Cluster-Based Strategy for Maximizing the Sum-Rate of a Distributed Reconfigurable Intelligent Surface (RIS)-Assisted Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) System.

This article proposes a distributed intelligent Coordinated Multi-Point Non-Orthogonal Multiple-Access (CoMP-NOMA) collaborative transmission model with the assistance of reconfigurable intelligent surfaces (RISs) to address the issues of poor communication quality, low fairness, and high system power consumption for edge users in multi-cellular networks. By analyzing the interaction mechanisms and influencing factors among RIS signal enhancement, NOMA user scheduling, and multi-point collaborative transmission, the model establishes RIS-enhanced edge user grouping and coordinates NOMA user clusters based on this. In the multi-cell RIS-assisted JT-CoMP NOMA downlink transmission, joint optimization of the power allocation (PA), user clustering (UC), and RIS phase-shift matrix design (PS) poses a challenging Mixed-Integer Non-Linear Programming (MINLP) problem. The original problem is decomposed by optimizing the formulas into joint sub-problems of PA, UC, and PA and PS, and solved using an alternating optimization approach. Simulation results demonstrate that the proposed scheme effectively reduces the system's power consumption while significantly improving the system's throughput and rates.

Establishment of 11-dehydro-thromboxane B2 time-resolved immunoassay and application in membranous nephropathy.

BACKGROUND: 11-Dehydro-thromboxane B2 (11-dehydro-TXB2) is the final stable metabolite of thromboxane A2 (TXA2) and is involved in thrombus formation. Patients with membranous nephropathy (MN) are prone to thromboembolism events. METHODS: Time-resolved fluorescence immunoassay (TRFIA) for 11-dehydro-TXB2 was established by indirect competitive method. The coated 11-dehydro-TXB2-BSA conjugate was used to bind the 11-dehydro-TXB2 antibody competitively to the 11-dehydro-TXB2 antigen in the samples, followed by Eu3+-labeled goat anti-mouse IgG antibody, to detect 11-dehydro-TXB2. This study measured 11-dehydro-TXB2 concentrations in serum samples from healthy individuals and patients with MN. RESULTS: The linear range of TRFIA was 16.38-2000 pg/mL, the sensitivity was 4.70 pg/mL, the average coefficients of variation from intra-assay and inter-assay were 3.50% and 4.95%, respectively, and the recovery was 99.38%. The serum level of 11-dehydro-TXB2 in patients with MN was significantly higher than that in healthy subjects (P < 0.05). The serum 11-dehydro-TXB2 concentration detected by TRFIA was highly consistent with that by ELISA (ρ = 0.900). DISCUSSION: This study successfully established a new highly sensitive method for the detection of 11-dehydro-TXB2 in serum. 11-Dehydro-TXB2 has great potential in evaluating the risk of thromboembolic events in patients with MN and is expected to be applied to other thromboembolic-related diseases.

Study on Quality Control of Compound Anoectochilus roxburghii (Wall.) Lindl. by Liquid Chromatography-Tandem Mass Spectrometry.

Compound Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) oral liquid (CAROL) is a hospital preparation of A. roxburghii and Ganoderma lucidum (G. lucidum), which have hepatoprotective effects. Eight active components (five nucleosides/nucleobases and three triterpenoid acids) in CAROL, A. roxburghii, and G. lucidum were simultaneously detected by high-performance liquid chromatography−tandem mass spectrometry (LC−MS/MS). The multiple reaction monitoring (MRM) mode was applied for the detection of analytes. These eight compounds were separated well within 12 min and quantified using the internal standard working curve method. The method showed good linearity (R2 > 0.9935) and high sensitivity (limit of detection = 0.29 ng/mL). The analyte recovery ranged from 85.07% to 97.50% (relative standard deviation < 3.31%). The content of the target analytes in four batches of CAROL, and the raw materials of G. lucidum and A. roxburghii from the five regions was determined using this method. The contents of guanosine and ganoderic acid A in four batches of oral liquid were high and stabilized and could be recommended as quality markers (Q-marker) for CAROL. Simultaneous qualitative and quantitative analysis of nucleosides and triterpenoid acids in CAROL, A. roxburghii, and G. lucidum by LC−MS/MS based on the MRM model was reported for the first time. The proposed method provides a sensitive, rapid, and reliable approach for the quality control of Chinese medicinal products.

