RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-ß pathway.

GBM is one of the most malignant tumor in central nervous system. The resistance to temozolomide (TMZ) is inevitable in GBM and the characterization of TMZ resistance seriously hinders clinical treatment. It is worthwhile exploring the underlying mechanism of aggressive invasion and TMZ resistance in GBM treatment. Bioinformatic analysis was used to analyze the association between RND1 and a series of EMT-related genes. Colony formation assay and cell viability assay were used to assess the growth of U87 and U251 cells. The cell invasion status was evaluated based on transwell and wound-healing assays. Western blot was used to detect the protein expression in GBM cells. Treatment targeted RND1 combined with TMZ therapy was conducted in nude mice to evaluate the potential application of RND1 as a clinical target for GBM. The overexpression of RND1 suppressed the progression and migration of U87 and U251 cells. RND1 knockdown facilitated the growth and invasion of GBM cells. RND1 regulated the EMT of GBM cells via inhibiting the phosphorylation of AKT and GSK3-ß. The promoted effects of RND1 on TMZ sensitivity was identified both in vitro and in vivo. This research demonstrated that the overexpression of RND1 suppressed the migration and EMT status by downregulating AKT/GSK3-ß pathway in GBM. RND1 enhanced the TMZ sensitivity of GBM cells both in vitro and in vivo. Our findings may contribute to the targeted therapy for GBM and the understanding of mechanisms of TMZ resistance in GBM.

Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial.

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).

Effects of co-infection with Clonorchis sinensis on T cell exhaustion levels in patients with chronic hepatitis B.

To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.

The impact of urbanization on ecosystem services: Both time and space are important to identify driving forces.

Rapid urbanization is one of the key factors in threatening regional ecological security and undermining human well-being. Understanding of the impacts of urbanization on ecosystem services (ESs) could provide comprehensive information for policy making to support ecological governance. In this study, the spatial and temporal distributions of four ESs, namely water yield (WY), soil conservation (SC), nitrogen export (NE), and habitat quality (HQ), and four factors of urbanization, namely construction land percentage, economic density, population density, and nighttime lighting, were analyzed in the Xiangjiang River Basin (XJRB) from 1990 to 2020. The impacts of urbanization on ESs at the sub-watershed and county level were investigated using the space-for-time and change-over-time methods. The results showed that: (1) WY, SC, and NE fluctuated throughout the study period, while HQ significantly decreased and urbanization factors significantly increased. (2) Each urbanization factor had a significant influence on the spatial heterogeneity of ESs, with the contribution at the county level being 2.88%-56.11% higher than that at the sub-watershed level. Moreover, there were enhanced interactions between factors in general, although spatial heterogeneity effects on NE and HQ were weaker at the county level. (3) Urbanization and ESs had a significant nonlinear relationship, and there was a threshold of relationship change between them, with the impact of urbanization on ESs showing evident spatial heterogeneity in terms of both the driving direction and intensity of change over time. (4) The change-over-time method identified 1992-1995 and 2008-2013 as key periods of change in the relationship between urbanization and ESs in the XJRB, and the method had the advantage of revealing the spatial heterogeneity of the effects of driving factors. These findings provide a reference for decision making related to urban planning.

BZW1 as an oncogene is associated with patient prognosis and the immune microenvironment in glioma.

BACKGROUND: Glioma is the most common primary tumor in the human central nervous system. This study was designed to explore the expression of BZW1 in glioma and its relevance to the clinicopathological features and outcome of glioma patients. METHODS: Glioma transcription profiling data were obtained from The Cancer Genome Atlas (TCGA). TIMER2, GEPIA2, GeneMANIA, and Metascape were searched in the present study. Cell and animal experiments were conducted to verify the effect of BZW1 on glioma cell migration in vitro and in vivo. Transwell assays, western blotting and immunofluorescence assays were performed. RESULTS: We found that BZW1 was highly expressed in gliomas and correlated with poor prognosis. BZW1 could promote glioma proliferation. GO/KEGG analysis revealed that BZW1 was involved in collagen-containing extracellular matrix and was correlated with ECM-receptor interactions, transcriptional misregulation in cancer and the IL-17 signaling pathway. In addition, BZW1 was also associated with the glioma tumor immune microenvironment. CONCLUSION: BZW1 can promote glioma proliferation and progression, and its high expression is correlated with a poor prognosis. BZW1 is also associated with the tumor immune microenvironment of glioma. This study may facilitate further understanding of the critical role of BZW1 in human tumors, including gliomas.

