Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis.

BACKGROUND: Numerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations. METHODS: An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4. RESULTS: A total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, P<0.001), and diastolic pressure (MD = 17.65, 95%CI: 12.37~22.93, P<0.001). Subgroup analyses revealed that the increase in systolic pressure in the hypertension model subgroup (MD = 29.56, 95%CI = 23.55-35.58, P<0.001) was more pronounced than that in the normotensive model subgroup (MD = 12.48, 95%CI = 3.51-21.45, P<0.001). CONCLUSION: This meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.

Intense FDG Uptake in Leiomyomatosis Peritonealis Disseminata With Fumarate Hydratase Deficiency.

ABSTRACT: A 35-year-old woman with a history of laparoscopic myomectomy presented with repeated abdominal pain. Contrast-enhanced abdominal and pelvic CT showed multiple enhancing solid or mixed cystic and solid peritoneal masses, and an enhancing uterine mass. All these masses showed intense FDG uptake on FDG PET/CT. The intraperitoneal and uterine masses were surgically removed. The histological and immunohistochemical findings of the peritoneal lesions were consistent with leiomyomatosis peritonealis disseminata with fumarate hydratase deficiency, and the uterine mass was adenomyosis. This case indicates fumarate hydratase-deficient extrauterine leiomyoma can show intense FDG uptake mimicking malignancy.

Gut microbiota changes in patients with hypertension: A systematic review and meta-analysis.

Hypertension is a major public health issue worldwide. The imbalance of gut microbiota is thought to play an important role in the pathogenesis of hypertension. The authors conducted the systematic review and meta-analysis to clarify the relationship between gut microbiota and hypertension through conducting an electronic search in six databases. Our meta-analysis included 19 studies and the results showed that compared with healthy controls, Shannon significantly decreased in hypertension [SMD = -0.13, 95%CI (-0.22, -0.04), p = .007]; however, Simpson [SMD = -0.01, 95%CI (-0.14, 0.12), p = .87], ACE [SMD = 0.18, 95%CI (-0.06, 0.43), p = .14], and Chao1 [SMD = 0.11, 95%CI (-0.01, 0.23), p = .08] did not differ significantly between hypertension and healthy controls. The F/B ratio significantly increased in hypertension [SMD = 0.84, 95%CI (0.10, 1.58), p = .03]. In addition, Shannon index was negatively correlated with hypertension [r = -0.12, 95%CI (-0.19, -0.05)], but had no significant correlation with SBP [r = 0.10, 95%CI (-0.19, 0.37)] and DBP [r = -0.39, 95%CI (-0.73, 0.12)]. At the phylum level, the relative abundance of Firmicutes [SMD = -0.01, 95%CI (-0.37, 0.34), p = .94], Bacteroidetes [SMD = -0.15, 95%CI (-0.44, 0.14), p = .30], Proteobacteria [SMD = 0.25, 95%CI (-0.01, 0.51), p = .06], and Actinobacteria [SMD = 0.21, 95%CI (-0.11, 0.53), p = .21] did not differ significantly between hypertension and healthy controls. At the genus level, compared with healthy controls, the relative abundance of Faecalibacterium decreased significantly [SMD = -0.16, 95%CI (-0.28, -0.04), p = .01], while the Streptococcus [SMD = 0.20, 95%CI (0.08, 0.32), p = .001] and Enterococcus [SMD = 0.20, 95%CI (0.08, 0.33), p = .002] significantly increased in hypertension. Available evidence suggests that hypertensive patients may have an imbalance of gut microbiota. However, it still needs further validation by large sample size studies of high quality.

DUSP1 regulates the JAK2/STAT3 signaling pathway through targeting miR-21 in cervical cancer cells.

