Schiff Base Compounds as Fluorescent Probes for the Highly Sensitive and Selective Detection of Al3+ Ions.

Two new Schiff base fluorescent probes (L and S) were designed for selectively detecting Al3+ ions in aqueous medium. Structural characterization of the purely synthesized compounds was acquired by IR, 1H NMR and 13C NMR. Moreover, their photochromic and fluorescent behaviors have been investigated systematically by UV-Vis absorption and fluorescence spectra. The two probes have both high selectivity and sensitivity toward Al3+ ions in aqueous medium. The 2:1 stoichiometry between the Al3+ and probes was verified by Job's plot. Moreover, the limits of detection (LOD) for Al3+ by L and S were 1.98 × 10-8 and 4.79 × 10-8 mol/L, respectively, which was much lower than most previously reported probes. The possible recognition mechanism was that the metal ions would complex with Schiff base probes because of the prevalence of the species optimal for complex formation, inhibiting the structural isomerization of conjugated double bonds (-C=N-), inhibiting the proton transfer process in the excited state of the molecules and resulting in changes of its color and fluorescence behavior. Furthermore, the probes will have potential applications for selectively, detecting Al3+ ions in the environmental system with high accuracy and providing a new strategy for the design and synthesis of multi-functional sensors.

2-Methoxyestradiol combined with ascorbic acid facilitates the apoptosis of chronic myeloid leukemia cells via the microRNA-223/Fms-like tyrosine kinase 3/phosphatidylinositol-3 kinase/protein kinase B axis.

Chronic myeloid leukemia (CML) is a malignant myeloproliferative tumor. 2-Methoxyestradiol (2-ME) is an endogenous estrogen metabolite that shows efficacy in human malignancies. Ascorbic acid (AA) possesses antioxidant activity. This study explored the mechanism of 2-ME combined with AA in the apoptosis of CML cells. Firstly, human CML cell lines were treated with 2-ME and AA. The cell viability, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were detected. miR-223 expression in CML cells was detected. In addition, CML cells were transfected with miR-223 inhibitor. The binding relationship between miR-223 and FLT3 was verified. Subsequently, the FLT3 was overexpressed or silenced for the function rescue experiment to confirm the role of FLT3 in CML cell apoptosis. The expression levels of key factors of the PI3K/AKT pathway were detected. Finally, xenograft nude mouse models were established for in vivo verification. 2-ME + AA treatment inhibited CML cell viability and promoted apoptosis, elevated ROS content, and reduced MMP. 2-ME + AA treatment promoted miR-223 expression in CML cells. miR-223 targeted FLT3. Moreover, miR-223 inhibitor or FLT3 overexpression partially annulled the effect of 2-ME + AA on CML cells. 2-ME + AA inhibited the PI3K/AKT pathway via the miR-223/FLT3 axis. Furthermore, 2-ME + AA suppressed CML xenograft growth in mice. Collectively, 2-ME + AA promoted miR-223 expression and suppressed FLT3 and the PI3K/AKT pathway, thereby facilitating the apoptosis of CML cells and inhibiting CML xenograft growth in mice.

Dynamic monitoring of serum liver function indexes in patients with COVID-19.

