A novel risk stratification approach and molecular subgroup characterization based on coagulation related genes in colon adenocarcinoma.

Colon adenocarcinoma (COAD) represents a significant health concern within the population. Advancing our understanding of COAD is imperative for early detection, enabling personalized treatment interventions, and facilitating the development of effective preventive measures. The coagulation system plays a role in tumor-related pathological processes; however, its specific involvement in COAD and potential contributors remain unclear.

Effect of Probiotic Supplements on Oxidative Stress Biomarkers in First-Episode Bipolar Disorder Patients: A Randomized, Placebo-Controlled Trial.

Currently no study has examined the effects of probiotic administration on the symptoms of anxiety, depression, and mania, as well as their correlations with the biomarkers of oxidative stress in patients with bipolar disorder (BPD). The aim of this study is to determine the effects of probiotic supplementation on plasma oxidative stress-related biomarkers and different domains of clinical symptom in patients suffering from BPD. Eighty first-episode drug-naive patients with BPD were recruited.

Disturbance of neurotransmitter metabolism in drug-naïve, first-episode major depressive disorder: a comparative study on adult and adolescent cohorts.

Neurotransmitter metabolism plays a critical role in the pathophysiology of major depressive disorder (MDD). However, whether the neurotransmitter metabolism in adolescent MDD is differentiated from adult MDD is still elusive. In the current study, plasma concentrations of monoamine and amino acid neurotransmitters as well as their metabolites, including tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillylmandelic acid (VMA), 3-methoxy-4-hydroxyphenylglycol (MHPG), glutamine (GLN), glutamate (GLU) and gamma-aminobutyric acid (GABA), were measured and compared in two cohorts of subjects (adult cohort: 31 first-episode MDD vs.

Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia.

Antipsychotic effects seem to decrease in relapsed schizophrenia patients and the underlying mechanisms remain to be elucidated. Based on the essential role of polyunsaturated fatty acids in brain function and the treatment of schizophrenia, we hypothesize that disordered fatty acid metabolism may contribute to treatment resistance in multi-episode patients. We analyzed the erythrocyte membrane fatty acids in 327 schizophrenia patients under various episodes (numbers of patients: first-episode drug naïve 89; 2-3 episodes 110; 4-6 episodes 80; over 6 episodes 48) and 159 age- and gender-matched healthy controls.

Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling.

Newly emerging evidence has implicated that progesterone receptor component 1 (PGRMC1) plays a novel role not only in the lipid disturbance induced by atypical antipsychotic drugs (AAPD) but also in the deterioration of glucose homoeostasis induced by clozapine (CLZ) treatment. The present study aimed to investigate the role of PGRMC1 signaling on hepatic gluconeogenesis and glycogenesis in male rats following CLZ treatment (20 mg/kg daily for 4 weeks). Recombinant adeno-associated viruses (AAV) were constructed for the knockdown or overexpression of hepatic PGRMC1.

Repurposing of Anti-Diabetic Agents as a New Opportunity to Alleviate Cognitive Impairment in Neurodegenerative and Neuropsychiatric Disorders.

Cognitive impairment is a shared abnormality between type 2 diabetes mellitus (T2DM) and many neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease (AD) and schizophrenia. Emerging evidence suggests that brain insulin resistance plays a significant role in cognitive deficits, which provides the possibility of anti-diabetic agents repositioning to alleviate cognitive deficits. Both preclinical and clinical studies have evaluated the potential cognitive enhancement effects of anti-diabetic agents targeting the insulin pathway.

A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits.

Ketamine exposure can model cognitive deficits associated with schizophrenia. Progesterone (PROG) and its active metabolite allopregnanolone (ALLO) have neuroprotective effects and the pathway involving progesterone receptor membrane component 1 (PGRMC1), epidermal growth factor receptor (EGFR), glucagon-like peptide-1 receptor (GLP-1R), phosphatidylinositol 3 kinase (PI3K), and protein kinase B (Akt) appears to play a key role in their neuroprotection. The present study aimed to investigate the effects of PROG (8,16 mg kg) and ALLO (8,16 mg kg) on the reversal of cognitive deficits induced by ketamine (30 mg kg) via the PGRMC1 pathway in rat brains, including hippocampus and prefrontal cortex (PFC).

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs.

Metabolic side effects such as weight gain and disturbed lipid metabolism are often observed in the treatment of atypical antipsychotic drugs (AAPDs), which contribute to an excessive prevalence of metabolic syndrome among schizophrenic patients. Great individual differences are observed but the underlying mechanisms are still uncertain. Research on pharmacogenomics indicates that gene polymorphisms involved in the pathways controlling food intake and lipid metabolism may play a significant role.

Quantitative monitoring of a panel of stress-induced biomarkers in human plasma by liquid chromatography-tandem mass spectrometry: an application in a comparative study between depressive patients and healthy subjects.

Using a metabolomic approach, we have found that stress can induce oxidative damage by disturbing the creatine/phosphocreatine shuttle system and purinergic pathway, leading to an excessive membrane breakdown. To further validate our findings and to monitor the biological impact of stress in research of clinical psychiatry, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine a panel of biomarkers comprising choline, creatine, purinergic metabolites, neurosteroids, lysophosphatidylcholines, and phosphatidylethanolamines in human plasma. After optimization of the extraction protocol, all the 15 analytes plus 4 internal standards with distinct polarities were extracted into an organic phase using methyl tert-butyl ether/methanol (1:1, v/v).

Effects of Differential Food Patterns on the Pharmacokinetics of Enteric-Coated Mesalazine Tablets in the Same Cohort of Healthy Chinese Volunteers.

This study aimed to simultaneously determine mesalazine (5-ASA) and its major metabolite N-Ac-5-ASA in the plasma and to evaluate the impact of different food patterns on the relative bioavailability and pharmacokinetics of a single oral dose of 5-ASA in healthy subjects. In this single-dose, open-label, 3-period, 3-treatment crossover study, the subjects received a single, oral dose of 500-mg enteric-coated mesalazine tablet together with either a low-fat or a high-fat breakfast or under fasting condition (reference). The pharmacokinetic parameters were determined by noncompartmental methods and analyzed with a linear mixed-effect model.

Recombinant cucurmosin-based immunotoxin targeting HER-2 with potent in vitro anti-cancer cytotoxicity.

Trastuzumab is a humanized monoclonal antibody against HER2 approved by FDA for breast and gastric cancer therapy. However, only a quarter of patients have the potential to benefit from it, and most of them develop resistance within therapy. The main purpose of this study is to broaden trastuzumab's therapeutic window by conjugating trastuzumab with recombinant cucurmosin to form an immunotoxin called T-CUS.

Genome-wide methylation analysis identifies novel prognostic methylation markers in colon adenocarcinoma.

Previous studies have indicated that abnormal methylation is a critical and early event in the pathogenesis of most types of human cancer, which contributes to tumorigenesis. However, there has been little focus on the potential of DNA methylation patterns as predictive markers for the prognosis of colon adenocarcinoma (COAD). In the present study, a genome-wide comparative analysis of DNA methylation profiles was performed between 315 COAD samples and 38 matched tumor-adjacent normal tissue samples.

A novel and safe approach: middle cranial approach for laparoscopic right hemicolon cancer surgery with complete mesocolic excision.

Background: Mastering right hemicolectomy techniques using laparoscopy in colorectal cancer surgery is very difficult. Although the long-term prognosis of laparoscopic right hemicolectomy (LRH) and complete mesocolic excision is unquestionable, different surgeons have their own opinions on routes of conducting LRH.

Objectives: LRH surgery is very complex due to the upper abdominal anatomical structure and vascular variation.