Remifentanil pretreatment attenuates brain nerve injury in response to cardiopulmonary bypass by blocking AKT/NRF2 signal pathway.

OBJECTIVE: This study aimed to explore the effect and mechanism of remifentanil on cardiopulmonary bypass (CPB)-induced cerebral nerve injury. METHODS: After pretreating with remifentanil, or dexmedetomidine (DEX), SD rats were subjected to the CPB for 2 h. The data of body temperature, blood gas and mean arterial pressure (MAP) and hematocrit (HCT) were recorded at different time points. The cerebral tissue water content of rats was determined and immunohistochemical (IHC) and H&E assays on the hippocampal CA1 region of rats was performed. The levels of interleukin (IL)-6, IL-10, soluble protein-100ß (S100ß) and neuron-specific enolase (NSE) were analyzed by ELISA, and those of the indexes for oxidative stress (malondialdehyde (MDA) and superoxide dismutase (SOD)) were detected by the commercial kits. Morris water maze was used to evaluate the learning and memory abilities. Western blot/qRT-PCR were used to detect the protein/mRNA expressions in hippocampus. RESULTS: CPB increased the levels/expressions of IL-6, IL-10, S100ß, NSE, MDA, cleaved caspase-3, Bax and decreased those of Bcl-2, SOD, p-AKT, HO-1, in serum and parietal cortex tissue, with increased brain water content, lesions in the hippocampal CA1 area, swimming distance, brain nerve injury and decreased escape latency, retention time on platform and times of crossing the platform of rats. The preconditioning of remifentanil or DEX partially attenuated CPB-induced injury and -decreased expressions on p-AKT and HO-1, while further promoting CPB-induced expression of nuclear Nrf2 expression and inhibiting that of cytoplasm Nrf2. CONCLUSION: This paper demonstrates that remifentanil preconditioning could partially attenuate CPB-induced brain nerve injury of rats.

Sodium butyrate modulates gut microbiota and immune response in colorectal cancer liver metastatic mice.

Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL-17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment.

The analgesic efficacy compared ultrasound-guided continuous transverse abdominis plane block with epidural analgesia following abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This review and meta-analysis aims to evaluate the analgesic efficacy of continuous transversus abdominis plane (TAP) block compared with epidural analgesia (EA) in adults after abdominal surgery. METHODS: The databases PubMed, Embase and Cochrane Central Register were searched from inception to June 2019 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy of continuous TAP block compared with EA after abdominal surgery. The weighted mean differences (WMDs) were estimates for continuous variables with a 95% confidence interval (CI) and risk ratio (RR) for dichotomous data. The pre-specified primary outcome was the dynamic pain scores 24 h postoperatively. RESULTS: Eight trials including 453 patients (TAP block:224 patients; EA: 229 patients) ultimately met the inclusion criteria and seven trials were included in the meta-analysis. Dynamic pain scores after 24 h were equivalent between TAP block and EA groups (WMD:0.44; 95% CI: 0.1 to 0.99; I2 = 91%; p = 0.11). The analysis showed a significant difference between the subgroups according to regularly administering (4 trials; WMD:-0.11; 95% CI: - 0.32 to 0.09; I2 = 0%; p = 0.28) non-steroidal anti-inflammatory drugs (NSAIDs) or not (3 trials; WMD:1.02; 95% CI: 0.09 to 1.96; I2 = 94%; p = 0.03) for adjuvant analgesics postoperatively. The measured time of the urinary catheter removal in the TAP group was significantly shorter (3 trials, WMD:-18.95, 95% CI:-25.22 to - 12.71; I2 = 0%; p < 0.01), as was time to first ambulation postoperatively (4 trials, WMD:-6.61, 95% CI: - 13.03 to - 0.19; I2 = 67%; p < 0.05). CONCLUSION: Continuous TAP block, combined with NSAIDs, can provide non-inferior dynamic analgesia efficacy compared with EA in postoperative pain management after abdominal surgery. In addition, continuous TAP block is associated with fewer postoperative side effects.

MicroRNA profile in HBV-induced infection and hepatocellular carcinoma.

BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection. CONCLUSION: Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.

Predictive nomogram models for atrial fibrillation in COPD patients: A comprehensive analysis of risk factors and prognosis.

