The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery. Using computer algorithms to analyze digitalized immunohistochemically stained slides, GDF15 expression and the presence of M2 macrophages based on the relative density of CD204- and CD68-positive macrophages were measured in prostate: (i) benign biopsy, (ii) cancer and (iii) tumor-adjacent benign (TAB) tissue. Both M2 macrophages (P = 0.0004) and GDF15 (P \u3c 0.0001) showed significant inter-region expression differences. Based on a Cox proportional hazards model, GDF15 expression was not associated with BCR but, in men where GDF15 expression differences between cancer and TAB were highest, the risk of BCR was significantly reduced (hazard ratio = 0.26; 95% confidence interval = 0.09-0.94). In addition, cases with high levels of M2 macrophages in prostate cancer had almost a 5-fold increased risk of BCR (P = 0.01). Expression of GDF15 in prostate TAB was associated with M2 macrophage levels in both prostate cancer and TAB and appeared to moderate M2-macrophage-associated BCR risk. In summary, the relationship of GDF15 expression and CD204-positive M2 macrophage levels is different in a prostate tumor environment compared with an earlier benign biopsy and, collectively, these markers may predict aggressive disease

Impact of continuous pharmaceutical care led by clinical pharmacists during transitions of care on medication adherence and clinical outcomes for patients with coronary heart disease: a prospective cohort study

Objectives: The study aimed to explore the impact of a continuous pharmaceutical care (CPC) program during care transitions on medication adherence and clinical outcomes for patients with coronary heart disease (CHD).Methods: A prospective cohort study was conducted from April 2020 to February 2021. Patients diagnosed with CHD were selected and divided into intervention (CPC) and usual care (UC) groups by nurses at equal intervals based on admission time. The intervention group received CPC services provided by clinical pharmacists (including medication reconciliation, disease education, medication guidance, lifestyle counseling, and follow-up services) and usual care. The UC group received only routine medical care. The study compared medication adherence, clinical indicators (low-density lipoprotein cholesterol [LDL-C], blood pressure [BP], glycated hemoglobin [HbA1c] control rates), the incidence of adverse drug reactions (ADRs), and readmission rates (overall, major adverse cardiovascular events [MACEs]-related, and CHD risk factors-related) at admission and 1, 3, and 6 months after discharge between the two groups.Results: A total of 228 patients with CHD completed the study, including 113 patients in the CPC group and 115 patients in the UC group. There were no significant differences (p > 0.05) in both groups in demographic and clinical characteristics at baseline. A total of 101 drug-related problems were identified in the CPC group (an average of 0.89 per person). The CPC group showed significantly higher medication adherence at 1, 3, and 6 months after discharge than the UC group (p < 0.05). At 3 and 6 months after discharge, the intervention group had significantly higher control rates of LDL-C (61.11% vs. 44.64% at 3 months, 78.18% vs. 51.43% at 6 months), and BP (91.15% vs. 77.39% at 3 months, 88.50% vs. 77.19% at 6 months). The CPC group had higher HbA1c control rates (53.85% vs. 34.21% at 3 months, 54.05% vs. 38.46% at 6 months) than the UC group. However, the differences were not statistically significant. The incidence of ADRs 6 months after discharge was significantly lower in the CPC group than in the UC group (5.13% vs. 12.17%, p < 0.05). The CPC group had a lower overall readmission rate (13.27% vs. 20.00%), MACE-related readmission rate (5.31% vs. 12.17%), and readmission rate related to CHD risk factors (0.88% vs. 2.61%) 6 months after discharge compared to the UC group. However, these differences were not statistically significant (p > 0.05).Conclusion: CPC led by clinical pharmacists during care transitions effectively improved medication adherence, safety, and risk factor control in patients with CHD

Global intron retention mediated gene regulation during CD4+ T cell activation.

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4(+) T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4(+) T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection

Macrophage-Stimulated Cardiac Fibroblast Production of IL-6 Is Essential for TGF β/Smad Activation and Cardiac Fibrosis Induced by Angiotensin II

Interleukin-6 (IL-6) is an important cytokine participating in multiple biologic activities in immune regulation and inflammation. IL-6 has been associated with cardiovascular remodeling. However, the mechanism of IL-6 in hypertensive cardiac fibrosis is still unclear. Angiotensin II (Ang II) infusion in mice increased IL-6 expression in the heart. IL-6 knockout (IL-6-/-) reduced Ang II-induced cardiac fibrosis: 1) Masson trichrome staining showed that Ang II infusion significantly increased fibrotic areas of the wild-type mouse heart, which was greatly suppressed in IL-6-/- mice and 2) immunohistochemistry staining showed decreased expression of α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGF-β1) and collagen I in IL-6-/- mouse heart. The baseline mRNA expression of IL-6 in cardiac fibroblasts was low and was absent in cardiomyocytes or macrophages; however, co-culture of cardiac fibroblasts with macrophages significantly increased IL-6 production and expression of α-SMA and collagen I in fibroblasts. Moreover, TGF-β1 expression and phosphorylation of TGF-β downstream signal Smad3 was stimulated by co-culture of macrophages with cardiac fibroblasts, while IL-6 neutralizing antibody decreased TGF-β1 expression and Smad3 phosphorylation in co-culture of macrophage and fibroblast. Taken together, our results indicate that macrophages stimulate cardiac fibroblasts to produce IL-6, which leads to TGF-β1 production and Smad3 phosphorylation in cardiac fibroblasts and thus stimulates cardiac fibrosis

