The role of long noncoding RNA MEG3 in fibrosis diseases.

Fibrosis is a prevalent pathological condition observed in various organs and tissues. It primarily arises from the excessive and abnormal accumulation of the extracellular matrix, resulting in the structural and functional impairment of tissues and organs, which can culminate in death. Many forms of fibrosis, including liver, cardiac, pulmonary, and renal fibrosis, are considered irreversible. Maternally expressed gene 3 (MEG3) is an imprinted RNA gene. Historically, the downregulation of MEG3 has been linked to tumor pathogenesis. However, recent studies indicate an emerging association of MEG3 with fibrotic diseases. In this review, we delve into the current understanding of MEG3's role in fibrosis, aiming to shed light on the molecular mechanisms of fibrosis and the potential of MEG3 as a novel therapeutic target.

What is already known on this topic ­ Fibrosis, a condition characterized by excess build-up of the extracellular matrix in various organs, can lead to organ failure and is often irreparable. This includes fibrosis of the liver, heart, lungs, and kidneys. MEG3, an RNA gene, which is known to be downregulated in tumors, has recently been linked to fibrosis. What is already known on this topic ­ Our review investigates this new connection between MEG3 and fibrosis. We aim to provide insights into the molecular mechanisms of fibrosis and illuminate the potential role of MEG3 as a promising therapeutic target for fibrosis treatments. What is already known on this topic ­ Our review investigates this new connection between MEG3 and fibrosis. We aim to provide insights into the molecular mechanisms of fibrosis and illuminate the potential role of MEG3 as a promising therapeutic target for fibrosis treatments.

Prognostic value of platelet-to-lymphocyte ratio in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization and tyrosine kinase inhibitors plus immune checkpoints inhibitors.

Purpose: To investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) in patients with unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) and tailored tyrosine kinase inhibitors (TKIs) plus immune checkpoints inhibitors (ICIs). Materials and methods: Ninety-eight patients from May 2018 to January 2022 in our hospital were enrolled in this study. The receiver operating characteristic (ROC) curve analysis was performed and the corresponding Youden index was used to determine the optimal PLR cut-off. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of patients were evaluated based on the PLR cut-off. The factors affecting survival were assessed using univariate and multivariate Cox proportional hazards regression analyses. Results: The PLR cut-off was 98.89. There were 49 patients in the low pretreatment PLR group (PLR ≤ 98.89) and 49 patients in the high PLR group (PLR > 98.89). Patients with low pretreatment PLR had significantly longer median OS (25.7 months vs 16.1 months; P < 0.001) and PFS (14.9 months vs 10.2 months; P < 0.001) than those with high pretreatment PLR. The multivariate analysis revealed that ALT, tumor size, and PLR are risk factors affecting OS. The three independent factors affecting PFS are tumor size, AFP, and PLR. The AEs were tolerable and manageable. Conclusion: The low pretreatment PLR (PLR ≤ 98.89) was an independent protective factor for the survival outcomes of patients in this study. PLR was helpful for clinicians to predict the prognosis and identify the patients with uHCC who were most likely to benefit from TACE + TKIs + ICIs.

LC-MS and GC-MS Metabolomics Analyses Revealed That Different Exogenous Substances Improved the Quality of Blueberry Fruits under Soil Cadmium Toxicity.

Exogenous substances (ESs) can regulate plant growth and respond to environmental stress, but the effects of different ESs on blueberry fruit quality under soil cadmium (Cd) toxicity and related metabolic mechanisms are still unclear. In this study, four ES treatments [salicylic acid (SA), spermidine (Spd), 2,4-epibrassinolide (EBR), and melatonin (MT)] significantly increased blueberry fruit size, single-fruit weight, sweetness, and anthocyanin content under soil Cd toxicity and effectively reduced fruit Cd content to safe consumption levels by promoting mineral uptake (Ca, Mg, Mn, Cu and Zn). Furthermore, a total of 445, 360, 429, and 554 differentially abundant metabolites (DAMs) (LC-MS) and 63, 48, 79, and 73 DAMs (GC-MS) were identified from four comparison groups (SA/CK, Spd/CK, EBR/CK and MT/CK), respectively. The analyses revealed that ESs improved blueberry fruit quality and tolerance to Cd toxicity mainly by regulating the changes in metabolites related to ABC transporters, the TCA cycle, flavonoid biosynthesis, and phenylpropanoid biosynthesis.