The protective role of protocatechuic acid against chemically induced liver fibrosis in vitro and in vivo.

Liver fibrosis is the result of long-term liver injury and has a high incidence worldwide. Protocatechuic acid (PCA) is ubiquitous in vegetables, nuts, brown rice and herbal medicines, which is reported to possess anti-asthmatic, anti-cancer, and anti-oxidation properties. Our research aimed to investigate the effect of PCA on liver fibrosis. In vitro, TNF-α-induced hepatic stellate cell (HSC) model was used to assess the anti-fibrosis effects of PCA. In vivo, mice were treated with thioacetamide (TAA) to develop liver fibrosis. Body weight, organ index, histological changes, and proteins alteration of factors associated with TGF-ß signaling pathway were used to assess the anti-fibrosis effects of PCA. Our results showed that PCA not only inhibited cell viability in TNF-α activated HSC-T6 cells in vitro, but also efficiently mitigated TAA-induced liver damage and fibrosis in vivo. Further experiments indicated that PCA played a protective role in liver fibrosis through regulation of the TGF-ß signaling pathway downregulating the protein expression of p-Smad2, p-ERK, c-Jun. In summary, our findings provide a pharmacological justification for the clinical application of PCA in preventing or treating liver fibrosis.

Upregulation of DKK3 by miR-483-3p plays an important role in the chemoprevention of colorectal cancer mediated by black raspberry anthocyanins.

It is reported that black raspberry (BRB) anthocyanins could act as a potential chemopreventive agent for colorectal cancer (CRC). However, the underlying mechanism by which BRB anthocyanins inhibits the carcinogenesis of CRC cells has not been elucidated. The abnormal expression of microRNAs (miRNAs) that target important tumor suppressor genes is usually associated with CRC development. In this study, we explored whether BRB anthocyanins could affect the expression of certain miRNAs in an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced CRC mouse model and human CRC cell lines. miRNA microarray analysis was used to determine the differences in miRNA expression between AOM/DSS-induced mice fed with a diet supplemented without or with BRB anthocyanins. The expression of one particular miRNA, miR-483-3p, was found to decrease dramatically in AOM/DSS-induced mice that were fed with a diet supplemented with BRB anthocyanins. Subsequent quantitative real-time polymerase chain reaction and Western blot analyses showed that the reduced expression of miR-483-3p was accompanied by an increased expression of Dickkopf 3 (DKK3), a potential target of miR-483-3p as predicted by bioinformatic analysis. The protein and messenger RNA levels of DKK3 were significantly upregulated when the miR-483-3p level was reduced by a miR-483-3p-specific inhibitor, suggesting that DKK3 might be the target gene of miR-483-3p. In addition, the downstream factors of the DKK3 signaling pathway, which included Wnt/ß-catenin, also played a role in the miR-483-3p-mediated anticancer effect of BRB anthocyanins. Thus, miR-483-3p might be a potential target in BRB anthocyanin-mediated prevention of CRC.

Evaluation of anemia, malnutrition, mineral, and bone disorder for maintenance hemodialysis patients based on bioelectrical impedance vector analysis (BIVA).

BACKGROUND: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined. METHODS: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed. RESULTS: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes. CONCLUSIONS: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.

Up-regulation of miR-24-1-5p is involved in the chemoprevention of colorectal cancer by black raspberry anthocyanins.

As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed ß-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target ß-catenin and trigger a negative regulatory loop for ß-catenin and its downstream target genes. ß-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of ß-catenin, and this may provide a novel chemopreventive and therapeutic strategy for ß-catenin signalling-driven colorectal cancer.