Fabrication of Functional Super-Hydrophilic TiO₂ Thin Film for pH Detection

A super-hydrophilic pH-sensitive electrode with a porous TiO2 thin film is proposed in this work and fabricated using the chemical etching method. In total, 30 groups of porous TiO2 thin film were obtained by immersing a Ti sheet in NaOH, with the solution concentration ranging from 0.5–4 M and the reaction time ranging from 15–240 min. SEM, XRD, XPS, and a contact angle meter were used to investigate the influence of the chemical etching parameters on the morphology, composition, and wettability of the fabricated electrodes. The chemical etching parameters were found to have a significant influence on the specific surface area and the component of the films, which strongly affected the wettability and pH sensing characteristics of the electrodes. The electrode obtained with a solution concentration of 1 M and reaction time of 120 min is the ideal product because of its excellent wettability, with a contact angle of 5.46°, and good pH sensing characteristics in pH buffer solutions. The electrode also showed good stability regarding its wettability and pH sensing properties during storage and utilization

A Convenient Stereoselective Reduction of <i>Gem</i>-Dibromides with a Combination of Dimethyl Phosphite and Potassium Carbonate

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Polyphenol Oxidase as a Promising Alternative Therapeutic Agent for Cancer Therapy

Cancers have always been the most difficult to fight, the treatment of cancer is still not considered. Thus, exploring new anticancer drugs is still imminent. Traditional Chinese medicine has played an important role in the treatment of cancer. Polyphenol oxidase (PPO) extracted from Edible mushroom has many related reports on its characteristics, but its role in cancer treatment is still unclear. This study aims to investigate the effects of PPO extracted from Edible mushroom on the proliferation, migration, invasion, and apoptosis of cancer cells in vitro and explore the therapeutic effects of PPO on tumors in vivo. A cell counting kit-8 (CCK8) assay was used to detect the effect of PPO on the proliferation of cancer cells. The effect of PPO on cancer cell migration ability was detected by scratch test. The effect of PPO on the invasion ability of cancer cells was detected by a transwell assay. The effect of PPO on the apoptosis of cancer cells was detected by flow cytometry. Female BALB/c mice (18–25 g, 6–8 weeks) were used for in vivo experiments. The experiments were divided into control group, model group, low-dose group (25 mg/kg), and high-dose group (50 mg/kg). In vitro, PPO extracted from Edible mushroom significantly inhibited the proliferation, migration, and invasion capability of breast cancer cell 4T1, lung cancer cell A549, and prostate cancer cell C4-2, and significantly promoted the apoptosis of 4T1, A549, and C4-2. In vivo experiments showed PPO inhibitory effect on tumor growth. Collectively, the edible fungus extract PPO could play an effective role in treating various cancers, and it may potentially be a promising agent for treating cancers

Dynamic evolution of spatial equilibrium degree of water resources composite system in system-region two stages: The case of Lianshui Basin, China

The water resources in Lianshui Basin is facing a prominent contradiction between production and ecology, as well as fierce competition among various regions. However, existing researches on spatial equilibrium typically tend to address only one of the dimensions among water resources system and other systems or among different regions, which can not meet the requirements for optimal allocation of water resources aiming for spatial equilibrium under the high-quality development strategy. The definition and quantitative evaluation method of spatial equilibrium remain unclear. In order to respond to the policy of spatial equilibrium and overcome the dilemma of water resources development and utilization under the new normal, the connotation of spatial equilibrium at two levels of system and region was presented, a quantitative dynamic evaluation method for the spatial equilibrium degree in system-region two stages was proposed in this study. A comprehensive evaluation indicators system was built for the water resources composite system composed of three subsystems: water resources, social economy and ecological environment, and a dynamic quantization model of coupling coordination degree based on the comprehensive evaluation indices of three subsystems was established, the temporal and spatial dynamic evolution process of the coupling coordination degree of water resources composite system was analyzed. At the same time, Theil index was used to research the dynamic evolution characteristics of the regional difference in coupling coordination degree in Lianshui Basin. This paper also identified the main source of difference based on the decomposition of Theil index, and the degree and trend of spatial equilibrium of water resources in Lianshui Basin were comprehensively analyzed. The results showed that the coupling coordination degree of the composite system of each district in Lianshui Basin was continuously improving, but there was no significant trend in the difference of coupling coordination degree among regions, which means the degree of spatial equilibrium in the “system stage” has notably improved, but the degree of spatial equilibrium in the “region stage” had no significant and stable increase. In addition, the difference within the region was always the main reason for the deficiency of spatial equilibrium