This study was to investigate the effect of DUSP1 on cervical cancer (CC) cells by targeting the miR-21 regulatory JAK2/STAT3 signaling pathway. For this purpose, fifteen CC patients treated at our hospital from January 2021 to February 2023 were selected. CC tissues and para-cancerous (PC) tissues were collected from the patients, and DUSP1 protein and mRNA expression levels were detected by Western blot and qPCR. The C33a control group (COG) and DUSP1 overexpression group (OVG) were set up: human cervical squamous carcinoma cells (CSCC) in the C33a COG were cultured without any treatment, while the DUSP1 OVG was cultured using DUSP1 gene overexpression lentivirus infection progeny. The proliferation ability of the three groups of cells was measured by CCK8, protein and mRNA expression by Western blot and qPCR, and cell migration and invasion ability by Transwell. It was found that DUSP1 protein and mRNA in CC tissues were reduced compared with those in PC tissues (P<0.05). The miR-21 in the DUSP1 OVG was reduced than those in the C33a COG (P<0.05). The expression of JAK2, STAT3 mRNA and protein in the DUSP1 OVG were reduced compared with those in the C33a COG (P<0.05). In conclusion, overexpression of DUSP1 can target and reduce the expression of miR-21, block the JAK2/STAT3 signaling pathway, reduce the viability of CC cells, inhibit the proliferation and migration and invasion ability of CC cells, and induce apoptosis of CC cells, thus providing a theoretical basis for the targeted treatment of clinical CC.

Residual neural network with mixed loss based on batch training technique for identification of EGFR mutation status in lung cancer.

Epidermal growth factor receptor (EGFR) is the key to targeted therapy with tyrosine kinase inhibitors in lung cancer. Traditional identification of EGFR mutation status requires biopsy and sequence testing, which may not be suitable for certain groups who cannot perform biopsy. In this paper, using easily accessible and non-invasive CT images, the residual neural network (ResNet) with mixed loss based on batch training technique is proposed for identification of EGFR mutation status in lung cancer. In this model, the ResNet is regarded as the baseline for feature extraction to avoid the gradient disappearance. Besides, a new mixed loss based on the batch similarity and the cross entropy is proposed to guide the network to better learn the model parameters. The proposed mixed loss utilizes the similarity among batch samples to evaluate the distribution of training data, which can reduce the similarity of different classes and the difference of the same classes. In the experiments, VGG16Net, DenseNet, ResNet18, ResNet34 and ResNet50 models with the mixed loss are trained on the public CT dataset with 155 patients including EGFR mutation status from TCIA. The trained networks are employed to the collected preoperative CT dataset with 56 patients from the cooperative hospital for validating the efficiency of the proposed models. Experimental results show that the proposed models are more appropriate and effective on the lung cancer dataset for identifying the EGFR mutation status. In these models, the ResNet34 with mixed loss is optimal (accuracy = 81.58%, AUC = 0.8861, sensitivity = 80.02%, specificity = 82.90%).

FDTrans: Frequency Domain Transformer Model for predicting subtypes of lung cancer using multimodal data.

BACKGROUND AND PURPOSE: Accurate identification of lung cancer subtypes in medical images is of great significance for the diagnosis and treatment of lung cancer. Despite substantial progress in existing methods, they remain challenging due to limited annotated datasets, large intra-class differences, and high inter-class similarities. METHODS: To address these challenges, we propose a Frequency Domain Transformer Model (FDTrans) to identify patients' lung cancer subtypes using the TCGA lung cancer dataset. We add a pre-processing process to transfer histopathological images to the frequency domain using a block-based discrete cosine transform and design a coordinate Coordinate-Spatial Attention Module (CSAM) to obtain critical detail information by reassigning weights to the location information and channel information of different frequency vectors. Then, a Cross-Domain Transformer Block (CDTB) is designed for Y, Cb, and Cr channel features, capturing the long-term dependencies and global contextual connections between different component features. At the same time, feature extraction is performed on the genomic data to obtain specific features. Finally, the image branch and the gene branch are fused, and the classification result is output through the fully connected layer. RESULTS: In 10-fold cross-validation, the method achieves an AUC of 93.16% and overall accuracy of 92.33%, which is better than similar current lung cancer subtypes classification detection methods. CONCLUSION: This method can help physicians diagnose the subtypes classification of lung cancer in patients and can benefit from both spatial and frequency domain information.

