Application Potential of Extracellular Vesicles Derived From Mesenchymal Stem Cells in Renal Diseases.

The high prevalence and complex etiology of renal diseases already impose a heavy disease burden on patients and society. In certain kidney diseases such as acute kidney injury and chronic kidney disease, current treatments are limited to slowing rather than stabilizing or reversing disease progression. Therefore, it is crucial to study the pathological mechanisms of kidney disease and discover new therapeutic targets and effective therapeutic drugs. As cell-free therapeutic strategies are continually being developed, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have emerged as a hot topic for research in the field of renal diseases. Studies have demonstrated that MSC-EVs not only reproduce the therapeutic effects of MSCs but also localize to damaged kidney tissue. Compared to MSCs, MSC-EVs have several advantages, including ease of preservation, low immunogenicity, an inability to directly form tumors, and ease of artificial modification. Exploring the detailed mechanisms of MSC-EVs by developing standardized culture, isolation, purification, and drug delivery strategies will help facilitate their clinical application in kidney diseases. Here, we provide a comprehensive overview of studies about MSC-EVs in kidney diseases and discuss their limitations at the human nephrology level.

Metabonomics analysis of aqueous humor samples from cataract patients with branch retinal vein occlusion.

Cataract (CAT) has a very high incidence rate among the middle-aged and elderly, with most patients complicated by branch retinal vein occlusion (BRVO), a key cause of blindness. In this study, through metabolomic analysis of aqueous humor samples from CAT patients with BRVO, a total of 319 different metabolites were found, most of which belonged to the categories of carboxylic acids and derivatives, fatty acyls, and organooxygen compounds. The most typical metabolites were 3-methylhistidine and biliverdin, which were up-regulated, as well as the down-regulated beta-glycerophosphoric acid. Tricosanoic acid showed the most significant correlation with CAT+BRVO. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the most commonly related keywords for differentially expressed metabolites were biosynthesis of unsaturated fatty acids and synaptic vesicle cycle. These results can not only help to further understand the pathogenesis of CAT complicated by BRVO in clinical practice, but also provide some new therapeutic research directions.

MIR503HG Overexpression Inhibits the Malignant Behaviors of Osteosarcoma Cells by Sponging miR-103a-3p.

Osteosarcoma (OS) is the most representative primary bone tumour in children and teenagers. This study explored the regulatory effects of long noncoding RNA MIR503HG (MIR503HG) on the biological functions of OS cells, and further investigated the potential mechanism of MIR503HG function exertion by analyzing the microRNA-103a-3p (miR-103a-3p) in OS cells and tissues. The expression of MIR503HG was examined using reverse transcription-quantitative PCR. OS cell proliferation was assessed by CCK-8 assay. Transwell assay was used to evaluate the migration and invasion of OS cells. The interaction between MIR503HG and miR-103a-3p was detected using the Dual-luciferase reporter assay. Forty-six paired OS tissues were collected, and the expression and correlation of MIR503HG and miR-103a-3p were evaluated. The expression of MIR503HG were significantly decreased in both OS cells and tissues. Over-expression of MIR503HG inhibited OS cell proliferation, migration and invasion. miR-103a-3p was directly targeted by MIR503HG in OS cells, and mediated the inhibitory effects of MIR503HG on OS cell malignant behaviors. miR-103a-3p expression was upregulated in OS tissues, which was negatively correlated with MIR503HG expression levels. The expression of MIR503HG was associated with OS patients' tumor size, differentiation, distant metastasis and clinical stage. Decreased MIR503HG in OS tissues and cell lines served as a tumor suppressor by inhibiting OS cell malignant behaviors through sponging miR-103a-3p. The findings of this study may provide evidence for the development of novel therapeutic targets of OS.

Percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction for the treatment of perinephric abscess: a case series.

