[LncRNA DRAIC regulates the proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells by targeting let-7i-5p].

Objective: To investigate the effects of lncRNA DRAIC on proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells and its mechanism. Methods: Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of DRAIC in lung cancer tissues and corresponding adjacent normal tissues of 40 patients with lung adenocarcinoma who underwent surgery in Tangshan People's Hospital from 2019 to 2020. Lung adenocarcinoma cells A549 and H1299 were cultured in vitro and divided into si-NC group, si-DRAIC group, miR-NC group, let-7i-5p mimics group, si-DRAIC+ inhibitor-NC group, and si-DRAIC+ let-7i-5p inhibitor group. CCK-8 method and clone formation experiment were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of Caspase-3, Caspase-9, Bcl-2 and Bax. The double luciferase reporter gene experiment was used to verify the regulatory relationship between DRAIC and let-7i-5p. Independent sample t test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and Pearson correlation analysis was used for correlation analysis. Results: Compared with adjacent tissues, the expression level of DRAIC in lung adenocarcinoma tissues increased (P<0.05), but the expression level of let-7i-5p decreased (P<0.05). The expression levels of DRAIC and let-7i-5p in lung adenocarcinoma tissues were negatively correlated (r=-0.737, P<0.05). The absorbance value of A549 and H1299 cells in the si-DRAIC group at 48, 72 and 96 hours were lower than those in the si-NC group (P<0.05), the number of clones formed [(91.00±6.08 vs. 136.67±6.51); (50.67±1.53 vs. 76.67±4.51)], the number of migration [(606.67±31.34 vs. 960.00±33.06); (483.33±45.96 vs. 741.67±29.67)], the number of invasion [(185.00±8.19 vs. 447.33±22.05); (365.00±33.87 vs. 688.00±32.97)] were lower than those in the si-NC group (P<0.05). However, the apoptosis rates of cells [(13.43±2.79)% vs. (4.53±0.42)%; (23.77±1.04)% vs. (6.60±1.42)%] were higher than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC group were higher than those in si-NC group, and the protein expression of Bcl-2 was lower than that in si-NC group (P<0.05). DRAIC is located in the cytoplasm. DRAIC targeted and negatively regulated the expression of let-7i-5p. The absorbance values of A549 and H1299 cells in the let-7i-5p mimics group at 48, 72 and 96 hours were lower than those in the miR-NC group (P<0.05), the number of clones formed [(131.33±14.47 vs. 171.33±6.11); (59.33±4.93 vs. 80.33±7.09)], the number of migration [(137.67±3.06 vs. 579.33±82.03); (425.00±11.14 vs. 669.33±21.13)], the number of invasion [(54.00±4.36 vs. 112.67±11.59); (80.00±4.58 vs. 333.33±16.80)] were lower than those in the miR-NC group (P<0.05). However, the apoptosis rates of cells [(14.57±1.10)% vs. (6.97±1.11)%; (23.97±0.42)% vs. (7.07±1.21)%] were higher than those in the miR-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in let-7i-5p mimics group were higher than those in miR-NC group, and the protein expression of Bcl-2 was lower than that in miR-NC group (P<0.05). The absorbance values of A549 and H1299 cells in the si-DRAIC+ let-7i-5p inhibitor group at 48, 72 and 96 hours were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05), the number of clones formed [(82.00±5.29 vs. 59.00±5.57); (77.67±4.93 vs. 41.33±7.57)], the number of migration [(774.33±35.81 vs. 455.67±19.04); (569.67±18.72 vs. 433.67±16.77)], the number of invasion [(670.33±17.21 vs. 451.00±17.52); (263.67±3.06 vs. 182.33±11.93)] were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05). However, the apoptosis rates of cells [(7.73±0.45)% vs. (19.13±1.50)%; (8.00±0.53)% vs. (28.40±0.53)%] were lower than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC+ let-7i-5p inhibitor group were higher than those in si-DRAIC+ inhibitor-NC group, and the protein expression of Bcl-2 was lower than that in si-DRAIC+ inhibitor-NC group (P<0.05). Conclusion: DRAIC is highly expressed in lung adenocarcinoma, and DRAIC promotes the proliferation, migration and invasion of lung adenocarcinoma cells and inhibits apoptosis by targeting let-7i-5p.