Phospholipase A2 Receptor Antibody IgG4 Subclass Improves Sensitivity and Specificity in the Diagnosis of Idiopathic Membranous Nephropathy.

AIMS: The aim of this study was to develop a new method for detecting anti-phospholipase A2 receptor-IgG4 to improve the sensitivity and specificity in the diagnosis of idiopathic membranous nephropathy (IMN). METHODS: A highly sensitive quantitative assay was developed for the detection of serum anti-phospholipase A2 receptor-IgG4 with europium chelation by time-resolved fluoroimmunoassay (TRFIA), and a mouse anti-human IgG4 tracer was prepared using europium chelation for detection. The specificity and sensitivity of anti-phospholipase A2 receptor-IgG4 in the diagnosis of IMN were further assessed in patients with different kidney diseases. RESULTS: The detection limit of anti-PLA2R-IgG4 was 0.69 ng/mL. The measurement range of anti-PLA2R-IgG4 TRFIA was 0.69-2,500 ng/mL. Mean serum anti-PLA2R-IgG4 was 21.27 ± 15.15 ng/mL in 45 healthy volunteers, 31.08 ± 18.17 ng/mL in 29 IgA nephropathy patients, 49.10 ± 34.32 ng/mL in 8 lupus nephropathy patients, and 10,324.11 ± 17,030.40 ng/mL in 30 IMN patients. The anti-PLA2R-IgG4 cutoff concentration was >161.2 ng/mL with the sensitivity of 90.0% and specificity of 100% in the diagnosis of IMN. However, the cutoff for other kidney diseases was lower than 161.2 ng/mL. CONCLUSION: The serum anti-phospholipase A2 receptor IgG4 detected with the method developed in this study has higher sensitivity and higher specificity than total IgG in the diagnosis of IMN.

Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma.

BACKGROUND: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of the intraocular disease is usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion of the choroid, sclera and optic nerve or more broadly via the ocular vasculature. Metastatic Rb patients have very high mortality rates. While current therapy for Rb is directed toward blocking tumor cell division and tumor growth, there are no specific treatments targeted to block Rb metastasis. Two such targets are matrix metalloproteinases-2 and -9 (MMP-2, -9), which degrade extracellular matrix as a prerequisite for cellular invasion and have been shown to be involved in other types of cancer metastasis. Cancer Clinical Trials with an anti-MMP-9 therapeutic antibody were recently initiated, prompting us to investigate the role of MMP-2, -9 in Rb metastasis. METHODS: We compare MMP-2, -9 activity in two well-studied Rb cell lines: Y79, which exhibits high metastatic potential and Weri-1, which has low metastatic potential. The effects of inhibitors of MMP-2 (ARP100) and MMP-9 (AG-L-66085) on migration, angiogenesis, and production of immunomodulatory cytokines were determined in both cell lines using qPCR, and ELISA. Cellular migration and potential for invasion were evaluated by the classic wound-healing assay and a Boyden Chamber assay. RESULTS: Our results showed that both inhibitors had differential effects on the two cell lines, significantly reducing migration in the metastatic Y79 cell line and greatly affecting the viability of Weri-1 cells. The MMP-9 inhibitor (MMP9I) AG-L-66085, diminished the Y79 angiogenic response. In Weri-1 cells, VEGF was significantly reduced and cell viability was decreased by both MMP-2 and MMP-9 inhibitors. Furthermore, inhibition of MMP-2 significantly reduced secretion of TGF-ß1 in both Rb models. CONCLUSIONS: Collectively, our data indicates MMP-2 and MMP-9 drive metastatic pathways, including migration, viability and secretion of angiogenic factors in Rb cells. These two subtypes of matrix metalloproteinases represent new potential candidates for targeted anti-metastatic therapy for Rb.

Oncogenic activin C interacts with decorin in colorectal cancer in vivo and in vitro.