A progressive phased attention model fused histopathology image features and gene features for lung cancer staging prediction.

PURPOSE: Identifying the stage of lung cancer accurately from histopathology images and gene is very important for the diagnosis and treatment of lung cancer. Despite the substantial progress achieved by existing methods, it remains challenging due to large intra-class variances, and a high degree of inter-class similarities. METHODS: In this paper, we propose a phased Multimodal Multi-scale Attention Model (MMAM) that predicts lung cancer stages using histopathology image data and gene data. The model consists of two phases. In Phase1, we propose a Staining Difference Elimination Network (SDEN) to eliminate staining differences between different histopathology images, In Phase2, it utilizes the image feature extractor provided by Phase1 to extract image features, and sends the multi-scale image features together with gene features into our Adaptive Enhanced Attention Fusion (AEAF) module for multimodal multi-scale features fusion to enable prediction of lung cancer staging. RESULTS: We evaluated the proposed MMAM on the TCGA lung cancer dataset, and achieved 88.51% AUC and 88.17% accuracy on classification prediction of lung cancer stages I, II, III, and IV. CONCLUSION: The method can help doctors diagnose the stage of lung cancer patients and can benefit from multimodal data.

Changes in the gut microbiome of patients with type a aortic dissection.

Objective: To investigate the characteristic changes in the gut microbiota of patients with type A aortic dissection (AAD) and provide a theoretical basis for future microbiome-oriented interventional studies. Methods: High-throughput 16S rDNA sequencing was performed on the stool samples of patients with and without (healthy control subjects) AAD. Using alpha and beta diversity analysis, we compared the gut microbiota composition of 20 patients with AAD and 20 healthy controls matched for gender, age, BMI, and geographical region. The accuracy of AAD prediction by differential microbiome was calculated using the random forest machine learning model. Targeted measurement of the plasma concentration of short-chain fatty acids (SCFAs), which are the main metabolites of the gut microbiome, was performed using gas chromatography-mass spectrometry (GC-MS). Spearman's correlation analysis was conducted to determine the relationships of gut microbiome and SCFAs with the clinical characteristics of subjects. Results: The differences in gut microbiota alpha diversity between patients with AAD and the healthy controls were not statistically significant (Shannon index: p = 0.19; Chao1: p = 0.4); however, the microbiota composition (beta diversity) was significantly different between the two groups (Anosim, p = 0.001). Bacteroidota was enriched at the phylum level, and the SCFA-producing genera Prevotella, Porphyromonas, Lachnospiraceae, and Ruminococcus and inflammation-related genera Fenollaria and Sutterella were enriched at the genus level in the AAD group compared with those in the control group. The random forest model could predict AAD from gut microbiota composition with an accuracy of 87.5% and the area-under-curve (AUC) of the receiver operating characteristic curve was 0.833. The SCFA content of patients with AAD was higher than that of the control group, with the difference being statistically significant (p < 0.05). The different microflora and SCFAs were positively correlated with inflammatory cytokines. Conclusion: To the best of our knowledge, this is the first demonstration of the presence of significant differences in the gut microbiome of patients with AAD and healthy controls. The differential microbiome exhibited high predictive potential toward AAD and was positively correlated with inflammatory cytokines. Our results will assist in the development of preventive and therapeutic treatment methods for patients with AAD.

End-to-End Automatic Classification of Retinal Vessel Based on Generative Adversarial Networks with Improved U-Net.

The retinal vessels in the human body are the only ones that can be observed directly by non-invasive imaging techniques. Retinal vessel morphology and structure are the important objects of concern for physicians in the early diagnosis and treatment of related diseases. The classification of retinal vessels has important guiding significance in the basic stage of diagnostic treatment. This paper proposes a novel method based on generative adversarial networks with improved U-Net, which can achieve synchronous automatic segmentation and classification of blood vessels by an end-to-end network. The proposed method avoids the dependency of the segmentation results in the multiple classification tasks. Moreover, the proposed method builds on an accurate classification of arteries and veins while also classifying arteriovenous crossings. The validity of the proposed method is evaluated on the RITE dataset: the accuracy of image comprehensive classification reaches 96.87%. The sensitivity and specificity of arteriovenous classification reach 91.78% and 97.25%. The results verify the effectiveness of the proposed method and show the competitive classification performance.

