Clinical analysis of Wernicke encephalopathy after liver transplantation.

BACKGROUND: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation. METHODS: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed. RESULTS: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia. CONCLUSIONS: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation.

[The molecular mechanism of survivin expression in activated human peripheral lymphocytes].

AIM: Investigate the molecular mechanism of regulating survivin expression and related signal transduction pathway, molecular cascade reaction and biological effects in activated PBMC. METHODS: The expression of survivin and related proteins were detected by Western blot in PBMC stimulated by PHA and rhIL-2 with or without JAK inhibitor-AG490 treatment, and FCM was performed to analyze cell cycle and cell division. RESULTS: Our results indicated that molecular and cellular reactions in PBMC activated by PHA and rhIL-2 were dependent on time series. At first, the phosphorylation of Stat3 and Stat5 were observed, then, protein levels of CyclinD3 and CyclinE increased, and the stimulated PBMC began to enter to S phage with survivin protein expression was initiated, which at last resulted in cell division with dramatically increasing expression of survivin protein. AG490 could significantly inhibit all these reactions but had no effect on the expressions of the cell cycle inhibitor-P21 and anti-apoptosis protein-Bcl-2. CONCLUSION: The expression of survivin in stimulated PBMC was dependent on the primarily activated JAK-STAT pathway, which upregulated CyclinD3 and CyclinE protein levels, initiated the cell cycle progression, and induced cell cycle-dependent survivin expression, and so survivin was involved in cell division and cell proliferation.

[Proteomic analysis of G2/M arrest of HL-60 cells induced by MG132].

BACKGROUND & OBJECTIVE: Proteasome inhibitor, which can induce apoptosis in various tumor cells, is a kind of potential antitumor drug. This study was to identify the proteins involved in G(2)/M arrest of leukemia cell line HL-60 exposed to proteasome inhibitor MG132 by proteomic techniques. METHODS: Flow cytometry was used to examine cell cycle of HL-60 cells exposed to 2.5 micromol/L MG132. Nuclear extracts of HL-60 cells were prepared, and the purity was detected by light microscopy and Western blot, and the differentially expressed protein spots were determined by two-dimensional gel electrophoresis and identified with MALDI-TOF-TOF/MS. RESULTS: There was a distinct G(2)/M phase arrest before the apoptosis of HL-60 cells induced by 2.5 micromol/L MG132. Twenty-three differentially expressed protein spots were found between MG132-treated and control HL-60 cells; 8 nuclear proteins were identified by MALDI-TOF-TOF/MS analysis. CONCLUSIONS: The detected proteins, such as eIF5A and splicing factor, may be involved in regulation of G(2)/M arrest of HL-60 cells. These findings will be helpful for revealing molecular mechanisms of proteasome inhibitor-induced G(2)/M phase arrest and apoptosis of leukemia cell line.

[The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].

To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were analyzed. The results showed that TSA could effectively induce G(2)/M arrest and apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1) were upregulated quickly before cell arrested in G(2)/M and began decreasing at the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the TSA induced G(2)/M arrest and apoptosis responses. This study also identified that the protein level of p21(WAF1/Cip-1) was highly associated with the cell cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT-4 cells to TSA meanwhile treatment with MG-132 increased the protein level of p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT-4 cells.

[Mechanism of G2/M cell cycle arrest before apoptosis in leukemia cell line HL-60 induced by proteasome inhibitor MG132].

BACKGROUND & OBJECTIVE: Proteasome inhibitor is a kind of potential anti-tumor drug,it can induce apoptosis in various tumor cells. This study was designed to investigate the molecular mechanism of apoptosis and G(2)/M arrest in leukemia cell line HL-60 induced by proteasome inhibitor MG132 (Z-Leu-Leu-Leu-CHO). METHODS: Apoptosis in HL-60 cells was observed under fluorescent microscope, flow cytometry and immunoblot were used to analyze cell apoptosis, cell cycle arrest, and the mechanisms. RESULTS: MG132 (2 micromol/L)induced apoptosis in HL-60 cells after 24-h treatment. Meanwhile, HL-60 cells were arrested at G(2)/M phase before apoptosis after induced by MG132. The percentage of G(2)/M phase in MG132-treated HL-60 cells at 12 h was 63.42+/-2.02,while that in untreated cells was 7.29+/-3.01 (P< 0.01). The percentage of apoptosis in MG132-treated HL-60 cells at 24 h was 16.67+/-1.48, while untreated cells had no death (P< 0.01). Compared to the treatment with MG132 only, caffeine (2 mmol/L) exposure can reduce G(2)/M arrest and apoptosis in MG132-treated HL-60 cells. Expression of cyclin-dependent kinase inhibitor p21waf/cip1 up-regulated after treated with MG132 for 3 h, but no p53 or p27 detected. CONCLUSIONS: Proteasome inhibitor MG132 can induce G2/M arrest before the apoptosis appeared in HL-60 cells. The obvious up-regulation of p21 indicated that it is p21(waf/cip1), but not p53 or p53-related proteins,that involved in the regulation of G(2)/M arrest and subsequent apoptosis induced by MG132 in HL-60 cells.