Abstract Background Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. ...This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. Methods This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. Results The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio95% CI, 6.092.08–17.83) or during hospitalization (4.181.62–10.78). Conclusion The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.
Heterotopic ossification (HO) is defined as the formation of bone tissues outside the bones, such as in the muscles. Currently, the mechanism of HO is still unclear. Tendon stem cells (TSCs) play ...important roles in the occurrence and development of HO. The inflammatory microenvironment dominated by macrophages also plays an important role in the course of HO. The commonly used clinical treatment methods, such as nonsteroidal anti-inflammatory drugs and radiotherapy, have relatively large side effects, and more efficient treatment methods are needed in clinical practice. Under physiological conditions, retinoic acid receptor (RAR) signal transduction pathway inhibits osteogenic progenitor cell aggregation and chondrocyte differentiation. We focus on palovarotene, a retinoic acid γ-receptor activator, showing an inhibitory effect on HO mice, but the specific mechanism is still unclear. This study was aimed at exploring the specific molecular mechanism of palovarotene by blocking osteogenic differentiation and HO formation of TSCs in vitro and in vivo in an inflammatory microenvironment. We constructed a coculture model of TCSs and polarized macrophages, as well as overexpression and knockdown models of the Smad signaling pathway of TCSs. In addition, a rat model of HO, which was constructed by Achilles tendon resection, was also established. These models explored the role of inflammatory microenvironment and Smad signaling pathways in the osteogenic differentiation of TSCs which lead to HO, as well as the reversal role played by palovarotene in this process. Our results suggest that, under the stimulation of inflammatory microenvironment and trauma, the injured site was in an inflammatory state, and macrophages were highly concentrated in the injured site. The expression of osteogenic and inflammation-related proteins, as well as Smad proteins, was upregulated. Osteogenic differentiation was performed in TCSs. We also found that TCSs activated Smad and NF-κB signaling pathways, which initiated the formation of HO. Palovarotene inhibited the aggregation of osteogenic progenitor cells and macrophages and attenuated HO by blocking Smad and NF-κB signaling pathways. Therefore, palovarotene may be a novel HO inhibitor, while other drugs or antibodies targeting Smad and NF-κB signaling pathways may also prevent or treat HO. The expressions of Smad5, Id1, P65, and other proteins may predict HO formation.
In this the antibacterial of quercetin against
Alicyclobacillus acidoterrestris
was evaluated by measuring the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). ...Subsequently, the effect of quercetin on
A. acidoterrestris
cell membrane was evaluated through scanning electron microscopy (SEM), surface hydrophobicity determination, diacetate fluorescein staining and propidium iodide (PI) staining. Additionally, the effects of quercetin on intracellular macromolecules and cell metabolism were explored by measuring the culture medium protein, bacterial protein and intracellular sodium and potassium adenosine triphosphate (ATP) enzyme activity. The results revealed that quercetin exhibited the MIC and MBC values of 100 ug/mL and 400 ug/mL, respectively, against
A. acidoterrestris
. The SEM results revealed that quercetin could induce irreversible damage to the cell membrane effectively. Moreover, quercetin could enhance the surface hydrophobicity of
A. acidoterrestris
. The results of flow cytometry and fluorescence microscopy analyses revealed that quercetin could promote cell damage by altering the cell membrane permeability of
A. acidoterrestris
, inducing the release of nucleic acid substances from the cells. Furthermore, the determination of protein content in the culture medium, bacterial protein content, and the Na(+)/K(+)-ATPase activity demonstrated that quercetin could reduce the intracellular protein content and impedes protein expression and ATPase synthesis effectively, leading to apoptosis.
Decellularized extracellular matrix hydrogel (ECM hydrogel), a natural material derived from normal tissue with unique biocompatibility properties, is widely used for tissue repair. However, there ...are still problems such as poor biological activity and insufficient antimicrobial property. To overcome these drawbacks, fibroblast growth factor 2 (FGF 2) containing exosome (exo.sup.FGF 2) was prepared to increase the biological activity. Furthermore, the antimicrobial capacity of ECM hydrogel was optimised by using copper ions as a ligand-bonded cross-linking agent. The decellularized extracellular matrix hydrogel, intricately cross-linked with copper ions through ligand bonds and loaded with FGF 2 containing exosome (exo.sup.FGF 2@ECM/Cu.sup.2+ hydrogel), has demonstrated exceptional biocompatibility and antimicrobial properties. In vitro, exo.sup.FGF 2@ECM/Cu.sup.2+ hydrogel effectively promoted cell proliferation, migration, antioxidant and inhibited bacterial growth. In vivo, the wound area of rat treated with exo.sup.FGF 2@ECM/Cu.sup.2+ hydrogels were significantly smaller than that of other groups at Day 5 (45.24% + or - 3.15%), Day 10 (92.20% + or - 2.31%) and Day 15 (95.22% + or - 1.28%). Histological examination showed that exo.sup.FGF 2@ECM/Cu.sup.2+ hydrogels promoted angiogenesis and collagen deposition. Overall, this hydrogel has the potential to inhibit bacterial growth and effectively promote wound healing in a variety of clinical applications.
