Efficacy of the combination of Chinese herbal medicine and negative pressure wound therapy in the treatment of patients with diabetic foot ulcer: A meta-analysis.

This study aimed to systematically evaluate the clinical efficacy of Chinese herbal medicine combined with negative pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFU). Computerised searches of the China National Knowledge Infrastructure, Wanfang, Chinese BioMedical Literature Database, PubMed, Cochrane Library and Embase databases were conducted for randomised controlled trials on the use of Chinese herbal medicines combined with NPWT for the treatment of DFU. The search period ranged from the time of establishment of each database to July 2023. Literature screening and data extraction were performed independently by two investigators, and the quality of the included studies was assessed. The meta-analysis was performed using Review Manager 5.4 software. A total of 25 studies were analysed, including 1777 DFUs, with 890 and 887 patients in the experimental and control groups, respectively. The results showed that the treatment of DFUs with a Chinese herbal medicine in combination with NPWT increased the overall effectiveness (odds ratio [OR] = 4.32, 95% confidence interval [CI]: 2.96-6.30, p < 0.001), wound healing rate (mean difference [MD] = 18.35, 95% CI: 13.07-23.64, p < 0.001) and ankle brachial index (MD = 0.10, 95% CI: 0.06-0.14, p < 0.001); reduced the wound healing time (MD = -11.01, 95% CI: -13.25 to -8.78, p < 0.001) and post-treatment wound area (MD = -1.73, 95% CI: -2.46 to -1.01, p < 0.001); decreased the C-reactive protein level (MD = -3.57, 95% CI: -5.13 to -2.00, p < 0.001); and increased vascular endothelial growth factor level (MD = 19.20, 95% CI: 8.36-30.05, p < 0.001). Thus, Chinese herbal medicines combined with NPWT can effectively promote wound healing, reduce inflammation and shorten the disease course in patients with DFU, while demonstrating precise clinical efficacy.

The Role of Iron Overload in Diabetic Cognitive Impairment: A Review.

It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment. The current review highlights the role of iron overload in diabetic cognitive impairment (DCI), including the specific location and regulation mechanism of iron deposition in the diabetic brain, the factors that trigger iron deposition, and the consequences of iron deposition. Finally, we also discuss possible therapies to improve DCI and brain iron deposition.

Systematic dissection of genomic features determining the vast diversity of conotoxins.

BACKGROUND: Conus, a highly diverse species of venomous predators, has attracted significant attention in neuroscience and new drug development due to their rich collection of neuroactive peptides called conotoxins. Recent advancements in transcriptome, proteome, and genome analyses have facilitated the identification of conotoxins within Conus' venom glands, providing insights into the genetic features and evolutionary patterns of conotoxin genes. However, the underlying mechanism behind the extraordinary hypervariability of conotoxins remains largely unknown. RESULTS: We analyzed the transcriptomes of 34 Conus species, examining various tissues such as the venom duct, venom bulb, and salivary gland, leading to the identification of conotoxin genes. Genetic variation analysis revealed that a subset of these genes (15.78% of the total) in Conus species underwent positive selection (Ka/Ks > 1, p < 0.01). Additionally, we reassembled and annotated the genome of C. betulinus, uncovering 221 conotoxin-encoding genes. These genes primarily consisted of three exons, with a significant portion showing high transcriptional activity in the venom ducts. Importantly, the flanking regions and adjacent introns of conotoxin genes exhibited a higher prevalence of transposon elements, suggesting their potential contribution to the extensive variability observed in conotoxins. Furthermore, we detected genome duplication in C. betulinus, which likely contributed to the expansion of conotoxin gene numbers. Interestingly, our study also provided evidence of introgression among Conus species, indicating that interspecies hybridization may have played a role in shaping the evolution of diverse conotoxin genes. CONCLUSIONS: This study highlights the impact of adaptive evolution and introgressive hybridization on the genetic diversity of conotoxin genes and the evolution of Conus. We also propose a hypothesis suggesting that transposable elements might significantly contribute to the remarkable diversity observed in conotoxins. These findings not only enhance our understanding of peptide genetic diversity but also present a novel approach for peptide bioengineering.

Attitudes and influencing factors associated with smoking cessation: An online cross-sectional survey in China.