The aim of the present study was to identify the independent risk factors and prognostic indicators for atrial fibrillation (AF) in patients with chronic obstructive pulmonary disease (COPD) and to develop predictive nomogram models. This retrospective study included a total of 286 patients with COPD who were admitted to the Second Affiliated Hospital of Guilin Medical College between January 2020 and May 2022. The average age of the patients was 77.11±8.67 years. Based on the presence or absence of AF, the patients were divided into two groups: The AF group (n=87) and the non-AF group (n=199). Logistic regression analysis was conducted to identify variables with significant differences between the two groups. Nomogram models were constructed to predict the occurrence of AF in COPD patients and to assess prognosis. Survival analysis was performed using the Kaplan-Meier method. The follow-up period for the present study extended until April 31, 2023. Survival time was defined as the duration from the date of the interview to the date the participant succumbed or the end of the follow-up period. In the present study, age, uric acid (UA) and left atrial diameter (LAD) were found to be independent risk factors for the development of AF in patients diagnosed with COPD. The stepwise logistic regression analysis revealed that age had an odds ratio (OR) of 1.072 [95% confidence interval (CI): 1.019-1.128; P=0.007], UA had an OR of 1.004 (95% CI: 1.001-1.008; P=0.010) and LAD had an OR of 1.195 (95% CI: 1.098-1.301; P<0.001). Univariate and multivariate Cox regression analysis revealed that LAD and UA were independent prognostic factors for long-term mortality in COPD patients with AF. LAD had a hazard ratio (HR) of 1.104 (95% CI: 1.046-1.165; P<0.001) and UA had an HR of 1.004 (95% CI: 1.000-1.008; P=0.042). Based on these findings, predictive nomogram models were developed for AF in COPD patients, which demonstrated good discrimination ability with an area under the curve of 0.886. The prognostic nomogram for COPD patients with AF also showed good predictive accuracy with a concordance index of 0.886 (95% CI: 0.842-0.930). These models can provide valuable information for risk assessment and prognosis evaluation in clinical practice. Age, UA and LAD are independent risk factors for AF in COPD patients. The developed nomogram models provide a reliable tool for predicting AF in COPD patients and for prognosis assessment.

Primary catastrophic antiphospholipid syndrome in children with midbrain infarction: a case report.

Background: Catastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes. Case presentation: In this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an "intracranial infection". After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly. Conclusion: This case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.

Gas-phase synthesis of Ti2CCl2 enables an efficient catalyst for lithium-sulfur batteries.

MXenes have aroused intensive enthusiasm because of their exotic properties and promising applications. However, to date, they are usually synthesized by etching technologies. Developing synthetic technologies provides more opportunities for innovation and may extend unexplored applications. Here, we report a bottom-up gas-phase synthesis of Cl-terminated MXene (Ti2CCl2). The gas-phase synthesis endows Ti2CCl2 with unique surface chemistry, high phase purity, and excellent metallic conductivity, which can be used to accelerate polysulfide conversion kinetics and dramatically prolong the cyclability of Li-S batteries. In-depth mechanistic analysis deciphers the origin of the formation of Ti2CCl2 and offers a paradigm for tuning MXene chemical vapor deposition. In brief, the gas-phase synthesis transforms the synthesis of MXenes and unlocks the hardly achieved potentials of MXenes.

Deep sequencing discovery of novel and conserved microRNAs in strawberry (Fragaria×ananassa).

In plants, microRNAs (miRNAs) play a critical role in post-transcriptional gene regulation and have been shown to control many genes involved in various biological and metabolic processes. There have been extensive studies to discover miRNAs and analyze their functions in model plant species, such as Arabidopsis and rice. Deep sequencing technologies have facilitated identification of species-specific or lowly expressed as well as conserved or highly expressed miRNAs in plants. In this research, we used Solexa sequencing to discover new miRNAs in cultivated strawberry (Fragaria×ananassa). A total of 23,282 ,309 reads representing 22,500 ,402 distinct sequences were obtained from a short RNA library generated from small RNAs extracted from strawberry fruit tissues. On the basis of sequence similarity and hairpin structure prediction, we found that 156,639 reads representing 153 sequences have good matches to known miRNAs. We also identified 37 novel miRNA candidates. These sequences had not been previously described in other plant species. Potential target genes were predicted for the majority of and novel miRNAs. These results show that regulatory miRNAs exist in the agriculturally important cultivated strawberry and may play an important role in its growth, development and response to disease.

Cryo-EM structure and protease activity of the type III-E CRISPR-Cas effector.

