Berberine alleviates contrast-induced nephropathy by activating Akt/Foxo3a/Nrf2 signalling pathway.

Contrast-induced nephropathy (CIN) is a condition that causes kidney damage in patients receiving angiography with iodine-based contrast agents. This study investigated the potential protective effects of berberine (BBR) against CIN and its underlying mechanisms. The researchers conducted both in vivo and in vitro experiments to explore BBR's renal protective effects. In the in vivo experiments, SD rats were used to create a CIN model, and different groups were established. The results showed that CIN model group exhibited impaired renal function, severe damage to renal tubular cells and increased apoptosis and ferroptosis. However, BBR treatment group demonstrated improved renal function, decreased apoptosis and ferroptosis. Similar results were observed in the in vitro experiments using HK-2 cells. BBR reduced ioversol-induced apoptosis and ferroptosis, and exerted its protective effects through Akt/Foxo3a/Nrf2 signalling pathway. BBR administration increased the expression of Foxo3a and Nrf2 while decreasing the levels of p-Akt and p-Foxo3a. In conclusion, this study revealed that BBR effectively inhibited ioversol-induced apoptosis and ferroptosis in vivo and in vitro. The protective effects of BBR were mediated through the modulation of Akt/Foxo3a/Nrf2 signalling pathway, leading to the alleviation of CIN. These findings suggest that BBR may have therapeutic potential for protecting against CIN in patients undergoing angiography with iodine-based contrast agents.

Berberine ameliorates contrast-induced acute kidney injury by regulating HDAC4-FoxO3a axis-induced autophagy: In vivo and in vitro.

In hospitals, contrast-induced acute kidney injury (CI-AKI) is a major cause of renal failure. This study evaluates berberine's (BBR) renal protection and its potential HDAC4 mechanism. CI-AKI in rats was induced with 10 mL kg-1 ioversol. Rats were divided into five groups: Ctrl, BBR, CI-AKI, CI-AKI + BBR, and CI-AKI + Tasq. The renal function of CI-AKI rats was determined by measuring serum creatinine and blood urea nitrogen. Histopathological changes and apoptosis of renal tubular epithelial cells were observed by HE and terminal deoxynucleotidyl transferase (TdTase)-mediated dUTP-biotin nick end labeling (TUNEL) staining. Transmission electron microscopy was used to observe autophagic structures. In vitro, a CI-AKI cell model was created with ioversol-treated HK-2 cells. Treatments included BBR, Rapa, HCQ, and Tasq. Analyses focused on proteins and genes associated with kidney injury, apoptosis, autophagy, and the HDAC4-FoxO3a axis. BBR showed significant protective effects against CI-AKI both in vivo and in vitro. It inhibited apoptosis by increasing Bcl-2 protein levels and decreasing Bax levels. BBR also activated autophagy, as indicated by changes in autophagy-related proteins and autophagic flux. The study further revealed that the contrast agent ioversol increased the expression of HDAC4, which led to elevated levels of phosphorylated FoxO3a (p-FoxO3a) and acetylated FoxO3a (Ac-FoxO3a). However, BBR inhibited HDAC4 expression, resulting in decreased levels of p-FoxO3a and Ac-FoxO3a. This activation of autophagy-related genes, regulated by the transcription factor FoxO3a, played a role in BBR's protective effects. BBR, a traditional Chinese medicine, shows promise against CI-AKI. It may counteract CI-AKI by modulating HDAC4 and FoxO3a, enhancing autophagy, and limiting apoptosis.

Free-hand technique of C7 pedicle screw insertion using a simply defined entry point without fluoroscopic guidance for cervical spondylotic myelopathy patients with C3 to C6 instrumented by lateral mass screws: a retrospective cohort study.

