Secondary bladder stone caused by delayed penetration of the bladder by a pubic fracture: A case report and literature review.

Pelvic fractures sometimes lead to injuries of the urinary bladder, which commonly present as gross hematuria, dysuria and lower abdominal pain. As a type of urinary stone, bladder stones are usually secondary to lower urinary tract obstruction, such as benign prostatic hyperplasia, urethral stricture, and neurogenic bladder. The present case report examines an unusual case of a delayed pubic fracture penetrating the bladder, which caused a secondary bladder stone. A 53-year-old man was first hospitalized at The Second Hospital of Jiaxing (Jiaxing, China) in January 2020 because of trauma-induced bleeding in the scalp and abdominal pain. The patient underwent abdominal exploration and partial bowel resection, and his condition stabilized after surgery. After discharge, the patient had regular outpatient check-ups every 2-3 weeks. However, after 3 months, in April 2020, the patient was readmitted to the hospital because of frequent urination, an urgent need for urination and dysuria. Abdominal computed tomography imaging and cystoscopy revealed a pubic fracture that had penetrated the bladder wall, accompanied by a bladder stone. Subsequently, cystolithotomy was performed, which provided significant relief of symptoms once the catheter was removed after 2 weeks. Since then, the patient has been followed up until January 2023 and had remained asymptomatic. Bladder stones caused by necrotic bone fragmentation are rare. Bladder injuries resulting from pelvic fractures can have delayed onset; therefore, clinicians should be aware of the possibility of urogenital injury in such patients. It is crucial for clinicians to comprehend the potential mechanisms involved, analyze the clinical data of patients, closely monitor their condition and implement appropriate treatment measures when necessary.

Citrus fruit intake and incidence of renal cell carcinoma: A meta-analysis of observational studies.

Observational studies on the association between citrus fruit intake and risk of renal cell carcinoma (RCC) have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis. PubMed and Embase databases search was conducted including relevant studies published up to January, 2020. We included epidemiological studies that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for the association between citrus fruit intake and RCC risk. A total of eight epidemiological studies consisting of five cohort and three case-control studies were included. The overall analysis showed a significantly reduced risk of RCC for high intake of citrus fruit (OR = 0.84, 95% CI 0.73-0.95). No heterogeneity was detected among the included studies (p = 0.497 for heterogeneity; I2 = 0). There was no significant publication bias by Begg's test (p = 0.266) or Egger's test (P = 0.578). A statistically significant association between citrus fruit intake and RCC was observed in case-control studies (OR = 0.84, 95% CI 0.71-0.98), while no association was observed in cohort studies (OR = 0.84, 95% CI 0.64-1.05). In addition, the dose-response analysis indicated that the RCC risk reduced by 13% (95%CI 1.0%-27%, p = 0.04 for heterogeneity) for each 100 grams per day increment of citrus fruit intake. In summary, our findings suggest an inverse association between citrus fruit intake and RCC incidence.

Prostate-specific antigen reduction after capecitabine plus oxaliplatin chemotherapy: A case report.

BACKGROUND: Prostate cancer (PC) is currently the most common malignant tumor of the genitourinary system in men. Radical prostatectomy (RP) is recommended for the treatment of patients with localized PC. Adjuvant hormonal therapy (AHT) can be administered postoperatively in patients with high-risk or locally advanced PC. Chemotherapy is a vital remedy for castration-resistant prostate cancer (CRPC), and may also benefit patients with PC who have not progressed to CRPC. CASE SUMMARY: A 68-year-old male was admitted to our hospital because of urinary irritation and dysuria with increased prostate-specific antigen (PSA) levels. After detailed examination, he was diagnosed with PC and treated with laparoscopic RP on August 3, 2020. AHT using androgen deprivation therapy (ADT) was performed postoperatively because of the positive surgical margin, extracapsular extension, and neural invasion but lasted only 6 mo. Unfortunately, he was diagnosed with rectal cancer about half a year after self-cessation of AHT, and was then treated with laparoscopic radical rectal resection and adjuvant chemotherapy using the capecitabine plus oxaliplatin (CapeOx) regimen. During the entire treatment process, the patient's PSA level first declined significantly after treatment of PC with laparoscopic RP and ADT, then rebounded because of self-cessation of ADT, and finally decreased again after CapeOx chemotherapy. CONCLUSION: CapeOx chemotherapy can reduce PSA levels in patients with high-risk locally advanced PC, indicating that CapeOx may be an alternative chemotherapy regimen for PC.