A Multi-market Comparison of the Intraday Lead-Lag Relations Among Stock Index-Based Spot, Futures and Options.

Using 1-min data, we explore the dynamic variation of the intraday lead-lag relations between stock indices and their derivatives through a comprehensive study with broader coverage of research objectives and methodologies. This paper provides explicit evidence that the futures and options exhibit price leadership over the spot market, and the options is ahead of the futures on most trading days in all three markets. This paper also reports a new finding that the relation between the derivative and its underlying index reverses when the index return has a significantly larger mean value, and the reversal phenomenon is also observed in the relations between the futures and the options, which enriches the empirical results of intraday lead-lag relations. Moreover, these conclusions still hold under the impact of extreme events, e.g., the outbreak of the Covid-19. Finally, we construct a pair trading strategy based on the intraday lead-lag relationships, which can get better performance than the corresponding spot index. Our findings can potentially help regulators understand the price discovery process between the index and its derivatives, and also be of great value for timely adjustment of investors intraday trading strategies.

The ferroxidases LPR1 and LPR2 control iron translocation in the xylem of Arabidopsis plants.

Iron (Fe) deficiency is common in agricultural crops and affects millions of people worldwide. Translocation of Fe in the xylem is a key step for Fe distribution in plants. The mechanism controlling this process remains largely unknown. Here, we report that two Arabidopsis ferroxidases, LPR1 and LPR2, play a crucial and redundant role in controlling Fe translocation in the xylem. LPR1 and LPR2 are mainly localized in the cell walls of xylem vessels and the surrounding cells in roots, leaves, and stems. Knockout of both LPR1 and LPR2 increased the proportion of Fe(II) in the xylem sap, and caused Fe deposition along the vascular bundles especially in the petioles and main veins of leaves, which was alleviated by blocking blue light. The lpr1 lpr2 double mutant displayed constitutive expression of Fe deficiency response genes and overaccumulation of Fe in the roots and mature leaves under Fe-sufficient supply, but Fe deficiency chlorosis in the new leaves and inflorescences under low Fe supply. Moreover, the lpr1 lpr2 double mutant showed lower Fe concentrations in the xylem and phloem saps, and impaired 57Fe translocation along the xylem. In vitro assays showed that Fe(III)-citrate, the main form of Fe in xylem sap, is easily photoreduced to Fe(II)-citrate, which is unstable and prone to adsorption by cell walls. Taken together, these results indicate that LPR1 and LPR2 are required to oxidize Fe(II) and maintain Fe(III)-citrate stability and mobility during xylem translocation against photoreduction. Our study not only uncovers an essential physiological role of LPR1 and LPR2 but also reveals a new mechanism by which plants maintain Fe mobility during long-distance translocation in the xylem.

Upregulation of miR-222-3p alleviates the symptom of aortic dissection through targeting STAT3.

OBJECTIVE: This study sought to investigate the differentially expressed miRNAs in Aortic dissection (AD) and explore the downstream mechanisms in regulating AD. METHODS: Exosomes of AD patients and healthy people were isolated by differential centrifugation, and the differentially expressed miRNAs were evaluated by RNA sequencing. The downstream target of miR-222-3p was predicted by bioinformatics method and validated by dual-luciferase assay. Angiotensin II and Promethazine were used to establish AD mouse model and platelet-derived growth factor BB (PDGF-BB) was used to induce human vascular smooth muscle cells (HVSMCs) to elucidate the effect of miR-222-3p upregulation on AD in vivo and in vitro. The relative level of miR-222-3p was evaluated by RT-qPCR. The level of several proteins was investigated by Western blot. Immunofluorescence staining was used to detect the stress fiber formation. Cell migration was evaluated by wound healing and Transwell assay. The proliferation, cell cycle and apoptosis of HVSMCs were assessed by CCK-8 and flow cytometry, respectively. RESULTS: MiR-222-3p was downregulated in AD and PDGF-BB induced HVSMCs. The upregulation of miR-222-3p alleviated the symptom of AD in vivo by targeting STAT3, and inhibited stress fiber formation, abnormal migration, proliferation and apoptosis of HVSMCs induced by PDGF-BB by regulating the expression of α-SMA, SM22α, MMP2, MMP9 and p-Smad2. CONCLUSION: The upregulation of miR-222-3p attenuates the progression of AD. Our study provides a theoretical basis for exploring new strategies against AD.