Activin C is a member of the transforming growth factor-ß (TGF-ß) superfamily with various biological activities. Decorin is a member of the small leucine-rich proteoglycan family, which can bind to TGF-ß and modulate TGF-ß-mediated signaling. In the decorin-deficient mouse model, we found that the expression of activin C was remarkably increased in the intestine of Dcn-/- mice compared to the expression of activin C in the intestine of Dcn+/+ mice. Addition of activin C protein to colorectal cancer cells or over-expression of activin C in these cells stimulated cell growth, migration, and invasion in vitro. Enhanced AP-1 expression in colorectal cancer cells was found to be associated with the oncoprotein-like effects of activin C through the JNK/AP-1 pathway, and not the Smad signaling pathway. However, these effects were abolished when decorin expression was restored by transfecting the cells with a decorin-expressing plasmid or by reducing the expression of activin C via interfering RNA. Further analysis demonstrated that decorin could directly bind to and accelerate the degradation of activin C. In conclusion, our data provided the first evidence demonstrating the oncogenic role of activin C in intestinal tumorigenesis of decorin-deficient mice and colorectal cancer cells. © 2015 Wiley Periodicals, Inc.

Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina.

Vascular endothelial cell growth factor (VEGF) is increased in diabetic macular edema. Compound 49b, a novel ß-adrenergic receptor agonist, is protective in a type 1 diabetic rat model. We questioned whether Compound 49b could decrease VEGF levels, suggesting that Compound 49b may be effective against edema. Two-month diabetic rats received topical Compound 49b for 7 days only and/or insulin-like growth factor binding protein 3 (IGFBP-3) siRNA. We also measured endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)ζ and PKCδ phosphorylation. Retinal endothelial cells (RECs) cultured in high glucose were treated with Compound 49b and IGFBP-3 siRNA for evaluation of the same signaling pathways. Compound 49b significantly decreased VEGF through increased IGFBP-3 in the diabetic retina. Compound 49b also reduced eNOS, PKCζ and PKCδ phosphorylation in the diabetic retina and REC. Compound 49b regulated a number of proteins involved in REC barrier properties.

IGFBP-3 reduces eNOS and PKCzeta phosphorylation, leading to lowered VEGF levels.

PURPOSE: In models of diabetic retinopathy, insulin-like growth factor binding protein-3 (IGFBP-3) is protective to the retina, especially retinal microvascular endothelial cells (RECs), but the underlying mechanisms are unclear. For this study, we hypothesized that IGFBP-3 may reduce vascular endothelial growth factor (VEGF) levels through reduced endothelial nitric oxide synthase (eNOS) activity, which may be protective against macular edema. METHODS: To test this hypothesis, we grew primary human retinal endothelial cells in normal glucose (5 mM) or high glucose (25 mM) for three days, treated with IGFBP-3 NB plasmid (a plasmid of IGFBP-3 that cannot bind IGF-1), followed by western blotting for eNOS, protein kinase C zeta (PKCzeta), and VEGF. Additionally, we treated some cells with recombinant eNOS or PKCzeta, after IGFBP-3 NB plasmid transfection to validate that these pathways regulate VEGF levels. Immunoprecipitation experiments were done with the eNOS antibody, followed by western blotting for PKCzeta, to determine if eNOS and PKCzeta interact directly. RESULTS: Our results suggest that 1) IGFBP-3 inhibits the endothelial nitric oxide synthase (eNOS) and protein kinase C zeta (PKCzeta) pathway, which in turn inhibits VEGF production, and 2) that eNOS plays a role in activating PKCzeta to increase VEGF levels in diabetic retinopathy. CONCLUSIONS: In conclusion, IGFBP-3 may be a novel treatment for macular edema through the inhibition of eNOS and PKCzeta activation, leading to reduced VEGF levels.

Etanercept restores normal insulin signal transduction in ß2-adrenergic receptor knockout mice.