BACKGROUND: Nowadays, both lateral mass screw (LMS) and pedicle screw were effective instrumentation for posterior stabilization of cervical spine. This study aims to evaluate the feasibility of a new free-hand technique of C7 pedicle screw insertion without fluoroscopic guidance for cervical spondylotic myelopathy (CSM) patients with C3 to C6 instrumented by lateral mass screws. METHODS: A total of 53 CSM patients underwent lateral mass screws instrumentation at C3 to C6 levels and pedicle screw instrumentation at C7 level were included. The preoperative 3-dimenional computed tomography (CT) reconstruction images of cervical spine were used to determine 2 different C7 pedicle screw trajectories. Trajectory A passed through the axis of the C7 pedicle while trajectory B selected the midpoint of the base of C7 superior facet as the entry point. All these 53 patients had the C7 pedicle screw inserted through trajectory B by free-hand without fluoroscopic guidance and the postoperative CT images were obtained to evaluate the accuracy of C7 pedicle screw insertion. RESULTS: Trajectory B had smaller transverse angle, smaller screw length, and smaller screw width but both similar sagittal angle and similar pedicle height when compared with trajectory A. A total of 106 pedicle screws were inserted at C7 through trajectory B and only 8 screws were displaced with the accuracy of screw placement as high as 92.5%. CONCLUSION: In CSM patients with C3 to C6 instrumented by LMS, using trajectory B for C7 pedicle screw insertion is easy to both identify the entry point and facilitate the rod insertion.

[Safety of modified T-piece resuscitator versus nasal cannula oxygen in electronic bronchoscopy for infants: a prospective randomized controlled study]. / 改良Tç»„åˆå¤è‹å™¨ä¸Žé¼»å¯¼ç®¡å¸æ°§ç”¨äºŽå©´å„¿ç”µå­æ”¯æ°”ç®¡é•œæ£€æŸ¥çš„å®‰å ¨æ€§æ¯”è¾ƒï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To optimize the oxygen therapy regimens for infants with pulmonary diseases during bronchoscopy. METHODS: A prospective randomized, controlled, and single-center clinical trial was conducted on 42 infants who underwent electronic bronchoscopy from July 2019 to July 2021. These infants were divided into a nasal cannula (NC) group and a modified T-piece resuscitator (TPR) group using a random number table. The lowest intraoperative blood oxygen saturation was recorded as the primary outcome, and intraoperative heart rate and respiratory results were recorded as the secondary outcomes. RESULTS: Compared with the NC group, the modified TPR group had a significantly higher level of minimum oxygen saturation during surgery and a significantly lower incidence rate of hypoxemia (P<0.05). In the modified TPR group, there were 6 infants with mild hypoxemia, 2 with moderate hypoxemia, and 1 with severe hypoxemia, while in the NC group, there were 3 infants with mild hypoxemia, 5 with moderate hypoxemia, and 9 with severe hypoxemia (P<0.05). The modified TPR group had a significantly lower incidence rate of intraoperative respiratory rhythm abnormalities than the NC group (P<0.05), but there was no significant difference in the incidence rate of arrhythmias between the two groups (P>0.05). CONCLUSIONS: Modified TPR can significantly reduce the risk of hypoxemia in infants with pulmonary diseases during electronic bronchoscopy, and TPR significantly decreases the severity of hypoxemia and the incidence of respiratory rhythm abnormalities compared with traditional NC.

Lab at home: a promising prospect for on-site chemical and biological analysis.

The continuing pursuit for a healthy life has led to the urgent need for on-site analysis. In response to the urgent needs of on-site analysis, we propose a novel concept, called lab at home (LAH), for building automated and integrated total analysis systems to perform chemical and biological testing at home. It represents an emerging research area with broad prospects that has not yet attracted sufficient attention. In this paper, we discuss the urgent need, challenges, and future prospects of this area, and the possible roadmap for achieving the goal of LAH has also been proposed.

Metabolic engineering of Escherichia coli for 2,4-dinitrotoluene degradation.