Effect of blackberry anthocyanins and its combination with tea polyphenols on the oxidative stability of lard and olive oil.

To investigate the protective effect of blackberry anthocyanins (BA), tea polyphenols (TP), and their binary mixture on the oxidative stability of edible oils during storage, BA, TP, and their binary mixture were added to lard and olive oil. The changes in peroxide value (PV), thiobarbituric acid reactive substances (TBARS), acid value (AV), and scavenging capacity of DPPH and ABTS•+ of oil samples were evaluated during accelerated storage. BA were found to have a remarkable capability to enhance antioxidant properties, delay lipid oxidation, and inhibit the deterioration both of lard and olive oil at high-temperature processes. Furthermore, the antioxidant synergistic effect of BA and TP was found both in lard and olive oil for the first time. All these results suggested that BA and its combination with TP might possess the potential value to protect the quality of edible oils.

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 µg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Proteins from Blackberry Seeds: Extraction, Osborne Isolate, Characteristics, Functional Properties, and Bioactivities.

Blackberry fruit contains high levels of nutrients and phenolic compounds. Blackberry pomace accounts for 20~30% of its whole fruit during processing and is generally treated as fertilizer. Blackberry pomace has many seeds that contain carbohydrates, polyphenols, flavonoids, pectin, protein, and other bioactive nutrients. However, its functional properties and seed protein compositions have not been reported. We used a single-factor experiment, response surface, and Osborne isolate method to extract protein isolate, albumin, globulin, glutelin, and prolamin from blackberry seeds for the first time and evaluated their characteristics and functional properties. Glutelin and protein isolate showed good water-holding capacity, emulsification, and foaming capacity, while albumin and globulin showed good oil-holding capacity and thermal stability. They were found to have good antioxidant activities that might be good DPPH free radical scavengers, especially prolamin, which has the lowest IC50 value (15.76 µg/mL). Moreover, globulin had the lowest IC50 value of 5.03 µg/mL against Hela cells, 31.82 µg/mL against HepG2 cells, and 77.81 µg/mL against MCF-7 cells and a high selectivity index (SI), which suggested globulin had better anti-cervical, antihepatoma, and anti-breast activity but relatively low cytotoxicity. These seed proteins may have great prospects for the development and application of food and drugs in the future.

Screening and Evaluation of Excellent Blackberry Cultivars and Strains Based on Nutritional Quality, Antioxidant Properties, and Genetic Diversity.

To screen and evaluate excellent blackberry cultivars and strains, 17 indexes of plant growth and fruit horticultural and nutritional characteristics were measured, 20 simple sequence repeat (SSR) markers were analyzed, the fingerprints of 23 blackberry cultivars and strains were constructed, and the processing characteristics of 10 excellent cultivars and strains were evaluated. The results showed that 'Chester' and 'Shuofeng' had the highest plant yield (6.5 kg per plant), of which the 'Chester' fruit also had the highest hardness (2.78 kg/cm2). 'Kiowa' had the highest single fruit weight (10.43 g). '10-5n-2' had the highest total anthocyanin content (225.4 mg/100 g FW) and total polyphenol content (3.24 mg/g FW), but a low plant yield. These results suggest that 'Shuofeng' and 'Chester' are the top two blackberry cultivars planted in Nanjing, with the best growth and comprehensive quality. Moreover, a total of 119 alleles were detected with an average number of 6 alleles per locus. The polymorphism information content (PIC) was 0.374~0.844, with an average of 0.739, indicating a high genetic diversity among the 23 blackberry cultivars and strains. This study provides insight into the plant growth, fruit characteristics and genetic diversity of the 23 blackberry cultivars and strains, and is thus conducive to the protection and utilization of blackberry cultivars and strains.