[Expression of miR-17-5p in the plasma of patients with multiple myeloma and its role in tumorigenesis and development].

Objective: To investigate the expression of miR-17-5p in the plasma of patients with multiple myeloma (MM) and its role in tumorigenesis and development. Methods: Patients diagnosed with unidentified monoclonal gammopathy of undetermined significance (MGUS) or MM in Cancer Hospital of Zhengzhou University from April 2013 to April 2018 were enrolled, as well as 20 healthy volunteers. Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-17-5p in plasma circulation and bone marrow mononuclear cells. There were 22 cases with newly diagnosed MM (NDMM), 11 cases with complete remission MM (CRMM) and 59 case with recurrent refractory MM (RRMM). The expression levels of miR-17-5p in each group were analyzed. The correlation analysis was used to evaluate the relationship between plasma miR-17-5p and the proportion of serum M protein and bone marrow plasma cells in patients with untreated multiple myeloma. Receiver operating characteristic (ROC) curve was used to evaluate the possibility of plasma miR-17-5p as a molecular marker related to MM diagnosis. After over expression or knockdown of miR-17-5p expression, CCK-8 method was used to detect the effect of miR-17-5p on the proliferation of MM cell line. The effect of miR-17-5p on the proliferation of MM cells was detected in nude mice subcutaneous tumorigenesis experiment. Results: The expression of miR-17-5p in bone marrow mononuclear cells in NDMM and RRMM group were higher than those in healthy volunteers [1.37 (0.47, 4.87), 2.68 (1.02, 5.02) vs 1.00 (1.00, 1.00), all P<0.05], and the expression levels of miR-17-5p in plasma were also higher than those in healthy control group [1.85 (0.92, 3.51), 2.79 (1.22, 5.04) vs 1.00 (1.00, 1.00), all P<0.05]. The expression of miR-17-5p in MM cell lines such as KMS-11, RPMI-8226, H929, MM-1R, U266B1 were higher than that in bone marrow mononuclear cells of healthy control group (3.96±0.68, 1.58±0.32, 3.51±0.55, 5.08±0.76, 3.22±0.75 vs 1.00±0, all P<0.05) ; Plasma miR-17-5p was positively correlated with the ratio of serum M protein and bone marrow plasma cells (r=0.50, P<0.05; r=0.60, P<0.01). ROC curve showed that the specificity was 0.591 and the sensitivity was 0.900 of plasma miR-17-5p as a molecular marker related to diagnosis (area under ROC curve=0.74, cut-off value: 0.491). CCK-8 results showed that over expression of miR-17-5p increased the proliferation of RPMI-8226 and NCI-H929 cell lines at 72 hours compared with the control group (1.37±0.11 vs 1.07±0.09, 2.14±0.09 vs 1.82±0.11, both P<0.05), and low expression of miR-17-5p reduced the proliferation of NCI-H929 and MM-1R cell lines at 72 hours compared with the control group (1.38±0.09 vs 1.83±0.11, 1.45±0.10 vs 1.73±0.09, both P<0.05). The subcutaneous tumorigenesis experiment in nude mice showed that the tumor volume of miR-17-5p over expression group was larger than that of the control group [(1 865±181) vs (1 389±227) mm3, P<0.05], and the tumor volume of miR-17-5p low expression group was smaller than that of the control group [ (1 006±171) vs (1 389±227) mm3, P<0.05]. Conclusion: miR-17-5p may play an oncogene role in MM cell lines as a plasma molecular marker related to the development of MM disease.

[Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells].

Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 µmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-ß1 (DMY+ TGF-ß1), transforming growth factor-ß1 (TGF-ß1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 µmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-ß1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-ß1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-ß1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-ß1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-ß1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-ß1 group were lower than those in DMY+ TGF-ß1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-ß1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-ß1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-ß1 group were higher than those in DMY+ TGF-ß1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-ß1 and promote cell apoptosis.

Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression, by C. Liu, L. Wang, Y.-W. Li, Y.-S. Cui, Y.-Q. Wang, S. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (8): 3277-3283-DOI: 10.26355/eurrev_201904_17689-PMID: 31081080" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17689.

Long noncoding RNA LUCAT1 promotes migration and invasion of prostate cancer cells by inhibiting KISS1 expression.

OBJECTIVE: Recent researches have revealed the role of long noncoding RNAs (lncRNAs) in tumor development. In this study, the potential function of lncRNA LUCAT1 in the progression of prostate cancer was identified. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect LUCAT1 expression in both prostate cancer cells and tissue samples. Moreover, the association between LUCAT1 expression level and overall survival of prostate cancer patients was analyzed. In addition, wound healing assay and transwell assay were conducted to evaluate the regulatory effect of LUCAT1 on prostate cancer cells. Furthermore, the underlying mechanism of LUCAT1 in regulating the development of prostate cancer was explored via qRT-PCR and Western blot. RESULTS: LUCAT1 expression was much higher in prostate cancer samples than controls. Besides, LUCAT1 expression was correlated with the overall survival of prostate cancer patients. Moreover, LUCAT1 overexpression promoted in vitro migration and invasion of prostate cancer cells. In addition, the mRNA and protein expression of KISS1 were downregulated after LUCAT1 overexpression. Furthermore, it was found that the expression level of KISS1 was negatively related to the expression level of LUCAT1 in prostate cancer tissues. CONCLUSIONS: LUCAT1 could enhance migration and invasion of prostate cancer cells by regulating KISS1, which might offer a potential therapeutic target for prostate cancer.

Correlations of the ZEB1 expression with the incidence and prognosis of non-small cell lung cancer.

OBJECTIVE: In order to investigate the role of the zinc finger E-box-binding homeobox 1 (ZEB1) expression in the incidence of non-small cell lung cancer (NSCLC), the effects of the ZEB1 expression on the pathogenesis and prognosis of NSCLC were investigated. PATIENTS AND METHODS: Correlations of the expression of ZEB1 in 88 clinical patients with NSCLC with clinicopathological features were determined. The patients were followed up for 60 months to study the correlation between the ZEB1 expression and the prognosis of NSCLC patients. To further explore the role of the ZEB1 expression in the incidence of NSCLC, the expressions of ZEB1 and E-cadherin in three NSCLC cell lines (A549, NCI-H1299 and NCI-H1975) and human normal lung epithelial BESA-2B cell line were measured, and the cell invasion ability was detected. The role of ZEB1 in NSCLC cell invasion was verified through the knockdown of ZEB1 by the short hairpin ribonucleic acids (shRNAs). In addition, its effects on the proliferation and apoptosis of NSCLC cells were confirmed by the overexpression of ZEB1. RESULTS: The expression of ZEB1 in NSCLC tissues was remarkably higher than that in normal tissues, and the expression level of ZEB1 was significantly related to the cancer stage and tumor size. The lower the expression of ZEB1 was, the higher the overall survival rate and the longer the survival time would be. The expression of ZEB1 was negatively correlated with that of E-cadherin in cell lines, and ZEB1-shRNAs markedly reduced the invasion ability of NSCLC cells. The overexpression of ZEB1 resulted in an increase in the proliferation activity and a significant decrease in the apoptosis of A549 cells. CONCLUSIONS: The expression of ZEB1 is closely related to the incidence and prognosis of NSCLC. Increased expression of ZEB1 is helpful for promoting the invasion of NSCLC and enhancing the proliferation activity of NSCLC.

[Effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury caused by fluoride in rat].