The aim of the present study was to survey the growth and astaxanthin production of E17, an astaxanthin-rich mutant of Chlorella zofingiensis, through feeding the low-cost carbon source cane ...molasses. In heterotrophic batch cultivation, E17 fed with pretreated molasses achieved biomass (1.79 g L⁻¹ day⁻¹) and astaxanthin (1.99 mg L⁻¹ day⁻¹) productivities comparable to those with glucose, which were about 2- and 2.8-fold of those fed with untreated molasses, respectively. Molasses-induced astaxanthin accumulation may be attributed to the elicited expression of carotenogenic genes, in particular the genes specifically responsible for the ketolation and hydroxylation of β-carotene to form astaxanthin. A two-stage fed-batch strategy was employed to grow E17 and induce astaxathin accumulation, resulting in 45.6 g L⁻¹ biomass and 56.1 mg L⁻¹ astaxanthin, the highest volumetric astaxanthin yield ever reported for this alga. In addition, the astaxanthin production by E17 was tested with a semi-continuous culture method, where the directly diluted raw molasses (giving 5 g L⁻¹ sugar) was used as the carbon source. Little growth inhibition of E17 was observed in the semi-continuous culture with a biomass productivity of 1.33 g L⁻¹ day⁻¹ and an astaxanthin productivity of 0.83 mg L⁻¹ day⁻¹. The mixotrophic semi-continuous cultures enhanced the biomass and astaxanthin productivities by 29.3 % and 42.2 %, respectively. This study highlights the potential of using the industrially cheap cane molasses towards large-scale cost-saving production of the high-value ketocarotenoid astaxanthin.
CircRNAs play crucial roles in multiple tumours. However, the functions of most circRNAs in cervical cancer remain unclear.
This study collected GSE113696 data from the GEO database to search for ...differentially expressed circRNAs in cervical cancer. Quantitative reverse transcription PCR was used to detect the expression level of circNEIL3 in cervical cancer cells and tissues. Then, functional experiments in vitro and in vivo were performed to evaluate the effects of circNEIL3 in cervical cancer.
CircNEIL3 was highly expressed in cervical cancer. In vivo and in vitro experiments verified that circNEIL3 enhanced the proliferation capacity of cervical cancer cells. RNA immunoprecipitation, luciferase reporter assay, pull-down assay, and fluorescent in situ hybridization confirmed the interaction between circNEIL3 and miR-137 in cervical cancer. A luciferase reporter assay showed that circNEIL3 adsorbed miR-137 and upregulated KLF12 to regulate the proliferation of cervical cancer cells.
CircNEIL3 is an oncogene in cervical cancer and might serve as a ceRNA that competitively binds to miR-137, thereby indirectly upregulating the expression of KLF12 and promoting the proliferation of cervical cancer cells.
Background
Alterations of epigenetic modification patterns are potential markers of cancer. The current study characterized six histone modifications in osteosarcoma and identified epigenetically ...dysregulated long non-coding RNAs (epi-lncRNAs).
Methods
Multi-omics data were obtained from osteosarcoma cell line SJSA1 and a normal cell line. Differentially expressed lncRNAs (DElncRNAs) between osteosarcoma and normal skeletal muscle were analyzed using Limma. MACS2 was applied to identify the “peaks” modified by each histone in the cell. Promoters or enhancers of DElncRNA were overlapped with differential histone-modified regions (DHMR) to screen epi-lncRNAs. Univariate and multivariate Cox regression analysis were performed to detect the genes closely related to the prognosis of osteosarcoma and to construct risk models.
Results
A total of 17 symbolic epi-lncRNA in osteosarcoma were screened, and 13 of them were differentially expressed between osteosarcoma and normal samples. Eight epi-lncRNAs were retained by Univariate Cox regression analysis. Four of these epi-lncRNAs were used to construct an epi-lncRNA signature. The risk score of each osteosarcoma sample in the high- or low-risk group was estimated according to the epi-lncRNA signature. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group. The area under the receiver operating characteristic (ROC) curve of the model was 0.79 and 0.82 for 1-, 3-, and 5-year OS, respectively.
Conclusion
Our results revealed the histone modification pattern in osteosarcoma and developed 4-epi-lncRNA signature to predict the prognosis of osteosarcoma, laying a foundation for the identification of highly specific epigenetic biomarkers for osteosarcoma.
Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the ...cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and pre- and post-task saliva samples were collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule and Positive and Negative Syndrome Scale. The results showed (1) that the cortisol response and negative emotions in patients with schizophrenia differed significantly from those in healthy volunteers, (2) there were significant interactions between the sampling time and diagnosis for saliva cortisol levels, (3) there were significant interactions between the scoring time and diagnosis for the negative affect score of the PANAS, and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. These findings indicated an abnormal cortisol profile in patients with schizophrenia, which might be a biological characteristic of the disease.
Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how ...microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility.
We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology.
FES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31
-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05).
Microglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis.
Chitin is the most abundant natural glycosaminoglycan that is derived from marine crustaceans and has enormous potential in biomedical applications because of its high similarity in chemical ...structure to the component of extracellular matrix. However, the key challenge remains the discovery of appropriate solvents for dissolving chitin and the limited understanding of the solution properties of chitin solutions, which hampers its development and applications. An aqueous KOH/urea solution was demonstrated to be a high-efficiency, energy-saving, and “green” solvent for chitin dissolution. Herein, we report the self-assembly and gelation behavior of chitin in aqueous KOH/urea solution using atomic force microscopy, fluorescence microscopy, rheology, wide-angle X-ray diffractometry, and differential scanning calorimetry. The molecular conformation, aggregate structure, and macroscopic solution properties of chitin in aqueous KOH/urea solution are affected by the temperature, chitin concentration, molecular weight, and aging time of the chitin solution. Understanding the self-assembly and gelation behavior of chitin solutions will enable accurate manipulation of the properties of chitin-based materials in potential applications such as structural materials, biomedicine, textile, and so on.
The molecular conformation, aggregate structure, microstructure, and macroscopic solution properties of the chitin solution in aqueous KOH/ urea solution are dominated by the temperature and aging time of the chitin solution. The aged chitin solution showed significantly different solution properties and thermo-reversible gelation behavior with the fresh chitin solution. Display omitted
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