Five blueberry anthocyanins and their antioxidant, hypoglycemic, and hypolipidemic effects in vitro.

The dual epidemic of obesity and diabetes mellitus is becoming an important worldwide public health issue. "Diabesity" is the term used to describe the combined detrimental health effects of both diabetes mellitus and obesity/overweight. Currently, food-derived bioactive compounds are suggested to alleviate diabesity. Blueberries are rich in bioactive anthocyanins, which are associated with contributing to preventing obesity and diabetes mellitus. However, the accurate active compounds and the underlying mechanism are still unclear. The objective of this study was to investigate the beneficial effects of blueberry anthocyanin on diabesity. In total, five anthocyanins (delphinidin-3-O-galactoside, delphinidin-3-O-glucoside, petunidin-3-O-galactoside, petunidin-3-O-glucoside, and malvidin-3-O-galactoside) were isolated from rabbiteye blueberry (Vaccinium virgatum) cultivar "Garden blue." All these anthocyanins exhibited oxygen radical absorbance capacity (ORAC), scavenging power of ABTS+, and DPPH-free radical and inhibitory activity of α-glucosidase in vitro. Moreover, some compounds improved glucose uptake and attenuated lipid accumulation in high glucose and oleic acid-treated HepG2 cells. All these results suggest that blueberry anthocyanins have potential antioxidant, hypoglycemic, and hypolipidemic effects, which may benefit the treatment of diabesity.

Adipose tissue macrophages as potential targets for obesity and metabolic diseases.

Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.

Effects of Different Light Wavelengths on Fruit Quality and Gene Expression of Anthocyanin Biosynthesis in Blueberry (Vaccinium corymbosm).

Different light wavelengths display diverse effects on fruit quality formation and anthocyanin biosynthesis. Blueberry is a kind of fruit rich in anthocyanin with important economic and nutritional values. This study explored the effects of different light wavelengths (white (W), red (R), blue (B) and yellow (Y)) on fruit quality and gene expression of anthocyanin biosynthesis in blueberry. We found that the B and W treatments attained the maximum values of fruit width, fruit height and fruit weight in blueberry fruits. The R treatment attained the maximum activities of superoxide dismutase (SOD) and peroxidase (POD), and the Y treatment displayed the maximum contents of ascorbic acid (AsA), glutathione (GSH) and total phenol in fruits, thus improving blueberry-fruit antioxidant capacity. Interestingly, there were differences in the solidity-acid ratio of fruit under different light-wavelength treatments. Moreover, blue light could significantly improve the expression levels of anthocyanin biosynthesis genes and anthocyanin content in fruits. Correlation and principal component analysis showed that total acid content and antioxidant enzymes were significantly negatively correlated with anthocyanin content in blueberry fruits. These results provide new insights for the application of light wavelength to improve blueberry fruit quality and anthocyanin content.

Polyphenols from Prunus mume: extraction, purification, and anticancer activity.

Prunus mume is an ancient medicinal herb and food that are commonly used in Asian countries with high nutritional ingredients and biological activities. Polyphenols are important functional components in Prunus mume. To obtain a more efficient extraction process of Prunus mume polyphenols, a single-factor test and response surface method were used. After extraction and purification, the final polyphenol content of Prunus mume (L1) was up to 90%. Biological experiments showed that L1 had high anticancer activity against HeLa (125.28 µg mL-1), HepG2 (117.24 µg mL-1), MCF-7 (170.19 µg mL-1), and A549 (121.78 µg mL-1) in vitro by MTT assay. The combination of DDP and DOX significantly enhanced the anticancer activity of the four cell lines, especially L1-DOX had the smallest IC50 value of 0.04 µg mL-1 against HepG2 cells, indicating the combination of drugs had synergistic effects. It is further demonstrated that L1 could inhibit cell proliferation by inducing apoptosis with ROS detection and confocal fluorescence images. The relative tumor proliferation rate (T/C) was 40.6%, and the tumor inhibition rate was 57.9%, indicating L1 to have no significant toxicity but high anti-HepG2 activity in vivo. Although the study is very limited, it is anticipated to provide a reference for further exploration of the functionality of the plant.

