Exploring Cr(VI)-induced blood-brain barrier injury and neurotoxicity in zebrafish and snakehead fish, and inhibiting toxic effects of astaxanthin.

Cr(VI) is a common hazardous heavy metal contaminant that seriously endangers human and aquatic animal health. GPX4 was the key enzyme that reduces heavy metal toxicity through inhibiting ferroptosis pathway. Astaxanthin was GPX4 activator that can weaken biological toxicity induced by Cr(VI) exposure. The present study was conducted to evaluate the major role of GPX4 in astaxanthin protects Cr(VI)-induced oxidative damage, blood-brain barrier injury and neurotoxicity in brain-liver axis through inhibiting ferroptosis pathway. In the current study, astaxanthin intervention can effectively alleviate Cr(VI)-induced oxidative stress, blood-brain barrier damage, and neurotoxicity. GPX4 plays a major role in mediating astaxanthin nutritional intervention to reduce ROS and liver non-heme iron accumulation, which would contribute to the reduction of ferroptosis. Meanwhile, astaxanthin maintains the stability of transport receptors and protein macromolecules such as TMEM163, SLC7A11, SLC3A2, FPN1 and GLUT1 in the brain liver axis, promoting substance exchange and energy supply. Moreover, astaxanthin alleviates Cr(VI)-induced neurotoxicity by promoting tight protein expression and reducing blood-brain barrier permeability.

A pilot study on the characteristics of circulating T follicular helper cells in liver transplant recipients.

Circulating CD4+CXCR5+ T follicular helper cells (cTfh) have been demonstrated to be involved in B cell-mediated systemic autoimmune diseases and alloreactive responses following kidney transplantation; however, whether cTfh cells are involved in alloreactive responses after liver transplantation (LT) remains unclear. Our present study aimed to investigate the characteristics of cTfh, as well as CXCR3+CCR6-Tfh1, CXCR3-CCR6-Tfh2, and CXCR3-CCR6+Tfh17 subsets in liver allograft recipients. A total of 30 liver transplant recipients were enrolled in this study. The frequencies of cTfh, Tfh1, Tfh2, and Tfh17 subsets, and interleukin (IL)-21-producing Tfh cells in the circulating blood were analyzed by flow cytometry. The capacity of cTfh cells to help B cells differentiate into plasmablasts was determined one day before and one month after LT. The results revealed that the frequency of cTfh cells remained unaltered before and after LT. However, the frequency of the cTfh subsets (e.g., Tfh1 and Tfh2 cells) and B cells were reduced one month after LT. Functionally, the capacity of Tfh cells to produce IL-21 was reduced one month after LT. In addition, cTfh cells exhibited the capacity to help B cells differentiate into plasmablasts in an IL-21-dependent manner in vitro, which was reduced after LT, despite the unaltered production of IgM and IgG by plasmablasts. Thus, our data suggest that cTfh cells may be involved in alloreactive responses following LT via helping B cells differentiate into plasmablasts and plasma cells.

Anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis during pregnancy: Clinical analysis of reported cases.

OBJECTIVE: To analyze the clinical features of 13 pregnant patients with anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis. MATERIALS AND METHODS: Retrospective review of thirteen reported cases was conducted for anti-NMDAR encephalitis patients during pregnancy. The clinical data were collected from papers published in PubMed prior to 16 February 2016. Statistical analysis of the data was performed, which encompasses the patients' age, past medical history, onset of symptoms, concomitant with ovarian teratomas, immunotherapy, outcomes of mothers and newborns. RESULTS: Thirteen cases were reported in 11 articles with a median age of 23 (interquartile range, 19-27) years old. There were eight cases in which the onset periods of gestation happened in the first trimester and five cases in the second trimester. Among 13 cases, five patients had a past medical history, one concomitant with autoimmune Graves' hyperthyroidism, one with bilateral ovarian teratomas removed history, one with anti-NMDAR encephalitis five years before pregnancy and two with psychiatric symptoms. Five patients were found with ovarian teratomas. Seven patients responded to first-line immunotherapy whereas all of two patients responded to second-line immunotherapy when the first-line immunotherapy failed. Following up all the 13 patients, most experienced a substantial recovery, except one had spasticity and dystonia in one hand, and one died of a superimposed infection. Three fetuses were miscarried or aborted in total. Most newborns were healthy, except two cases (2/10) with abnormal neurologic signs. CONCLUSIONS: Clinical analysis of the data indicates that most patients respond to first-line immunotherapy. A second-line immunotherapy is effective when first-line immunotherapy fails. It has also been found that most mothers and newborns can have good outcomes.

Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: incidence and risk factors.

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma (HCC) in Chinese patients with primary biliary cirrhosis (PBC). METHODS: We reviewed the data of 52 PBC-associated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13% (52/1255) and was significantly higher in the males (9.52%) than in the females (3.31%). Among the 52 PBC patients with HCC, 55.76% (29/52) were diagnosed with HCC and PBC simultaneously, and 5.76% (3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCC were more likely than the females to have undergone blood transfusion (18.75% vs 8.33%, P = 0.043), consumed alcohol (31.25% vs 8.33%, P = 0.010), smoked (31.25% vs 8.33%, P = 0.010), had a family history of malignancy (25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (P < 0.05). Conditional logistic regression analysis revealed that body mass index (BMI) ≥ 25 [adjusted odds ratio (AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake (AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

The ratio of circulating regulatory T cells (Tregs)/Th17 cells is associated with acute allograft rejection in liver transplantation.

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) and Th17 cells are known to be involved in the alloreactive responses in organ transplantation, but little is known about the relationship between Tregs and Th17 cells in the context of liver alloresponse. Here, we investigated whether the circulating Tregs/Th17 ratio is associated with acute allograft rejection in liver transplantation. In present study, thirty-eight patients who received liver transplant were enrolled. The patients were divided into two groups: acute allograft rejection group (Gr-AR) (n = 16) and stable allograft liver function group (Gr-SF) (n = 22). The frequencies of circulating Tregs and circulating Th17 cells, as well as Tregs/Th17 ratio were determined using flow cytometry. The association between Tregs/Th17 ratio and acute allograft rejection was then analyzed. Our results showed that the frequency of circulating Tregs was significantly decreased, whereas the frequency of circulating Th17 cells was significantly increased in liver allograft recipients who developed acute rejection. Tregs/Th17 ratio had a negative correlation with liver damage indices and the score of rejection activity index (RAI) after liver transplantation. In addition, the percentages of CTLA-4(+), HLA-DR(+), Ki67(+), and IL-10(+) Tregs were higher in Gr-SF group than in Gr-AR group. Our results suggested that the ratio of circulating Tregs/Th17 cells is associated with acute allograft rejection, thus the ratio may serve as an alternative marker for the diagnosis of acute rejection.

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed annulation with diarylethynes.

When Boc-L-Val-OH was used as a ligand for the enantioselective Pd(II)-catalyzed annulation of N,N-substituted aminomethyl ferrocene derivatives with diarylethynes, ferrocenes with planar chirality could be achieved with excellent enantioselectivity (up to 99% ee).

Enantioselective synthesis of planar chiral ferrocenes via palladium-catalyzed direct coupling with arylboronic acids.

Enantioselective Pd(II)-catalyzed direct coupling of aminomethylferrocene derivatives with boronic acids was realized. With commercially available Boc-L-Val-OH as a ligand, planar-chiral ferrocenes could be synthesized in yields of 14-81% with up to 99% ee under mild conditions.