Objective: To explore the effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury of rats caused by excessive fluoride intake. Methods: All 40 Wistar rats were randomly divided into four groups, control group, low fluoride group, medium fluoride group and high fluoride group. The rats in control group were fed with tap water (fluoride concentration=0.344 mg/L) and the experimental rats were fed with the water contaminated fluoride with the dose of 5, 10 and 20 mg/L. 10 rats (female: male=1∶1) in each group were sacrificed after 8 months of exposure through drinking water. The contents of urine fluoride were detected by fluorine ion selective electrode method. Morphology of thyroid was observed through light microscope and apoptosis in thyroid were detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were analyzed by RT-PCR and immunohistochemistry respectively, and results were compared among groups. Results: The contents of urine fluoride in all fluoride treated groups were separately (4.74±1.88), (7.70±2.82) and (10.50±2.92) mg/L, which were gradually higher than that of control group (2.23±0.54) mg/L (P<0.05). Morphological changes were found in thyroid tissues of fluoride treated groups, thyroid follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis in thyroid were notably increased in fluoride treated groups. The mRNA expression levels of GRP78 in all fluoride treated groups were separately 1.30±0.42, 1.39±0.29 and 1.50±0.27, which were significantly higher than that of control group (0.93±0.24) (P<0.05). And the mRNA expression levels of CHOP in medium and high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were significantly higher than that of control group (0.91±0.20) (P<0.05). The protein expression levels of GRP78 and CHOP in medium and high fluoride groups were respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were significantly higher than those in the control group (separately 23.80±6.36, 2.27±0.89) (P<0.05). Conclusion: Excessive-fluoride intake can induce thyroid injury, and endoplasmic reticulum stress-induced apoptosis might be involved in the injury.

Expressions and effects of G250, Bax and Bcl-2 in rats with renal clear cell carcinoma.

OBJECTIVE: To investigate the expressions and effects of G250, B-cell lymphoma-2 associated X protein (Bax) and Bcl-2 in rats with renal clear cell carcinoma (RCCC). MATERIALS AND METHODS: A total of 66 male Sprague-Dawley (SD) rats were selected, among which 56 were selected to establish RCCC rat model and the remaining 10 were selected as control group. Three weeks after modeling, 4 rats failed in the modeling. Expressions of G250 in RCCC rat model group and healthy rat model control group were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR); expressions of Bcl-2 and Bax in each group were detected by Western blot and their effects were analyzed. RESULTS: The positive expression rates of G250 in 52 RCCC rats in model group and 10 healthy rats in control group were 83.3% and 0%, respectively. The results showed that expression of G250 had a certain correlation with the pathological changes of RCCC (p < 0.01). Expressions of Bax and Bcl-2 were up-regulated in the RCCC group, while expressions were down-regulated in the healthy control group (p < 0.05). CONCLUSIONS: G250, as a new specific marker of renal cell carcinoma, is involved in the pathological changes of renal cell carcinoma. Joint detection of Bax and Bcl-2 can be used as an important index for the diagnosis of RCCC.

[Effects of fluoride exposure on thyroid hormone level and intelligence in rats].

