Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

No abstract

Background Satellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle‐specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored. Methods RNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1SC/WT and Tfr1SC/KO (n = 6–8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects. Results By comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell‐autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin‐1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus‐expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin‐1 to improve running time (P = 0.0257) and distance (P = 0.0248). Conclusions Satellite cell‐specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases.

Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi‐omics data, transferrin receptor 1 (Tfr1) is identified as a candidate for regulating thermogenesis in beige adipocytes. Furthermore, it is shown that mice lacking Tfr1 specifically in adipocytes have impaired thermogenesis, increased insulin resistance, and low‐grade inflammation accompanied by iron deficiency and mitochondrial dysfunction. Mechanistically, the cold treatment in beige adipocytes selectively stabilizes hypoxia‐inducible factor 1‐alpha (HIF1α), upregulating the Tfr1 gene, and thermogenic adipocyte‐specific Hif1α deletion reduces thermogenic gene expression in beige fat without altering core body temperature. Notably, Tfr1 deficiency in interscapular brown adipose tissue (iBAT) leads to the transdifferentiation of brown preadipocytes into white adipocytes and muscle cells; in contrast, long‐term exposure to a low‐iron diet fails to phenocopy the transdifferentiation effect found in Tfr1‐deficient mice. Moreover, mice lacking transmembrane serine protease 6 (Tmprss6) develop iron deficiency in both inguinal white adipose tissue (iWAT) and iBAT, and have impaired cold‐induced beige adipocyte formation and brown fat thermogenesis. Taken together, these findings indicate that Tfr1 plays an essential role in thermogenic adipocytes via both iron‐dependent and iron‐independent mechanisms.

Aim: To determine whether there is a long-term benefit of MRI-guided bilateral anterior capsulotomy in the treatment of refractory schizophrenia. Methods: 116 patients (16 patients did not complete the follow-up evaluation) with refractory schizophrenia who underwent capsulotomy were included. The treatment effect was evaluated using a series of international rating scales. Evaluations were performed at baseline, 3 weeks and 24 months after surgery. Results: The rate of effectiveness was 74% according to the Clinical Global Impression evaluation, and there was an obvious improvement based on the statistical analysis for Positive and Negative Symptom Scale (baseline vs. 24 months after surgery, 6.86 ± 8.12, 10.70 ± 8.70 vs. 26.65 ± 4.85, 21.66 ± 7.19), Brief Psychiatric Rating Scale (14.75 ± 13.21 vs. 44.97 ± 9.36), Activities of Daily Living Scale (18.06 ± 6.58 vs. 24.61 ± 8.95), Social Disability Screening Schedule (6.69 ± 6.12 vs. 15.06 ± 3.18) and Global Assessment Scale (74.35 ± 12.75 vs. 48.74 ± 9.18). Among all the symptoms of schizophrenia, aggressive behavior (82% response rate), hallucination, (71% response rate) and delusion (70% response rate) showed the best response. Conclusion: Our research indicates that capsulotomy is a relatively safe and effective intervention for patients with refractory schizophrenia. It could be an alternative therapy for those patients with chronic and severe schizophrenia. But there must be strict inclusion criteria considering the complications and irreversibility of this procedure.

ABSTRACT Ulcerative colitis (UC) is a gastrointestinal disease. The link between gut microbiota and the inflammatory response in the gut has been recently established. Restoration of gut microbiota suppresses inflammatory signaling. Kuijieling (KJL) decoction, an experimental Chinese medicine formula could ameliorate the symptom of colitis. However, the involvement of gut microbiota in its curative effect remains known. Here, we would like to assess the therapeutic effect of KJL in DSS-induced UC model. Mouse feces were collected, followed by 16S rRNA sequencing. Kuijieling decoction improved gut microbial homeostasis and suppressed inflammation in the UC model. A 5-fold cross-validation and random forest analysis identified seven signature bacterial taxa representing the DSS-mediated pathogenic condition and recovery stage upon KJL decoction treatment. Overall, the findings support the notion of KJL decoction-mediated restoration of gut microbiota as a critical step of inducing remission and alleviating UC symptoms. In the present investigation, we aimed to address the question of whether KJL decoction alleviates the UC symptoms by manipulating the gut microbial structure and function.

IBD is a chronic nonspecific inflammatory disease. IBD is characterized by a wide range of lesions, often involving the entire colon, and is characterized mainly by ulcers and erosions of the colonic mucosa.

Objective: Cervical carcinoma (CC) is a serious threat to women's health and few effective therapeutic methods have been discovered. The purpose of this study is to explore the underlying mechanism of miR-145-5p in CC. Methods: Bioinformatics methods were employed to analyze the gene expression data of CC from TCGA database. qRT-PCR was used to detect the expression of miR-145-5p and KLF5 in CC cells, and Western blot was employed for the examination of KLF5 protein level. The targeted relationship between miR-145-5p and KLF5 was verified by a dualluciferase reporter assay. Moreover, CCK-8, wound healing assay and transwell invasion assay were used to analyze the effects of miR-145-5p overexpression or KLF5 silencing on the proliferation, migration and invasion of CC cells. Results: miR-145-5p was shown to be down-regulated in CC tissues and cells, while KLF5 was up-regulated. miR-145-5p could bind to the complementary sequence within the wild type KLF5 3ʹUTR rather than the mutant one. In addition, miR-145-5p could effectively down-regulate KLF5, in turn inhibiting the proliferation, migration and invasion of CC cells. Conclusion: miR-145-5p regulates the proliferation, migration and invasion of CC cells by targeting KLF5.