BACKGROUND: Drainage is indicated in many patients with a perinephric abscess (PA). Surgical drainage is associated with trauma and slow recovery, while percutaneous drainage can be ineffective in some patients. We report on 11 patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia. METHODS: This case series included 11 PA patients operated on from January 2013 to June 2020. All patients received percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction. Data, including operation time, volume of intraoperative blood loss, volume of intraoperative pus suction, time of postoperative drainage tube indwelling, time to restore normal body temperature, length of postoperative hospital stay, and intraoperative and postoperative complications, were collected. RESULTS: The age of the patients was 59 (53-69) years. Eight, six, two, and two patients had hypertension, type 2 diabetes, rheumatoid arthritis, and renal calculi, respectively. The operations were successful forall11 patients. Eight, two, and one patients required one, two, and three channels, respectively, to clear their abscess. The average operation time was 44 (30-65) min, and intraoperative blood loss was 16 (10-20) ml. The volume of intraoperative pus suction was 280 (200-400) ml, time of postoperative drainage tube indwelling was 8.2 (6-12) days, and time to restoring normal body temperature was 0.8 (0.5-2) days. The average postoperative hospital stay was 9.8 (7-14) days. No severe intraoperative or postoperative complications occurred. The postoperative follow-up time was typically 4.8 (3-8) months, and there were no recurrences. CONCLUSION: Percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction might be a feasible method for treating PA.

Clinical outcome of laparoscopic versus robot-assisted radical cystectomy for patients with bladder cancer: a retrospective study.

BACKGROUND: With the development of minimally invasive surgery technology, patients with bladder cancer are increasingly receiving laparoscopic radical cystectomy (LRC) or robotic-assisted radical cystectomy (RARC) treatment. The main purpose of this study was to compare the long-term outcomes of bladder cancer patients treated with LRC versus RARC. METHODS: A retrospective study to identify patients with clinical stage Ta/T1/Tis to T3 bladder cancer who underwent RARC or LRC has been performed. The perioperative outcome, recurrence, and overall survival (OS) of the two surgical methods were compared. RESULTS: 218 patients were identified from March 2010 to December 2019 in our department, which including 82 (38%) patients who received LRC and 136 (62%) patients who received RARC. There was no significant difference between the two groups in terms of lymph node collection, lymph node positive rate, resection margin positive rate, and postoperative pathological staging. Compared with the LRC group, patients in the RARC group had a median estimated blood loss (180 vs. 250 ml; P = 0.02) and reduced complications at 90 days postoperatively (30.8% vs. 46.3%; P = 0.01). Recurrence, all-cause death, and cancer-specific death occurred in 77 (35%), 55 (25%), and 39 (18%) patients, respectively. The 5-year OS rate was 54.63% and 54.65% in the RARC and LRC group (P > 0.05). The 5-year cancer-specific survival (CSS) rate was 73.32% and 61.55% in RARC and LRC group (P > 0.05). There was no significant difference in OS [hazard ratio (HR) 1.083, 95% confidence interval (CI) 0.626-1.874; P = 0.78], and CSS (HR 0.789, 95%CI 0.411-1.515; P = 0.61) between two groups. CONCLUSIONS: Both RARC and LRC were safe and effective with a similar long-term clinical outcomes. Moreover, RARC had significantly lower median estimated blood loss and reduced postoperative complications.

Benzoxazole Derivative K313 Induces Cell Cycle Arrest, Apoptosis and Autophagy Blockage and Suppresses mTOR/p70S6K Pathway in Nalm-6 and Daudi Cells.

Benzoxazole derivative K313 has previously been reported to possess anti-inflammatory effects in lipopolysaccharide-induced RAW264.7 macrophages. To date, there have been no related reports on the anticancer effects of K313. In this study, we found that K313 reduced the viability of human B-cell leukemia (Nalm-6) and lymphoma (Daudi) cells in a dose-dependent manner without affecting healthy peripheral blood mononuclear cells (PBMCs) and induced moderate cell cycle arrest at the G0/G1 phase. Meanwhile, K313 mediated cell apoptosis, which was accompanied by the activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). Furthermore, cells treated with K313 showed a significant decrease in mitochondrial membrane potential (MMP), which may have been caused by the caspase-8-mediated cleavage of Bid, as detected by Western blot analysis. We also found that K313 led to the downregulation of p-p70S6K protein, which plays an important role in cell survival and cell cycle progression. In addition, treatment of these cells with K313 blocked autophagic flux, as reflected in the accumulation of LC3-II and p62 protein levels in a dose- and time-dependent manner. In conclusion, K313 decreases cell viability without affecting normal healthy PBMCs, induces cell cycle arrest and apoptosis, reduces p-p70S6K protein levels, and mediates strong autophagy inhibition. Therefore, K313 and its derivatives could be developed as potential anticancer drugs or autophagy blockers in the future.