Objective: To investigate the effects of fluoride exposure on the thyroid hormone level and intelligence in rats and to investigate the biomarkers of intellectual impairment induced by high fluoride exposure. Methods: A total of 24 clean healthy Sprague-Dawley rats were randomly divided into control group (tap water containing 0.344 mg/L fluoride) and low-, medium-, and high-fluoride exposure groups (tap waters containing 10, 50, and 100 mg/L sodium fluoride, respectively). One male rat was cohabited with two female rats in the same group. After the offspring rats were weaned, 12 offspring rats (male/female ratio=1∶1) with a similar body weight in each group were subjected to the same treatment for the parental offspring. The offspring rats were sacrificed on the 60th day after birth. The weight of offspring rats was measured. Serum thyrotropin (TSH) , free triiodothyronine (FT(3)) , and free thyroxine (FT(4)) levels were measured by enzyme-linked immunosorbent assay. The learning and memory abilities of the rats were evaluated by Morris water maze test. The expression of mitochondrial fission 1 (Fis1) and mitofusin 1 (Mfn1) in blood was measured by Western blot. Results: The offspring rats in the medium-and high-fluoride exposure groups had significantly lower serum TSH and FT(4) levels than those in the control group (P<0.05). The place navigation test showed that the offspring rats in the medium-and high-fluoride exposure groups had significantly longer escape latency than those in the control group (P<0.05) , and the high-fluoride exposure group had a significantly longer escape distance than those in the control group (P<0.05). The spatial probe test showed that the offspring rats in the low-, medium-, and high-fluoride exposure groups had significantly shorter swimming time and distance in the target quadrant and total swimming time and distance than those in the control group (P<0.05). Compared with the offspring rats in the control group, those in the low-, medium-, and high-fluoride exposure groups had significantly higher expression of Fis1 (P<0.05) , and those in the low- and medium-fluoride exposure groups had significantly higher expression of Mfn1 (P<0.05) . Conclusion: High fluoride exposure can reduce the secretion of thyroid hormone and the abnormality of mitochondrial dynamics in peripheral lymphocytes may provide a clue to identifying the biomarkers of intellectual impairment induced by fluoride exposure.

Calcineurin inhibitor avoidance and withdrawal for kidney transplantation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Many studies have compared the safety and efficacy of the calcineurin inhibitor (CNI) avoidance or CNI withdrawal regimens with typical CNI regimens, but the results remain controversial. The aim of this systematic review and meta-analysis is to make a profound review and an objective appraisal of the safety and efficacy of the CNI avoidance and CNI withdrawal protocols. METHODS: We searched PUBMED, EMBASE, and the reference lists of retrieved studies to identify randomized controlled trials (RCTs) that referred to CNI-free regimens, CNI avoidance, or CNI withdrawal for kidney transplantation. Eight publications involving 27 different RCTs and a total of 3953 patients were used in the analysis. RESULTS: Use of mammalian target of rapamycin inhibitors, namely sirolimus (SRL), in combination with mycophenolate, conserve graft function at 1 year (glomerular filtration rage [GFR]: mean difference MD 6.21, 95% CI 0.02-12.41, P = .05; serum creatinine: MD -0.11, 95% CI -0.19 to -0.03, P = .01, respectively) and 2 years post-transplant (GFR: MD 13.96, 95% CI 7.32-20.60, P < .0001). Similarly, early withdrawal (≤ 6 months) of CNIs protect graft function at 1 year after transplant (GFR: MD 7.03, 95% CI 4.84-9.23, P < .00001, serum creatinine: MD -0.21, 95% CI -0.22 to -0.19, P < .00001, respectively). CNI avoidance and withdrawal strategies are associated with higher incidence of acute rejection at 1 year post-transplant (odds ratio OR 1.74, 95% CI 1.08-2.81, P = .02; OR 1.78, 95% CI 1.35-2.34, P < .0001, respectively). At 2 years after transplant, there was no significant difference (OR 0.92, 95% CI 0.33-2.51, P = .86; OR 2.42, 95% CI 1.01-5.82, P = .05, respectively). Meanwhile, neither adverse events nor patient/graft survival differed significantly between the CNI-free and CNI protocols at 1 and 2 years. Referring to long-term results in the published RCTs, use of CNI-free and CNI withdrawal regimens achieve better renal function vs CNI regimens, with no significant difference in patient and graft survival, acute rejection, and most reported adverse events. CONCLUSIONS: In conclusion, this systematic review and meta-analysis suggests that renal recipients with early withdrawal of CNI drugs or avoiding CNI with SRL perform better to conserve graft function at 1 and 2 years post-transplant. Though the use of CNI regimens performs no better in 2-year acute rejection vs the contrast group, they greatly decrease the incidence of acute rejection at the first year after transplantation. CNI avoidance and withdrawal regimens improve the long-term renal function and perform similarly in the acute rejection, patient and graft survival, and adverse events. Due to the limited amounts of long-term studies, more high-quality RCTs are needed.

