Laser hemorrhoidoplasty vs. rubber band ligation: a randomized trial comparing 2 mini-invasive treatment for grade II hemorrhoids.

PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.

Ubiquitin ligase subunit FBXO9 inhibits V-ATPase assembly and impedes lung cancer metastasis.

BACKGROUND: The evolutionarily conserved protein FBXO9 acts as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase and is implicated in cancer, exhibiting either tumor-suppressive or oncogenic effects depending on the specific tumor type. However, their role in lung cancer metastasis remains unclear. METHODS: Lentiviral vectors carrying miRNA-based shRNA sequences for gene-specific knockdown were generated, and Lenti-CRISPR-Cas9 vectors containing gene-specific sgRNA sequences were designed. Gene overexpression was achieved using doxycycline-inducible lentiviral constructs, while gene knockdown or knockout cells were generated using shRNA and CRISPR-Cas9, respectively. Functional assays included migration, clonogenic survival assays, tumor sphere assays, and protein interaction studies using mass spectrometry, immunoprecipitation, and immunoblot analysis. RESULTS: This study identified FBXO9 as a crucial regulator that suppresses lung cancer cell migration, tumor sphere growth and restricts metastasis. We showed that FBXO9 facilitates the ubiquitination of the catalytic subunit A (ATP6V1A) of the Vacuolar-type H+-ATPase (V-ATPase), resulting in its interaction with the cytoplasmic chaperone HSPA8 and subsequent sequestration within the cytoplasm. This process hinders the assembly of functional V-ATPase, resulting in reduced vesicular acidification. In contrast, depletion of FBXO9 reduced ATP6V1A ubiquitination, resulting in increased V-ATPase assembly and vesicular acidification, thus promoting pro-metastatic Wnt signaling and metastasis of lung cancer cells. Furthermore, we demonstrated the effectiveness of inhibitors targeting V-ATPase in inhibiting lung cancer metastasis in a mouse model. Finally, we established a correlation between lower FBXO9 levels and poorer survival outcomes in patients with lung cancer. CONCLUSION: These findings collectively elucidate the critical role of FBXO9 in regulating V-ATPase assembly and provide a molecular basis for FBXO9's function in inhibiting lung cancer metastasis. This highlights the potential therapeutic opportunities of FBXO9 supplementation.

Deciphering Recursive Polyploidization in Lamiales and Reconstructing Their Chromosome Evolutionary Trajectories.

Lamiales is an order of core eudicots with abundant diversity, and many Lamiales plants have important medicinal and ornamental values. Here, we comparatively reanalyzed 11 Lamiales species with well-assembled genome sequences and found evidence that Lamiales plants, in addition to a hexaploidization or whole-genome triplication (WGT) shared by core eudicots, experienced further polyploidization events, establishing new groups in the order. Notably, we identified a whole-genome duplication (WGD) occurred just before the split of Scrophulariaceae from the other Lamiales families, such as Acanthaceae, Bignoniaceae, and Lamiaceae, suggesting its likely being the causal reason for the establishment and fast divergence of these families. We also found that a WGT occurred ∼68-78 Mya, near the split of Oleaceae from the other Lamiales families, implying that it may have caused their fast divergence and the establishment of the Oleaceae family. Then, by exploring and distinguishing intra- and inter-genomic chromosomal homology due to recursive polyploidization and speciation, respectively, we inferred that the Lamiales ancestral cell karyotype had 11 proto-chromosomes. We reconstructed the evolutionary trajectories from these proto-chromosomes to form the extant chromosomes in each Lamiales plant under study. We must note that most of the inferred 11 proto-chromosomes, duplicated during a WGD thereafter, have been well preserved in Jacaranda (Jacaranda mimosifolia) genome, showing the credibility of the present inference implementing a telomere-centric chromosome repatterning model. These efforts are important to understand genome repatterning after recursive polyploidization, especially shedding light on the origin of new plant groups and angiosperm cell karyotype evolution.

