A novel near-infrared fluorescence probe for detecting and imaging Hg2+ in living cells.

Fluorescence imaging, as one of the important means of biological lesion analysis, is widely used in medical analysis. To improve detection specificity, near-infrared emission fluorescent probes have been developed. Sensitive and selective near-infrared (NIR) fluorescent probes for Hg2+ , which is a heavy metal ion harmful to human health, are urgently needed to investigate the physiological toxicity of Hg2+ . The NIR fluorophore based on the traditional structure of rhodamine was prepared by introducing anthocyanin functional groups, and a rhodamine spiro ring structure was constructed to recognize Hg2+ (CCS-Hg). The probe CCS-Hg demonstrated good selectivity and high detection sensitivity for Hg2+ and the most likely mechanism was verified through theoretical calculations. We applied the probe CCS-Hg in the examination of Hg2+ distribution in living cells by NIR fluorescence imaging. This work provides a promising molecular tool for studying the toxicological effects of mercury ions in cell.

Comparative efficacy of nonhormonal drugs on menopausal hot flashes.

PURPOSE: The effects of nonhormonal drugs on menopausal hot flashes are still not well quantified. We therefore did a model-based meta-analysis (MBMA) to quantitate and compare the efficacy features of nonhormonal drugs on menopausal hot flashes. METHODS: Literature was searched in the public databases to extract data of clinical trials on nonhormonal drugs, including selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), gabapentin, clonidine, and soy isoflavones. Pharmacodynamic models were used for the quantitative analysis of each drug. RESULTS: Thirty-nine studies were included in the analysis. The results revealed a classic pharmacodynamic maximal effect (Emax) model could describe the time course of hot-flash reduction by nonhormonal drugs. After deducting placebo effects, the Emax of SSRIs/SNRIs, gabapentin, clonidine, and soy isoflavones was 13.9 %, 14.8 %, 18.5 %, and 25.0 %, respectively. The time to achieve half of the maximal effect (ET50) of SSRIs/SNRIs, gabapentin, clonidine, and soy isoflavones was 0.18 weeks, 0 weeks, 0 weeks, and 11.6 weeks, respectively. The results showed that SSRIs/SNRIs, gabapentin, and clonidine had a rapid onset, which could reach the maximum effect immediately. However, the onset of soy isoflavones was very slow, and a duration of 16.6 weeks was needed to surpass the efficacy of paroxetine (a type of SSRIs). CONCLUSIONS: The information provided in this study can be used as valuable supplementary information for treatment guidelines of nonhormonal drugs on menopausal hot flashes.

Effect of different conditions on the germination of coix seed and its characteristics analysis.

Coix seed (CS) has high nutritional value, but the deep processing of CS is relatively limited. Sprouting can significantly improve nutritional value, laying the foundation for efficient consumption or further processing. The optimal conditions for the germination of CS are a soaking temperature of 36 °C for 10 h and a germination temperature of 29 °C for 24 h. Under these conditions, the final germination rate of CS reached 90%. Additionally, the content of γ-aminobutyric acid was 21.205 mg/100 g; soluble protein, free amino acids, γ-aminobutyric acid, and other essential substances increased in CS. Especially after germination, the γ-aminobutyric acid (GABA) content increased by 7.8 times compared with the GABA content of ungerminated CS. Therefore, the nutritional value and flavor of germinated CS are better than those of ungerminated ones, which establishs a solid foundation for its application in developing various products such as compound health drinks, coix yogurt, and others.

Gastric cancer fibroblasts affect the effect of immunotherapy and patient prognosis by inducing micro-vascular production.

Introduction: Immunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy. Methods: We assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis. Results: We then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group. Discussion: CAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.

Analyses of Long Noncoding RNA and mRNA Profiles in Subjects with the Phlegm-Dampness Constitution.