INTRODUCTION: Quitting smoking, the critical path to reach the global targets of reducing tobacco use, can bring major and immediate health benefits to smokers. Exploring factors that help individuals to quit smoking is of great importance. The present study explored influencing factors on smoking cessation, in order to provide comprehensive reference for tobacco control policies. METHODS: Ex-smokers and current smokers were recruited online in this cross-sectional survey, from 1 October to 31 November 2022, in China. The observational data were collected using a questionnaire to collect information with respect to sociodemographic characteristics of smokers, attitudes towards smoking cessation, details of smoking cessation, and different potential factors related to smoking cessation through open-ended questions. RESULTS: A total of 638 smokers from 30 provinces were recruited as eligible respondents, with a mean age of 37.3 ± 11.7 years and a mean smoking history of 15.9 ± 13.7 years. The percentage of males was 92.3%. Of the 638 respondents, only 3.9% had no intention to stop smoking. Among 155 subjects who had quitted smoking successfully, willpower (55.5%) was considered as the most important contributing factor. Among 365 subjects who tried to quit but failed, lack of willpower (28.2%), tobacco dependence (16.2%), influence of surrounding smokers or smoking environments (15.9%), bad moods (9.9%), stress from work or life (7.9%), habits (7.1%), socialization (4.1%), and easy availability of tobacco (2.7%) were considered as the adverse factors leading to failure in quitting smoking. CONCLUSIONS: Willpower and support from family members were the vital factors that lead to successful smoking cessation. Future tobacco control policies should also focus on addressing withdrawal symptoms and creating smoke-free environments as well as other factors.

Effects of liraglutide on astrocyte polarization and neuroinflammation in db/db mice: focus on iron overload and oxidative stress.

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1ß, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic cognitive impairment.

Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis.

Studies have shown that diabetes is associated with the occurrence of neurodegenerative diseases and cognitive decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The superior efficacy of liraglutide (LIRA) for cognitive impairment and numerous neurodegenerative diseases has been widely demonstrated. This study determined the effects of LIRA on diabetic cognitive impairment and on the levels of oxidative stress, lipid peroxidation, iron metabolism and ferroptosis in the hippocampus. Mice were injected daily with liraglutide (200 µg/kg/d) for 5 weeks. LIRA could repair damaged neurons and synapses, and it increased the protein expression levels of PSD 95, SYN, and BDNF. Furthermore, LIRA significantly decreased oxidative stress and lipid peroxidation levels by downregulating the production of ROS and MDA and upregulating SOD and GSH-Px in the serum and hippocampus, and the upregulation of SOD2 expression was also proven. The decreased levels of TfR1 and the upregulation of FPN1 and FTH proteins observed in the LIRA-treated db/db group were shown to reduce iron overload in the hippocampus, whereas the increased expression of Mtft and decreased expression of Mfrn in the mitochondria indicated that mitochondrial iron overload was ameliorated. Finally, LIRA was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4; simultaneously, the damage to the mitochondria observed by TEM was also repaired. For the first time, we proved in the T2DM model that ferroptosis occurs in the hippocampus, which may play a role in diabetic cognitive impairment. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetic cognitive disorders and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma.

Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

A novel method for in situ visualization of the growth kinetics, structures and behaviours of gas-phase fabricated metallic alloy nanoparticles.

Modulation of gas-phase nanoparticles is unmethodical as there is a lack of information on the growth kinetics and its determinants. Here, we developed a novel in situ evaporation-and-deposition (EAD) method inside a transmission electron microscope which enables direct visualization of the nucleation, growth, coalescence and shape/phase evolution of gas-phase fabricated nanoparticles. Using a Bi49Pb18Sn12In21 alloy as a sample, the critical factors that determine the feasibility of this EAD method are revealed. By direct observation, it is unambiguously evidenced that pristine nanoparticles with ultra-clean surfaces are extremely energetic during growth. Coalescence between EAD-fabricated nanoparticles takes place in a manner beyond conventional understanding acquired by postmortem analyses. Moreover, the EAD-fabricated diverse nanoparticles show distinct size distributions and sandwich-type or Janus-type phase segregations. These features offer an effective tool to identify atomic surface steps of thin films and can provide an ideal case for exploring the phase diagrams of nanoalloys in the future.

Association between KITLG Gene Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-analysis.

It has been reported that c-KIT ligand (KITLG) gene polymorphisms may be associated with testicular germ cell tumors (TGCT). Owing to mixed and inconclusive results, we conducted a systematic review and meta-analysis to summarize and clarify this association. A systematic search of studies on the association between KITLG gene polymorphisms and TGCT susceptibility was conducted in databases. Odds ratios and 95% confidence intervals were used to pool the effect size. Six articles were included in our systematic review and meta-analysis. Compared with adenine (A), KITLG rs995030 guanine (G) might be associated with increased risk of TGCT. There are insufficient data to fully confirm the association between KITLG rs4474514 and TGCT susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.

SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma.

BACKGROUND: Deregulation of microtubules and centrosome integrity is response for the initiation and progression of human cancers. Sperm-associated antigen 5 (SPAG5) is essential for the spindle apparatus organization and chromosome segregation, but its role in hepatocellular carcinoma (HCC) remains undefined. METHODS: The expression of SPAG5 in HCC were examined in a large cohort of patients by RT-PCR, western blot and IHC. The clinical significance of SPAG5 was next determined by statistical analyses. The biological function of SPAG5 in HCC and the underlying mechanisms were investigated, using in vitro and in vivo models. RESULTS: Here, we demonstrated that SPAG5 exhibited pro-HCC activities via the activation of PI3K/AKT signaling pathway. SPAG5 expression was increased in HCC and correlated with poor outcomes in two independent cohorts containing 670 patients. High SPAG5 expression was associated with poor tumor differentiation, larger tumor size, advanced TNM stage, tumor vascular invasion and lymph node metastasis. In vitro and in vivo data showed that SPAG5 overexpression promoted tumor growth and metastasis, whereas SPAG5 knockdown led to the opposite phenotypes. SPAG5 interacted with centrosomal protein CEP55 to trigger the phosphorylation of AKT at Ser473. Inhibition of PI3K/AKT signaling markedly attenuated SPAG5-mediated cell growth. Furthermore, SPAG5 expression was suppressed by miR-363-3p which inhibited the activity of SPAG5 mRNA 3'UTR. Ectopic expression of SPAG5 partly abolished the miR-363-3p-caused cell cycle arrest and suppression of cell proliferation and migration. CONCLUSIONS: Collectively, these findings indicate that SPAG5 serves a promising prognostic factor in HCC and functions as an oncogene via CEP55-mediated PI3K/AKT pathway. The newly identified miR-363-3p/SPAG5/CEP55 axis may represent a potential therapeutic target for the clinical intervention of HCC.

CBX1 Indicates Poor Outcomes and Exerts Oncogenic Activity in Hepatocellular Carcinoma.

Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion. Patients with elevated expression of CBX1 were frequently accompanied with unfavorable overall and disease-free survivals in two independent cohorts consisting of 648 HCC cases. The prognostic value of CBX1 was further confirmed by stratified survival analyses. Multivariate cox regression model suggested CBX1 as an independent factor for overall survival (hazard ratio = 1.735, 95% confident interval: 1.342-2.244, P < .001). In vitro data demonstrated that CBX1 overexpression promoted cell proliferation and migration, whereas the knockdown of CBX1 resulted in the opposite phenotypes. Mechanistically, CBX1 interacted with transcription factor HMGA2 to activate the Wnt/ß-Catenin signaling pathway. Suppression of ß-Catenin by siRNA or specific inhibitor XAV-939 markedly attenuated CBX1-mediated cell growth. Collectively, our findings indicate that CBX1 functions as an oncogene and may serve as a potential prognostic biomarker in HCC.

TRIM65 triggers ß-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma.

Deregulation of ubiquitin ligases contributes to the malignant progression of human cancers. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase and has been implicated in human diseases, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we showed that TRIM65 expression was increased in HCC tissues and associated with poor outcome in two independent cohorts containing 888 patients. In vitro and in vivo data demonstrated that overexpression of TRIM65 promoted cell growth and tumor metastasis, whereas knockdown of TRIM65 resulted in opposite phenotypes. Further studies revealed that TRIM65 exerted oncogenic activities via ubiquitylation of Axin1 to activate the ß-catenin signaling pathway. TRIM65 directly bound to Axin1 and accelerated its degradation through ubiquitylation. Furthermore, HMGA1 was identified as an upstream regulator of TRIM65 in HCC cells. In clinical samples, TRIM65 expression was positively correlated with the expression of HMGA1 and nuclear ß-catenin. Collectively, our data indicate that TRIM65 functions as an oncogene in HCC. The newly identified HMGA1/TRIM65/ß-catenin axis serves as a promising prognostic factor and therapeutic target.

CEP131 indicates poor prognosis and promotes cell proliferation and migration in hepatocellular carcinoma.

