Berberine alkaloids inhibit the proliferation and metastasis of breast carcinoma cells involving Wnt/ß-catenin signaling and EMT.

Berberine alkaloids belong to the class of isoquinoline alkaloids that have been shown to possess anticancer potential, berberine exhibits inhibitory effects on breast cancer development. However, the exact mechanisms of action for anti-breast carcinoma of the alkaloids, including epiberberine, berberrubine and dihydroberberine are still unclear. MTT assay, colony formation, wound healing and transwell invasion assays detected these alkaloids suppressed proliferation, migration and invasion of breast cancer cells. Hoechst and Annexin V-FITC/PI staining were used to analyze the apoptosis of breast cancer cells. Western blotting investigated the changes noted in the expression levels of the key proteins involved in the Wnt/ß-catenin signaling pathway and epithelial to mesenchymal transition (EMT). The results showed that inhibited the proliferation of breast cancer cells. Berberine alkaloids inhibited the cell cycle at G2/M phase in MCF-7 cells, but in MDA-MB-231 cells berberine alkaloids arrested the cell cycle in G0/G1 and G2/M phases. By decreasing ß-catenin expression, increasing GSK-3ß expression and decreasing N-cadherin expression, increasing E-cadherin expression, which proved that epiberberine, berberrubine and dihydroberberine inhibited of metastasis of breast cancer cells through Wnt signaling pathway and reversed EMT except berberine. Furthermore, berberine alkaloids exert their anti-breast cancer effects through the synergistic action of intrinsic and extrinsic pathways of apoptosis. These findings highlight the different effects of different berberine alkaloids on breast cancer cells and confirm that berberine alkaloids may be potentially used in the treatment of breast cancer.

Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis.

OBJECTIVE: The purpose of this study is to determine whether TAM receptors and ligands associated with the activity and severity of lupus nephritis. METHODS: Clinical data were statistically analysed and studied in 122 SLE patients, diagnosed from 2013 to 2016 in First Hospital Affiliated to Harbin Medical University. Levels of TAM receptors and ligands in the plasma of 122 SLE patients were measured by ELISA. Renal biopsies were performed to confirm lupus nephritis (LN) by histopathology in 68 patients. The associations of TAM receptors and ligands with clinical and serological parameters were analysed in 68 LN patients. RESULTS: Amongst patients with SLE, those with LN had significantly higher plasma sMer, sAxl and GAS6 levels than those without renal involvement (P < 0.01 for all comparisons). Additional comparisons on the renal function-associated clinical parameters confirmed an indicative role of the sMer, sAXL and GAS6 levels in the cohort of patients with more severe nephritis. Patients with higher sMer, sAXL and GAS6 levels of LN patients tended to suffer from proliferative glomerulonephritis. The sAXL and GAS6 levels had a strong positive correlation with activity index (AI) in LN patients. Furthermore, there was a significant drop of the sMer, sAXL and GAS6 concentrations from the time of the biopsy to month t6, but no further decrease from months t6 to t12. CONCLUSIONS: These results suggest that plasma sMer, sAxl and GAS6 can be an additional clinical marker related to the disease activity and severity in LN.

Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy.

OBJECTIVE: To characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE) and its complication lupus nephritis (LN) in a large cohort of patients. METHODS: Clinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002-2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG). Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain. RESULTS: Simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001). Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery. CONCLUSIONS: Simultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG) may indicate severe nephropathy in patients with SLE.

Simultaneous positivity for anti-DNA, anti-nucleosome and anti-histone antibodies is a marker for more severe lupus nephritis.

OBJECTIVE: The purpose of this study is to examine autoantibody profile of systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) and to establish the correlation between the antibody reactivity and disease activity of LN. METHODS: Autoantibodies and serological parameters were measured and analyzed in 589 SLE patients. The associations of the co-positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) with clinical, serological and outcome parameters were analyzed. RESULTS: At the study entry, the prevalence for anti-dsDNA (61.52 % vs. 34.11 %, P < 0.0001), anti-nucleosome (56.09 % vs. 37.21 %, P = 0.0002) and anti-histone (49.35 % vs. 33.33 %, P = 0.0013) antibodies in patients with LN were significantly higher than that in patients without LN. Patients with 3-pos had a higher proportion of proliferative renal lesions (class III + IV). The incidence of a poor renal outcome (7.14 % vs. 2.52 %, P = 0.0174) in LN patients with 3-pos was significantly higher than those without 3-pos. Moreover, the rate of remission (73.63 % vs. 82.37 %, P = 0.0245) was significantly reduced and recurrence increased (58.90 % vs. 23.44 %, P < 0.0001) in 3-pos patients as compared to that in non 3-pos within the LN group. CONCLUSION: Our data indicate a strong association between the 3-pos and renal disease activities, especially proliferative glomerulonephritis. The ability of 3-pos to predict renal flares may lead to major additional benefits in the follow-up of these patients.

Pseudomonas aeruginosa isolates of distinct sub-genotypes exhibit similar potential of antimicrobial resistance by drugs exposure.

Pseudomonas aeruginosa, a wide-spread opportunistic pathogen, often complicates clinical treatments due to its resistance to a large variety of antimicrobials, especially in immune compromised patients, occasionally leading to death. However, the resistance to antimicrobials varies greatly among the P. aeruginosa isolates, which raises a question on whether some sub-lineages of P. aeruginosa might have greater potential to develop antimicrobial resistance than others. To explore this question, we divided 160 P. aeruginosa isolates collected from cities of USA and China into distinct genotypes using I-CeuI, a special endonuclease that had previously been proven to reveal phylogenetic relationships among bacteria reliably due to the highly conserved 26-bp recognition sequence. We resolved 10 genotypes by I-CeuI analysis and further divided them into 82 sub-genotypes by endonuclease cleavage with SpeI. Eight of the 10 genotypes contained both multi-drug resistant (MDR) and less resistant isolates based on comparisons of their antimicrobial resistance profiles (ARPs). When the less resistant or susceptible isolates from different genotypes were exposed to eight individual antimicrobials, they showed similar potential to become resistant with minor exceptions. This is to our knowledge the first report to examine correlations between phylogenetic sub-lineages of P. aeruginosa and their potential to become resistant to antimicrobials. This study further alerts the importance and urgency of antimicrobial abuse control.