BACKGROUND: Inhibition of TNFα protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFα induces deleterious retinal changes is not known. Previously, we have shown that TNFα can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Müller cells. Additionally, ß2-adrenergic receptor knockout mice (ß2KO) have increased TNFα levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFα in ß2KO mice would increase normal insulin signaling, leading to improved retinal function. METHODS: C57BL6 or ß2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3× a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFα, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins. RESULTS: Etanercept significantly reduced TNFα levels in ß2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in ß2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated ß2KO mice. Etanercept improved ERG amplitudes in ß2KO mice. CONCLUSIONS: Inhibition of TNFα by etanercept protects the retina likely through reduced TNFα-mediated insulin resistance, leading to reduced apoptosis.

ß1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo.

PURPOSE: Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of ß2-adrenergic receptor signaling. METHODS: Using retinas from 3-month-old ß2-adrenergic receptor-deficient mice, we treated mice with our novel ß1-/ß2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on ß1-adrenergic receptors due to the absence of ß2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for ß1- and ß2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-α, SOCS3, IRS-1(Ser307), and IR(Tyr960). Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. RESULTS: A 2-month treatment of ß2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel ß1- and ß2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-α and SOCS3) observed in untreated ß2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating ß1-adrenergic receptors on retinal endothelial cells or Müller cells can compensate for the loss of ß2-adrenergic receptor signaling on Müller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. CONCLUSIONS: Since our previous studies with ß1-adrenergic receptor knockout mice confirmed that the reverse also occurs (ß2-adrenergic receptor stimulation can compensate for the loss of ß1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance-based retinal cell apoptosis.

IGFBP-3 inhibits TNF-α production and TNFR-2 signaling to protect against retinal endothelial cell apoptosis.

In models of diabetic retinopathy, insulin-like growth factor binding protein-3 (IGFBP-3) protects against tumor necrosis factors-alpha (TNF-α)-mediated apoptosis of retinal microvascular endothelial cells (REC), but the underlying mechanisms are unclear. Our current findings suggest that at least two discrete but complimentary pathways contribute to the protective effects of IGFBP-3; 1) IGFBP-3 directly activates the c-Jun kinase/tissue inhibitor of metalloproteinase-3/TNF-α converting enzyme (c-Jun/TIMP-3/TACE), pathway, which in turn inhibits TNF-α production; 2) IGFBP-3 acts through the IGFBP-3 receptor, low-density lipoprotein receptor-related protein 1 (LRP1), to inhibit signaling of TNF-α receptor 2 (TNFR2). Combined, these two IGFBP-3 pathways substantially reduce REC apoptosis and offer potential targets for the treatment of diabetic retinopathy.

Comparing efficacy and safety of mirabegron, tamsulosin, and solifenacin in ureteral stent-related symptoms: outcomes from a network meta-analysis.

Background: Although ureteral stents are a well-established and commonly used method for renal drainage, the ureteral stent-related symptoms (SRSs) they cause in patients cannot be ignored. It is currently unclear whether mirabegron has a place in the treatment of SRSs. Our study aims to systematically evaluate the efficacy and safety of mirabegron in treating SRSs in adult patients. Methods: Through a systematical search of multiple scientific databases before August 2023, we performed a systematic review and meta-analysis of the primary outcomes of interest according to the PRISMA. Analysis was performed under multivariate random-effects network models and effects of drugs was ranked with surface under the cumulative ranking curves (SUCRA) probabilities. Results: Sixteen studies involving 2,002 patients were included. All regimens (including mirabegron, solifenacin, and tamsulosin) were significantly better than placebo in urinary symptoms. Solifenacin was associated with more adverse drug events than mirabegron and tamsulosin. The SUCRA values showed that mirabegron was the best in the outcomes of body pain (71.5%), sexual matters (76.4%), and adverse events (70.5%). Solifenacin was the best in the outcomes of urinary symptoms (73.1%), general health (81.0%), and work performance (85.1%). Tamsulosin had the lowest rate of all outcomes. Conclusions: Compared with traditional drugs for relieving SRSs, mirabegron performs best in terms of alleviating body pain, sexual matters, and adverse events, with little difference in urinary symptoms and general health. Further high-quality prospective double-blinded randomized controlled trials (RCTs) are required to provide sufficient evidence supporting our observations.