The recently discovered type III-E CRISPR-Cas effector Cas7-11 shows promise when used as an RNA manipulation tool, but its structure and the mechanisms underlying its function remain unclear. Here we present four cryo-EM structures of Desulfonema ishimotonii Cas7-11-crRNA complex in pre-target and target RNA-bound states, and the cryo-EM structure of DiCas7-11-crRNA bound to its accessory protein DiCsx29. These data reveal structural elements for pre-crRNA processing, target RNA cleavage and regulation. Moreover, a 3' seed region of crRNA is involved in regulating RNA cleavage activity of DiCas7-11-crRNA-Csx29. Our analysis also shows that both the minimal mismatch of 4 nt to the 5' handle of crRNA and the minimal matching of the first 12 nt of the spacer by the target RNA are essential for triggering the protease activity of DiCas7-11-crRNA-Csx29 towards DiCsx30. Taken together, we propose that target RNA recognition and cleavage regulate and fine-tune the protease activity of DiCas7-11-crRNA-Csx29, thus preventing auto-immune responses.

Structural and functional investigations of syn-copalyl diphosphate synthase from Oryza sativa.

The large superfamily of labdane-related diterpenoids is defined by the cyclization of linear geranylgeranyl pyrophosphate (GGPP), catalyzed by copalyl diphosphate synthases (CPSs) to form the basic decalin core, the copalyl diphosphates (CPPs). Three stereochemically distinct CPPs have been found in plants, namely (+)-CPP, ent-CPP and syn-CPP. Here, we used X-ray crystallography and cryo-EM methods to describe different oligomeric structures of a syn-copalyl diphosphate synthase from Oryza sativa (OsCyc1), and provided a cryo-EM structure of OsCyc1D367A mutant in complex with the substrate GGPP. Further analysis showed that tetramers are the dominant form of OsCyc1 in solution and are not necessary for enzyme activity in vitro. Through rational design, we identified an OsCyc1 mutant that can generate ent-CPP in addition to syn-CPP. Our work provides a structural and mechanistic basis for comparing different CPSs and paves the way for further enzyme design to obtain diterpene derivatives with specific chirality.

Neuroprotective potentials of ferulic acid against intracerebral hemorrhage COVID-19 through using network pharmacology approach and molecular docking analysis.

Intracerebral hemorrhage (ICH) refers to severe stroke subtype that may be life-threatening or even cause death. It is clinically observed that coronavirus disease 2019 (COVID-19) may be associated with the high mortality in ICH patients. Ferulic acid, one of the functional bioactive ingredients from medicinal herbs, has been preclinically proven with beneficial activities, including neuroprotection and anti-inflammation actions. Based on current findings, we assumed that ferulic acid may play the potentials against COVID-19 when ICH. In this study, preclinical approach including network pharmacology and molecular docking was applied to detect and identify the core targets and pharmacological mechanisms involved in ferulic acid on COVID-19 and ICH. The network pharmacology analysis identified total eleven core targets in ferulic acid and COVID-19/ICH. The molecular mechanisms of ferulic acid against COVID-19 and ICH were mostly involved in induction of antiviral activity, modulation of inflammatory reaction. Molecular docking model revealed that ferulic acid might effectively bind to epidermal growth factor receptor (EGFR) protein based on strong binding capability. Current findings reflected the preclinical pharmacological activities of ferulic acid that might use for management of COVID-19 and ICH. Although there are the limitations that are absence of experimental validation, these bioinformatic results underline that ferulic acid may exert simultaneous potentials against COVID-19 and ICH through modulating integrative mechanisms and key biotargets.

BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells.

BACKGROUND: Activated hepatic stellate cells (aHSCs) are the major source of cancer-associated fibroblasts in the liver. Although the crosstalk between aHSCs and colorectal cancer (CRC) cells supports liver metastasis (LM), the mechanisms are largely unknown. AIM: To explore the role of BMI-1, a polycomb group protein family member, which is highly expressed in LM, and the interaction between aHSCs and CRC cells in promoting CRC liver metastasis (CRLM). METHODS: Immunohistochemistry was carried out to examine BMI-1 expression in LM and matched liver specimens of CRC. The expression levels of BMI-1 in mouse liver during CRLM (0, 7, 14, 21, and 28 d) were detected by Western blotting (WB) and the quantitative polymerase chain reaction (qPCR) assay. We overexpressed BMI-1 in HSCs (LX2) by lentivirus infection and tested the molecular markers of aHSCs by WB, qPCR, and the immunofluorescence assay. CRC cells (HCT116 and DLD1) were cultured in HSC-conditioned medium (LX2 NC CM or LX2 BMI-1 CM). CM-induced CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) phenotype, and transforming growth factor beta (TGF-ß)/SMAD pathway changes were investigated in vitro. A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs (LX2 NC or LX2 BMI-1) and CRC cells to investigate the effects of HSCs on tumor growth and the EMT phenotype in vivo. RESULTS: Positive of BMI-1 expression in the liver of CRLM patients was 77.8%. The expression level of BMI-1 continued to increase during CRLM in mouse liver cells. LX2 overexpressed BMI-1 was activated, accompanied by increased expression level of alpha smooth muscle actin, fibronectin, TGF-ß1, matrix metalloproteinases, and interleukin 6. CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability, EMT phenotype and activation of the TGF-ß/SMAD pathway. In addition, the TGF-ßR inhibitor SB-505124 diminished the effect of BMI-1 CM on SMAD2/3 phosphorylation in CRC cells. Furthermore, BMI-1 overexpressed LX2 HSCs promoted tumor growth and the EMT phenotype in vivo. CONCLUSION: High expression of BMI-1 in liver cells is associated with CRLM progression. BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver, and aHSCs promote proliferation, migration, and the EMT in CRC cells partially through the TGF-ß/SMAD pathway.