2,4-Dinitrotoluene (2,4-DNT) as a common industrial waste has been massively discharged into the environment with industrial wastewater. Due to its refractory degradation, high toxicity, and bioaccumulation, 2,4-DNT pollution has become increasingly serious. Compared with the currently available physical and chemical methods, in situ bioremediation is considered as an economical and environmentally friendly approach to remove toxic compounds from contaminated environment. In this study, we relocated a complete degradation pathway of 2,4-DNT into Escherichia coli to degrade 2,4-DNT completely. Eight genes from Burkholderia sp. strain were re-synthesized by PCR-based two-step DNA synthesis method and introduced into E. coli. Degradation experiments revealed that the transformant was able to degrade 2,4-DNT completely in 12 h when the 2,4-DNT concentration reached 3 mM. The organic acids in the tricarboxylic acid cycle were detected to prove the degradation of 2,4-DNT through the artificial degradation pathway. The results proved that 2,4-DNT could be completely degraded by the engineered bacteria. In this study, the complete degradation pathway of 2,4-DNT was constructed in E. coli for the first time using synthetic biology techniques. This research provides theoretical and experimental bases for the actual treatment of 2,4-DNT, and lays a technical foundation for the bioremediation of organic pollutants.

Basic Helix-Loop-Helix Transcription Factors: Regulators for Plant Growth Development and Abiotic Stress Responses.

Plant basic helix-loop-helix (bHLH) transcription factors are involved in many physiological processes, and they play important roles in the abiotic stress responses. The literature related to genome sequences has increased, with genome-wide studies on the bHLH transcription factors in plants. Researchers have detailed the functionally characterized bHLH transcription factors from different aspects in the model plant Arabidopsis thaliana, such as iron homeostasis and abiotic stresses; however, other important economic crops, such as rice, have not been summarized and highlighted. The bHLH members in the same subfamily have similar functions; therefore, unraveling their regulatory mechanisms will help us to identify and understand the roles of some of the unknown bHLH transcription factors in the same subfamily. In this review, we summarize the available knowledge on functionally characterized bHLH transcription factors according to four categories: plant growth and development; metabolism synthesis; plant signaling, and abiotic stress responses. We also highlight the roles of the bHLH transcription factors in some economic crops, especially in rice, and discuss future research directions for possible genetic applications in crop breeding.

Rapid Color-Switching of MnO2 Hollow-Nanosphere Films in Dynamic Water Vapor for Reversible Optical Encryption.

Drop-casting manganese oxide (MnO2 ) hollow nanospheres synthesized via a simple surface-initiated redox route produces thin films exhibiting angle-independent structural colors. The colors can rapidly change in response to high-humidity dynamic water vapor (relative humidity > 90%) with excellent reversibility. When the film is triggered by dynamic water vapor with a relative humidity of ≈100%, the color changes with an optimal wavelength redshift of ≈60 nm at ≈600 ms while there is no shift under static water vapor. The unique selective response originates from the nanoscale porosity formed in the shells by randomly stacked MnO2 nanosheets, which enhances the capillary condensation of dynamic water vapor and promotes the change of their effective refractive index for rapid color switching. The repeated color-switching tests over 100 times confirm the durability and reversibility of the MnO2 film. The potential of these films for applications in anti-counterfeiting and information encryption is further demonstrated by reversible encoding and decoding initiated exclusively by exposure to human breath.

The RNA demethylase ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the stability of the LncRNA PVT1.

BACKGROUND: N6-methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in human cancer progression. However, the biological function of m6A methylation requires further studied in cancer, especially in tumor angiogenesis. METHODS: A public database was used to analyze the expression and overall survival of ALKBH5 and PVT1 in lung cancer patients. CCK-8 and colony formation assays were performed to detect cell proliferation, a transwell assay was used to assess cell migration, and a tube formation assay was performed to assess angiogenic potential in vitro. A zebrafish lung cancer xenograft model was used to verify the function of ALKBH5 and PVT1 in vivo. Western blot assays were used to measure the relative protein expression in lung cancer cells. SRAMP predictor analysis and RNA stability experiments were used to examine the potential m6A modification. RESULTS: Bioinformatics analysis showed that the expression levels of m6A-related genes were changed significantly in lung cancer tissues compared with normal lung tissues. We then identified that ALKBH5 was upregulated in lung cancer tissues and associated with poor prognosis of lung cancer patients by analyzing a public database. Knockdown of ALKBH5 inhibited the proliferation and migration of cultured lung cancer cell lines. Zebrafish lung cancer xenografts showed that ALKBH5 silencing also suppressed the growth and metastasis of lung cancer cells. Moreover, knockdown of ALKBH5 inhibited the angiogenesis of lung cancer in vitro and in vivo. Mechanistic studies showed that knockdown of ALKBH5 decreased the expression and stability of PVT1 in lung cancer cells. We next observed that PVT1 promoted the progression of lung cancer cells in vitro and in vivo and regulated the expression of VEGFA and angiogenesis in lung cancer. Finally, rescue experiments revealed that ALKBH5 regulated the proliferation, migration and angiogenesis of lung cancer cells, partially through PVT1. CONCLUSION: Our results demonstrate that ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the expression and stability of PVT1, which provides a potential prognostic and therapeutic target for lung cancer patients.