Numerical Investigation on the Thermodynamic Characteristics of a Liquid Film upon Spray Cooling Using an Air-Blast Atomization Nozzle.

This paper developed a three-dimensional model to simulate the process of atomization and liquid film formation during the air-blast spray cooling technological process. The model was solved using the discrete phase model method. Several factors including the thermodynamic characteristics of the liquid film as well as the spray quality with different spray mass flow rates under different spray heights were numerically investigated and discussed. The results show that the varied spray height has little effect on the Sauter Mean Diameter (d32) of the spray droplet, while the thermodynamic characteristics of liquid film including the liquid film height, the liquid film velocity, and the liquid film generation rate are sensitive to the change of the spray height. With the growth of spray mass flow rates, d32, the liquid film generation rate and liquid film height become larger, while the liquid film velocity with different spray mass flow rates has a similar velocity distribution, indicating that the spray mass flow rate has little effect on the liquid film velocity. The average d32 of droplet size shows a sharp drop when sprayed from the nozzle in a short period of time (<1.5 ms), then approaching smoothness, below a value of 40 µ m , the spray status tends to be stable.

Preparative Purification of Polyphenols from Aronia melanocarpa (Chokeberry) with Cellular Antioxidant and Antiproliferative Activity.

The aim of this study was the purification process of polyphenols from Aronia melanocarpa (chokeberry), and the purification parameters were optimised by adsorption and desorption tests. By comparing adsorption and desorption ability of polyphenols from chokeberry on six kinds of macroporous resin, XAD-7 resin was selected. Experiments prove that the best purification parameters of static adsorption and desorption were sample pH = 4.0 with 4 h of adsorption; and desorption solvent is 95% ethanol (pH = 7.0) with 2 h of desorption. The best dynamic parameters were 9.3 bed volume (BV) of sample loading amount at a feeding flow rate of 2 BV/h, and washing the column with 5.8 BV of water, followed by subsequent elution with an eluent volume of 5.0 mL at an elution flow rate of 2 BV/h. Next the antioxidant and antiproliferative activity of polyphenols from chokeberry, blueberries, haskap berries was studied on HepG2 human liver cancer cells. The results show that polyphenol from chokeberry has a strong antioxidant effect. Taking into account the content of polyphenols in fruit, polyphenols from chokeberry represent a very valuable natural antioxidant source with antiproliferative products.

Fragile X mental retardation protein participates in non-coding RNA pathways.

Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells. Subsequent studies showed that the Drosophila FMRP participates in piRNA pathway by interacting with Aub, Ago1 and Piwi in the maintenance of normal chromatin structures and genomic stability. More recent studies showed that FMRP is associated with lncRNA pathway, suggesting a potential role for the involvement in the clinical manifestations. In this review, we summarize the novel findings and explore the relationship between FMRP and non-coding RNA pathways, particularly the piRNA pathway, thereby providing critical insights on the molecular pathogenesis of Fragile X syndrome, and potential translational applications in clinical management of the disease.

Correction to: Robot-assisted laparoscopic reconstructed management of multiple aneurysms in renal artery primary bifurcations: a case report and literature review.

CORRECTION: After publication of this work [1] it was noticed the author - Jie Wang's name was in the wrong order. The original article was corrected. The publisher apologises for this error.

Robot-assisted laparoscopic reconstructed management of multiple aneurysms in renal artery primary bifurcations: a case report and literature review.