Regional Thermal Radiation Characteristics of FY Satellite Remote Sensing Based on Big Data Analysis.

It is of great significance to study the thermal radiation anomalies of earthquake swarms in the same area in terms of selecting abnormal characteristic determination parameters, optimizing and determining the processing model, and understanding the abnormal machine. In this paper, we investigated short-term and long-term thermal radiation anomalies induced by earthquake swarms in Iran and Pakistan between 2007 and 2016. The anomalies were extracted from infrared remote sensing black body temperature data from the China Geostationary Meteorological Satellites (FY-2C/2E/2F/2G) using the multiscale time-frequency relative power spectrum (MS T-FRPS) method. By analyzing and summarizing the thermal radiation anomalies of series earthquake groups with consistency law through a stable and reliable MS T-FRPS method, we first obtained the relationship between anomalies and ShakeMaps from USGS and proposed the anomaly regional indicator (ARI) to determine seismic anomalies and the magnitude decision factor (MDF) to determine seismic magnitude. In addition, we explored the following discussions: earthquake impact on regional thermal radiation background and the relationship between thermal anomalies and earthquake magnitude and the like. Future research directions using the MS T-FRPS method to characterize regional thermal radiation anomalies induced by strong earthquakes could help improve the accuracy of earthquake magnitude determination.

Gut Microbiota Combined with Metabolomics Reveal the Mechanisms of Sika Deer Antler Protein on Cisplatin-Induced Hepatorenal Injury in Mice.

Cisplatin is a widely used antineoplastic drug, though its adverse effects, particularly its hepatorenal toxicity, limit its long-term application. Sika deer antler is a valuable traditional Chinese medicine (TCM) documented to possess the capacity for tonifying the kidney and regulating the liver, of which the sika deer antler protein is an important active ingredient. In this study, two protein fractions, SVPr1 and SVPr2, of sika deer antler were purified and administered to mice treated with cisplatin, and serum metabolome and fecal microbiota were measured using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and 16S rRNA gene sequencing. SVPr1 and SVPr2 significantly ameliorated cisplatin-induced liver and kidney injury and reduced mitochondrial dysfunction, oxidative stress, inflammatory response, and apoptosis. In addition, SVPr1 and SVPr2 impacted the gut microbiota structure of mice, significantly increasing the relative abundances of Lactobacillus, which deserves to be scrutinized. Moreover, SVPr1 and SVPr2 antagonism of cisplatin-induced hepatorenal injury may be related to the regulation of lysine degradation, tryptophan metabolism, and riboflavin metabolism pathways, significantly altering the levels of L-saccharopine, L-lysine, L-kynurenine, 3-methylindole, xanthurenic acid, riboflavin, and D-ribulose-5-phosphate. A correlation between the differential metabolites and Lactobacillus was identified. These findings increased the knowledge of the gut microbiota-metabolites axis mediated by SVPr1 and SVPr2, and may be able to contribute to the development of new therapeutic strategies for the simultaneous prevention and treatment of liver and kidney injury from cisplatin treatment.

Comparative Efficacy and Safety of Chinese Patent Medicines for Cervical High-risk Human Papillomavirus Infection: A Bayesian Network Meta-analysis.