Identification of geographical origin and different parts of Wolfiporia cocos from Yunnan in China using PLS-DA and ResNet based on FT-NIR.

INTRODUCTION: Wolfiporia cocos, as a kind of medicine food homologous fungus, is well-known and widely used in the world. Therefore, quality and safety have received worldwide attention, and there is a trend to identify the geographic origin of herbs with artificial intelligence technology. OBJECTIVE: This research aimed to identify the geographical traceability for different parts of W. cocos. METHODS: The exploratory analysis is executed by two multivariate statistical analysis methods. The two-dimensional correlation spectroscopy (2DCOS) images combined with residual convolutional neural network (ResNet) and partial least square discriminant analysis (PLS-DA) models were established to identify the different parts and regions of W. cocos. We compared and analysed 2DCOS images with different fingerprint bands including full band, 8900-6850 cm-1 , 6300-5150 cm-1 and 4450-4050 cm-1 of original spectra and the second-order derivative (SD) spectra preprocessed. RESULTS: From all results: the exploratory analysis results showed that t-distributed stochastic neighbour embedding was better than principal component analysis. The synchronous SD 2DCOS is more suitable for the identification and analysis of complex mixed systems for the small-band for Poria and Poriae cutis. Both models of PLS-DA and ResNet could successfully identify the geographical traceability of different parts based on different bands. The 10% external verification set of the ResNet model based on synchronous 2DCOS can be accurately identified. CONCLUSION: Therefore, the methods could be applied for the identification of geographical origins of this fungus, which may provide technical support for quality evaluation.

MicroRNA398: A Master Regulator of Plant Development and Stress Responses.

MicroRNAs (miRNAs) play crucial roles in plant development and stress responses, and a growing number of studies suggest that miRNAs are promising targets for crop improvement because they participate in the regulation of diverse, important agronomic traits. MicroRNA398 (miR398) is a conserved miRNA in plants and has been shown to control multiple stress responses and plant growth in a variety of species. There are many studies on the stress response and developmental regulation of miR398. To systematically understand its function, it is necessary to summarize the evolution and functional roles of miR398 and its target genes. In this review, we analyze the evolution of miR398 in plants and outline its involvement in abiotic and biotic stress responses, in growth and development and in model and non-model plants. We summarize recent functional analyses, highlighting the role of miR398 as a master regulator that coordinates growth and diverse responses to environmental factors. We also discuss the potential for fine-tuning miR398 to achieve the goal of simultaneously improving plant growth and stress tolerance.

Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma.

Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.

The Protective Effects of Helicobacter pylori Infection on Allergic Asthma.

As an ancient Gram-negative bacterium, Helicobacter pylori has settled in human stomach. Eradicating H. pylori increases the morbidities of asthma and other allergic diseases. Therefore, H. pylori might play a protective role against asthma. The "disappearing microbiota" hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in our early life, contributing to the development of some diseases. And the Hygiene Hypothesis links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent immune-mediated diseases. H. pylori can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. H. pylori can also target dendritic cells to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. The remote regulation of lung immune function by H. pylori is consistent with the gut-lung axis theory. Perhaps, H. pylori also protects against asthma by altering levels of stomach hormones, affecting the autonomic nervous system and lowering the expression of heat shock protein 70. Therapeutic products from H. pylori may be used to prevent and treat asthma. This paper reviews the possible protective influence of H. pylori on allergic asthma and the possible application of H. pylori in treating asthma.