BACKGROUND: Renal artery aneurysm (RAA) is rare and its incidence in the general population remains elusive. There have been few reports on the repair of multiple aneurysms conducted with the Da Vinci robot-assisted surgical platform (Intuitive Surgical Inc., Sunnyvale, CA, USA), especially for those located in renal artery primary bifurcations. CASE PRESENTATION: We report our experience in the surgical management of two expanding right-sided RAAs in a 64-year-old man using a robot-assisted laparoscopic approach. Two aneurysms were located in renal artery primary bifurcations, whose diameter was 1.8 and 1.2 cm. The aneurysms were resected and the renal artery branch reconstructed by in situ arteriorrhaphy. The operation lasted for 2 h and 35 min with a warm ischemia time of 26 min and estimated blood loss of 150 ml. The hospital stay was 6 days. The computed tomography (CT) scan performed 2 months after the surgery showed resolution of the aneurysms. Additionally, split renal function indicated the preservation of right renal function in the follow-up period. CONCLUSIONS: The robot-assisted laparoscopic procedure is a safe and effective surgical technique, which may be considered as an alternative to open surgery for complex multiple RAAs in the future.

[Hypospadias induced by maternal exposure to di-n-butyl phthalate and its mechanisms in male rat offspring , , , , ,].

OBJECTIVE: To induce hypospadias in male rat offspring by maternal exposure to di-n-butyl phthalate (DBP) during late pregnancy and further investigate its mechanisms. METHODS: We randomly divided 20 pregnant rats into a DBP exposure and a control group, the former treated intragastrically with DBP while the latter with soybean oil at 750 mg per kilogram of the body weight per day from gestation days (GD) 14 to 18. On postnatal day (PND) 1, we recorded the incidence rate of hypospadias and observed the histopathological changes in the genital tubercle of the hypospadiac rats. We also measured the level of serum testosterone (T) by radioimmunoassay and determined the mRNA and protein expressions of the androgen receptor (AR), sonic hedgehog (Shh), bone morphogenetic protein 4 (Bmp4) and fibroblast growth factor 8 (Fgf8) in the genital tubercle by real-time PCR and Western blot. RESULTS: No hypospadiac male rats were found in the control group. The incidence rate of hypospadias in male offspring was 43.6% in the DBP-treatment group. Histological analysis confirmed hypospadiac malformation. The serum testosterone concentration was decreased in the hypospadiac male rats as compared with the controls (ï¼»0.49 ± 0.05ï¼½ vs ï¼»1.12 ± 0.05ï¼½ ng/ml, P <0.05). The mRNA expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle were significantly lower in the hypospadiac male rats than in the controls (AR: 0.50 ± 0.05 vs 1.00 ± 0.12, P <0.05; Shh: 0.65 ± 0.07 vs 1.00 ± 0.15, P <0.05; Bmp4: 0.42 ± 0.05 vs 1.00 ± 0.13, P <0.05; Fgf8: 0.46 ± 0.04 vs 1.00 ± 0.12, P <0.05), and so were their protein expressions (AR: 0.34 ± 0.05 vs 1.00 ± 0.09, P <0.05; Shh: 0.51 ± 0.07 vs 1.00 ± 0.12, P <0.05; Bmp4: 0.43 ± 0.05 vs 1.00 ± 0.11, P <0.05; Fgf8: 0.57 ± 0.04 vs 1.00 ± 0.13, P <0.05). CONCLUSIONS: Maternal exposure to DBP during late pregnancy can induce hypospadias in the male rat offspring. DBP affects the development of the genital tubercle by reducing the serum T concentration and expressions of AR, Shh, Bmp4 and Fgf8 in the genital tubercle, which might underlie the mechanism of DBP inducing hypospadias.

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.

This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.

Expression of Wnt5a during development of anorectal malformations in a rat model of prenatal exposure to di(n-butyl) phthalate.

Mounting evidence has indicated the crucial role of Wnt5a in the embryonic development including guts. However, the Wnt5a involvement in the process of anorectal malformations (ARMs) remains unclear. In this study, we examined the expression of Wnt5a during ARMs development in the offspring of di(n-butyl) phthalate (DBP)-treated pregnant rats. During the neonatal period, Wnt5a expression was evaluated in the terminal rectum of ARM offspring, non-ARM littermates and controls. Using real-time polymerase chain reaction (real-time PCR), western-blot analysis and immunohistochemistry approaches, we found a significant decrease of Wnt5a expression in DBP-induced ARMs rats. Collectively, our results demonstrate the aberrant expression of Wnt5a during anorectal development, which suggests that Wnt5a might be involved in DBP-induced ARMs.

