and the progress of CRC cells. RESULTS: In this study, we found that stress-induced epinephrine (EPI) promotes the proliferation, metastasis and CSC generation of CRC primarily through the ß2-adrenergic receptor. Furthermore, our studies also confirmed that chronic stress decreased the stability of p53 protein by promoting p53 ubiquitination. Results of transcriptome sequencing indicated that TRIM2 was overexpressed in cells treated with EPI. Further studies indicated that TRIM2 could regulate the stability of p53 protein by promoting p53 ubiquitination. Finally, we further proved that CEBPB was regulated by EPI and acts as the upstream transcription factor of TRIM2. CONCLUSIONS: Our studies proved that stress-induced EPI promotes the development and stemness of CRC through the CEBPB/TRIM2/P53 axis.

PLAGL2 promotes the proliferation and migration of gastric cancer cells via USP37-mediated deubiquitination of Snail1.

Rationale: PLAGL2 (pleomorphic adenoma gene like-2), a zinc finger PLAG transcription factor, is aberrantly expressed in several malignant tumors. However, the biological roles of PLAGL2 and its underlying mechanism in gastric cancer (GC) remain unclear. Methods: A series of experiments in vitro and in vivo were conducted to reveal the role of PLAGL2 in GC progression. Results: The data revealed that PLAGL2 promotes GC cell proliferation, migration, invasion, and EMT in vitro and in vivo. Mechanistically, we demonstrated the critical role of PLAGL2 in the stabilization of snail family transcriptional repressor 1 (Snail1) and promoting Snail1-mediated proliferation and migration of GC cells. PLAGL2 activated the transcription of deubiquitinase USP37, which then interacted with and deubiquitinated Snail1 protein directly. In addition, GSK-3ß-dependent phosphorylation of Snail1 protein is essential for USP37-mediated Snail1 deubiquitination regulation. Conclusions: In general, PLAGL2 promotes the proliferation and migration of GC cells through USP37-mediated deubiquitination of Snail1 protein. This work provided potential therapeutic targets for GC treatment.

Development and validation of MMR prediction model based on simplified clinicopathological features and serum tumour markers.

BACKGROUND: Although simplified clinicopathological features and serum tumour markers (STMs) were reported to be associated with the status of mismatch repair (MMR) in colorectal cancer (CRC) patients, their predictive value alone or in combination for MMR status remains unknown. METHODS: A retrospective analysis of 3274 participants with MMR testing and STMs measurements from two institutions was conducted. The prediction model was developed in the primary cohort that consisted of 1964 participants. Best subset regression was applied to select the most useful predictors from the primary dataset. The performance of the nomogram was evaluated with respect to its calibration, discrimination, and clinical usefulness. External validation was performed in an independent validation cohort of 1310 consecutive CRC patients. FINDINGS: Among the ten simplified clinicopathological features, seven variables were selected as the best subset of risk factors to develop pathology-based model, including age, tumour diameters, histology, tumour location, perineural invasion, the number of sampled lymph nodes (LNs) and positive LNs. The model showed good calibration and discrimination, with an AUC of 0.756 (95% CI, 0.722 to 0.789) in the primary cohort and 0.754 (95% CI, 0.715 to 0.793) in the validation cohort. After the addition of CEA and CA 72-4, the performance of pathology-based model was significantly improved in in both the primary cohort (AUC: 0.805 (0.774-0.835) vs. 0.756 (0.722-0.789), P < 0.001) and validation cohort (AUC: 0.796 (0.758-0.835) vs. 0.754 (0.715-0.793), P < 0.001). The results of decision curve analysis revealed that using our models to predict the status of MMR would add more benefit than either the detect-all-patients scheme or the detect-none scheme. INTERPRETATION: The models based on simplified clinicopathological features alone or in combination with STMs can be conveniently used to facilitate the postoperative individualized prediction of MMR status in CRC patients.

MicroRNA-214-3p targets the PLAGL2-MYH9 axis to suppress tumor proliferation and metastasis in human colorectal cancer.

Evidence has shown that microRNAs (miRNAs) participate in the progression of CRC. Previous studies have indicated that miR-214-3p is abnormally expressed in various malignant tumors. However, the biological function it plays in CRC and the potential mechanism are unclear. Here, we demonstrated that miR-214-3p was obviously downregulated in CRC. Moreover, we found a strong correlation between the miR-214-3p level and tumor size and lymphatic metastasis. Furthermore, when miR-214-3p was decreased by an Lv-miR-214-3p inhibitor, the proliferation and migration of SW480 and HCT116 cells were significantly increased. As expected, the ability of proliferation and migration was significantly suppressed when miR-214-3p was overexpressed in DLD1 cells. According to the dual-luciferase reporter results, PLAGL2 was found to be a direct downstream molecule of miR-214-3p. Chromatin immunoprecipitation (CHIP) confirmed that MYH9, a well-known cytoskeleton molecule in CRC, was a direct targeting gene of PLAGL2. Silencing PLAGL2 or MYH9 could reverse the effect of a miR-214-3p inhibitor on CRC cells. In summary, our studies proved that low expression of miR-214-3p and overexpression of downstream PLAGL2 in CRC indicated a poor prognosis. MiR-214-3p suppressed the malignant behaviors of colorectal cancer by regulating the PLAGL2/MYH9 axis. MiR-214-3p might be a novel therapeutic target or prognostic marker for CRC.