Background: Many Chinese patent medicines have been reported to show anti-tumor cell effects on cervical cancer. To estimate the comparative effectiveness and safety of Chinese patent medicines for cervical high-risk human papillomavirus (HR-HPV) infection. Methods: Randomized controlled trials (RCTs) of Chinese patent medicines for HR-HPV infection were searched in eight databases until 31 August 2022, and two review authors independently extracted data and assessed the risk of bias. Outcomes concerning efficacy were evaluated as odds ratio (OR) and 95% credible intervals (CrI) utilizing R 4.1.2 and Stata 16.1. The protocol was registered on the International Prospective Register of Systematic Reviews (CRD42022351120). Results: We ultimately identified 60 RCTs that involved 5,951 participants and 8 interventions. Chinese patent medicines combined with recombinant human interferon (rhIFN) have better treatment effects than rhIFN alone. The results showed that Baofukang suppository (BFK) combined with rhIFN is greater for the rate of HR-HPV clearance follow-up at 6 months (SUCRA = 78.16%). Kushen gel (KS) combined with rhIFN ranked first for the rate of HR-HPV clearance after treatment (SUCRA = 90.77%). Furthermore, KS + rhIFN is most likely to be the best intervention for improving the clinical effectiveness rate (SUCRA = 87.39%). Adverse reactions were not statistically significant in BFK + rhIFN versus BFK, BFK + rhIFN versus rhIFN, and BFK versus rhIFN. Conclusion: The combination of Chinese patent medicines with rhIFN may demonstrate a higher efficacy than rhIFN alone in clearing the virus and improving cervical symptoms. Weighing with the clinical comprehensive efficacy, BFK + rhIFN and KS + rhIFN maybe the optimal treatments for cervical HR-HPV infection. However, more high-quality randomized controlled trials are needed in the future to further confirm the efficacy and safety of proprietary Chinese medicines for cervical HR-HPV infection.

Photo-crosslinking hydrogel for wound healing in a pilonidal sinus patient after open surgery.

Pilonidal sinus is a chronic infectious disease with large incision and high risk of relapse after surgical management. Therefore, effective intervention strategies are urgently needed to reduce the relapse and shorten the wound healing time. Hydrogels have been widely used in regenerative medicine for its great biocompatibility, however, it remains challenging to integrate the material with wound tissues. Here, we reported a case of pilonidal sinus patient using a novel tissue integration material, Photo-crosslinking hydrogel after open surgery. A 38-year-old man with a pilonidal sinus for ˃5 years underwent open surgery. When the surgery was finished, the wound was injected with hydrogel that was irradiated with a ultraviolet light source until covered and solidified completely. Hydrogel needed to be changed 1-2 times per week. We evaluated the healing time as primary outcome and then followed up for ˃1 year to observe the relapse. The wound healed completely in 46 days after open surgery, which was shorter than that reported in other studies. Meanwhile, no recurrence was detected during follow-up. Photo-crosslinking hydrogel effectively promoted wound healing and has the potential to be easily applied in Pilonidal sinus patients after open surgery.

An effective and considerable treatment of pilonidal sinus disease by laser ablation.

The treatment of sacrococcygeal pilonidal disease (SPD) is still challenging. Although many non-surgical and surgical methods exist, no consensus has been reached on the best treatment. This study aimed to evaluate the efficacy of laser ablation using 1470-nm radial diode laser fiber in treating SPD. We retrospectively studied the data of our 48 patients who operated on this technique between March 2019 and July 2022. All patients were treated with laser ablation using 1470-nm radial diode laser fiber. The healing rate and recurrence rate, demographic and surgical data, postoperative pain, complications (wound infection, wound bleeding), the time of returning to regular work and life, and the time of wound healing were recorded. Postoperative pain was measured based on the visual analog scale (VAS) score. Postoperative follow-up was performed in the outpatient clinic every 1 week for 1 month. Among the 48 patients, 41 males and 7 females, with a mean age of 27.7 years (range 14-42), the healing rate was 100%, and the average healing time was 28.3 ± 5.5 days. Mean operative time was 15.5 ± 3.3 min. The recurrence rate was 2.1%. One patient relapsed 3 months after the operation. The patient underwent laser ablation again, and the sinus tract was closed. The median visual analog scale (VAS) score on the day of operation was 0(0,2). The median VAS score on the first, third, seventh, and fourteenth day after operation was 0(0,2), 0(0,1), 0(0,1), and 0(0,0), respectively. There was no wound infection or bleeding after the operation. The mean time to normal work/life was 7.1 ± 3.2 days. Almost all the patients felt very satisfied with the operation. Laser ablation using 1470-nm radial diode laser fiber is effective in SPD treatment. It is associated with minor wounds and mild postoperative pain. It is a simple, safe, and minimally invasive technique and its clinical application for acute and chronic SPD in the absence of abscess is promising.