BACKGROUND: Constitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases. Phlegm-dampness constitution (PDC) is one of the nine constitutions in TCM, susceptible to metabolic disorders, which is mainly manifested by profuse phlegm, loose abdomen, and greasy face. Epidemiologic, genomic, and epigenetic studies have been carried out in previous works, confirming that PDC represents a distinctive population with microcosmic changes related to metabolic disorders. However, whether long noncoding RNAs (lncRNAs) play a regulatory role in metabolic disease in subjects with PDC remains largely unknown. We aimed to investigate distinct lncRNA and mRNA expression signatures and lncRNA-mRNA regulatory networks in the phlegm-dampness constitution (PDC). METHODS: The peripheral blood mononuclear cells (PBMCs) were isolated from the subjects with PDC (n = 13) and balanced constitution (BC) (n = 9). The profiles of lncRNAs and mRNAs in PBMCs were analyzed using microarray and further validated with RT-qPCR. Subsequently, pathway analysis was performed to investigate the function of differentially expressed mRNAs by using Ingenuity Pathway Analysis (IPA). RESULTS: Results suggested that some mRNAs, which were regulated by the differentially expressed lncRNAs, were mainly enriched in lipid metabolism and immune inflammation-related pathways. This was consistent with the molecular characteristics of previous studies, indicating that the clinical characteristics of metabolic disorders in PDC might be regulated by lncRNAs. Furthermore, by making coexpression network construction as well as cis-regulated target gene analysis, several lncRNA-mRNA pairs with potential regulatory relationships were identified by bioinformatic analyses, including RP11-317J10.2-CA3, RP11-809C18.3-PIP4K2A, LINC0069-RFTN1, TTTY15-ARHGEF9, and AC135048.13-ORAI3. CONCLUSIONS: This study first revealed that the expression characteristics of lncRNAs/mRNAs may be potential biomarkers, indicating that the distinctive physical and clinical characteristics of PDC might be partially attributed to the specific expression signatures of lncRNAs/mRNAs.

A novel near-infrared fluorescent probe for the dynamic monitoring of the concentration of glutathione in living cells.

In this study, a water-soluble, near-infrared fluorescent probe (EQR-S) was designed for the measurement of the glutathione (GSH) concentration. Responses of different interfering substances to the developed probe were investigated, and the luminescence mechanism was examined by theoretical calculations. Results revealed that EQR-S can be applied for the rapid, sensitive determination of the GSH concentration with a detection limit of 69 nM. Based on the above advantages, EQR-S was successfully applied to investigate the fluctuation in the GSH concentration of living cells under high-temperature stress.

Model-based comparing efficacy of fluoxetine between elderly and non-elderly participants with major depressive disorder.

BACKGROUND: The high heterogeneity was existed among the studies of the elderly participants with major depressive disorder (MDD), which may lead to incorrect conclusions in the previous meta-analysis. This study used model based meta-analysis to compare the efficacy of fluoxetine between the elderly and non-elderly participants with MDD and to explain the heterogeneity among the studies. METHODS: A comprehensive literature search was conducted in the public databases, involving utilization of fluoxetine for treating MDD in the acute-phase. The time-efficacy model was established based on the changes of the Hamilton Depression Rating Scale (HDRS) score compared to baseline level. The efficacy features and related factors of fluoxetine in the elderly participants were investigated by comparing with the non-elderly population. RESULTS: Sixty-one studies encompassing 4058 participants were included in the analysis. We found the trial design of placebo controlled vs. comparator controlled was a significant impact factor for the efficacy of fluoxetine. The typical decrease rate of HDRS score in the elderly participants was strikingly lower than that of the non-elderly participants at week 8, with 39.9% vs. 49.1% in the placebo controlled trial and 46.5% vs. 57.2% in the comparator controlled trial. LIMITATION: The efficacy of other antidepressants except fluoxetine in the elderly participants need to be explored in the future study. CONCLUSIONS: The efficacy of fluoxetine in the elderly participants was lower than that of the non-elderly participants. The heterogeneity of the trial design should be distinguished when comparing the efficacy of antidepressants between the elderly and non-elderly MDD participants.

Quantitative analysis of placebo response and factors associated with menopausal hot flashes.

OBJECTIVE: The aim of the study was to quantitatively analyze the placebo response and the factors associated with menopausal hot flashes. METHODS: The PubMed and Cochrane Library databases were searched for placebo-controlled trials that reported the treatment of menopausal hot flashes, with a retrieval deadline of December 31, 2015. The clinical and demographic characteristics of participants and placebo responses, defined as the percentage of reduction in hot flashes at each observation time point compared with that of baseline values, were extracted from the studies. Model-based meta-analysis was used to describe the time course of placebo response and identify the related factors. RESULTS: Eighty-five trials in 78 articles, involving 8,302 women, were included in the analysis. Of these, 47 trials were about hormonal drugs, 37 were about nonhormonal drugs, and 1 included both hormonal and nonhormonal drugs. Our results indicated that the placebo responses for hot flashes increased in a time-dependent manner and reached a plateau after week 12. Additionally, the placebo responses were significantly higher in the trials of hormonal drugs than in the trials of nonhormonal drugs at week 24 (-51.2% vs -40.4%; P < 0.05), and the difference between them was comparable with the effect of paroxetine. CONCLUSIONS: The placebo response for menopausal hot flashes was related to the active comparator; a higher response rate was observed in trials of hormonal drugs than in trials of nonhormonal drugs. These findings suggest that subjective expectations affect the treatment efficacy of menopausal hot flashes.