Evaluation of China's Environmental Pressures Based on Satellite NO2 Observation and the Extended STIRPAT Model.

China's rapid urbanization and industrialization have affected the spatiotemporal patterns of nitrogen dioxide (NO2) pollution, which has led to greater environmental pressures. In order to mitigate the environmental pressures caused by NO2 pollution, it is of vital importance to investigate the influencing factors. We first obtained data for NO2 pollution at the city level using satellite observation techniques and analyzed its spatial distribution. Next, we introduced a theoretical framework, an extended stochastic impacts by regression on population, affluence, and technology (STIRPAT) model, to quantify the relationship between NO2 pollution and its contributing natural and socio-economic factors. The results are as follows. Cities with high NO2 pollution are mainly concentrated in the North China Plain. On the contrary, southwestern cities are characterized by low NO2 pollution. In addition, we find that population, per capita gross domestic product, the share of the secondary industry, ambient air pressures, total nighttime light data, and urban road area have a positive impact on NO2 pollution. In contrast, increases in the normalized difference vegetation index (NDVI), relative humidity, temperature, and wind speed may reduce NO2 pollution. These empirical results should help the government to effectively and efficiently implement further emission reductions and energy saving policies in Chinese cities in a bid to mitigate the environmental pressures.

Improving risk management by using the spatial interaction relationship of heavy metals and PAHs in urban soil.

Identifying combined pollution risk areas is difficult because of the complex pollutant sources and heterogeneous soil properties in urban systems. This study used bivariate local Moran's I to analyze the spatial interaction between heavy metals and PAHs, revealed the causes of spatial interaction patterns through PMF, and proposed a risk zoning approach for combined pollution in urban areas. The results showed that both heavy metals and PAHs had high spatial heterogeneity in urban soil. Bivariate LISA maps revealed the spatial interactions between heavy metals and PAHs. The historical area was the hotspot of combined pollution. The overlay of pollutant sources and sinks was responsible for the spatial interaction patterns of combined organic and inorganic pollution. Coal consumption was the main emission source for heavy metal and PAHs pollution, accounting for 31% and 21%, respectively. We used bivariate LISA as the auxiliary variable to reduce the uncertainty of identification combined pollution risk zones. More than 11% of the total area clustered significantly where concentration of both heavy metals and PAHs ware in excess of the risk threshold. This study indicates that we can provide better decision-making support for soil risk management based on the knowledge derived from spatial interaction analysis.

The effects of poloxamer 188 on the autophagy induced by traumatic brain injury.

Poloxamer 188 (P188) has been reported to reseal plasma membranes and attenuate TBI-induced neuronal death by suppressing apoptosis. Recent studies also confirm increased autophagy after traumatic brain injury (TBI). The present study aimed to investigate the effects of plasmalemmal resealing by P188 on neuronal autophagy in TBI. Scratch test was performed in rat cell line PC-12 in vitro, followed by immunofluorescence analysis of LC3 24h after PC-12 cell stretch-injury in vitro. CD1 mice were randomized into saline and P188-treatment groups (both undergoing intravenous injection of 4mg/ml, 100µl via the caudal vein 30min after TBI) as well as sham group. To analyze the effect of P188 on autophagy, the LC3 protein levels were assessed by western blotting 1h, 6h, 12h, 24h, and 48h after TBI. The autophagy-associated protein levels of Beclin-1, Bcl-2, and p62 were likewise determined. In vitro, the scratch test showed that the wound healing rate was significantly improved at 12h and 24h in P188 groups, and LC3 immunofluorescence analysis indicated that P188 induced extensive formation of LC3 puncta in PC-12 cells. In vivo, western blotting analyses revealed elevations of the LC3-II/LC3-I and Beclin-1/bcl-2 ratios as well as downregulation of p62 in the saline group, in contrast with the more significant increases of LC3-II/LC3-I and Beclin-1/bcl-2 ratios and the further downregulation of p62 in P188-treated group. These results revealed that plasma membranes were resealed after TBI, in which P188 aggravated autophagy in vivo.

Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury.

The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

The neuroprotective effect of apelin-13 in a mouse model of intracerebral hemorrhage.