Development and Experimental Validation of a Novel Prognostic Signature for Gastric Cancer.

BACKGROUND: Gastric cancer is a malignant tumor with high morbidity and mortality. Therefore, the accurate recognition of prognostic molecular markers is the key to improving treatment efficacy and prognosis. METHODS: In this study, we developed a stable and robust signature through a series of processes using machine-learning approaches. This PRGS was further experimentally validated in clinical samples and a gastric cancer cell line. RESULTS: The PRGS is an independent risk factor for overall survival that performs reliably and has a robust utility. Notably, PRGS proteins promote cancer cell proliferation by regulating the cell cycle. Besides, the high-risk group displayed a lower tumor purity, higher immune cell infiltration, and lower oncogenic mutation than the low-PRGS group. CONCLUSIONS: This PRGS could be a powerful and robust tool to improve clinical outcomes for individual gastric cancer patients.

DAZL regulates proliferation of human primordial germ cells by direct binding to precursor miRNAs and enhances DICER processing activity.

Understanding the molecular and cellular mechanisms of human primordial germ cells (hPGCs) is essential in studying infertility and germ cell tumorigenesis. Many RNA-binding proteins (RBPs) and non-coding RNAs are specifically expressed and functional during hPGC developments. However, the roles and regulatory mechanisms of these RBPs and non-coding RNAs, such as microRNAs (miRNAs), in hPGCs remain elusive. In this study, we reported a new regulatory function of DAZL, a germ cell-specific RBP, in miRNA biogenesis and cell proliferation. First, DAZL co-localized with miRNA let-7a in human PGCs and up-regulated the levels of >100 mature miRNAs, including eight out of nine let-7 family, miR21, miR22, miR125, miR10 and miR199. Purified DAZL directly bound to the loops of precursor miRNAs with sequence specificity of GUU. The binding of DAZL to the precursor miRNA increased the maturation of miRNA by enhancing the cleavage activity of DICER. Furthermore, cell proliferation assay and cell cycle analysis confirmed that DAZL inhibited the proliferation of in vitro PGCs by promoting the maturation of these miRNAs. Evidently, the mature miRNAs up-regulated by DAZL silenced cell proliferation regulators including TRIM71. Moreover, DAZL inhibited germline tumor cell proliferation and teratoma formation. These results demonstrate that DAZL regulates hPGC proliferation by enhancing miRNA processing.

CaMKII orchestrates endoplasmic reticulum stress and apoptosis in doxorubicin-induced cardiotoxicity by regulating the IRE1α/XBP1s pathway.

Doxorubicin (Dox), an anthracycline antibiotic with potent antitumor effects, has limited clinical applications due to cumulative cardiotoxicity. Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is implicated in the pathological progression of Dox-induced cardiotoxicity. This study examined the hypothesis that CaMKII exacerbates Dox-induced cardiotoxicity by promoting endoplasmic reticulum stress and apoptosis through regulation of the inositol-requiring enzyme 1α (IRE1α)/spliced X-box binding protein 1 (XBP1s) pathway. Our results demonstrated that CaMKII activation and IRE1α/XBP1s pathway were involved in Dox-treated hearts. CaMKII inhibition with KN-93 ameliorated Dox-induced cardiac dysfunction and pathological myocardial changes. In addition, CaMKII inhibition prevented Dox-induced endoplasmic reticulum stress and apoptosis. Moreover, CaMKII inhibition increased the expression of IRE1α and XBP1s in Dox-treated hearts. The IRE1α inhibitor 4µ8C blocked the protective effect of CaMKII inhibition against Dox-induced cardiotoxicity. Mechanistically, 4µ8C prevented the effects of CaMKII inhibition on Dox-induced endoplasmic reticulum stress and apoptosis by inhibiting the expression of IRE1α and XBP1s. Additionally, treatment with rhADAMTS13 decreased the protein level of thrombospondin 1 (TSP1) and the phosphorylation of CaMKII in Dox-treated human AC16 cardiomyocytes. Taken together, these results demonstrate that the ADAMTS13-TSP1 axis regulates CaMKII activation and exacerbates Dox-induced cardiotoxicity by triggering endoplasmic reticulum stress and apoptosis by inhibiting the IRE1α/XBP1s pathway.

