Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.

Phosphoglycerate mutase 1 that is essential for glycolysis may act as a novel metabolic target for predicating poor prognosis for patients with gastric cancer.

BACKGROUND: To identify a novel marker for gastric cancer, we examined the usefulness of phosphoglycerate mutase 1 (PGAM1) as a potential diagnostic marker using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics and evaluated its clinical significance. METHODS: Proteins from a discovery group of four paired gastric cancer tissues and adjacent gastric tissues were labeled with iTRAQ reagents and then identified and quantified using LC-MS/MS. The expression of PGAM1 was further validated in 139 gastric cancer patients using immunohistochemistry. Furthermore, the correlation of PGAM1 expression with clinical parameters was analyzed. Gene set enrichment analysis (GSEA) was performed to identify gene sets that were activated in PGAM1-overexpressing patients with gastric cancer. RESULTS: PGAM1 was significantly overexpressed in most cancers but particularly so in gastric cancer, with a sensitivity of 82.01% (95% confidence interval [CI]: 75.5%-88.5%) and specificity of 79.13% (95% CI: 72.3%-86%). Its expression was significantly associated with histological grade II and III tumors (p = 0.033), lymph node metastasis (p = 0.031), and TNM III-IV staging (p = 0.025). The area under the receiver operating characteristic (ROC) curve for the detection of PGAM1 overexpression in gastric cancer was 0.718 (p < 0.01). Furthermore, GSEA revealed that several important pathways such as glycolysis pathway and immune pathways were significantly enriched in patients with gastric cancer with PGAM1 overexpression. CONCLUSIONS: This study provided a sensitive method for detecting PGAM1, which may serve as a novel indicator for poor prognosis of gastric cancer, as well as a potent drug target for gastric cancer.

Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer.

OBJECTIVE: The sensitivity and specificity of current biomarkers for gastric cancer were insufficient. The aim of the present study was to screen novel biomarkers and determine the diagnostic values of ornithine aminotransferase (OAT) and carbamoyl phosphate synthetase 1 (CPS1) for detecting gastric cancer. METHODS: With stable isotope tags, we labelled an initial discovery group of four paired gastric cancer tissue samples and identified with LC-ESI-MS/MS. A validation group of 159 gastric cancer samples and 30 healthy controls were used to validate the candidate targets. GSEA was used to explore the pathways activated in gastric cancer. RESULTS: Four hundred and thirty one proteins were found differentially expressed in gastric cancer tissues. Of these proteins, OAT and CPS1 were found over-expressed in gastric cancer patients, with sensitivity of 70.4% (95% CI: 63.3%-77.6%) and specificity of 80.5% (95% CI: 74.3%-86.7%) for ornithine aminotransferase, and with sensitivity of 68.6% (95% CI: 61.3%-75.8%) and specificity of 73% (95% CI: 66%-79.9%) for carbamoyl phosphate synthetase 1. The co-expression of OAT and CPS1 in gastric cancer tissues has a sensitivity of 81% (95% CI: 73.2%-88.8%) and specificity of 89% (95% CI: 83%-95%). Furthermore, both OAT and CPS1 were overexpressed in patients with local invasion T3 and T4 stages than those in patients with T1 and T2 stages. The co-expression of OAT and CPS1 was strongly correlated with histological grade I 68% (95% CI: 58.7%-77.3%) and TNM stage I/II 52% (95% CI: 42%-62%). The areas under ROC curves were up to 0.758 for the co-expression of OAT and CPS1 in gastric cancer. GSEA results showed that two gene sets and 30 gene sets were activated in OAT high- and CPS1 high-expression patients with gastric cancer, respectively. CONCLUSIONS: The present findings indicated a tight correlation between the co-expression of OAT and CPS1 and the histological grade, local invasion, and TNM stages of gastric cancer. Therefore, OAT and CPS1 might be predictors for gastric cancer invasion and potential targets for anticancer drug design for gastric cancer.

Identification and validation of PGLS as a metabolic target for early screening and prognostic monitoring of gastric cancer.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6-phosphogluconolactonase (PGLS) in gastric cancer. METHODS: The protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8-plex) reagents, and followed by LC-ESI-MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan-Meier plotter database. RESULTS: The present study found that PGLS was significantly up-regulated in gastric cancer by using iTRAQ-based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post-progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e-05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her-2 (-). CONCLUSIONS: These findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post-progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow-up monitoring for gastric cancer.

Advances in Repetitive Transcranial Magnetic Stimulation for the Treatment of Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops and persists after an individual experiences a major traumatic or life-threatening event. While pharmacological treatment and psychological interventions can alleviate some symptoms, pharmacotherapy is time-consuming with low patient compliance, and psychological interventions are costly. Repetitive Transcranial Magnetic Stimulation (rTMS) is a safe and effective technique for treating PTSD, with advantages such as high compliance, low cost, and simplicity of implementation. It can even simultaneously improve depressive symptoms in some patients. Current research indicates that high-frequency rTMS shows better therapeutic effects compared to low-frequency rTMS, with no significant difference in the likelihood of adverse reactions between the two. Theta Burst Stimulation (TBS) exhibits similar efficacy to high-frequency rTMS, with shorter duration and significant improvement in depressive symptoms. However, it carries a slightly higher risk of adverse reactions compared to traditional high-frequency rTMS. Combining rTMS with psychological therapy appears to be more effective in improving PTSD symptoms, with early onset of effects and longer duration, albeit at higher cost and requiring individualized patient control. The most common adverse effect of treatment is headache, which can be improved by stopping treatment or using analgesics. Despite these encouraging data, several aspects remain unknown. Given the highly heterogeneous nature of PTSD, defining unique treatment methods for this patient population is quite challenging. There are also considerable differences between trials regarding stimulation parameters, therapeutic effects, and the role of combined psychological therapy, which future research needs to address.

