Green Tea Diet Can Effectively Antagonize the Toxicity Induced by Environmental-Related Concentrations of BPA: An Implication from In Vivo and In Silico Studies.

The neurotoxicity of bisphenol A (BPA) exposure has been confirmed in vitro and in vivo, and inflammatory response is considered the main pathway. Green tea is a healthy life habit as it is rich in various anti-inflammatory components. To confirm that green tea diet is an effective measure to antagonize BPA-induced neurotoxicity, mice were treated with 0.5 and 5000 µg/kg/day of BPA from postnatal days (PNDs) 10-50 and supplemented with green tea on PND 21. From PND 51, behavioral tests were conducted on mice to assess their emotional, cognitive, and spatial learning memory capabilities. The open field test and elevated plus maze test indicated anxiety-like behaviors induced by BPA. Interestingly, green tea diet significantly alleviated BPA-induced anxiety-like behaviors. Meanwhile, the green tea diet effectively reversed BPA-induced microglia activation and morphological changes in the hippocampus of mice. Molecularly, green tea inhibited hippocampal neuroinflammation of mice by reducing BPA-induced expressions of NLRP3, ASC, cleaved-caspase-1, GSDMD-N, IL-6, and IL-1ß, as well as significantly reducing the expression of Bak1, Bax, caspase-9, and Cytc c genes (p < 0.05). Molecular docking suggests that various anti-inflammatory components of green tea can competitively bind to the estrogen receptors with BPA. In general, a green tea diet alleviates BPA-induced emotional disorders by inhibiting microglial polarization and hippocampal pyroptosis, indicating its effective antagonistic ability against the neurotoxicity induced by environmental BPA exposure.

A Case of Adult Hereditary Spherocytosis Concomitant with Gilbert Syndrome Caused by Mutations in SPTB and UGT1A1.

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 µmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.

A high-throughput method for the determination of 14 UV-filters in human plasma by LC-MS/MS: Minimize interferences from proteins and phospholipids in the matrix.

Accurate monitoring of UV-filters exposure levels in human plasma is a challenge because of the significant differences in the physicochemical properties of UV-filters, as well as the matrix effect caused by abundant proteins and phospholipids in plasma. Therefore, an effective and rapid method for simultaneous determination of 14 UV-filters in human plasma using protein precipitation-solid phase extraction (SPE) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Acetonitrile with 0.1 % formic acid and 10 % isopropanol (v/v) were used as mobile phases. A gradient elution on an ACQUITY UPLC BEH-C18 column at 30 °C and 0.3 mL/min flow rate was applied for separation. The electrospray ionization positive or negative modes were selected to determine the corresponding analyte to increase selectivity and sensitivity. Results showed that acetonitrile-tetrahydrofuran (v/v, 8:2) as the extraction solvent can effectively precipitate protein in plasma and improve the solubility of UV-filters. The HybridSPE cartridge improved the removal efficiency of phospholipids, while 1 mL of methanol elution increased the extraction recoveries of targets. Fourteen UV-filters achieved good linearities, low detection limits (0.050 to 0.10 µg/L) and quantification limits (0.10 to 1.0 µg/L). Method accuracy and precision, extraction recoveries, and storage stabilities of all analytes met the criterion of 80-120 %. Moreover, this method was successfully applied for the determination of UV-filters in plasma randomly collected from adults. Nine of 14 UV-filters were determined and their concentrations were distributed widely, suggesting a big variation of individual UV-filters exposure.

The Pathogenesis and Treatment of Cardiovascular Autonomic Dysfunction in Parkinson's Disease: What We Know and Where to Go.

Cardiovascular autonomic dysfunctions (CAD) are prevalent in Parkinson's disease (PD). It contributes to the development of cognitive dysfunction, falls and even mortality. Significant progress has been achieved in the last decade. However, the underlying mechanisms and effective treatments for CAD have not been established yet. This review aims to help clinicians to better understand the pathogenesis and therapeutic strategies. The literatures about CAD in patients with PD were reviewed. References for this review were identified by searches of PubMed between 1972 and March 2021, with the search term "cardiovascular autonomic dysfunctions, postural hypotension, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension, and nondipping". The pathogenesis, including the neurogenic and non-neurogenic mechanisms, and the current pharmaceutical and non-pharmaceutical treatment for CAD, were analyzed. CAD mainly includes four aspects, which are OH, SH, postprandial hypotension and nondipping, among them, OH is the main component. Both non-neurogenic and neurogenic mechanisms are involved in CAD. Failure of the baroreflex circulate, which includes the lesions at the afferent, efferent or central components, is an important pathogenesis of CAD. Both non-pharmacological and pharmacological treatment alleviate CAD-related symptoms by acting on the baroreflex reflex circulate. However, pharmacological strategy has the limitation of failing to enhance baroreflex sensitivity and life quality. Novel OH treatment drugs, such as pyridostigmine and atomoxetine, can effectively improve OH-related symptoms via enhancing residual sympathetic tone, without adverse reactions of supine hypertension. Baroreflex impairment is a crucial pathological mechanism associated with CAD in PD. Currently, non-pharmacological strategy was the preferred option for its advantage of enhancing baroreflex sensitivity. Pharmacological treatment is a second-line option. Therefore, to find drugs that can enhance baroreflex sensitivity, especially via acting on its central components, is urgently needed in the scientific research and clinical practice.

Tumor-forming plasmacytoid dendritic cells in acute myelocytic leukemia: a report of three cases and literature review.

Plasmacytoid dendritic cells (PDCs), through their production of type I interferons (IFNs) and other pro-inflammatory cytokines, link the innate and adaptive immunity, and provide anti-viral resistance. It is reported PDCs accumulated in inflammatory and human neoplasms, including hematopoietic malignancies. To date, the clinical significance of tumor-forming PDCs (TF-PDCs) in AML is largely unknown. Here, we designed an integral scheme using flow cytometry, by which we accurately have detected the TF-PDCs in cases of AML. Combined the case characters and progress, we suggested that: TF-PDCs in AML maybe originate from the bone marrow mononuclear precursor cells, so it often associated with mononuclear line-related myeloid tumors; the accumulation of PDCs indicated highly aggressive tumor with poor progress and probably potential myelodysplasia or dysplasia.