Monolayer NbSe2 Favors Ultralow Friction and Super Wear Resistance.

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

Macroscale Superlubricity with Ultralow Wear and Ultrashort Running-In Period (∼1 s) through Phytic Acid-Based Complex Green Liquid Lubricants.

Liquid superlubricity has attracted much attention, due to its ability to significantly reduce friction on the macroscale. However, the severe wear caused by the long running-in period is still one of the bottlenecks restricting the practical application of liquid superlubricating materials. In this work, the obtained polyethylene glycol-phytic acid (PEG-PA) composite liquid lubricants showed outstanding superlubricating properties (µ ≈ 0.006) for Si3N4/glass friction pairs with an ultrashort running-in period (∼1 s) under high Hertzian contact pressure of ∼758 MPa. More importantly, even after up to 12 h (∼700 m of travel), only about 100 nm deep wear scars were found on the surface of the glass sheet (wear rate = 2.51× 10-9 mm3 N-1 m-1). From the molecular point of view, the water molecules anchored between the two friction pairs have extremely low shear force during the friction process, and the strong hydrogen bond interaction between PEG and PA greatly improves the bearing capacity of the lubricant. This work addresses the challenge of liquid superlubricant simultaneously exhibiting low shear force and high load-carrying capacity and makes it possible to obtain liquid superlubrication performance with an extremely short running-in time.

Lower Platelet-to-Lymphocyte Ratio Was Associated with Poor Prognosis for Newborn Patients in NICU.

Background: Platelet-to-lymphocyte ratio (PLR) is reported to be related to the outcome of intensive care unit (ICU) patients. However, little is known about their associations with prognosis in newborn patients in neonatal ICU (NICU). The aim of the present study was to investigate the prognostic significance of the PLR for newborn patients in the NICU. Methods: Data on newborn patients in the NICU were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. The initial PLR value of blood examinations within 24 h was analyzed. Spearman's correlation was used to analyze the association of PLR with the length of hospital and ICU stays. The chi-square test was used to analyze the association of PLR with mortality rate. Multivariable logistic regression was used to determine whether the PLR was an independent prognostic factor of mortality. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive ability of models combining PLR with other variables. Results: In total, 5240 patients were enrolled. PLR was negatively associated with length of hospital stay and ICU stay (hospital stay: ρ = −0.416, p < 0.0001; ICU stay: ρ = −0.442, p < 0.0001). PLR was significantly correlated with hospital mortality (p < 0.0001). Lower PLR was associated with higher hospital mortality (OR = 0.85, 95% CI = 0.75−0.95, p = 0.005) and 90-day mortality (OR = 0.85, 95% CI = 0.76−0.96, p = 0.010). The prognostic predictive ability of models combining PLR with other variables for hospital mortality was good (AUC for Model 1 = 0.804, 95% CI = 0.73−0.88, p < 0.0001; AUC for Model 2 = 0.964, 95% CI = 0.95−0.98, p < 0.0001). Conclusion: PLR is a novel independent risk factor for newborn patients in the NICU.

Long noncoding RNA-LINC00478 promotes the progression of clear cell renal cell carcinoma through PBX3.

Long noncoding RNAs play an important regulatory role in the development and progression of tumors. Our study found that LINC00478 was upregulated in clear cell renal cell carcinoma (ccRCC), so we made an in-depth exploration into its mechanism. In Caki-2 cells, we established the oe-LINC00478 cell line overexpressing LINC00478, and established underexpressing sh-LINC00478 cell line by short hairpin RNA silencing. The abilities of oe-LINC00478 cell invasion and metastasis were significantly enhanced, and the cell proliferative potential was also improved. The cellular expressions of PBX3, CDCA8, and CDK2 were upregulated, while in the sh-LINC00478 cells, the proliferative potential and metastatic and invasive abilities were weakened. Similarly, we established the PBX3-overexpressing oe-PBX3 cell line and the PBX3-underexpressing sh-PBX3 cell line, finding that the PBX3 overexpression enhanced the metastatic and invasive abilities of Caki-2 cells. When we overexpressed LINC00478 in PBX3-knockout Caki-2-PBX3- / - cells, no significant changes were noted in the metastatic or invasive ability. Through RNA pull-down and RNA-binding protein immunoprecipitation assays, we found that LINC00478 could facilitate the transcription-translation processes of PBX3 by binding to it, thus further promoting the expression of downstream cyclins to exert its action. In animal experimentation, the oe-LINC00478 and sh-LINC00478 Caki-2 cells were separately seeded, revealing that the tumor volume was significantly larger in the oe-LINC00478 group than in the sh-LINC00478 group. This study finds that by promoting the PBX3 transcription, LINC00478 can further regulate the expressions of downstream cyclins, thereby facilitating the metastasis and invasion of ccRCC.