A Cryptic Plant Terpene Cyclase Producing Unconventional 18- and 14-Membered Macrocyclic C25 and C20 Terpenoids with Immunosuppressive Activity.

A versatile terpene synthase (LcTPS2) producing unconventional macrocyclic terpenoids was characterized from Leucosceptrum canum. Engineered Escherichia coli and Nicotiana benthamiana expressing LcTPS2 produced six 18-/14-membered sesterterpenoids including five new ones and two 14-membered diterpenoids. These products represent the first macrocyclic sesterterpenoids from plants and the largest sesterterpenoid ring system identified to date. Two variants F516A and F516G producing approximately 3.3- and 2.5-fold, respectively, more sesterterpenoids than the wild-type enzyme were engineered. Both 18- and 14-membered ring sesterterpenoids displayed significant inhibitory activity on the IL-2 and IFN-γ production of T cells probably via inhibition of the MAPK pathway. The findings will contribute to the development of efficient biocatalysts to create bioactive macrocyclic sesterterpenoids, and also herald a new potential in the well-trodden territory of plant terpenoid biosynthesis.

A novel basic helix-loop-helix transcription factor, ZjICE2 from Zoysia japonica confers abiotic stress tolerance to transgenic plants via activating the DREB/CBF regulon and enhancing ROS scavenging.

KEY MESSAGE: ZjICE2 works as a positive regulator in abiotic stress responses and ZjICE2 is a valuable genetic resource to improve abiotic stress tolerance in the molecular breeding program of Zoysia japonica. The basic helix-loop-helix (bHLH) family transcription factors (TFs) play an important role in response to biotic or abiotic stresses in plants. However, the functions of bHLH TFs in Zoysia japonica, one of the warm-season turfgrasses, remain poorly understood. Here, we identified ZjICE2 from Z. japonica, a novel MYC-type bHLH transcription factor that was closely related to ICE homologs in the phylogenetic tree, and its expression was regulated by various abiotic stresses. Transient expression of ZjICE2-GFP in onion epidermal cells revealed that ZjICE2 was a nuclear-localized protein. Also, ZjICE2 bound the MYC cis-element in the promoter of dehydration responsive element binding 1 of Z. japonica (ZjDREB1) using yeast one-hybrid assay. A phenotypic analysis showed that overexpression of the ZjICE2 in Arabidopsis enhanced tolerance to cold, drought, and salt stresses. The transgenic Arabidopsis and Z. japonica accumulated more transcripts of cold-responsive DREB/CBFs and their downstream genes than the wild type (WT) after cold treatment. Furthermore, the transgenic plants exhibited an enhanced Reactive oxygen species (ROS) scavenging ability, which resulted in an efficient maintenance of oxidant-antioxidant homeostasis. In addition, overexpression of the ZjICE2 in Z. japonica displayed intensive cold tolerance with increases in chlorophyll contents and photosynthetic efficiency. Our study suggests that ZjICE2 works as a positive regulator in abiotic stress responses and the ICE-DREB/CBFs response pathway involved in cold stress tolerance is also conserved in Z. japonica. These results provide a valuable genetic resource for the molecular breeding program especially for warm-season grasses as well as other leaf crop plants.

Protease-activated receptor 2 deficiency in hematopoietic lineage protects against myocardial infarction through attenuated inflammatory response and fibrosis.