Spatiotemporal Analysis and Risk Assessment Model Research of Diabetes among People over 45 Years Old in China.

Diabetes, which is a chronic disease with a high prevalence in people over 45 years old in China, is a public health issue of global concern. In order to explore the spatiotemporal patterns of diabetes among people over 45 years old in China, to find out diabetes risk factors, and to assess its risk, we used spatial autocorrelation, spatiotemporal cluster analysis, binary logistic regression, and a random forest model in this study. The results of the spatial autocorrelation analysis and the spatiotemporal clustering analysis showed that diabetes patients are mainly clustered near the Beijing−Tianjin−Hebei region, and that the prevalence of diabetes clusters is waning. Age, hypertension, dyslipidemia, and smoking history were all diabetes risk factors (p < 0.05), but the spatial heterogeneity of these factors was weak. Compared with the binary logistic regression model, the random forest model showed better accuracy in assessing diabetes risk. According to the assessment risk map generated by the random forest model, the northeast region and the Beijing−Tianjin−Hebei region are high-risk areas for diabetes.

FGFR2-BRD4 Axis Regulates Transcriptional Networks of Histone 3 Modification and Synergy Between Its Inhibitors and PD-1/PD-L1 in a TNBC Mouse Model.

Epigenetic reprogramming is an independent mode of gene expression that often involves changes in the transcription and chromatin structure due to tumor initiation and development. In this study, we developed a specifically modified peptide array and searched for a recognized epigenetic reader. Our results demonstrated that BRD4 is not only an acetylation reader but of propionylation as well. We also studied the quantitative binding affinities between modified peptides and epigenetic regulators by isothermal titration calorimetry (ITC). Furthermore, we introduced the Fgfr2-S252W transgenic mouse model to confirm that this acetylation is associated with the activation of c-Myc and drives tumor formation. Targeted disruption of BRD4 in Fgfr2-S252W mouse tumor cells also confirmed that BRD4 is a key regulator of histone 3 acetylation. Finally, we developed a tumor slice culture system and demonstrated the synergy between immune checkpoint blockade and targeted therapy in triple-negative breast cancer (TNBC). These data extend our understanding of epigenetic reprogramming and epigenetics-based therapies.

Triplication is the main evolutionary driving force of NLP transcription factor family in Chinese cabbage and related species.

The NODULE-INCEPTION-like protein (NLP) is a plant-specific transcription factor (TF) family that plays an important role in both signal transduction and nitrate assimilation. However, the NLP gene family in Chinese cabbage (Brassica rapa) has yet to be studied. Here we identified 17, 16, and 32 NLP genes in Chinese cabbage, Brassica oleracea, and Brassica napus, respectively. We found that duplication of those NLP genes almost always originated from genome-wide duplication events. Further analysis (using Arabidopsis as a reference) revealed that the NLP family in Chinese cabbage and B. oleracea was characterized by direct expansion caused by whole-genome duplication. By contrast, indirect expansion characterized B. napus, which arose from hybridization and fusion of the two species. In addition, phylogenetic and homology analyses showed that the Brassica NLP gene family has been highly conserved in evolution. Finally, we also identified optimal codons for four studied species. Altogether, through comparative genome analysis methods, we presented compelling evidence that triplication is the main driving force for the NLP TF family's evolution in Chinese cabbage and related Brassica plants, a process evidently highly conserved. This work will help in better understanding the impact of genome-wide duplication on gene families of plants.

MarkovHC: Markov hierarchical clustering for the topological structure of high-dimensional single-cell omics data with transition pathway and critical point detection.