Identification of Potential Serum Protein Biomarkers in Thymoma with Myasthenia Gravis After Docetaxel Treatment.

INTRODUCTION: Myasthenia gravis (MG) is a devastating acquired autoimmune disease that can seriously affect the patient's quality of life. It is also a common complication of thymoma. Previous studies have shown that docetaxel alleviates myasthenic symptoms in thymoma with MG (TMG). However, little is known about the protein expression profiles and biomarkers for efficacy after docetaxel treatment. METHODS: We recruited 9 healthy controls and 30 patients with TMG for the serum proteomics study with data-independent acquisition (DIA) technology. We further recruited additional 30 patients for the key protein validation by enzyme-linked immunosorbent assay (ELISA). RESULTS: We identified 43 proteins by trend analysis and analyzed the interaction between these proteins and MG pathogenic proteins from the DisGNET database and the correlation analysis with clinical data of patients with TMG. Among these, KRAS and SELP were screened out and validated. KRAS and SELP increased in patients with TMG and decreased significantly after docetaxel treatment. CONCLUSIONS: Our study revealed that the serum proteins were differentially expressed after docetaxel treatment, suggesting their important role in patients with TMG, as well as the critical role of KRAS and SELP as biomarkers in evaluating the efficacy of docetaxel treatment.

Coinfection of Clonorchis sinensis and hepatitis B virus: clinical liver indices and interaction in hepatic cell models.

BACKGROUND: In China, people infected with hepatitis B virus (HBV) are commonly found in areas with a high prevalence of Clonorchis sinensis, a trematode worm. Published studies have reported that the progression of hepatitis B is affected by coinfection C. sinensis. METHODS: Clinical data from a total of 72 patients with C. sinensis and HBV (as sole infection or with coinfections) and 29 healthy individuals were analysed. We also incubated the hepatic stellate cell line LX-2 with total proteins from C. sinensis adult worms (CsTPs) and HBV-positive sera. In addition, the human hepatoblastoma cell line HepG2.2.15 was treated with the antiviral drug entecavir (ETV), CsTPs and the anti-C. sinensis drug praziquantel (PZQ). RESULTS: Our clinical data indicated that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and hyaluronic acid (HA) were significantly higher in patients with coinfection than in those infected with HBV only. In cell models, compared with the model in which LX-2 cells were incubated with HBV-positive sera (HBV group), transcripts of alpha-smooth muscle actin and types I and III collagen were significantly elevated in the models of LX-2 cells treated with CsTPs and HBV-positive sera (CsTP+HBV group), while the messenger RNA levels of tumour necrosis factor-α, interleukin (IL)-1ß and IL-6 in the CsTP+HBV group were clearly lower. The HBV surface antigen and hepatitis B e-antigen levels were higher in the HepG2.2.15 cells treated with ETV and CsTPs than in those in the ETV group and in the cells administered a mixture of ETV, CsTPs and PZQ. CONCLUSIONS: These results confirmed that C. sinensis and HBV coinfection could aggravate the progression of liver fibrosis. CsTPs might promote chronic inflammation of the liver in individuals with HBV infection, resulting in the development of hepatic fibrosis.

PGCLCs of human 45,XO reveal pathogenetic pathways of neurocognitive and psychosocial disorders.