Adipocytokine apelin-13 is a peptide which could reportedly protect the brain against ischemic reperfusion injury and traumatic brain injury (TBI). Whether apelin-13 has any roles to play in intracerebral hemorrhage (ICH) has not been clarified. We aimed to investigate the roles of apelin-13 in ICH and effects on ICH-induced apoptosis. Firstly, CD-1 mice were subjected to infusion of Type IV collagenase (to induce ICH) or saline (for shams) into the left striatum. ICH animals received intracerebroventricular administration of vehicle, apelin-13 (50µg dissolved in 5µl saline) immediately after ICH. The motor function and the cerebral water content (CWC) as well as blood brain barrier (BBB) disruption were measured, coupled with determination of ICH-induced neural cell death by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). The apoptosis-associated proteins caspase-3 and Bcl-2 as well as the brain edema-associated proteins aquaporin-4 (AQP4) and MMP-9 were all assessed with western blotting. The results showed that apelin-13 decreased CWC and reduced Evans blue leakage into injured hemispheres, with the motor function significantly improved. Additionally, apelin-13 also acutely decreased the number of ICH-induced TUNEL-positive (TUNEL(+)) cells at 48h after ICH. The expressions of AQP4, MMP-9, caspse-3 and Bcl-2 were all downregulated by apelin-13 at 24h and 48h after ICH. All these results revealed that apelin-13 attenuated brain edema and reduced cellular death by suppressing apoptosis after ICH in mice.

[Mechanism of TRIM24 to Regulate Resistance of Gefitinib in NSCLC cells].

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance significantly limits its use in clinical practice. Study found that TRIM24 was overexpressed in non-small cell lung cancer (NSCLC) tissues and regulate cell growth, cell cycle and apoptosis in lung cell lines. The aim of this study is to explore the mechanism of TRIM24 to regulate resistance of Gefitinib in NSCLC cells. METHODS: MTT and apoptosis were used to detect the change of cell grow and cell apoptosis with down-expression TRIM24 and ShTRIM24 with presence of Gefitinib. Meanwhile, Western blot was used to detect the expression of protein related to apoptosis and AKT signal path. RESULTS: TRIM24 interference could improve the effect of gefitinib on cell growth inhibition and upregulate the cell apoptosis in A549 cell. Down-regulated of endogenous TRIM24 and ShTRIM24 with Gifitinib could also reduce the protein related apoptosis, such as p-BAD and Bcl-2, and the protein PIK3CA related AKT signal path in A549 cell. CONCLUSIONS: TRIM24 could regulate required resistance to Gefitinib via Akt pathway in NSCLC.

[Regulation Mechanism of MTA3 in the Apoptosis of NSCLC Cells].

BACKGROUND: Metastasis-associated protein 3 (MTA3) was originally found as a member of a small protein family (including MTA1, MTA2 and MTA3), and it has been proven that MTA3 had different roles in different types of human cancers. The aim of this study is to explore the function of MTA3 to regulate the cell apoptosis in lung cancer. METHODS: Western blot and Real-time PCR were used to detect the expression level of MTA3 after transfection in non-small cell lung cancer (NSCLC) cells A549 and H157. Apoptosis analysis was used to detect the change of cell apoptosis with upregulated/downregulated of MTA3, and Western blot was used to detect the the expression of the protein related with apoptosis, while downregulate the expression of MTA3 in NSCLC cells A549 and H157. RESULTS: Downregulated of endogenous MTA3 could promote apoptosis in NSCLC cells, meanwhile, siMTA3 could upregulate the protein of BAX, Cleved-Caspase-3, p-PARP, and dowmregulate the protein of Bcl-2. CONCLUSIONS: The data we present here indicate that MTA3 suppress apoptosis of A549 an H157 cells by inhibiting BAX, PARP expression.
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Apelin-13 attenuates traumatic brain injury-induced damage by suppressing autophagy.

The adipocytokine apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous and cardiovascular systems. Previous studies had found apelin-13 reduces brain injuries and postischemic cerebral edema through blocking programmed cell death, Apelin-13 is also able to inhibit glucose deprivation induced cardiomyocyte autophagy in a concentration dependent fashion. To observe the effect of Apelin-13 on the brain injury induced by traumatic brain injury (TBI), and explore the effect of Apelin-13 on autophagy in TBI, We performed The neurological test, and the numbers of TBI-induced neural cell death were also counted by propidium iodide labeling. At last, the autophagy associated proteins LC3, Beclin-1, Bcl-2, p62 were also assessed with western-blotting. Compared with saline vehicle groups, the neural cell death, lesion volume, and neural dysfunction were attenuated by apelin-13 after TBI. In additionally, Apelin-13 also reversed TBI induced downregulation of LC3, Beclin-1, Bcl-2, p62 expression, compared with saline vehicle groups, at 24 and 48 h post TBI. Apelin-13 attenuates TBI induced brain damage by suppressing autophagy. All these results revealed that Apelin-13 suppressed autophagy. The autophagy may be involved in the mechanism of Apelin-13 rescue the subsequent damaged neuron in TBI.