Vitamin B-6 Prevents Heart Failure with Preserved Ejection Fraction Through Downstream of Kinase 3 in a Mouse Model.

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation. OBJECTIVES: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF. METHODS: HFpEF model was elicited by a combination of high-fat diet and Nω-nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules. RESULTS: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor. CONCLUSIONS: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

Apelin/ELABELA-APJ system in cardiac hypertrophy: Regulatory mechanisms and therapeutic potential.

Heart failure is one of the most significant public health problems faced by millions of medical researchers worldwide. And pathological cardiac hypertrophy is considered one of the possible factors of increasing the risk of heart failure. Here, we introduce apelin/ELABELA-APJ system as a novel therapeutic target for cardiac hypertrophy, bringing about new directions in clinical treatment. Apelin has been proven to regulate cardiac hypertrophy through various pathways. And an increasing number of studies on ELABELA, the newly discovered endogenous ligand, suggest it can alleviate cardiac hypertrophy through mechanisms similar or different to apelin. In this review, we elaborate on the role that apelin/ELABELA-APJ system plays in cardiac hypertrophy and the intricate mechanisms that apelin/ELABELA-APJ affect cardiac hypertrophy. We also illuminate and make comparisons of the newly designed peptides and small molecules as agonists and antagonists for APJ, updating the breakthroughs in this field.

A simple and accurate method to quantify real-time contraction of vascular smooth muscle cell in vitro.

Vascular smooth muscle cells (VSMCs) constitute the medial layer of the blood vessel wall. Their contractile state regulates blood flow in physiological and pathological conditions. Current methods for assessing the contractility of VSMCs are not amenable to the high-throughput screening of pharmaceutical compounds. This study aimed to develop a method to address this shortcoming in the field. Real-time contraction was visualized in living VSMCs using the exogenous expression of green fluorescent protein (GFP). Image-Pro Plus software (IPPS) was used to measure various morphological cell indices. In phenylephrine-treated VSMCs, GFP fluorescence imaging was more accurate than brightfield imaging or phalloidin staining in representing VSMC morphology, as measured using IPPS. Among the multiple indices of VSMC shape, area and mean-diameter were more sensitive than length in reflecting the morphological changes in VSMC. We developed a new index, compound length, by combining the mean-diameter and length to differentiate contracted and uncontracted VSMCs. Based on the compound length, we further generated a contraction index to define a single-VSMC contractile status as single-VSMC contraction-index (SVCI). Finally, compound length and SVCI were validated to effectively assess cell contraction in VSMCs challenged with U46619 and KCl. In conclusion, GFP-based indices of compound length and SVCI can accurately quantify the real-time contraction of VSMCs. In future, the new method will be applied to high-throughput drug screening or basic cardiovascular research.

Effects of curcumin nanoparticles on proliferation and VEGF expression of human retinal pigment epithelial cells.

AIM: To investigate the effects of curcumin (Cur) nanoparticles loaded with chitosan derivatives grafted by deoxycholic acid (Chit-DC) on human retinal pigment epithelial (hRPE) cell proliferation and vascular endothelial growth factor (VEGF) mRNA expression. METHODS: Cur nanoparticles were synthesized with Chit-DC as the carrier and Cur as the supported drug. Cell counting kit-8 (CCK-8) method was used to detect the effects of different concentrations of Cur/Chit-DC, Chit-DC, and Cur on the proliferation of hRPE cells for different times. The changes of Cur/Chit-DC and Cur on hRPE cell cycle were determined by flow cytometry. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of VEGF in hRPE cells treated with Cur, Chit-DC and Cur/Chit-DC at 10 µg/mL for 24h. RESULTS: Different concentrations of Chit-DC nanoparticle treated hRPE cells had no significant difference in terms of optical density (OD) values compared with the control group at 24h and 48h. Moreover, there was no change in the cell morphology under a light microscope. After 24h treatment with Cur/Chit-DC and Cur, the percentage of G0-G1 phase cells increased and the percentage of S phase cells decreased in all concentration groups. Cur/Chit-DC and Cur in all concentration groups inhibited the proliferation of hRPE cells in a time and dose dependent manner, and reduced the expression level of VEGF mRNA. CONCLUSION: The Cur/Chit-DC nanoparticles can release Cur continuously and have sustained release function. Both Cur/Chit-DC nanoparticles and Cur could inhibit hRPE cells cultured in vitro, and could reduce the expression level of VEGF mRNA in hRPE cells.