BACKGROUND: Neurocognitive disorders and psychosocial difficulties are common in patients with Turner syndrome and multiple neurodegenerative diseases, yet there is no effective cure. Human primordial germ cells (hPGCs) are pluripotent germline stem cells in early embryo, which pass genetic information from one generation to the next, whereas all somatic cells will die along with the end of life. However, it is not known whether patient hPGCs with Turner syndrome contain information of neurocognitive and psychosocial illness. RESULTS: In this report, we used a high-density of culture system of embryoids derived from iPSCs of a patient with Turner syndrome to ask how pathogenetic pathways are associated with onset of neurocognitive and psychosocial disorders. The hPGC-Like Cells (hPGCLCs) were in vitro specified from iPSCs of 45,XO, 46,XX and 46,XY by the high-density induction of embryoids. Amazingly, we found that the specification process of the hPGCLCs in 45,XO, compared to those in 46,XX and 46,XY, enriched several common pathogenetic pathways regulating neurocognitive and psychosocial disorders, that shared among multiple neurodegenerative diseases and Turner syndrome. The downregulated chemical synaptic transmission pathways, including glutamatergic, GABAergic, and nicotine cholinergic synapses, indicated synaptic dysfunctions, while upregulated pathways that were associated with imbalance of mitochondrial respiratory chain complexes and apoptosis, may contribute to neuronal dysfunctions. Notably, downregulation of three types of ubiquitin ligases E1-E2-E3 and lysosome-associated sulfatases and RAB9A, owing to haploinsufficiency and parental preference of the X chromosome expression, indicated that two pathways of cellular degradation, lysosome and ubiquitin-proteasome, were impaired in the specification process of 45,XO hPGCLCs. This would lead to accumulation of undesired proteins and aggregates, which is a typically pathological hallmark in neurodegenerative diseases. CONCLUSIONS: Our data suggest that the specification process of the hPGCLCs in 45,XO, compared to those in 46,XX and 46,XY, enriched pathogenetic pathways that are associated with the onset of neurocognitive and psychosocial disorders.

Effects of co-infection with Clonorchis sinensis on the sex hormones levels in male patients with chronic hepatitis B.

OBJECTIVE: We evaluated the levels of sex hormones in male hepatitis B patients co-infected with Clonorchis sinensis (C. sinensis). METHODS: A total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono-infection, 19 patients with only chronic hepatitis B, 18 patients with post-hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co-infected with C. sinensis, and 18 post-hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured. RESULTS: The results showed that compared with the LC group, the LC+ C. sinensis co-infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB+ C. sinensis co-infected patients were significantly higher than those in CHB mono-infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono-infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono-infected patients and HCs. CONCLUSION: This study suggests that C. sinensis co-infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.

Chest CT tomography vs. intracavitary electrocardiogram guidance in predicting the length of PICC placement.

BACKGROUND: To evaluate chest computed tomography (CT) compared to intracavitary electrocardiogram (ECG) in predicting the length of peripherally inserted central catheter (PICC) placement and analyzing the accuracy of the positioning methods. METHODS: This study included a total number of 436 patients who underwent PICC placement. The patients enrolled were randomly divided into two groups: ECG group (n = 218, received IC-ECG) and chest CT group (n = 218, received chest CT). The tip length of the catheter in the superior vena cava, the measured length of the catheter and the actual insertion length of the catheter were observed and recorded in the two groups. RESULTS: The best catheterization rate of tip positioning and the one-time placement rate of tip positioning in ECG group were significantly higher than that in the chest CT group (all P < 0.05). The comfort level and satisfaction rate in ECG group was significantly higher than that of chest CT group (all P < 0.05). CONCLUSION: Accurate catheterization length could be achieved by both chest CT and intracavitary electrocardiogram guidance in the process of predicting PICC placement length. However, IC-ECG guided procedure was more worthy of promotion in clinic.

Single-cell transcriptomics and network pharmacology reveal therapeutic targets of Jianpi Yiqi Bugan Yishen decoction in immune cell subsets of children with myasthenia gravis.