The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry.

Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L1) had antiproliferative effect on cervical cancer cells (Hela, 51.98 µg/mL), liver cancer cells (HepG2, 23.57 µg/mL), breast cancer cells (MCF-7, 113.39 µg/mL), and lung cancer cells (A549, 76.10 µg/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the IC50 value was 0.02 µg/mL. This was further evidence that L1 could inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be L1 interacting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that L1 extract can be used as a functional agent against hepatoma carcinoma cells.

Research on Anthocyanins from Rubus "Shuofeng" as Potential Antiproliferative and Apoptosis-Inducing Agents.

Blackberries have high nutritional value and strong biological activities, such as antiproliferative activity. Anthocyanins are important functional components in blackberries. We collected 25 kinds (lines) of blackberries from our nursery to investigate antiproliferative agents in natural foods. Among them, the Shuofeng variety had the highest anthocyanin content, with 2.54 mg/g of fresh fruit, which increased to 357.75 mg/g of dried powder through ultrasound-assisted solvent extraction and macroporous resin adsorption. Additional experiments showed that Shuofeng's anthocyanin content had high anti-HepG2 activity in vitro and in vivo, as well as activity against Hela (68.62 µg/mL), HepG2 (55.85 µg/mL), MCF-7 (181.21 µg/mL), and A549 cells (82.01 µg/mL), as determined by MTT assay. It also had no apparent toxic effects. The combination of DDP and DOX significantly enhanced the antiproliferative activity of the four cell lines. The IC50 value of Shuofeng's anthocyanin content combined with DOX in HepG2 cells was the lowest at only 0.08 µg/mL, indicating that the combination of drugs had additive and synergistic effects. Shuofeng's anthocyanin content might intercalate into DNA and alter or destroy DNA, causing apoptosis and inhibiting cell proliferation. Our results show that blackberry anthocyanins can inhibit the proliferation of cancer cells and their possible mechanisms. However, we must study the deeper mechanism and explore its targeting effects in the future.

Integrated Physiological and Metabolomic Analyses Reveal the Differences in the Fruit Quality of the Blueberry Cultivated in Three Soilless Substrates.

With improving living standards, traditional blueberry planting modes cannot meet commercial demands, and blueberry cultivation with soilless substrate has become a popular solution in the blueberry industry. In this study, different soilless substrate treatments were found to markedly influence fruit appearance and intrinsic quality. The fruit in the 50:50 peat/pine bark (v/v) (FPB) treatment group had the maximum single fruit weight, largest vertical diameter, and brightest color, as well as the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) value, solid-acid ratio and anthocyanin content. The fruit in the 50:50 pine bark/rice husk (v/v) (FBR) treatment group had the highest total phenol and flavonoid levels, largest drip loss value, and lowest total pectin content and firmness value. Metabolomic analysis showed that flavonoid, carbohydrate, and carbohydrate conjugate, and amino acid, peptide, and analog levels were significantly different between groups. Fruit in the FPB group had the highest sucrose, D-fructose 1,6-bisphosphate, salidroside, tectorigenin, naringenin chalcone, trifolirhizin, and galangin contents. The increase in the relative expression of phenylalanine (Phe) promoted the synthesis of fruit polyphenols in the FBR group. Our results provide new insights into the effects of different substrates on the quality of blueberries and a reference for the soilless substrate cultivation of blueberries.

Overexpression of RuFLS2 Enhances Flavonol-Related Substance Contents and Gene Expression Levels.