Effect of Breast Milk Oral Care on Mechanically Ventilated Preterm Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefits of breast milk oral care in mechanically ventilated preterm infants remain controversial. This study aimed to systematically review the evidence on the benefits of breast milk oral care in mechanically ventilated preterm infants. Methods: The randomized controlled trials of breast milk oral care for mechanically ventilated preterm infants were searched in EMBASE, PubMed, Cochrane Library, Web of Science, WANFANG Date and China National Knowledge Infrastructure databases. The retrieval language was limited to Chinese and English, and the final search was conducted until March 2022. Outcome measures included ventilator-associated pneumonia (VAP), mechanical ventilation time (MVT), length of stay (LOS), necrotizing enterocolitis (NEC), late-onset sepsis, mortality during hospitalization, time of full intestinal feeding and time of full oral feeding. Two researchers independently screened the literature, extracted the data, and conducted the literature quality assessment. Meta-analysis was mainly performed using RevMan 5.3. Results: Eight articles involving 1,046 preterm infants were included. Our meta-analysis showed that compared with the control group, breast milk oral care could reduce the incidence of VAP [RR = 0.41, 95% CI (0.23, 0.75), P = 0.003] and NEC [RR = 0.54, 95% CI (0.30, 0.95), P = 0.03], and shorten the MVT [MD = -0.45, 95% CI (-0.73, -0.18), P = 0.001] and LOS [MD = -5.74, 95% CI (-10.39, -1.10), P = 0.02]. There were no significant differences in the mortality during hospitalization [RR = 0.94, 95% CI (0.67, 1.33), P = 0.74], the incidence of late-onset sepsis [RR = 0.79, 95% CI (0.40, 1.59), P = 0.51], the time of full intestinal feeding [MD = -2.42, 95% CI (-5.37, 0.52), P = 0.11] and the time of full oral feeding [MD = -3.40, 95% CI (-10.70, 3.91), P = 0.36] between the two groups. Conclusions: Oral care of breast milk can reduce the incidence of VAP and NEC, shorten MVT and LOS in mechanically ventilated preterm infants. However, due to the quality and quantity limitations of the included studies, larger sample size and more strictly designed clinical trials are still needed in the future to further confirm the findings of this study.

Meta-Analysis: Shouldn't Prophylactic Corticosteroids be Administered During Cardiac Surgery with Cardiopulmonary Bypass?

Background: Corticosteroids can effectively inhibit systemic inflammation induced by cardiopulmonary bypass. Recently clinical trials and meta-analyses and current guidelines for cardiac surgery do not support corticosteroids prophylaxis during cardiac surgery because of an increase in myocardial infarction and no benefit for patients. The aim of this study is to determine whether specific corticosteroids dose ranges might provide clinical benefits without increasing myocardial infarction. Methods: The PubMed, Web of Science, Embase, Clinical Trials, and Cochrane databases were searched for randomized controlled trials (RCTs) published before August 1, 2021. Results: 88 RCTs with 18,416 patients (17,067 adults and 1,349 children) were identified. Relative to placebo and high-dose corticosteroids, low-dose corticosteroids (≤20 mg/kg hydrocortisone) during adult cardiac surgery did not increase the risks of myocardial infarction (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.43-2.17; p = 0.93). However, low-dose corticosteroids were associated with lower risks of atrial fibrillation (OR: 0.58, 95% CI: 0.44-0.76; p < 0.0001) and kidney injury (OR: 0.29, 95% CI: 0.09-0.96; p = 0.04). Furthermore, low-dose corticosteroids significantly shortened the mechanical ventilation times (mean difference [MD]: -2.74 h, 95% CI: -4.14, -1.33; p = 0.0001), intensive care unit (ICU) stay (MD: -1.48 days, 95% CI: -2.73, -0.22; p = 0.02), and hospital stay (MD: -2.29 days, 95% CI: -4.51, -0.07; p = 0.04). Conclusion: Low-dose corticosteroids prophylaxis during cardiac surgery provided significant benefits for adult patients, without increasing the risks of myocardial infarction and other complications.