Case report: Advanced modified pneumatic retinopexy for treating simultaneous bilateral rhegmatogenous retinal detachment.

Background: Simultaneous bilateral rhegmatogenous retinal detachment (RRD) is a rare and challenging condition in ophthalmology. This case report focuses on a modified pneumatic retinopexy technique, designed to improve treatment outcomes for this difficult condition. Case presentation: A 59-year-old male presented with decreased visual acuity in his right eye for one week. Examination revealed extensive retinal detachment in the right eye with multiple superior breaks and macula off, separated by approximately 3 clock hours. The left eye exhibited one quartile of retinal detachment with superior breaks and macula on. Bilateral simultaneous PR was performed for retinal repair. In the modified PR procedure, 0.7 ml of low-concentration perfluoropropane and 0.7 ml of filtered pure air were intravitreally injected into the right and left eyes, respectively. A head position maneuver was then employed to sequentially close retinal breaks, followed by laser photocoagulation once the surrounding retina reattached. Two days after gas injection, both retinas were completely reattached. Best corrected visual acuity improved to 0.6 in the right eye and 0.9 in the left eye at the 8-month follow-up. Conclusion: The innovative modified pneumatic retinopexy technique presented in this case report offers a promising new approach for effectively treating simultaneous bilateral rhegmatogenous retinal detachment.

Anomaly Detection With Representative Neighbors.

Identifying anomalies from data has attracted increasing attention in recent years due to its broad range of potential applications. Although many efforts have been made for anomaly detection, how to effectively handle high-dimensional data and how to exactly explore neighborhood information, a fundamental issue in anomaly detection, have not yet received sufficient concerns. To circumvent these challenges, in this article, we propose an effective anomaly detection method with representative neighbors for high-dimensional data. Specifically, it projects the high-dimensional data into a low-dimensional space via a sparse operation and explores representative neighbors with a self-representation learning technique. The neighborhood information is then transformed into similarity relations, making the data converge or disperse. Eventually, anomalies are discriminated by a tailored graph clustering technique, which can effectively reveal structural information of the data. Extensive experiments were conducted on ten public real-world datasets with 11 popular anomaly detection algorithms. The results show that the proposed method has encouraging and promising performance compared to the state-of-the-art anomaly detection algorithms.

Pneumatic Retinopexy Involving the Use of Intravitreal Air Injection and Laser Photocoagulation for Rhegmatogenous Retinal Detachment in Phakic Eyes.

The clinical efficacy of pneumatic retinopexy (PR) using intravitreal pure air injection and laser photocoagulation for rhegmatogenous retinal detachment (RRD) remains unknown. Thirty-nine consecutive patients with RRD (39 eyes) were included in this prospective case series. All patients underwent two-step PR surgery containing pure air intravitreal injection and laser photocoagulation retinopexy during hospitalization. The main outcomes were best-corrected visual acuity (BCVA) and primary anatomic success rates after PR treatment. The mean follow-up was 18.3 ± 9.7 months, ranging from 6 to 37 months. The primary anatomic success rate was 89.7% (35/39) after PR treatment. Final reattachment of the retina was achieved in 100% of cases. Macular epiretinal membrane was developed in two patients (5.7%) among successful PR cases during the follow-up. The mean logMAR BCVA value was significantly improved from 0.94 ± 0.69 before surgery to 0.39 ± 0.41 after surgery. The average central retinal thickness was significantly thinner in the RRD eyes of macula-off patients (206.8 ± 56.13 µm) when compared with the fellow eyes (234.6 ± 48.4 µm) at the last follow-up (p = 0.005). This study concluded that an inpatient PR procedure with pure air injection and laser photocoagulation is a safe and effective approach to treating patients with RRD, who may achieve a high single-operation success rate and good visual acuity recovery.

Molecular mechanism of di-n-butyl phthalate promotion of bladder cancer development.