As an emerging third-generation fruit, blackberry has high nutritional value and is rich in polyphenols, flavonoids and anthocyanins. Flavonoid biosynthesis and metabolism is a popular research topic, but no related details have been reported for blackberry. Based on previous transcriptome data from this research group, two blackberry flavonol synthase genes were identified in this study, and the encoded proteins were subjected to bioinformatics analysis. RuFLS1 and RuFLS2 are both hydrophobic acidic proteins belonging to the 2OG-Fe(II) dioxygenase superfamily. RuFLS2 was expressed at 27.93-fold higher levels than RuFLS1 in red-purple fruit by RNA-seq analysis. Therefore, RuFLS2-overexpressing tobacco was selected for functional exploration. The identification of metabolites from transgenic tobacco showed significantly increased contents of flavonoids, such as apigenin 7-glucoside, kaempferol 3-O-rutinoside, astragalin, and quercitrin. The high expression of RuFLS2 also upregulated the expression levels of NtF3H and NtFLS in transgenic tobacco. The results indicate that RuFLS2 is an important functional gene regulating flavonoid biosynthesis and provides an important reference for revealing the molecular mechanism of flavonoid accumulation in blackberry fruit.

Molecular pathogenesis: Connections between viral hepatitis-induced and non-alcoholic steatohepatitis-induced hepatocellular carcinoma.

Hepatocellular carcinoma(HCC) is the sixth most common cancer in the world and is usually caused by viral hepatitis (HBV and HCV), alcoholic, and non-alcoholic fatty liver disease(NAFLD). Viral hepatitis accounts for 80% of HCC cases worldwide. In addition, With the increasing incidence of metabolic diseases, NAFLD is now the most common liver disease and a major risk factor for HCC in most developed countries. This review mainly described the specificity and similarity between the pathogenesis of viral hepatitis(HBV and HCV)-induced HCC and NAFLD-induced HCC. In general, viral hepatitis promotes HCC development mainly through specific encoded viral proteins. HBV can also exert its tumor-promoting mechanism by integrating into the host chromosome, while HCV cannot. Viral hepatitis-related HCC and NASH-related HCC differ in terms of genetic factors, and epigenetic modifications (DNA methylation, histone modifications, and microRNA effects). In addition, both of them can lead to HCC progression through abnormal lipid metabolism, persistent inflammatory response, immune and intestinal microbiome dysregulation.

Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism.

BACKGROUND: Tertiary lymphoid structures (TLSs) are formed by the aggregation of tumour-infiltrating lymphocytes (TILs), which is driven by chemokines or cytokines in the tumour microenvironment. Studies have shown that TLSs are associated with good prognosis in patients with various solid tumours and can improve patient responses to immunotherapy. However, the role of TLSs in hepatocellular carcinoma (HCC) remains controversial, and the underlying molecular mechanism is unclear. METHODS: According to haematoxylin-eosin (HE) staining results, HCC patients in Xijing Hospital data and TCGA data were divided into TLS+ and TLS- groups, and Kaplan-Meier (KM) analysis was performed to assess overall survival (OS) and recurrence-free survival (RFS). Immunofluorescence (IF) and immunohistochemistry (IHC) were used to identify TILs in the TLS+ group. Lymphocyte-specific protein tyrosine kinase (LCK), a molecule involved in TLS formation, was explored in LinkedOmics. TILs were divided into two groups by drawing receiver operating characteristic (ROC) curves to calculate cut-off values. Spearman correlation analysis was used to calculate the correlation between LCK and TILs, and the molecular pathways by which LCK regulates immunotherapy were clarified through enrichment analysis. The half-maximal inhibitory concentration (IC50) distribution of sorafenib was observed in groups that varied in LCK expression. RESULTS: According to the HE results, 61 cases in the Xijing Hospital cohort and 195 cases in the TCGA cohort had TLSs, while 89 cases and 136 cases did not. The KM results showed that TLSs had no effect on the OS of HCC patients but significantly affected RFS. The IF/IHC results showed that higher TIL numbers in TLSs were correlated with better prognosis in HCC patients. Spearman correlation analysis showed that LCK expression was positively correlated with TIL numbers. Enrichment analysis showed that upregulation of LCK expression mainly regulated the cytokine signalling pathway, the chemokine signalling pathway and T-cell activation. The IC50 scores of sorafenib in HCC patients with high LCK expression were lower, and the sensitivity was higher. CONCLUSION: TLSs mainly affected the early RFS of HCC patients but had no effect on OS. The high expression of the TLS formation-related gene LCK can increase the sensitivity of HCC patients to ICIs.