Effect of Magnetic Nanoparticles on Hormone Level Changes During Perimenopausal Period and Regulation of Bone Metabolism.

This work aimed to explore the effect of nerve magnetic stimulation based on superparamagnetic Fe3O4 nanoparticle (NP) on bone metabolism during the perimenopausal period. First, the multifunctional water-soluble polymer PTMP-PMAA was utilized as the ligand. PTMP-MAA@ Fe3O4 NP with high magnetization was prepared by the co-precipitation method, and NPX diffraction pattern analysis and in vitro stability analysis were implemented. Then, NPs were co-cultured with 293T cells, and the cytotoxicity was detected by the CCK-8 method. Subsequently, 3-month-old female young SD rats and 11~15-month-old natural menopausal SD rats were taken as the research objects. According to the vaginal smear, the rats were randomly rolled into a young control, perimenopausal period model, estrogen treatment, and osteoporosis prevention groups. Rats in the estrogen treatment group were given Premarin suspension by gavage. Rats in the osteoporosis prevention group were injected stereotaxically with PTMP-MAA@ Fe3O4 NP suspension, and a rotating magnetic field was applied to the brain for nerve magnetic stimulation. The rats were sacrificed three days after treatment and brain tissues were taken for pathological analysis. Rat humerus was weighted and dual-energy X-ray was utilized to determine bone density and bone mineral content. Serum was collected and radioimmunoassay and ELISA were employed to detect estradiol (E2), osteocalcin (Boneglaprotein, BGP), oxytocin (OT), bone alkaline phosphatase (BALP), type I collagen carboxy-terminated cross-linked peptide (CTX-I), and tartrate-resistant acid phosphatase (TRACP-5b) in the serum of rats in each group. The results showed that PTMP-MAA@ Fe3O4 NP had good biocompatibility, and the CCK-8 test results showed that PTMP-MAA@ Fe3O4 NP had low cytotoxicity. Compared with the young control group, the humeral dry weight, wet weight, bone density, and bone mineral content, serum E2, OT, and BGP content in the perimenopausal period model group were reduced, while the serum BALP, CTX-I, and TRACP -5b content was increased (P<0.05). It was verified that nerve magnetic stimulation based on PTMP-MAA@ Fe3O4 NP increased the serum estrogen level of female rats during the perimenopausal period, increased the bone density of rats, promoted bone formation, and regulated bone metabolism.

Correction: Khan et al. Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes. Molecules 2019, 24, 2544.

Due to the previous incorrect characterization of compound C1, the authors wish to make the following corrections to this paper [...].

Research on Medical Knowledge Graph for Stroke.

Knowledge graph can effectively analyze and construct the essential characteristics of data. At present, scholars have proposed many knowledge graph models from different perspectives, especially in the medical field, but there are still relatively few studies on stroke diseases using medical knowledge graphs. Therefore, this paper will build a medical knowledge graph model for stroke. Firstly, a stroke disease dictionary and an ontology database are built through the international standard medical term sets and semiautomatic extraction-based crowdsourcing website data. Secondly, the external data are linked to the nodes of the existing knowledge graph via the entity similarity measures and the knowledge representation is performed by the knowledge graph embedded model. Thirdly, the structure of the established knowledge graph is modified continuously through iterative updating. Finally, in the experimental part, the proposed stroke medical knowledge graph is applied to the real stroke data and the performance of the proposed knowledge graph approach on the series of Trans ∗ models is compared.