Bmi-1 confers adaptive radioresistance to KYSE-150R esophageal carcinoma cells.

Radiotherapy (RT) is a major modality of cancer treatment. However, tumors often acquire radioresistance, which causes RT to fail. The exact mechanisms by which tumor cells subjected to fractionated irradiation (FIR) develop an adaptive radioresistance are largely unknown. Using the radioresistant KYSE-150R esophageal squamous cell carcinoma (ESCC) model, which was derived from KYSE-150 parental cells using FIR, the role of Bmi-1 in mediating the radioadaptive response of ESCC cells to RT was investigated. The results showed that the level of Bmi-1 expression was significantly higher in KYSE-150R cells than in the KYSE-150 parental cells. Bmi-1 depletion sensitized the KYSE-150R cells to RT mainly through the induction of apoptosis, partly through the induction of senescence. A clonogenic cell survival assay showed that Bmi-1 depletion significantly decreased the radiation survival fraction in KYSE-150R cells. Furthermore, Bmi-1 depletion increased the generation of reactive oxygen species (ROS) and the expression of oxidase genes (Lpo, Noxo1 and Alox15) in KYSE-150R cells exposed to irradiation. DNA repair capacities assessed by γ-H2AX foci formation were also impaired in the Bmi-1 down-regulated KYSE-150R cells. These results suggest that Bmi-1 plays an important role in tumor radioadaptive resistance under FIR and may be a potent molecular target for enhancing the efficacy of fractionated RT.

Computational identification of MicroRNAs in strawberry expressed sequence tags and validation of their precise sequences by miR-RACE.

MicroRNAs (miRNAs) are small, endogenously expressed, nonprotein-coding RNAs that regulate gene expression at the post-transcriptional level in both animals and plants through repressing translation or inducing mRNA degradation. A comprehensive strategy to identify new miRNA homologs by mining the repository of available strawberry expressed sequence tags (ESTs) was developed. By adopting a range of filtering criteria, we identified 11 potential miRNAs belonging to 5 miRNA families from 47 890 Fragaria vesca EST sequences. Using 2 specific 5' and 3' miRNA RACE PCR reactions and a sequence-directed cloning method, we accurately determined both end sequences of 5 candidate miRNAs. Meanwhile, qRT-PCR was used to detect the expression of these 5 miRNAs in different strawberry organs and tissues at several growing stages. These newly identified F. vesca miRNAs (fve-miRNAs) and their expression information can improve our understanding of possible roles of fve-miRNAs in regulating the growth and development of F. vesca.

Preclinical findings reveal the pharmacological targets of ferulic acid in the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is characterized by cellular damage and inflammation in lesioned brain tissue. Ferulic acid has been shown to have a melioration effect on neurological functions. However, the active pharmacological effects and the underlying mechanisms of ferulic acid against TBI remain unclear. On the basis of network pharmacology and molecular docking methodology, this study aimed to investigate the beneficial effects of ferulic acid in treating TBI, and characterized the detailed biotargets and mechanisms of these actions. The identified core targets were validated via in silico simulation. We identified 91 overlapping targets associated with ferulic acid and TBI. In-silico simulation analysis validated the putative core targets of tumor protein p53, mitogen-activated protein kinase (MAPK) 1, and estrogen receptor 1. The Gene Ontology-enriched annotations and findings were largely associated with cell proliferation, apoptosis, and inflammation in nerve cells. Additional Kyoto Encyclopedia of Genes and Genomes enrichment analysis unmasked the pharmacological pathways of ferulic acid in treating TBI, including the MAPK signaling pathway and hypoxia-inducible factor-1 signaling pathway. Bioinformatic analyses and findings provide a new preclinical strategy for revealing the core targets and network pathways of ferulic acid in treating TBI. Moreover, some bioinformatic findings were computationally validated in silico for exhibiting the neuroprotective action of ferulic acid against TBI.