PURPOSE: To determine whether di-n-butyl phthalate (DBP) promotes the occurrence of bladder cancer (BCa) and explore the action of DBP acts on BCa cells at the cellular and molecular levels. METHODS: MTT and Transwell assays were used to investigate the tumorigenic actions of DBP on BCa cells. Second-generation sequencing was used to identify differences in gene expression before and after DBP treatment. Differential gene expression was verified by q-PCR and analyzed using bioinformatics. Cells were transfected to overexpress genes of interest and proliferation and migration were measured using MTT and Transwell assays, respectively. RESULTS: DBP treatment stimulated both proliferation and invasion in BCa cells. Second-generation sequencing identified differences in the expression of FOSB, JUND, ATP6V1C2, and RHOQ before and after DBP treatment. FOSB expression was confirmed by q-PCR and bioinformatic analyses. FOSB overexpression increased both proliferation and invasion in BCa cells. CONCLUSION: DBP promoted BCa tumorigenesis by inducing changes in gene expression.

Anticancer activity of Germacrone terpenoid in human osteosarcoma cells is mediated via autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions and cell migration inhibition.

Germacrone a sesquiterpene is a potential pharmacological agent with important medicinal applications. It is a potential anticancer agent and has been reported for anticancer activity against hepatoma cells and breast cancer cells, additionally, it has also shown anti-inflammatory, antioxidant, and antifungal activity. Therefore, this study was designed to testify anticancer activity of germacrone terpenoid in human osteosarcoma cells along with studying its effects of autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions and cell migration inhibition. Cell proliferation rate was examined by MTT assay and phase contrast inverted microscopy was performed for morphological analysis. Further, flowcytometry was implemented to examine different cell cycle phases. Transwell assay was executed for the monitoring of cell migratory tendency of osteosarcoma cells. Finally, the levels of pro-autophagic and cell cycle allied proteins were checked by Western blot analysis. MTT assay results designated potential inhibition of osteosarcoma cell viability by germacrone drug in a dose and time-reliant manner. Further, phase contrast inverted microscopy depicted significant morphological changes in osteosarcoma cells after germacrone exposure, which were indicative of autophagic cell death. Next, transmission electron microscopy evaluated the formation of autophagic vesicles which are the trademark for autophagy. The autophagy allied protein expressions were observed through Western blotting indicating enhanced levels of pro-autophagic proteins (Becalin-1, LC3-I and -II). Hence, it may be depicted that the anti-proliferation effects of germacrone may be of autophagy inducing potential. Next, flowcytometric analysis revealed the cell cycle inhibitory effects of germacrone in osteosarcoma cells and the results indicated cell cycle arrest at S-phase. Cell cycle allied protein levels indicated declination in their expressions after germacrone exposure. Finally, transwell assay specified inhibitory effects on cell migration of osteosarcoma cells by germacrone in a dose-reliant manner. In conclusion, the results of the present investigation specified that germacrone drug is a potential anticancer agent against osteosarcoma cells. The anticancer effects were found to be mediated via autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions, and cell migration inhibition.

Comprehensive analysis of aerobic glycolysis-related genes for prognosis, immune features and drug treatment strategy in prostate cancer.

Background: The dysregulated expression of aerobic glycolysis-related genes is closely related to prostate cancer progression and metastasis. However, reliable prognostic signatures based on aerobic glycolysis have not been well established. Methods: We screened aerobic glycolysis-related gene modules by weighted gene co-expression network analysis (WGCNA) and established the aerobic glycolysis-related prognostic risk score (AGRS) by univariate Cox and lasso-Cox. In addition, enriched pathways, genomic mutation, and tumor-infiltrating immune cells were analyzed in AGRS subgroups and compared to each other. We also assessed chemotherapeutic drug sensitivity and immunotherapy response among two subgroups. Results: An aerobic glycolysis-related 14-gene prognostic model has been established. This model has good predictive prognostic performance both in the training dataset and in two independent validation datasets. Higher AGRS group patients had better immunotherapy response. Different AGRS patients were also associated with sensitivity of multiple prostate cancer chemotherapeutic drugs. We also predicted eight aerobic glycolysis-related small-molecule drugs by differentially expressed genes. Conclusion: In summary, the aerobic glycolysis-derived signatures are promising biomarkers to predict clinical outcomes and therapeutic responses in prostate cancer.