High-Affinity Sulfate Transporter Sultr1;2 Is a Major Transporter for Cr(VI) Uptake in Plants.

Chromate (Cr[VI]) is a highly phytotoxic contaminant that is ubiquitous in soils. However, how Cr(VI) is taken up by plant roots remains largely unknown. Here, we show that the high-affinity sulfate transporter Sultr1;2 is responsible for Cr(VI) uptake by the roots of Arabidopsis thaliana. Sultr1;2 showed a much higher transport activity for Cr(VI) than Sultr1;1 when expressed in yeast cells. Knockdown of Sultr1;2 expression in Arabidopsis markedly reduced the Cr(VI) uptake rate, whereas knockout of Sultr1;1 had no or little effect. A double-knockout mutant (DKO) of the two genes lost the ability of Cr(VI) uptake almost completely. The Sultr1;2 knockdown mutant or DKO plants displayed higher resistance to Cr(VI) under normal sulfate conditions as a consequence of the lower tissue Cr accumulation. Overexpression of Sultr1;2 substantially increased Cr(VI) uptake with shoot Cr concentration being 1.6-2.0 times higher than that in the wild-type. These results indicate that Sultr1;2 is a major transporter responsible for Cr(VI) uptake in Arabidopsis, while Sultr1;1 plays a negligible role. Taken together, our study has identified a major transporter for Cr(VI) uptake in plants, providing potential strategies for engineering plants with low Cr accumulation and consequently enhanced Cr(VI) resistance and also plants with enhanced accumulation of Cr for the purpose of phytoremediation.

Anti-angiogenic therapy in ovarian cancer: current situation & prospects.

Ovarian cancer (OC) is one of five leading causes of cancer related death among women worldwide. Although treatment has been improving, the survival rate has barely improved over the past 30 years. The fatality rate is due to asymptomatic early signs and the lack of long-term effective treatment strategies for advanced disease. Angiogenesis is an important process in tumour growth and metastasis and is the creation of new blood vessels from existing blood vessels. It is a dynamic and complex process involving various molecular regulatory pathways and multiple mechanisms. The inhibition of angiogenesis has become a recognized therapeutic strategy for many solid tumours. While benefits in progression-free survival have been observed, the OS is far from satisfactory for OC patients who receive antiangiogenic therapy. In this article, the present research status of angiogenesis in OC was reviewed and the reasons for poor antiangiogenic therapeutic effects was explored with the aim to identify potential therapeutic targets that may improve the effect of antiangiogenic therapies.

Synthesis of a series of novel In(III) 2,6-diacetylpyridine bis(thiosemicarbazide) complexes: structure, anticancer function and mechanism.

The anticancer function and anticancer mechanism of indium (In) complexes still remain mysterious to date. Furthermore, it is greatly challenging to design a multi-functional metal agent that not only kills cancer cells but also inhibits their invasion and metastasis. Thus, to develop novel next-generation anticancer metal agents, we designed and synthesized a series of novel In(iii) 2,6-diacetylpyridine bis(thiosemicarbazide) complexes (C1-C4) for the first time and then investigated their structure-activity relationships with human urinary bladder cancer (T-24) cells. In particular, C4 not only showed higher cytotoxicity to cancer cells and less toxicity toward normal cells relative to cisplatin but also inhibited cell invasion and metastasis of T-24 cells. Interestingly, C4 acted against T-24 cells exhibiting multiple mechanisms: (1) arresting the S-phase of cell cycle via regulation of cytokine kinases, (2) activating the mitochondrial-mediated apoptosis, endoplasmic reticulum-stress-mediated cell death, PERK and c-Jun N-terminal kinase 1 (JNK) cell signaling pathways, and (3) inhibiting the expression of telomerase via the regulation of c-myc and h-TERT proteins. Our results suggested that C4 may be developed as a potential multi-functional and multi-targeting anticancer candidate.