The efficacy and safety of alemtuzumab and daclizumab versus antithymocyte globulin during organ transplantation: a meta-analysis.

OBJECTIVE: The objective of this study was to compare efficacy and safety of alemtuzumab, antithymocyte globulin (ATG), and daclizumab for induction therapy in organ transplantation. METHODS: We searched PUBMED, EMBASE, and Cochrane databases to identify randomized controlled trials that compared alemtzumab, ATG, and daclizumab for induction therapy in kidney as well as pancreas transplantation. According to the inclusion criteria, the collected data included general characteristics of the studies and their major outcomes. The meta-analysis was performed using RevMan 5.0.25 software. RESULTS: We identified 9 studies involving 777 patients. No differences between alemtuzumab, daclizumab, and ATG were observed in terms of patient survival, graft survival, or acute rejection episodes at a 24-month follow-up (P = .62, P = .55, and P = .08, respectively). Infections within 36 months were greater between the alemtuzumab and the ATG group (P = .03). There was no significant difference in terms of infection at 24 months. CONCLUSIONS: Alemtuzumab and daclizumab appeared to be as effective as ATG for induction therapy in kidney transplantation at a follow-up of 24 months. However, alemtuzumab showed a lower rate of infection at 36 months compared with ATG.

Valproic acid increases white matter repair and neurogenesis after stroke.

Acute treatment of stroke with histone deacetylase (HDAC) inhibitors has been shown to reduce ischemic cell damage; however, it is unclear whether delayed treatment with HDAC inhibitors will contribute to the brain repair and plasticity. In the present study, we investigated the effects of delayed treatment of stroke with a pan HDAC inhibitor, valproic acid (VPA), on white matter injury and neurogenesis during stroke recovery. Administration of VPA at a dose of 100mg/kg for 7 days starting 24h after middle cerebral artery occlusion (MCAo) in rats significantly improved neurological outcome measured 7-28 days post-MCAo. In addition, the VPA treatment significantly increased oligodendrocyte survival and newly generated oligodendrocytes, which was associated with elevation of myelinated axonal density in the ischemic boundary 28 days after MCAo. VPA treatment also increased the expression of glutamate transporter 1 (GLT1) in the ischemic boundary after stroke, and increased acetylated histone H4 expression in neuroblasts and the number of new neurons in striatal ischemic boundary region. This study provides new evidence that the delayed VPA treatment enhances white matter repair and neurogenesis in ischemic brain, which may contribute to improved functional outcome.

Synthesis and aldose reductase inhibitory activities of novel N-nitromethylsulfonanilide derivatives.

A novel series of 14 N-nitromethylsulfonanilide derivatives were synthesized and evaluated for their ability to inhibit recombinant aldose reductase. Computational docking simulations provided a good explanation for the observed structure-activity relationships. Kinetic analysis of (2-fluoro-5-methyl-N-methyl)-N-nitromethylsulfonanilide, 11, one of the most potent compounds in this series with an IC50 = 0.35 M, showed uncompetitive inhibition. Subsequent in vitro culture studies of rat lenses with 11 indicated that this series of aldose reductase inhibitors are effective in either preventing or retarding sugar cataract formation associated with diabetes.

Syntheses and SH-enzyme inhibitory activities of new epoxysuccinic acid piperazine derivatives against mu-calpain and cathepsin B.

New chiral epoxysuccinic acid derivatives 5 approximately 23 bearing various amino acids and N-substituted piperazines were synthesized to evaluate their inhibitory activities against mu-calpain and cathepsin B. After screening these compounds, 1-[(2S,3S)-epoxysuccinyl-L-leucyl]-4-(2-chlorophenyl)piperazine 9 proved to exhibit fairly strong inhibitory activity against both cysteine proteases. L-Valyl derivative 19 exhibited selective inhibitory activity against cathepsin B in comparison with that against mu-calpain.