AID and TET2 co-operation modulates FANCA expression by active demethylation in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in the germinal centre (GC). However, whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL has not been well characterized. Our data demonstrate that the proto-oncogene Fanconi anaemia complementation group A (FANCA) is highly expressed in DLBCL patients and cell lines, respectively. AID recruits demethylation enzyme ten eleven translocation family member (TET2) to bind the FANCA promoter. As a result, FANCA is demethylated and its expression increases in DLBCL. On the basis of our findings, we have developed a new therapeutic strategy to significantly inhibit DLBCL cell growth by combination of the proteasome inhibitor bortezomib with AID and TET2 depletion. These findings support a novel mechanism that AID has a crucial role in active demethylation for oncogene activation in DLBCL.     

Gray matter atrophy and corresponding impairments in connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.

     

Facial emotion perception abilities are related to grey matter volume in the culmen of cerebellum anterior lobe in drug-naïve patients with first-episode schizophrenia

Brain Imaging and Behavior - Impaired capability for understanding and interpreting the expressions on other people's faces manifests itself as a core feature of schizophrenia, contributing to...     

Rapid screening of hepatitis B using Raman spectroscopy and long short-term memory neural network

Lasers in Medical Science - This study presents a rapid method to screen hepatitis B patients using serum Raman spectroscopy combined with long short-term memory neural network (LSTM). The serum...     

The effect of intradialytic combined exercise on hemodialysis efficiency in end-stage renal disease patients: a randomized-controlled trial

Purpose

Insufficient dialysis is a difficult problem for patients undergoing hemodialysis, and causes cardiovascular complications and increases mortality. Increasing aerobic exercise and resistance exercise have been shown to be beneficial to physical fitness of patients undergoing hemodialysis, but a few studies have focused on combined exercise (combination of aerobic and resistance exercise training) and the interaction effect of combined exercise and intervention duration on hemodialysis efficiency. This study aimed to investigate the effects of 24-week combined exercise on hemodialysis efficiency, blood pressure, exercise capacity, and quality of life in patients undergoing hemodialysis.

Methods

In total, 47 eligible subjects were randomly allocated to exercise group and control group. The intervention group performed a 24-week, three times weekly, and moderate-intensity intradialytic combined exercise. Patients in the control group received usual care. The primary outcome was hemodialysis efficiency, which recorded every 4 weeks. Secondary outcomes included blood pressure, exercise capacity, and quality of life, measured at baseline and after 24 weeks of intervention.

Results

In intervention group, sp Kt/V significantly improved by 13.2%, and systolic blood pressure and diastolic blood pressure significantly decreased by 8.5 mmHg and 6.5 mmHg, respectively. The 6-min walking distance increased significantly by 43 m (9.8%), but there was no significant change in quality of life.

Conclusion

Combined exercise and intervention duration had an interaction effect on hemodialysis efficiency. Combined exercise improved blood pressure and physical fitness for patients undergoing hemodialysis, but did not affect quality of life. The extensive benefits of combined exercise provide evidence for the exercise development for patients undergoing hemodialysis.