Composition and Antioxidant Activity of Anthocyanins and Non-Anthocyanin Flavonoids in Blackberry from Different Growth Stages.

The high nutritional value and unique flavor of blackberries make them a popular food choice among consumers. Anthocyanin content (AC) and non-anthocyanin flavonoid content (NAFC) are important functional components in blackberry. We tested the AC, NAFC, and antioxidant activities of two blackberry-Ningzhi 1 and Hull-during the following ripening stages: green-fruit stage (GFS), color-turning stage (CTS), reddening stage (RDS), and ripening stage (RPS). The results showed that NAFC decreased and AC increased gradually during the ripening stages. The NAFC of Hull blackberry was the highest during GFS (889.74 µg/g), while the AC of Ningzhi 1 blackberry was the highest during RPS (1027.08 µg/g). NAFC was the highest at the initial stage and gradually decreased with ripening. Anthocyanin accumulation mainly occurred during the later ripening stages. These results provide a reference for comparing the NAFC, AC, and antioxidant activity of Ningzhi 1 and Hull and their changes during different ripening stages.

Serum Creatinine/Cystatin C Ratio as a Predictor of In-hospital Mortality in Patients Hospitalized with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Low serum creatinine/cystatin C ratio (CCR) is associated with unfavorable characteristics in patients with chronic obstructive pulmonary disease (COPD); however, the relationship between CCR and in-hospital mortality of patients with acute exacerbation of COPD (AECOPD) is unexplored. Our objective was to assess the value of CCR for predicting in-hospital mortality of patients hospitalized with AECOPD. METHODS: Patients with AECOPD (n = 597) were retrospectively enrolled. Patient's clinical characteristics and laboratory tests, including serum cystatin C and creatinine, were reviewed. The prediction value of CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. Factors potentially impacting in-hospital mortality were investigated using univariate and multivariate logistic regression analyses. RESULTS: Mortality rate during hospitalization was 10.05%. CCR was lower in non-surviving vs. survived patients (41.67 vs. 61.52, P < 0.001). AUC value for CCR for in-hospital mortality prediction was 0.79 [95% confidence interval (CI) 0.73-0.85]. On multivariate logistic regression analysis, in-hospital mortality was strongly associated with CCR < 52.27 [odds ratio (OR) 6.23, 95% CI (3.00-12.92), P < 0.001], age ≥ 81 years [OR 2.97, 95% CI (1.20-7.37), P = 0.019], oxygenation index < 300 [OR 3.28, 95% CI (1.27-8.44), P = 0.014], CRP > 8 mg/L [OR 1.84, 95% CI (1.15-2.95), P = 0.012], and D-dimer > 500 ng/L [OR 5.19, 95% CI (1.51-17.79), P = 0.009]. CONCLUSIONS: CCR was significantly lower, and is a potential prognostic indicator, in patients with AECOPD who died during hospitalization.

Research Progress on Long Noncoding RNAs and N6-Methyladenosine in Hepatocellular Carcinoma.

N6-methyladenosine (m6A) is an epigenetic modification that widely exists in long noncoding RNAs (lncRNAs) and is involved in the regulation of oncogenes or tumor suppressor genes that form complex enzymes to affect the occurrence of tumors. The abnormal modification of m6A methylation can alter the overall m6A level and thus contribute to the malignant biological behaviors of hepatocellular carcinoma (HCC). LncRNAs related to m6A methylation are involved in lipogenesis, the proliferation, migration and invasion of HCC cells, the stemness of tumor cells and sorafenib resistance. In this review, we systematically elaborated the occurrence mechanism of lncRNA and m6A methylation modification in HCC and the effect of m6A methylation modification of lncRNA on the occurrence of HCC, suggesting that the combination of m6A methylation modification and lncRNA will be more meaningful as molecular markers or prognostic markers. It is helpful to provide further ideas for exploring the pathogenesis of HCC and identifying new targets for HCC treatment and diagnosis and achieve precise individual treatment of liver cancer.