Cancer­associated fibroblasts under therapy­induced senescence in the tumor microenvironment (Review).

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

Effects of high-intensity intermittent exercise on glucose and lipid metabolism in type 2 diabetes patients: a systematic review and meta-analysis.

Objective: To evaluate the effects of high-intensity interval training (HIIT) on glycolipid metabolism among type 2 diabetes patients. Methods: HIIT is consistent with an exercise program (65%-90%VO2max or 75%-95% HRmax; exercise cycle≥2 weeks; frequency ≥ 2 times/week). A meta-analysis was conducted utilizing the random effects model to synthesize the data. Results: A total of 22 RCT studies with 1034 diabetic patients were included. Compared to moderate-intensity aerobic exercise or conventional controls, HIIT yields noteworthy effects on FBG (MD: -0.55; 95% CI: -0.85- -0.25, Hedges' g =0.98), 2h-PG (MD: -0.36; 95% CI: -0.57- -0.14, Hedges' g =1.05), FINS (MD: -0.41; 95% CI: -0.79- -0.03, Hedges' g =1.07), HbA1c (MD: -0.60; 95% CI: -0.84- -0.36, Hedges' g =2.69), TC (MD: -0.58; 95% CI: -0.80- -0.36, Hedges' g =2.36), TG (MD: -0.50; 95% CI: -0.86- -0.14, Hedges' g =1.50), HDL (MD: 0.62; 95% CI: 0.29-0.95, Hedges' g =1.19) and LDL (MD: -0.31; 95% CI: -0.56- -0.08, Hedges' g =0.91), all of the above p<0.01. Conclusions: HIIT has been shown to improve glucose and lipid metabolism in patients with type 2 diabetes, especially in HbA1c, TC, TG, and HDL. For patients between the ages of 40 and 60 with less than 5 years of disease, exercise programs of moderate to longer duration or moderate to high intensity will produce more favorable results.

Regulation of retinal endothelial cell apoptosis through activation of the IGFBP-3 receptor.

The goal of this study was to investigate whether insulin-like growth factor binding protein-3 receptor (IGFBP-3 receptor) is required for IGFBP-3 to inhibit retinal endothelial cell (REC) apoptosis. REC were grown in normal glucose (5 mM) or high glucose medium (25 mM) for 3 days. Once cells reached confluence, they were transfected with an endothelial- specific IGFBP-3 plasmid DNA (non-IGF binding; IGFBP-3 NB) at 1 µg/ml for 24 h. Cell proteins were extracted and analyzed for IGFBP-3 receptor expression by Western blotting or use in coimmunoprecipitation or co-localization experiments for detection of IGFBP-3 and IGFBP-3 receptor binding. REC were also transfected with or without IGFBP-3 receptor siRNA before IGFBP-3NB plasmid DNA transfection. Cell lysates were processed for a cell death ELISA, a cleaved caspase 3 ELISA, and Western blotting to measure key pro- and anti-apoptotic markers: Bcl-xL, Bax, Cytochrome C and Akt. The IGFBP-3 receptor is present on REC. Overexpression of IGFBP-3 in REC significantly increased protein levels of IGFBP-3 receptor (p < 0.05). Significant increases in cell death were found in cells transfected with IGFBP-3 receptor siRNA versus not treated samples (p < 0.05). Data suggest that IGFBP-3 inhibits retinal endothelial cell death through activation of an IGFBP-3 receptor in a hyperglycemic environment. This is the first demonstration of the involvement of IGFBP-3 receptor in inhibition of REC cell death. Future studies will investigate the mechanism by which IGFBP-3 receptor may inhibit retinal endothelial cell death.