M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine.

Gemcitabine (GEM) is one of the first choice drugs for treating bladder cancer. In this study, we loaded M1 macrophage-derived exosomes (M1-Exo) with GEM by ultrasonication technique to derive an M1-Exo-GEM drug delivery system, and then explored its effects on bladder cancer. After inducing M1 polarization of macrophages in vitro, ultracentrifugation was performed to obtain M1-Exo, followed by construction of M1-Exo-GEM via ultrasonication technique. Mouse bladder cancer MB49 cells were chosen for study. CCK-8, PI staining and flow cytometry (FCM) assays were employed to assess the cell viability and apoptosis level. Inflammatory cytokines were detected by ELISA, while the protein expressions of Bcl-2, Bax and Caspase-3 were examined through Western-Blotting. After injecting M1-Exo-GEM into the tumor-bearing mouse model, the pathological changes were observed by H&E staining, the cancer cell damage was detected by TUNEL staining, and the apoptosis pathway activation was analyzed through immunohistochemical (IHC) staining and protein expression assays for Caspase-3 and Bax. Our results showed that M1-Exo and GEM had cytotoxic effects on MB49 cells, which increased the apoptosis level and the inflammatory cytokine expressions. Compared to M1-Exo and GEM, M1-Exo-GEM was significantly more cytotoxic to MB49 cells while markedly up-regulating the expressions of inflammatory cytokines. In the tumor-bearing mouse model, M1-Exo-GEM significantly inhibited tumor growth and damaged tumor cells, which outperformed GEM. Meanwhile, it also increased the tissue levels of inflammatory cytokines. This study finds that the drug delivery system composed of M1-Exo and GEM can act synergistically with GEM to exert cytotoxicity and induce inflammatory damage of bladder cancer cells.

[Water migration and kinetics of Arecae Semen during moistening process].

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

How different nitrogen fertilizers affect arsenic mobility in paddy soil after straw incorporation?

In straw return fields, nitrogen-fertilizers are added to mitigate microbial competition for nitrogen with plants. However, in arsenic (As)-contaminated paddy fields, the specific effects of different nitrogen fertilizers on As mobility after straw incorporation and the interactions among iron(Fe)/carbon(C)/nitrogen(N)/As are not well understood. In the reported microcosm experiment we monitored As-mobility as a function of different dosages of KNO3, NH4Cl and rice straw incorporation. Addition of both KNO3 and NH4Cl significantly inhibited the As mobilization induced by straw incorporation. Following the KNO3 addition, the As concentration in porewater dropped by 51-66% after 2 days of the incubation by restraining Fe reduction and enhancing Fe oxidation. High-dose NH4Cl addition reduced As in porewater by 22-43% throughout the incubation by decreasing porewater pH. High-throughput sequencing results demonstrated that KNO3 addition enriches both the denitrifying and Fe-oxidizing bacteria, while diminishing Fe-reducing bacteria; NH4Cl addition has the opposite effect on Fe-reducing bacteria. Network analysis revealed that As and Fe concentrations in porewater were positively correlated with the abundance of denitrifying and Fe-reducing bacteria. This study broadens our insight into the As biogeochemistry associated with the N/C/Fe balance in soil, which are of great significance for agronomic management and mitigation the risk of As-contaminated paddy fields.

Association between acute kidney injury and prognoses of cardiac surgery patients: Analysis of the MIMIC-III database.