Ischaemic heart disease is one of the leading causes of death. Protease-activated receptor 2 (PAR2) is widely expressed within the cardiovascular system and is known to mediate inflammatory processes in various immunocytes, such as macrophages, mastocytes and neutrophils. Here, we investigated whether activating macrophage PAR2 modulates cardiac remodelling in a murine model of myocardial infarction. Myocardial infarction was produced by the permanent ligation of the left anterior descending coronary artery (LAD) in C57BL/6J background wild-type (WT) mice transplanted with bone marrow from WT or PAR2 knockout (PAR2 KO) mice. Hematopoietic deficiency of PAR2 had improvement of left ventricular systolic dysfunction and dilatation and decreased fibrosis deposition in remote zone at 1 week after LAD ligation. Inactivation of PAR2 also led to less recruitment of macrophages in myocardium, which was accompanied by decreased expression of pro-inflammatory cytokines. Furthermore, cultured cardiac fibroblasts (CFs) were activated and showed a fibrotic phenotype after being co-cultured in medium containing PAR2-activating macrophage, which enhances interferon-beta (INF-ß) expression. The beneficial effects of macrophages with INF-ß neutralisation or PAR2-deletion ameliorates the JAK/STAT3 pathway in CFs, which might be attributed to CF activation. These data suggest that macrophage-derived IFN-ß plays a crucial role in adverse cardiac remodelling after myocardial infarction, at least in part, through a PAR2-dependent mechanism.

The key candidate genes in tubulointerstitial injury of chronic kidney diseases patients as determined by bioinformatic analysis.

Pathologic changes such as renal tubular atrophy and interstitial fibrosis are common in chronic kidney disease (CKD), which in turn, leads to loss of renal function. The aims of present study were to screen critical genes with tubulointerstitial lesion in CKD by weighted gene correlation network analysis (WGCNA). Gene expression data including 169 tubulointerstitial samples of CKD and 21 controls downloaded from Gene Expression Omnibus (GEO) database. Totally 294 differentially expressed genes (DEGs) were screened, including 180 upregulated and 114 downregulated genes. Meanwhile, 90 expression data of tubulointerstitial samples combined with clinic information were applied to explore the potential mechanisms of tubulointerstitial lesion. As a consequence, the blue, brown and yellow modules which included the most DEGs compared to the other modules and exhibited strongly association with eGFR, were significantly enriched in several signalling pathways that have been reported involved in pathogenesis of CKD. Furthermore, it was found that the four genes (PLG, ITGB2, CTSS and CCL5) was one of the DEGs which also be identified as hub genes according to Kwithin. Finally, the Nephroseq online tool showed that the tubulointerstitial expression levels of PLG significantly positively correlated with the estimated glomerular filtration rate (eGFR), while ITGB2, CTSS and CCL5 connected negatively to the eGFR of CKD patients. Taken together, WGCNA is an efficient approach to system biology. By this procedure, the present study enhanced the understanding of the transcriptome status of CKD and might shed a light on the further investigation on the mechanisms of renal tubulointerstitial injury in CKD. SIGNIFICANCE OF STUDY: Traditional molecular biology can only explain the local part of the biological system, and difficult to make comprehensive exploration of the whole biological system in the chronic kidney disease (CKD). In this study, we gave an explicit elucidation of dysregulated protein coding genes by the analysis of microarray datasets in GEO database. We have presented a novel approach using weighted gene correlation network analysis (WGCNA) to explore the DEGs which implicated in CKD process. In this study, we conducted WGCNA to explore the potential mechanisms of renal tubular damage, and provided novel biomarkers associated with the molecular mechanisms underlying renal tubulointerstitial injury in CKD.

MicroRNA-7b attenuates ischemia/reperfusion-induced H9C2 cardiomyocyte apoptosis via the hypoxia inducible factor-1/p-p38 pathway.

OBJECTIVE: MicroRNAs (miRNAs) have been shown to play crucial roles in the occurrence, development, and treatment of many cardiovascular diseases. Coronary heart disease (CAD)-related miRNAs are still a growing research area. miR-7b was reported to be downregulated in acute myocardial infarction (AMI) myocardium tissues. However, it remains largely unknown whether miR-7b is involved in the pathogenesis and progression of the AMI ischemia/reperfusion (I/R) injury. METHODS: Male C57BL/6 J mice and H9C2 cells were used as models in this study. Masson staining, real-time polymerase chain reaction, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling immunofluorescence staining assays were performed to detect the related indicators in the study. SPSS 17.0 software was used to calculate the experimental data. RESULTS: The results showed that miR-7b expression is downregulated after I/R in mice, and miR-7b could inhibit apoptosis in I/R-induced H9C2 cells via upregulating hypoxia-inducible factor 1a (HIF1a). The inhibitory effect of miR-7b on I/R-induced apoptosis in H9C2 cells was blocked by HIF1a silencing. In addition, our data suggested that the p-P38 pathway may be involved in the role of miR-7 in I/R-induced H9C2 cell apoptosis. CONCLUSION: We confirmed that the overexpression of miR-7b inhibits I/R-induced apoptosis in H9C2 cells by targeting the HIF1a/p-P38 pathway. Our findings not only demonstrate the potential role of miR-7b in attenuating I/R-induced apoptosis but also provide a new insight into the better prevention of the I/R injury by mediating HIF-1 and p-P38.

