Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) often leads to sudden cardiac death. Persistent myocardial ischemia increases oxidative stress and impairs mitochondrial function, contributing significantly to postinfarction cardiac dysfunction and remodeling, and the subsequent progression to heart failure (HF). Tetrahydrocurcumin (THC), isolated from the rhizome of turmeric, has antioxidant properties and has been shown to protect against cardiovascular diseases. However, its effects on HF after MI are poorly understood. PURPOSE: The objective was the investigation of the pharmacological effects of THC and its associated mechanisms in the pathogenesis of HF after MI. METHODS: A total of 120 mice (C57BL/6, male) were used for the in vivo experiments. An MI mouse model was created by permanent ligation of the left anterior descending coronary artery. The mice received oral dose of THC at 120 mg/kg/d and the effects on MI-induced myocardial injury were evaluated by assessment of cardiac function, histopathology, myocardial oxidative levels, and mitochondrial function. Molecular mechanisms were investigated by intraperitoneal injection of 50 mg/kg of the SIRT3 selective inhibitor 3-TYP. Meanwhile, mouse neonatal cardiomyocytes were isolated and cultured in a hypoxic incubator to verify the effects of THC in vitro. Lastly, SIRT3 and Nrf2 were silenced using siRNAs to further explore the regulatory mechanism of key molecules in this process. RESULTS: The mouse hearts showed significant impairment in systolic function after MI, together with enlarged infarct size, increased myocardial fibrosis, cardiac hypertrophy, and apoptosis of cardiomyocytes. A significant reversal of these changes was seen after treatment with THC. Moreover, THC markedly reduced reactive oxygen species generation and protected mitochondrial function, thus mitigating oxidative stress in the post-MI myocardium. Mechanistically, THC counteracted reduced Nrf2 nuclear accumulation and SIRT3 signaling in the MI mice while inhibition of Nrf2 or SIRT3 reversed the effects of THC. Cell experiments showed that Nrf2 silencing markedly reduced SIRT3 levels and deacetylation activity while inhibition of SIRT3 signaling had little impact on Nrf2 expression. CONCLUSION: This is the first demonstration that THC protects against the effects of MI. THC reduced both oxidative stress and mitochondrial damage by regulating Nrf2-SIRT3 signaling. The results suggest the potential of THC in treating myocardial ischemic diseases.

Resilience, Insight, Self-Compassion, and Empowerment (RISE): A Randomized Controlled Trial of a Psychoeducational Group Program for Nurses.

BACKGROUND: Nurses tend to be vulnerable to burnout and compassion fatigue due to constant workplace stressors. There is a need to provide advocacy, education, programming, and resources in the areas of positive coping and self-care to reduce burnout symptoms and promote well-being. RISE is an 8-week psychoeducational group intervention for nurses with four themes: resilience, insight, self-compassion, and empowerment. AIMS: This randomized controlled trial examined the effects of RISE on mental well-being. METHODS: The sample included 75 registered nurses who work in a hospital-based setting. Outcomes included resilience, insight, self-compassion, empowerment, stress mind-set, perceived stress, and burnout. Independent-samples t tests were conducted to compare outcomes between intervention and wait-list control groups at baseline and 1-month follow-up, as well as at 3-month follow-up. Supplemental analyses included paired-samples t tests and linear mixed models to compare the outcomes of the intervention group participants at baseline to 1-month follow-up, as well as at 3-month and 6-month follow-ups. RESULTS: Participants in the intervention group showed improved levels of insight (i.e., engagement in self-reflection), perceived stress, and burnout (i.e., emotional exhaustion) when compared with the control group and improved levels of resilience, self-compassion, stress mind-set, and perceived stress when compared with their baseline. CONCLUSIONS: This study informs how RISE affects nurse well-being and may be an effective intervention for reducing burnout and stress. This type of whole-person intervention can support nurses to improve their well-being and ability to cope amid the complex interplay of factors at the individual, unit, and organizational levels.