Clustering cells and depicting the lineage relationship among cell subpopulations are fundamental tasks in single-cell omics studies. However, existing analytical methods face challenges in stratifying cells, tracking cellular trajectories, and identifying critical points of cell transitions. To overcome these, we proposed a novel Markov hierarchical clustering algorithm (MarkovHC), a topological clustering method that leverages the metastability of exponentially perturbed Markov chains for systematically reconstructing the cellular landscape. Briefly, MarkovHC starts with local connectivity and density derived from the input and outputs a hierarchical structure for the data. We firstly benchmarked MarkovHC on five simulated datasets and ten public single-cell datasets with known labels. Then, we used MarkovHC to investigate the multi-level architectures and transition processes during human embryo preimplantation development and gastric cancer procession. MarkovHC found heterogeneous cell states and sub-cell types in lineage-specific progenitor cells and revealed the most possible transition paths and critical points in the cellular processes. These results demonstrated MarkovHC's effectiveness in facilitating the stratification of cells, identification of cell populations, and characterization of cellular trajectories and critical points.

Illegitimate Recombination between Duplicated Genes Generated from Recursive Polyploidizations Accelerated the Divergence of the Genus Arachis.

The peanut (Arachis hypogaea L.) is the leading oil and food crop among the legume family. Extensive duplicate gene pairs generated from recursive polyploidizations with high sequence similarity could result from gene conversion, caused by illegitimate DNA recombination. Here, through synteny-based comparisons of two diploid and three tetraploid peanut genomes, we identified the duplicated genes generated from legume common tetraploidy (LCT) and peanut recent allo-tetraploidy (PRT) within genomes. In each peanut genome (or subgenomes), we inferred that 6.8-13.1% of LCT-related and 11.3-16.5% of PRT-related duplicates were affected by gene conversion, in which the LCT-related duplicates were the most affected by partial gene conversion, whereas the PRT-related duplicates were the most affected by whole gene conversion. Notably, we observed the conversion between duplicates as the long-lasting contribution of polyploidizations accelerated the divergence of different Arachis genomes. Moreover, we found that the converted duplicates are unevenly distributed across the chromosomes and are more often near the ends of the chromosomes in each genome. We also confirmed that well-preserved homoeologous chromosome regions may facilitate duplicates' conversion. In addition, we found that these biological functions contain a higher number of preferentially converted genes, such as catalytic activity-related genes. We identified specific domains that are involved in converted genes, implying that conversions are associated with important traits of peanut growth and development.

Conversion between 100-million-year-old duplicated genes contributes to rice subspecies divergence.

BACKGROUND: Duplicated gene pairs produced by ancient polyploidy maintain high sequence similarity over a long period of time and may result from illegitimate recombination between homeologous chromosomes. The genomes of Asian cultivated rice Oryza sativa ssp. indica (XI) and Oryza sativa ssp. japonica (GJ) have recently been updated, providing new opportunities for investigating ongoing gene conversion events and their impact on genome evolution. RESULTS: Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19-5.77% of genes duplicated across the three rice genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~ 0.4 mya, with more (7.77-9.53%) showing conversion of only portions of genes. Independently converted duplicates surviving in the genomes of different subspecies often use the same donor genes. The ongoing gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes, 11 and 12, in each rice genome being most affected. Notably, ongoing gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangements after polyploidization are associated with ongoing gene conversion events, and they directly restrict recombination and inhibit duplicated gene conversion between homeologous regions. Furthermore, we found that the converted genes tended to have more similar expression patterns than nonconverted duplicates. Gene conversion affects biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, contributing to the occurrence of the gene conversion. CONCLUSION: Duplicated genes in rice subspecies generated by grass polyploidization ~ 100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies.

Metabolic pathways of Chlorella sp. cells induced by exogenous spermidine against nitric oxide damage from coal-fired flue gas.