Screening of intestinal probiotics and the effects of feeding probiotics on the growth, immune, digestive enzyme activity and intestinal flora of Litopenaeus vannamei.

In this experiment, 426 strains were isolated from the intestinal tract of Litopenaeus vannamei, and 11 strains showed strong digestive enzyme production activity and antagonistic effect against common bacterial pathogens of shrimp. After hemolysis activity test and drug sensitivity test, 2 candidate probiotics with good bacteriostatic activity, strong enzyme production ability and relatively sensitive to antibiotics were screened out, and were identified by 16s rDNA molecular identification and Biolog-System as Enterobacter hominis (E3) and lactobacillus (L3). First, the biological characteristics of 2 candidate probiotics were studied. The optimum growth conditions of E3: temperature, 30 °C; pH, 8.0; NaCl, 2.5%; bovine bile salt, 0.15%; and the optimum growth conditions of L3: temperature, 40 °C; pH, 6.0; NaCl, 0.5%; bovine bile salt, 0.0015%. Secondly, a 28-day feeding experiment was conducted using probiotic concentration of 107 CFU g-1 to determine the changes of the activities of blood related immune enzymes (SOD, PPO, ACP, POD, CAT, LZM) and intestinal digestive enzymes (NP, AL, LPS) during the feeding process of shrimp, the results showed that during the course of feeding, the activities of immune enzyme and digestive enzyme of shrimp fed with probiotics showed an increasing trend, and the growth rate of body weight of shrimp was higher than that of control group. After feeding, the cumulative mortality of probiotics groups were significantly lower than that of the control group after WSSV infection. And the mid-gut of L. vannamei was observed by electron microscope, the results showed that the intestinal mucosa was tight and the epithelium cells showed an active secretory state in probiotics group. Finally, the intestinal microbial communities of shrimp were compared and analyzed by using Biolog-ECO method in the later period of feeding, the results showed: compared with the control group, the average color change rate of the experimental group fed with probiotics increased significantly, indicating that probiotics enhanced the intestinal microorganism activity; The ability of intestinal microorganism to utilize carbon source was significantly enhanced in the experimental group, which indicated that the digestive enzyme secreted by probiotics could improve the digestion and absorption rate of prawn feed, thus promoting the rapid growth of shrimp; The Shannon index, Simpson index and McIntosh index of probiotics groups showed significant difference in 1st and 5th days, but tended to be the same in the 10th day, the results showed that probiotics could maintain in L. vannamei intestines at least 5 days.

Sevoflurane promotes migration, invasion, and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane's effects. We showed that exposure to 1%-4% sevoflurane did not change the cell proliferation, but concentration-dependently increased the invasion of human glioblastoma U251 cells. Furthermore, 4% sevoflurane significantly increased the migration and colony-forming ability of U251 cells. Similar results were observed in human glioblastoma A172 cells. Exposure to sevoflurane concentration-dependently increased the activity of calpains, a group of cysteine proteinases, and CD44 protein in U251 and A172 cells. Knockdown of CD44 with siRNA abolished sevoflurane-induced increases in calpain activity, migration, invasion, and colony-forming ability of U251 cells. Inhalation of 4% sevoflurane significantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain. The aggravation by sevoflurane was attenuated by CD44 silencing. In conclusion, sevoflurane increases the migration, invasion, and colony-forming ability of human glioblastoma cells in vitro, and their tumor volume and invasion/migration in vivo. Sevoflurane enhances these cancer cell biology features via increasing the expression of CD44.