Siglec-15 as an Emerging Target for Next-generation Cancer Immunotherapy.

Immunomodulatory agents blocking the PD-1/PD-L1 pathway have shown a new way to treat cancer. The explanation underlying the success of these agents may be the selective expression of PD-L1 with dominant immune-suppressive activities in the tumor microenvironment (TME), supporting a more favorable tumor response-to-toxicity ratio. However, despite the big success of these drugs, most patients with cancer show primary or acquired resistance, calling for the identification of new immune modulators in the TME. Using a genome-scale T-cell activity array in combination with bioinformatic analysis of human cancer databases, we identified Siglec-15 as a critical immune suppressor with broad upregulation on various cancer types and a potential target for cancer immunotherapy. Siglec-15 has unique molecular features compared with many other known checkpoint inhibitory ligands. It shows prominent expression on macrophages and cancer cells and a mutually exclusive expression with PD-L1, suggesting that it may be a critical immune evasion mechanism in PD-L1-negative patients. Interestingly, Siglec-15 has also been identified as a key regulator for osteoclast differentiation and may have potential implications in bone disorders not limited to osteoporosis. Here, we provide an overview of Siglec-15 biology, its role in cancer immune regulation, the preliminary and encouraging clinical data related to the first-in-class Siglec-15 targeting mAb, as well as many unsolved questions in this pathway. As a new player in the cancer immunotherapeutic arena, Siglec-15 may represent a novel class of immune inhibitors with tumor-associated expression and divergent mechanisms of action to PD-L1, with potential implications in anti-PD-1/PD-L1-resistant patients.

Isotope tracers for lead and strontium sources in the Tieguanyin tea garden soils and tea leaves.

The concentrations of Pb & Sr in Tieguanyin tea leaves and soils from 15 tea gardens of Anxi, China, were determined and the sources of Pb & Sr in soil and leaf samples were analysed using isotope tracing technology. The results showed pH in soils had significant correlations to both acid-extractable Pb & Sr in soils and new leaves. The Pb concentration in leaves was significantly lower than that in soils, especially the acid-extractable Pb in soils. The low Bio-concentration Factor (BCF) indicated the bioavailable Pb in soils could not easily be transferred to leaves. The contribution rates of parent material were 61%-100% and 45%-100% for total Pb isotope and acid-extractable Pb isotope in soils, respectively, indicating a low impact of human activity. A sizeable influence of parent material for leaves was also observed, suggesting that Pb may be present in the dust-fall. Although Sr concentrations in leaves were not high, they exceeded that in soils. The high BCF also indicated that tea has a high capacity to accumulate Sr, with the coincidence that Sr87/Sr86 in the acid-extractable isotope in soils were similar to new leaves. A Pb-Sr joint tracer indicated that Sr in old and new leaves may be influenced by parent material and anthropogenic sources, respectively.

Potential exposure to metals and health risks of metal intake from Tieguanyin tea production in Anxi, China.

The metal content of Tieguanyin tea from Anxi, Southeast China, was studied. Leaching experiments were designed based on the local tea-drinking habits, and tea infusions were prepared using three types of water and two methods of soaking tea. Twelve metals (Cd, As, Cr, Pb, Se, Sb, Ag, Tl, Cu, Zn, Be, and Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS), and a human health risk assessment was performed. The results showed that the quality of water used for steeping tea has a direct effect on the leaching concentrations of metals in the tea infusion and this effect can be reduced by using pure water or commercially available drinking water. Further, the two tea-soaking methods used by local residents can reduce the metal intake. The health risk assessment determined that the carcinogenic risk values of Cr, As, and Pb (Cr > Pb > As) were within an acceptable range (10-7-10-4); therefore, the concentrations of these metals in tea infusions do not pose substantial carcinogenic risk to tea drinkers. The results also indicate that the high concentrations of Tl in the tea infusions pose a substantial noncarcinogenic risk and may result from the dissolution characteristics of Tl and the water quality.