Background: Myasthenia gravis (MG) is an acquired autoimmune disease of the neuromuscular junction. As immunosuppressive agents used to treat MG have a significant impact on the growth and development of children, treatment is extremely challenging. Jianpi Yiqi Bugan Yishen Decoction (JYBYD) has been developed to treat MG and has achieved satisfactory results in clinical practice. This study aimed to explore its action mechanism and evaluate its active ingredients and potential therapeutic targets. Methods: Single-cell transcriptome sequencing of peripheral blood immune cells of children with MG was performed to reveal the changes in immune cell profiles before and after JYBYD treatment. Lewis rats were included in the model, with classic MG induced by subcutaneous injection of the immunogen acetylcholine receptor (AChR). Twenty rats were divided into two groups and administered normal saline and JYBYD by gavage daily. Results: An increase in cell populations characterized by cortactin expression was observed, which has a potential effect on the recovery of lesions at the neuromuscular junction in patients with MG. Based on the differential expression of genes in various immune cells and the predicted targets of traditional Chinese medicine (TCM) compounds, the possible therapeutic targets of JYBYD in different cell subsets were identified, among which STAT1, MCL1, and FOS were the most frequent. Comprehensive network pharmacological analysis suggested quercetin, luteolin, and resveratrol as important active ingredients of JYBYD for the treatment of children with MG. JYBYD could relieve myasthenia symptoms and reduce the AChR-Ab titer in the rat model. Immunohistochemistry results of the muscle showed that JYBYD treatment decreased the expression of STAT1, MCL1, and c-FOS proteins in the muscles of MG rat models. Conclusions: The results of this study are of significance for the clinical application of JYBYD and drug development against MG in children.

Clinical significance of different atlas of intracavitary electrocardiogram for PICC localization in 961 cases.

PURPOSE: To explore the application of ECG-guided localization technology in PICC catheterization and the clinical significance of different maps of intracavitary ECG in PICC tip localization. METHODS: In the process of catheter placement under the guidance of ultrasound, the technique of intracavitary ECG location was used. The length of the catheter was measured on the body's surface. The amplitude of the P-wave and the QRS-wave groups of electrocardiograms before and during catheter placement was recorded. Nine hundred sixty-one patients who underwent X-ray chest film examination after catheterization were imaged on the chest film at the tip of the catheter. RESULTS: Eight hundred four cases had a characteristic P wave, 83.66%, of which, 331 cases (50% < P/R ≤80%) had 99.09%; 425 cases (80% < P/R ≤100%) had 99.29%; 48 cases (P/R >100%) had 100%. One hundred eighteen cases of non-specific P wave accounted for 12.28% and 79.66% of chest radiographs, of which 72 cases of P/R <50% were 100%; 46 cases of unchanged P wave were 47.83%; 34 cases of special cases accounted for 3.54% and 55.88% of chest radiographs; five cases of interference wave accounted for 0.25%, and the chest radiographs were self-control. The in-place rate of the body contrast catheter was 80%. CONCLUSIONS: The accuracy of the ECG characteristic map in guiding the location of the PICC tip is higher than that of the non-characteristic P wave, and it has more clinical significance in locating the best position of the PICC tip.

MiR-18a-5p Promotes Proliferation, Migration, and Invasion of Endometrial Cancer Cells by Targeting THBD.

The purpose of this study was to elucidate the role that the miR-18a-5p/THBD regulatory pathway plays in endometrial cancer (EC), which could provide a theoretical basis for potential therapeutic targets. Differentially expressed genes in EC tissue and normal tissue were determined by bioinformatics analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to compare the expression of miR-18a-5p and THBD mRNA in normal human endometrial cells and human EC cells. CCK-8 assay was used to compare the proliferative ability of EC cells in different treatment groups. Transwell assay was used to detect the migratory and invasive abilities of EC cells in different treatment groups. Dual-luciferase assay was used to verify the targeting relationship between miR-18a-5p and THBD. Western blot assay was used to detect THBD protein expression level. qRT-PCR results showed that miR-18a-5p was significantly upregulated in EC cells, and expression of its target gene, THBD, was significantly downregulated. CCK-8 and transwell assays showed that miR-18a-5p could enhance the proliferative, migratory, and invasive abilities of EC cells, whereas THBD could weaken those abilities. Dual-luciferase assay confirmed that miR-18a-5p could negatively regulate THBD expression. In addition, rescue experiments revealed that the oncogenic effect of miR-18a-5p on EC cells was inhibited by THBD overexpression. We conclude that miR-18a-5p could promote the proliferation, migration, and invasion of EC cells by targeting and downregulating THBD expression, and the miR-18a-5p/THBD regulatory pathway might be a therapeutic target. The results of this study may serve as a theoretical basis for related drug development.