Grainyhead-like 2 enhances the human telomerase reverse transcriptase gene expression by inhibiting DNA methylation at the 5'-CpG island in normal human keratinocytes.

We recently identified Grainyhead-like 2 (GRHL2) as a novel transcription factor that binds to and regulates the activity of the human telomerase reverse transcriptase (hTERT) gene promoter. In this study, we investigated the biological functions of GRHL2 and the molecular mechanism underlying hTERT gene regulation by GRHL2. Retroviral transduction of GRHL2 in normal human keratinocytes (NHK) led to a significant extension of replicative life span, whereas GRHL2 knockdown notably repressed telomerase activity and cell proliferation. Using promoter magnetic precipitation coupled with Western blotting, we confirmed the binding of GRHL2 to the hTERT promoter and mapped the minimal binding region at -53 to -13 of the promoter. Furthermore, mutation analysis revealed the three nucleotides from -21 to -19 to be critical for GRHL2 binding. Because hTERT expression is regulated in part by DNA methylation, we determined the effects of GRHL2 on the methylation status of the hTERT promoter. Senescent NHK exhibited hypermethylation of the CpG island, which occurred with the loss of hTERT expression. On the contrary, the promoter remained hypomethylated in GRHL2-transduced NHK, irrespective of cell proliferation status. Also, knockdown of endogenous GRHL2 led to hypermethylation of the promoter. These results indicate that GRHL2 regulates the hTERT expression through an epigenetic mechanism and controls the cellular life span.

FaPYR1 is involved in strawberry fruit ripening.

Although the plant hormone abscisic acid (ABA) has been suggested to play a role in the ripening of non-climatic fruit, direct genetic/molecular evidence is lacking. In the present study, a strawberry gene homologous to the Arabidopsis ABA receptor gene PYR1, named FaPYR1, was isolated and characterized. The 627 bp cDNA includes an intact open reading frame that encodes a deduced protein of 208 amino acids, in which putative conserved domains were detected by homology analysis. Using tobacco rattle virus-induced gene silencing (VIGS), the FaPYR1 gene was silenced in strawberry fruit. Down-regulation of the FaPYR1 gene not only significantly delayed fruit ripening, but also markedly altered ABA content, ABA sensitivity, and a set of ABA-responsive gene transcripts, including ABI1 and SnRK2. Furthermore, the loss of red colouring in FaPYR1 RNAi (RNA interference) fruits could not be rescued by exogenously applied ABA, which could promote the ripening of wild-type fruits. Collectively, these results demonstrate that the putative ABA receptor FaPYR1 acts as a positive regulator in strawberry fruit ripening. It was also revealed that the application of the VIGS technique in strawberry fruit could be used as a novel tool for studying strawberry fruit development.

Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1.

Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation (8 Gy × 3) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.

Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis.

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition (EMT), while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT. The effects of BMI-1 in CRC cells were related to upregulating snail via AKT/GSK-3ß pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, reduced HCT116 and LOVO liver metastasis in immunodeficient mice. Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.

Efficacy and safety of dexmedetomidine in patients receiving mechanical ventilation: Evidence from randomized controlled trials.

At present, the efficacy and safety of dexmedetomidine in patients receiving mechanical ventilation (MV) is still controversial. Therefore, the purpose of this research was to assess the efficacy and safety of dexmedetomidine in MV patients by reviewing the results of randomized controlled trials (RCT). RCTs evaluating the efficacy of dexmedetomidine in the treatment of MV patients were obtained by searching relevant online databases, including PubMed, EMbase, Web of Science, the Cochrane Library, Medline, OVID, and ClinicalTrials.gov. Literature meeting the inclusion criteria were selected and evaluated by two researchers independently. Risk ratio (RR)/standardized mean difference (SMD) and 95% confidence interval (CI) were used to express the differences between groups. Seven RCTs were included in our study, with 986 participants in the dexmedetomidine group and 862 participants in the control group. Summary analysis results displayed no reduction in 30-day mortality (RR = 0.77, 95% CI: 0.59 to 1.02), delirium (RR = 0.77, 95% CI: 0.57 to 1.03), and adverse events (RR = 1.06, 95% CI: 0.22 to 5.08) in the dexmedetomidine group compared with the control group. As the length of stay in the intensive care unit (ICU) were presented as median and interquartile range (IQR)/standard deviation (SD), descriptive analysis of the results were performed. Generally, for 99.65% (953/986) of patients, dexmedetomidine was not better than the control group in reducing ICU length of stay. Our results demonstrate that for patients requiring MV, dexmedetomidine was not superior to the control group. However, analysis of more RCTs is required to confirm this conclusion.