BACKGROUND: Some patients with the novel 2019 coronavirus disease (COVID-19) display elevated liver enzymes. Some antiviral drugs that can be used against COVID-19 are associated with a risk of hepatotoxicity. AIM: To analyze the clinical significance of the dynamic monitoring of the liver function of patients with COVID-19. METHODS: This was a retrospective study of patients diagnosed with COVID-19 in January and February 2020 at the Department of Infection, Shantou Central Hospital. The exclusion criteria for all patients were: (1) History of chronic liver disease; (2) History of kidney disease; (3) History of coronary heart disease; (4) History of malignancy; or (5) History of diabetes. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase, and total bilirubin of patients with COVID-19 were measured on days 1, 3, 7 and 14 after admission, and compared to non-COVID-19 patents. RESULTS: Twelve patients with COVID-19 (seven men and five women) and twelve controls (eight men and four women) were included. There were one, two, and nine patients with severe, mild, and moderate COVID-19, respectively. There were no differences in age and sex between the two groups (both P > 0.05). No significant differences were found in albumin, ALT, AST, γ-glutamyltransferase, or total bilirubin between the controls and the patients with COVID-19 on day 1 of hospitalization (all P > 0.05). Serum albumin showed a decreasing trend from days 0 to 7 of hospitalization, reaching the lowest level on day 7. Total bilirubin was higher on day 3 than on day 7. ALT, AST, and γ-glutamyltransferase did not change significantly over time. The severe patient was observed to have ALT levels of 67 U/L and AST levels of 75 U/L on day 7, ALT of 71 U/L and AST of 35 U/L on day 14, and ALT of 210 U/L and AST of 123 U/L on day 21. CONCLUSION: Changes in serum liver function indicators are not obvious in the early stage of COVID-19, but clinically significant changes might be observed in severe COVID-19.

[Clinical analysis of early damage in multiple extra-pulmonary organs in COVID-19].

OBJECTIVE: To analyze the clinical manifestations of heart, liver and kidney damages in the early stage of COVID-19 to identify the indicators for these damages. METHODS: We analyzed the clinical features, underlying diseases, and indicators of infection in 12 patients with COVID-19 on the second day after their admission to our hospital between January 20 and February 20, 2020.The data including CK-MB, aTnI, BNP, heart rate, changes in ECG, LVEF (%), left ventricular general longitudinal strain (GLS, measured by color Doppler ultrasound) were collected.The changes of liver function biochemical indicators were dynamically reviewed.BUN, UCR, eGFR, Ccr, and UACR and the levels of MA, A1M, IGU, and TRU were recorded. RESULTS: The 12 patients included 2 severe cases, 8 common type cases, and 2 mild cases.Four of the patients presented with sinus tachycardia, ECG changes and abnormal GLS in spite of normal aTNI and LVEF; 1 patient had abnormal CKMB and BNP.On the first and third days following admission, the patients had normal ALT, AST and GGT levels.On day 7, hepatic function damage occurred in the severe cases, manifested by elevated ALT and AST levels.Abnormalities of eGFR, Ccr and UACR occurred in 8, 5 and 5 of the patients, respectively.Abnormal elevations of MA, A1M, IGU and TRU in urine protein were observed in 4, 4, 5, and 2 of the patients, respectively. CONCLUSIONS: In patients with COVID-19, heart damage can be identified early by observing the GLS and new abnormalities on ECG in spite of normal aTNI and LVEF.Early liver injury is not obvious in these patients, but dynamic monitoring of the indicators of should be emplemented, especially in severe cases. In cases with normal CR and BUN, kidney damage can be detected early by calculating eGFR, Ccr and UACR and urine protein tests.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Bisphenol A triggers the malignancy of acute myeloid leukemia cells via regulation of IL-4 and IL-6.

Acute myeloid leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. The progression of AML can be regulated by estrogenic signals. Our present data showed that an industrial endocrine-disrupting chemical, bisphenol A (BPA), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin and cytarabine treatment. Among the tested cytokines, BPA treatment can decrease the expression of interleukin-4 (IL-4) while increasing the expression of IL-6. Overexpression of IL-4 or neutralization antibody of IL-6 (anti-IL-6) can attenuate BPA-induced proliferation of AML cells and reverse BPA-suppressed chemosensitivity. Furthermore, activation of nuclear factor kappa B is essential for BPA-induced upregulation of IL-6 in AML cells. As to IL-4, BPA can increase the expression of NFAT1 to inhibit its transcription. Collectively, our data showed that BPA can trigger the malignancy of AML cells via regulation of IL-4 and IL-6.