The association of severe anemia, red blood cell transfusion and necrotizing enterocolitis in neonates.

BACKGROUND: The relationship between severe anemia, red blood cell transfusion and Neonatal necrotizing enterocolitis (NEC) remains controversial. The purpose of this study was to determine the association of severe anemia and RBC transfusion with NEC in neonates. METHODS: The clinical characteristics of NEC were observed in 467 infants with different birth weights from January 2012 to July 2020. A 1:1 ratio case-control study was performed in very low birth weight (VLBW) infants. Severe anemia, RBC transfusion, and confounding factors, including maternal and perinatal complications, feeding, and antibiotics administration were collected in both groups. Univariate and multivariate analyses were used to investigate effects on the risk of NEC. RESULTS: The day of NEC onset and mortality were inversely associated with birth weight. In VLBW infants, adjusting for other factors, severe anemia within 72 h [OR = 2.404, P = 0.016], RBC transfusion within 24 h [OR = 4.905, P = 0.016], within 48 h [OR = 5.587, P = 0.008], and within 72 h [OR = 2.858, P = 0.011] increased the risk of NEC. CONCLUSION: Both severe anemia and RBC transfusion appears to increase the risk of NEC in VLBW infants. The early prevention and treatment of anemia, strict evaluation of the indications for transfusion and enhanced monitoring after transfusion is encouraged in the NICU.

[Clinical features of very preterm infants with prelabor rupture of membranes and predictive factors for major adverse outcomes].

OBJECTIVE: To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death. METHODS: A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours (n=107), 18 hours to < 3 days (n=111), 3 days to < 14 days (n=144), and ≥ 14 days (n=37). According to the presence or absence of EOS, the infants were divided into EOS (n=42) and non-EOS groups (n=357). According to the survival state, the infants were divided into a survival group (n=359) and a death group (n=40). Clinical features were analyzed for very preterm infants with different times of PROM. A multivariate logistic regression analysis was used to investigate the predictive factors for EOS and death in very preterm infants with PROM. RESULTS: There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM (P > 0.05). Birth weight < 1 000 g (OR=4.353, P=0.042), grade Ⅲ amniotic fluid contamination (OR=4.132, P=0.032), and grade Ⅲ-Ⅳ respiratory distress syndrome (RDS) (OR=2.528, P=0.021) were predictive factors for EOS in very preterm infants with PROM. Lower birth weights (< 1 000 g or 1 000-1 499 g; OR=11.267 and 3.456 respectively; P=0.004 and 0.050 respectively), grade Ⅲ-Ⅳ RDS (OR=5.572, P < 0.001), and neonatal sepsis (OR=2.631, P=0.012) were predictive factors for death in very preterm infants with PROM. CONCLUSIONS: Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.

Genetic deletion of Rnd3 suppresses apoptosis through NF­κB signaling in the brain.

Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase­dependent signaling pathway. The present study revealed a novel role of RND3 in the regulation of apoptosis in the brain. Using immunofluorescence and TUNEL assays, a decreased rate of brain apoptosis was observed in Rnd3­knockout mice. In addition, the function of RND3 in promoting apoptosis was determined in PC12 cells by immunoblotting assays and flow cytometry analysis in RNA interference and overexpression experiments. Furthermore, the present study demonstrated that Rnd3 and P65 protein interacted using immunoprecipitation analysis, and Rnd3 regulated apoptosis via its association with NF­κB P65. Notably, Rnd3 blocked the anti­apoptotic action of NF­κB P65 in vitro by downregulating P65. Therefore, RND3­NF­κB P65 represents a novel signaling pathway in the regulation of brain apoptosis. The present study suggested an alternative approach for the treatment of neurodegenerative diseases through regulation of apoptosis via the RND3­NF­κB P65 signaling pathway in the central nervous system.

Polysaccharides from natural resources exhibit great potential in the treatment of ulcerative colitis: A review.

The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.

Cultivated Land Change, Driving Forces and Its Impact on Landscape Pattern Changes in the Dongting Lake Basin.