Centrosomal proteins have been implicated in the progression of human diseases. CEP131 plays important roles in centrosome duplication and genome stability, but its role in cancers remains largely unknown. Here, we showed that CEP131 expression was increased in hepatocellular carcinoma (HCC), compared to the paracarcinoma tissues, at both mRNA and protein levels. High CEP131 expression was closely associated with tumor size (P=0.020), tumor capsule (P=0.043), TNM stage (P=0.007) and tumor differentiation (P=0.019). Furthermore, patients with high expression of CEP131 were accompanied with worse overall and disease-free survivals in our and TCGA cohorts consisting of a total of 802 cases. The prognostic value of CEP131 was further confirmed by stratified survival analysis. Multivariate cox regression model indicated that CEP131 was an independent factor for overall survival (hazard ratio=1.762, 95% confident interval: 1.443-2.151, P<0.001). In vitro data demonstrated that nucleophosmin (NPM) physically bound to CEP131 and maintained its protein stability. Overexpression of CEP131 in HCC cell lines enhanced cell proliferation and migration, whereas the knockdown of CEP131 led to the opposite phenotypes. Further studies demonstrated that CEP131 exhibited oncogenic activity via activation of PI3K/AKT signaling pathway. Taken together, our findings suggest CEP131 serves as a potential prognostic biomarker in HCC, and functions as an oncogene in this deadly disease.

FOXK2, regulted by miR-1271-5p, promotes cell growth and indicates unfavorable prognosis in hepatocellular carcinoma.

The forkhead transcription factor FOXK2 has been implicated in the progression of human cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) have not been explored. Here we showed that FOXK2 expression was increased and associated with tumor size, TNM stage and vascular invasion. High FOXK2 expression was correlated with poor overall and disease-free survival in two independent cohorts consisting of 864 patients with HCC. The prognostic value of FOXK2 was validated by stratified survival analyses in subgroups difined by factors contributing to worse survival. Multivariate Cox regression model revealed that FOXK2 served as an independent factor for overall survival. The FOXK2 expression was reversely connected with miR-1271-5p in clinical samples. Re-introduction of miR-1271 decreased FOXK2 at both mRNA and protein levels. Luciferase assay confirmed that FOXK2 was a direct target of miR-1271 in HCC cells. Overexpression of FOXK2 enhanced the cell growth and migration, whereas FOXK2 silence resulted in the opposite phenotypes. Further studies demonstrated that FOXK2 exerted oncogenic activity via activation of PI3K/AKT signaling pathway. Collectively, our data suggest FOXK2 as an oncogene and a promising prognostic biomarker in HCC. Targeting the newly identified miR-1271/FOXK2/AKT axis may represent a potential strategy for HCC intervention.

PDZ binding kinase, regulated by FoxM1, enhances malignant phenotype via activation of ß-Catenin signaling in hepatocellular carcinoma.

Deregulation of serine/threonine kinase contributes to the development and progression of human diseases. PDZ-binding kinase (PBK) has been implicated in the malignant process of cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remains unclear. Here we show that PBK expression is increased and associated with larger tumor size, presence of vascular invasion, lymph node metastasis and poor overall and disease-free survivals in two independent cohorts of 879 patients with HCC. In vitro and in vivo data demonstrate PBK exerts oncogenic functions in HCC via activation of ß-Catenin signaling pathway. The inhibition of ß-Catenin by siRNAs or XAV-939 significantly attenuates PBK-mediated malignant phenotypes. PBK is further identified as a downstream effector of FoxM1. In clinical samples, PBK expression is positively correlated with the expression of FoxM1 and nuclear ß-Catenin. Collectively, these findings suggest PBK functions as an oncogene in HCC and the newly identified FoxM1/PBK/ß-Catenin axis serves as a promising prognostic factor as well as therapeutic intervention for HCC.

Prognostic factors of regression and relapse of complex atypical hyperplasia and well-differentiated endometrioid carcinoma with conservative treatment.

OBJECTIVE: To evaluate possible prognostic factors regarding regression and relapse of complex atypical hyperplasia (CAH) and well-differentiated endometrioid adenocarcinoma (WDC) treated with conservative treatment. METHODS: The retrospective study reviewed clinicopathologic, treatment, regression and relapse data from patients diagnosed with CAH or WDC who were treated with conservative treatment at 4 institutions. Potential factor evaluation was performed. SPSS 16 was used for statistical analyses. RESULTS: Eighty-eight patients were included (51 had WDC, and 37 had CAH). Regression was evaluated in 88 patients, with a median follow-up of 61 (range 15-95) months. Seventy-seven (87.5%) patients regressed, and 11 (12.5%) had persistent or progressive disease. Univariate and multivariate analyses showed no factors associated with regression. Relapse was evaluated in 71 patients, with median follow-up of 54 (range 8-86) months. Twenty-five/71 (35.2%) patients experienced relapse. On univariate analysis, body mass index (BMI) 30 or higher (p=0.001), WCD at initial biopsy (p=0.017) and positive expression of post-treatment ki67 (p=0.033) were associated to a higher relapse probability. However, only BMI 30 or higher was significant on multivariate analysis (p=0.012). The Kaplan-Meier analysis revealed a higher relapse probability in the patients with BMI 30 or higher (p=0.001). CONCLUSION: Obesity seems to be a risk factor for relapse of CAH or WDC with conservative treatment.

Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients.

The aim of this study was to evaluate the frequency and prognostic impact of changes in the estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent/metastatic lesions (RML). We investigated 133 breast cancer patients for ER, PR and HER2 status of primary and RML and their follow-up records. Among 133 patients with RML, discordance rate for ER, PR, and HER2 was 18.8, 33.8, and 6.8%, respectively. ER, PR and HER2 discordance were observed in 20.0, 38.1 and 6.7% of the patients with distant metastasis, and in 14.3, 17.9 and 7.1% of the patients with locoregional recurrence. The mean time between the primary diagnosis and last contact or death was 57 (range 22-78) months and between the recurrence biopsy and last contact or death was 17 (range 1-33) months. Among 133 patients with RML, the ER-discordant cases and ER-loss cases experienced a worse overall survival (OS) (p=0.001 and p=0.016, respectively) and post-recurrence survival (PRS) (p=0.001 and p=0.018, respectively), compared with the respective concordant cases. The HER2-discordant patients and HER2-loss patients had a poorer OS (p=0.008 and p=0.001, respectively) and PRS (p=0.004 and p=0.000, respectively) than the respective concordant cases. Among 105 patients with distant metastasis, ER discordance, ER loss, HER2 discordance and HER2 loss, compared with the respective concordant cases, resulted in a worse OS and PRS (p<0.05 for all). Our findings show an evident change in ER, PR and HER2 between breast primary tumors and relapsing tumors. The unstable status for ER or HER2 in breast cancer seems to be clinically significant and to correlate with a worse prognosis.

Prognostic role of nucleophosmin in colorectal carcinomas.

AIM: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. METHODS: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. RESULTS: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). CONCLUSION: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer.

Previous studies have reported conflicting results regarding the impact of neoadjuvant chemotherapy (NAC) on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in breast cancer. Our aim was to investigate whether NAC induces some selective change in the breast biomarkers. We retrospectively detected the immunohistochemical results of ER, PR and HER2 between the core biopsy and surgical excision specimens in 113 patients with NAC. As a control group, we analyzed sample pairs from 102 patients without NAC. Fourteen (12.4%) of 113 patients undergoing NAC showed the ER status modulation in the surgically removed specimen as compared with only 4 (3.9%) of 102 women without NAC (p=0.025). Eighteen (15.9%) of 113 patients given NAC appeared in the PR status alteration in the final surgical specimen, whereas only 7 (6.9%) of 102 patients without NAC did (p=0.038). The HER2 status shift was found in 17 (15.0%) of 113 patients with NAC and in 6 (5.9%) of 102 patients without NAC, respectively (p=0.030). Neoadjuvant chemotherapy does change ER, PR and HER2 status in a statistically significant manner. Retesting these biomarkers of the residual tumor should be considered to improve future tailored adjuvant therapies.

Toxic effects of erythromycin, ciprofloxacin and sulfamethoxazole exposure to the antioxidant system in Pseudokirchneriella subcapitata.

We tested antioxidant responses of the green microalga Pseudokirchneriella subcapitata exposed to different concentrations of the three antibiotics erythromycin (ETM), ciprofloxacin (CPF) and sulfamethoxazole (SMZ). Measurements included the level of lipid peroxidation, the total antioxidative capacity and three major antioxidant mechanisms: the ascorbate-glutathione cycle, the xanthophyll cycle and the enzyme activities of catalase (CAT), superoxide dismutase (SOD), guaiacol glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Three antibiotics significantly affect the antioxidant system of P. subcapitata, but in different ways the alga was more tolerant to CPF and SMZ exposures than to ETM exposure. ETM caused reductions in AsA and GSH biosynthesis, ascorbate-glutathione cycle, xanthophylls cycle and antioxidant enzyme activities. The toxicity of CPF seems to be mainly overcome via induction of the ascorbate-glutathione cycle and CAT, SOD and GPX activities, while the toxicity of SMZ on the photosynthetic apparatus is predominantly reduced by the xanthophyll cycle and GST activity.