To protect microalgae that are used for photosynthetic CO2 fixation against high NO concentrations from coal-fired flue gas, 500 µM exogenous spermidine was added into Chlorella sp. solution resulting in an elevation of biomass yield by 30.5% under 327 ppm NO. Metabolomics, proteomics and enzyme activities were analyzed, revealing three effects of spermidine on Chlorella sp. resistance to NO stress. First, spermidine induced NO fixation in amino acids and their metabolites, mainly in form of 5-oxoproline (1.51-fold), which occurred through intracellular conversion reactions between citrulline and arginine. Accordingly, cellular respiration was strengthened along with a weakened NO inhibition, which enhanced active transport with ATP consumption. Second, spermidine guarded Chlorella sp. against peroxidation damage by improving activity of antioxidant enzymes. Finally, it protected the photosynthetic system of Chlorella sp. by increasing abundance of related enzymes to enhance carbon fixation. Thus exogenous spermidine improved biomass production against NO environment.

Curcumol inhibits KLF5-dependent angiogenesis by blocking the ROS/ERK signaling in liver sinusoidal endothelial cells.

AIMS: Liver fibrosis is a difficult problem in the medical field. We previously reported that curcumol, a bioactive substance, may inhibit the pathological angiogenesis of liver sinusoidal endothelial cells (LSECs) and play a good anti-hepatic fibrosis effect. However, the mechanism of curcumol inhibiting angiogenesis in LSEC needs to be further clarified. Here, we focus on how curcumol inhibits LSEC angiogenesis in liver fibrosis. MATERIALS AND METHODS: Primary rat LSECs were cultured in vitro, and various molecular experiments including real-time PCR, western blot, immunofluorescence, tube formation assay and transwell migration assay were used to clarify the potential mechanism of curcumol. Carbon tetrachloride (CCl4) was applied to create a mouse liver fibrosis model. Blood and livers were taken to elucidate the efficacy of curcumol in vivo. KEY FINDINGS: We found that curcumol could effectively inhibit LSEC angiogenesis in vitro. Interestingly, this process may depend on curcumol's inhibition of the expression of transcription factor KLF5. Mice experiment also showed that curcumol could alleviate chronic liver injury by reducing KLF5 expression. In addition, we suggested that curcumol could reduce the production of mitochondrial ROS and improve mitochondrial morphology in LSEC. More importantly, we proved that curcumol could suppress KLF5-mediated LSEC angiogenesis by inhibiting ROS/ERK signaling. SIGNIFICANCE: We suggested that transcription factor KLF5 could be considered as a new target molecule of curcumol in improving liver fibrosis, and pointed out that curcumol targeted ROS/ERK-mediated KLF5 expression could inhibit LSEC angiogenesis. This provided a new theoretical basis for curcumol to ameliorate liver fibrosis.

Protection against acute renal injury by naturally occurring medicines which act through Nrf2 signaling pathway.

The cellular defense pathway plays a key role in maintaining the homeostasis, tissues and organisms. Nuclear factor E2-related factor 2 (Nrf2), as a key cell signaling pathway, plays an important role in encoding detoxification enzymes and other stress response mediators. Recent studies have shown that it is closely related to the prevention and treatment of acute kidney injury (AKI). Therefore, this article reviews the protective effects of Nrf2-related signaling pathways on acute kidney injury, and summarizes the strategies of natural pharmaceutical ingredients such as flavonoids, alkaloids, terpenes, phenylpropionic acid, polyphenols, and polysaccharides to prevent and treat acute kidney injury. It is of great significance to further study the relationship between Nrf2 regulated signal pathway and kidney disease and the development of new medicines for acute kidney injury treatment. It can also provide new ideas and treatment strategies for clinical treatment of acute kidney injury. PRACTICAL APPLICATIONS: This article reviewed the mechanisms by which the active ingredients of natural medicines slow down acute kidney injury through the Nrf2 pathway. It will help us to understand the regulatory role of the Nrf2 pathway in AKI more comprehensively, and provide a theoretical basis for further exploring the mechanism of more natural drugs to reduce acute kidney injury.