Serum Metabolomics Analysis of the Anti-Inflammatory Effects of Gallic Acid on Rats With Acute Inflammation.

Background: Gallic acid (GA) is a natural small-molecule polyphenol having a wide range of pharmacological activities. Until now, some works have studied the effect and the mechanisms of GA against inflammation. However, whether or how gallic acid regulates the downstream metabolic disorder against acute inflammation remains unclear. The present study explored the protective effect and the potential mechanism of GA on acute inflammation through the metabolomics approach. Methods: An acute inflammation rat model was induced by local injection of carrageenin. Local swelling on paw and serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were assessed in Control, Model and Gallic acid groups, respectively. Serum metabolomics based on high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) was also established to collect rats' metabolic profiles and explore the metabolic changes related to GA pretreatment. Results: Compared to the Modal group, local pain, redness, and swelling induced by carrageenin were significantly alleviated in GA groups in addition to the dose-dependent decreases of TNF-α and IL-6. Metabolomics analysis found significant alterations in metabolic signatures between the carrageenin-induced inflammation and control groups. Twelve potential biomarkers were further identified in acute inflammation by principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA). In addition, when rats were pretreated with gallic acid, serum levels of eleven biomarkers were observed to restore partially. Metabolic pathway and networks analysis revealed that GA might invert the pathological process of acute inflammation by regulating the key biomarkers involved in linoleic acid metabolism, ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and arachidonic acid (AA) metabolism pathways. Conclusion: The study elucidates the protective effect of gallic acid against acute inflammation and its possible regulating mechanism from a metabolomic perspective. These results could provide a theoretical basis for clarifying gallic acid's mechanism and potential medicinal value in curing inflammation disorder in the clinic.

COVID-19 patients with hypertension are at potential risk of worsened organ injury.

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3-25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.

Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression.

Gallic acid (GA), a hydrolyzable tannin, has a wide range of pharmacological activities. This study revealed that, GA significantly inhibited T24 cells viability in a concentration- and time- dependent manner. The IC50 of GA stimulating T24 cells for 24, 48, and 72 h were 21.73, 18.62, and 11.59 µg/ml respectively, and the inhibition rate was significantly higher than the positive control drug selected for CCK-8 assay. Meanwhile, after GA treatment, the morphology of T24 cells were changed significantly. Moreover, GA significantly inhibited T24 cells proliferation and blocked T24 cells cycle in S phase (p < 0.001). GA induced T24 cells apoptosis (p < 0.001), accompanied by reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) depolarization. Western blotting analysis showed that GA significantly increased Cleaved caspase-3, Bax, P53, and Cytochrome C (Cyt-c) proteins expression, and decreased Bcl-2, P-PI3K, P-Akt, P-IκBα, P-IKKα, and P-NF-κB p65 proteins expression in T24 cells (p < 0.05). Real-Time PCR results verified that GA significantly promoted Caspase-3, Bax, P53, and Cyt-c genes expression, and inhibited Bcl-2, PI3K, Akt, and NF-κB p65 genes expression (p < 0.001). However, on the basis of GA (IC50) stimulation, NAC (an oxidative stress inhibitor) pretreatment reversed the apoptotic rate of T24 cells and the expression of Bax, Cleaved caspase-3, P53, Bcl-2 proteins, and the MMP level in T24 cells, as well as the expression of Cyt-c protein in T24 cells mitochondria and cytoplasm. In addition, GA significantly suppressed T24 cells migration and invasion ability with VEGF protein inhibition (p < 0.001). Briefly, GA can inhibit T24 cells proliferation, metastasis and promote apoptosis, and the pro-apoptotic activity is closely associated with mitochondrial dysfunction and PI3K/Akt/NF-κB signaling suppression. Our study will help in finding a safe and effective treatment for bladder cancer.

Clinical characteristics of rehospitalized patients with COVID-19 in China.

This study aims to observe the clinical characteristics of recovered patients from Coronavirus Disease 2019 (COVID-19) with positive in reverse transcription-polymerase chain reaction (RT-PCR) or serum antibody. The profile, clinical symptoms, laboratory outcomes, and radiologic assessments were extracted on 11 patients, who tested positive for COVID-19 with RT-PCR or serum antibody after discharged and was admitted to Hubei No. 3 People's Hospital of Jianghan University for a second treatment in March 2020. The average interval time between the first discharge and the second admission measured 16.00 ± 7.14 days, ranging from 6 to 27 days. In the second hospitalization, one patient was positive for RT-PCR and serum antibody immunoglobulin M (IgM)-immunoglobulin G (IgG), five patients were positive for both IgM and IgG but negative for RT-PCR. Three patients were positive for both RT-PCR and IgG but negative for IgM. The main symptoms were cough (54.55%), fever (27.27%), and feeble (27.27%) in the second hospitalization. Compared with the first hospitalization, there were significant decreases in gastrointestinal symptoms (5 vs 0, P = .035), elevated levels of both white blood cell count (P = .036) and lymphocyte count (P = .002), remarkedly decreases in C-reactive protein and serum amyloid A (P < .05) in the second hospitalization. Additionally, six patients' chest computed tomography (CT) exhibited notable improvements in acute exudative lesions. There could be positive results for RT-PCR analysis or serum IgM-IgG in discharged patients, even with mild clinical symptoms, however, their laboratory outcomes and chest CT images would not indicate the on-going development in those patients.