Improving Public Toilet Environment and Hygiene Practices in an Asian City: Voices From Hong Kong Residents.

Toilet hygiene is an important preventive measure for infectious diseases, including severe acute respiratory syndrome (SARS) and COVID-19. This study explored public's opinions on improving toilet environment and hygiene practices in Hong Kong. A mixed-method approach was applied. We conducted 4 focus groups plus 3 individual interviews among the Hong Kong Chinese, followed by a questionnaire survey with 300 respondents recruited from various districts. Difference in response distributions between groups with different demographics was tested by Pearson χ2 test. Instead of advocating for advanced toilet facilities, respondents were mostly concerned about basic hygiene issues. Malfunctioning facilities resulting from poor toilet management, such as clogged toilets, stained facilities, and problematic flushing systems, were most cited as barriers to toilet hygiene practices. Three quarters of the survey respondents expressed concerns over worn and poorly maintained toilets, shortage of janitors, and cleansing supplies. However, respondents who were older (P < .001), less educated (P < .001), and had lower income (P = .001) were significantly more likely to find hygiene conditions in public toilets satisfactory. The findings reflected the substandard of the current provisions as a developed city in Asia. Enhanced efforts by the government to maintain basic toilet supplies and facilities is the key to improving public compliance to toilet hygiene practices.

A mixed-methods study on toilet hygiene practices among Chinese in Hong Kong.

BACKGROUND: Public toilets are a common transmission vector of infectious diseases due to environmental contamination. Research on Chinese people's hygiene practices in public lavatories are lacking. This study examined Chinese people's hygiene practices in public lavatories in Hong Kong. METHODS: We conducted qualitative interviews and a self-administered questionnaire survey with local residents from June 2016 to April 2018. Four focus group discussions and three individual interviews informed the design of the questionnaire. We recruited interviewees and survey respondents via social service centers. The interviews and questionnaire focused on the public's daily practices and hygiene behaviors in public toilets. Content analysis of qualitative data was conducted. Multivariable logistic regressions were used to examine the association between age and toilet hygiene behaviors. RESULTS: Our qualitative component revealed a range of handwashing practices, from not washing at all, washing without soap, to washing for a longer time than instructions. Other toilet use practices were identified, such as not covering toilet lid before flushing and stepping on toilet seats due to dirtiness, and spitting into toilet bowls or hand basin. Totally, 300 respondents completed the questionnaire. Among them, 212 (70.9%) were female and 246 (86.1%) were aged 65 or below. More than two thirds always washed hands with soap (68.7%) and dried hands with paper towels (68.4%). Up to 16.2% reported stepping on toilet seats and 43.9% never covered the toilet lid before flushing. Over one fourth (26.4%) spit into squat toilets/ toilet bowl. Regression analyses showed that the elderly group were less likely to report stepping on toilet seats (adjusted odds ratio, AOR = 0.17, 95%CI 0.03-0.88), flushing with the toilet lid closed (AOR = 0.40, 0.16-0.96), but more likely to spit into squat toilets/ toilet bowl (AOR = 4.20, 1.50-11.74). CONCLUSIONS: Hong Kong Chinese's compliance to hygiene practices in public toilets is suboptimal. Stepping on toilet seat is a unique Chinese practice due to the dirtiness of toilet seats. Spitting practices may increase the risk of airborne infectious diseases and need improvement. Measures are needed to improve toilet hygiene behaviors, including public education campaigns and keeping toilet environment clean.