Comprehending the dynamic change characteristics of land use/cover and the driving factors causing the change are prerequisites for protecting land resources. This paper analyzes changes in cultivated land, the driving factors that cause them, and their tremendous impact on landscape pattern changes in the Dongting Lake Basin. For this purpose, we used mathematical statistics, buffer analysis, trend analysis, landscape pattern index, and logistic regression model to analyze the land use data of the study area from 1980 to 2018. The results show that the cultivated land showed a decreasing trend, with the total area decreased by 4.76% (or 716.13 km2) from 1980 to 2018, and the activity of mutual transformation with other land use types decreased. The spatial distribution pattern of cultivated land and landscape shows the change characteristics gradually from Dongting Lake to the surroundings. Among the driving factors of cultivated land changes, the influence of human activities was gradually increasing, while the natural factors were decreasing. The cultivated land landscape pattern index and the overall landscape pattern index have a significant positive correlation, showing relatively consistent change trend and spatial distribution characteristics. We believe that the decrease of cultivated land area has a certain relationship with the increase of landscape fragmentation in the Dongting Lake Basin. Our research is expected to provide a reference for strengthening regional cultivated land management and rational development and utilization of regional land resources.

Engineering of α-PD-1 antibody-expressing long-lived plasma cells by CRISPR/Cas9-mediated targeted gene integration.

Long-lived plasma cells (LLPCs) are robust specialized antibody-secreting cells that mainly stay in the bone marrow and can persist a lifetime. As they can be generated by inducing the differentiation of B-lymphocytes, we investigated the possibility that human LLPCs might be engineered to express α-PD-1 monoclonal antibody to substitute recombinant α-PD-1 antitumor immunotherapy. To this end, we inserted an α-PD-1 cassette into the GAPDH locus through Cas9/sgRNA-guided specific integration in B-lymphocytes, which was mediated by an integrase-defective lentiviral vector. The edited B cells were capable of differentiating into LLPCs both in vitro and in vivo. Transcriptional profiling analysis confirmed that these cells were typical LLPCs. Importantly, these cells secreted de novo antibodies persistently, which were able to inhibit human melanoma growth via an antibody-mediated checkpoint blockade in xenograft-tumor mice. Our work suggests that the engineered LLPCs may be utilized as a vehicle to constantly produce special antibodies for long-term cellular immunotherapy to eradicate tumors and cellular reservoirs for various pathogens including human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV).

RND2 attenuates apoptosis and autophagy in glioblastoma cells by targeting the p38 MAPK signalling pathway.

BACKGROUND: Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be determined. Identifying new factors that can regulate p38 MAPK signalling is important for tumour treatment. METHODS: Flow cytometry, TUNEL assays, immunofluorescence, JC-1 assays, and western blot analyses were used to detect the apoptosis of GBM cells. The specific methods used to detect autophagy levels in GBM cells were western blot analysis, LC3B protein immunofluorescence, LC3B puncta assays and transmission electron microscopy. The functions of these critical molecules were further confirmed in vivo by intracranial xenografts in nude mice. Tumour tissue samples and clinical information were used to identify the correlation between RND2 and p62 and LC3B expression, survival time of patients, and tumour volumes in clinical patients. RESULTS: By summarizing data from the TCGA database, we found that expression of the small GTPase RND2 was significantly increased in human glioblastomas. Our study demonstrated that RND2 functions as an endogenous repressor of the p38 MAPK phosphorylation complex. RND2 physically interacted with p38 and decreased p38 phosphorylation, thereby inhibiting p38 MAPK signalling activities. The forced expression of RND2 repressed p38 MAPK signalling, which inhibited glioblastoma cell autophagy and apoptosis in vitro and induced tumour growth in the xenografted mice in vivo. By contrast, the downregulation of RND2 enhanced p38 MAPK signalling activities and promoted glioma cell autophagy and apoptosis. The inhibition of p38 phosphorylation abolished RND2 deficiency-mediated GBM cell autophagy and apoptosis. Most importantly, our study found that RND2 expression was inversely correlated with patient survival time and was positively correlated with tumour size. CONCLUSIONS: Our findings revealed a new function for RND2 in GBM cell death and offered mechanistic insights into the inhibitory effects of RND2 with regard to the regulation of p38 MAPK activation.