Exploration of resting-state brain functional connectivity as preclinical markers for arousal prediction in prolonged disorders of consciousness: A pilot study based on functional near-infrared spectroscopy.

BACKGROUND: There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near-infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. METHODS: Five minutes resting-state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting-state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut-off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. RESULTS: The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)-based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR-based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut-off value of resting-state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. CONCLUSION: Resting-state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut-off values of resting-state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients.

Preliminary Study of Vagus Nerve Magnetic Modulation in Patients with Prolonged Disorders of Consciousness.

Background: The number of patients with prolonged disorders of consciousness (pDOC) is increasing. However, its clinical treatment remains challenging. To date, no studies have reported the effect of vagus nerve modulation (VNM) using repetitive transcranial magnetic stimulation (rTMS) in patients with pDOC. We aimed to evaluate the effect of vagus nerve magnetic modulation (VNMM) on pDOC patients. Methods: We performed VNMM in 17 pDOC patients. The Revised Coma Recovery Scale (CRS-R), Glasgow scale (GCS), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) were assessed before and after treatment. Results: Both CRS-R and GCS results showed significant improvement in p DOC patients after VNMM treatment. The CRS-R improved from 7.88 ± 2.93 to 11.53 ± 4.94. The GCS score also improved from 7.65 ± 1.9 to 9.18 ± 2.65. The number of BAEP grades I increased from 3 to 5 after treatment. The number of BAEP grades I increased from 3 to 5, grade II increased by 1, and grade III decreased from 4 to 1. Conclusion: This study provides a preliminary indication of the potential of VNMM in the rehabilitation of pDOC patients. It provides the basis for a Phase 2 or Phase 3 study of VNMM in patients with pDOC.

Prism adaptation combined with eye movement training for unilateral spatial neglect after stroke: Study protocol for a single-blind prospective, randomized controlled trial.

Background: Unilateral spatial neglect (USN) is a complex neurological syndrome that often reduces rehabilitation outcomes, prolongs patients' hospital stays, and decreases their quality of life. However, the current therapies for USN have varying efficacy. We will explore a new treatment option that combines prism adaptation (PA) with eye movement training (EMT) for the treatment of USN after stroke. Methods: We will conduct a single-blind, prospective, randomized controlled trial to assess the efficacy of the combined intervention (PA & EMT) on USN in an inpatient rehabilitation setting. The study aims to recruit 88 patients with USN after an ischemic or hemorrhagic stroke. Participants will be randomly assigned to the following four groups: (1) PA group (n = 22), (2) EMT group (n = 22), (3) PA and EMT group (n = 22), and (4) control group (n = 22). All groups will receive 10 sessions of interventions over 2 weeks, 5 times per week. Blinded assessors will conduct a baseline assessment, a post-intervention assessment, and a follow-up assessment (2 weeks post-intervention). The primary outcome measure will use the Behavioral Inattention Test-Conventional Subset (BIT-C) and Catherine Bergego Scale (CBS) to assess the levels of USN. Secondary outcome measures will assess the patient's ability to perform activities of daily living using the Modified Barthel Index (MBI). Patients who completed all treatment and assessment sessions will be included in the final analysis. Discussion: This study will explore the effects of 10 sessions of combined interventions (PA & EMT) on USN and functional capacity. This study has the potential to identify a new, evidence-based treatment option and provide new ideas for the treatment of USN. Ethics and dissemination: The study protocol has been approved by the Nanchong Central Hospital. Written informed consent will be obtained from all the participants. The results of this study will be disseminated to the public through scientific conferences and a peer-reviewed journal. Trial registration: ChiCTR, ChiCTR2100049482. Registered on 2 August 2021, http://www.chictr.org.cn/showproj.aspx?proj=130823.

Polybrominated diphenyl ethers (PBDEs) in the Danjiangkou Reservoir, China: identification of priority PBDE congeners.

Although the production of polybrominated diphenyl ethers (PBDEs) has been phased out over the past decade worldwide, they are still potentially hazardous to the environment due to their persistence and toxicity. This study investigated the levels of 55 PBDEs in water and sediments from the Danjiangkou Reservoir, China. The levels of PBDEs were in the range of not detected (ND)-286.67 ng/L in water and ND-236.04 ng/g in sediments. BDE209 was the predominant PBDE congener and constituted 15-50% and 44-68% of the total PBDEs in water and sediments, respectively. Commercial pentaBDE products (70-5DE, DE-71) were the dominant source of tetraBDE, pentaBDE, and hexaBDE, while commercial octaBDE (79-8DE) and decaBDE (102E and 82-0DE) products were the main sources of nonaBDE and decaBDE in water. PBDEs in sediments mainly stemmed from commercial decaBDE products and combustion sources. BDE-209 posed high ecological risks to aquatic organisms and dominated the total ecological risks of PBDEs. No cancer risks and non-cancer risks were observed for PBDEs. A ranking method based on four criteria, i.e., detection frequency, concentration, ecological risk, and health risks, was proposed, and 17 PBDEs were identified as high priority PBDEs for future monitoring and management in the Danjiangkou Reservoir.