Background: Acute kidney injury (AKI) is the most common major complication of cardiac surgery field. The purpose of this study is to investigate the association between acute kidney injury and the prognoses of cardiac surgery patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database. Methods: Clinical data were extracted from the MIMIC-III database. Adult (≥18 years) cardiac surgery patients in the database were enrolled. Multivariable logistic regression analyses were employed to assess the associations between acute kidney injury (AKI) comorbidity and 30-day mortality, 90-day mortality and hospital mortality. Different adjusting models were used to adjust for potential confounders. Results: A total of 6,002 patients were involved, among which 485 patients (8.08%) had comorbid AKI. Patients with AKI were at higher risks of prolonged ICU stay, hospital mortality, 90-day mortality (all P < 0.001), and 30-day mortality (P = 0.008). AKI was a risk factor for hospital mortality [Model 1, OR (95% CI) = 2.50 (1.45-4.33); Model 2, OR (95% CI) = 2.44 (1.48-4.02)], 30-day mortality [Model 1, OR (95% CI) = 1.84 (1.05-3.24); Model 2, OR (95% CI) = 1.96 (1.13-3.22)] and 90-day mortality [Model 1, OR (95% CI) = 2.05 (1.37-3.01); Model 2, OR (95% CI) = 2.76 (1.93-3.94)]. Higher hospital mortality, 30-day mortality and 90-day mortality was observed in higher KDIGO grade for cardiac surgery patients with AKI (all P < 0.05). Conclusion: Comorbid AKI increased the risk of hospital mortality, 30-day mortality, and 90-day mortality of cardiac surgery patients in the MIMIC-III database.

Establishment of Rat Model of Insulin Resistance Exposed to Chronic Renal Allograft Dysfunction.

BACKGROUND: The main cause of chronic renal allograft dysfunction (CRAD) still remains unclear. Insulin resistance (IR) may be a potential inducement, but there is insufficient evidence about this association. We aimed to establish a rat model of CRAD complicated with IR and to explore the function and pathologic changes of the renal allograft induced by IR. METHODS: F344-to-Lewis rats of CRAD were fed a high-fat diet to induce IR. They were divided into 3 groups: IR (CRAD+IR), CRAD, and control (CTL). Serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to evaluate the renal function. The Homeostasis Model Assessment (HOMA)-IR index was detected by comparing the values of fasting serum insulin levels (FINS) with fasting blood glucose levels (FBG). The pathologic analysis was conducted by the degree of renal lesions including glomerular lesions, renal tubular lesions, hemorrhage, inflammatory cell infiltration, fibrillation, and hyperplasia of the renal interstitium. RESULTS: In the second, third, and fourth month after surgery, serum levels of Scr and BUN in the IR group were reduced more than those in the CRAD group, while they were both higher compared to the CTL group, suggesting that renal function in the CRAD group was declined. The HOMA-IR in the IR group was greater than that in the CRAD and CTL groups, showing that simple high-fat diet feeding significantly and steadily increased FINS and FBG in CRAD complicated with IR rats. Pathologic changes indicated that the CRAD rat model was successfully constructed and was still in the early-middle stages of renal lesions 4 months after surgery, yet IR presented a significant effect on CRAD. CONCLUSION: These results indicate that the stable CRAD complicated with IR rat model can be established through a high-fat diet in CRAD rats in 4 months, and IR could be an influencing factor.

Effect of processing on the contents of amino acids and fatty acids, and glucose release from the starch of quinoa.

The effects of processing on the content of amino acids and fatty acids and the release of glucose from quinoa grains were evaluated in this paper. The processes included dehulling, boiling, extrusion, heating under pressure, and baking (infrared heating). The retention rate (AR) of essential amino acids and fatty acids of dehulled and boiled quinoa was 100%. The oil content of the extruded quinoa samples of two varieties was 47.71% and 39.75% lower than the corresponding raw quinoa samples. Baking and heating under pressure had different effects on the essential amino acid content, fatty acid content, and hydrolysis rate of quinoa starch. The results indicated the different cooking methods affect the essential amino acid content, fatty acid composition, release of glucose, and nutritional quality of quinoa, and moderate processing should be adopted to fully utilize the essential amino acids, fatty acids, and starch in quinoa.

Resveratrol Nanoparticle Complex: Potential Therapeutic Applications in Myocardial Ischemia Reperfusion Injury.

Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.

TVT-O vs TVT-S for female stress urinary incontinence: A systematic review and meta-analysis.

BACKGROUND: Tension-free vaginal tape obturator (TVT-O) and tension-free vaginal tape secur (TVT-S) are common surgeries for the treatment of stress urinary incontinence (SUI), several randomised controlled trials (RCTs) have compared the effects of TVT-O and TVT-S, yet the results remained inconsistent. Therefore, we attempted to conduct this systematic review and meta-analysis to analyse the role of TVT-O and TVT-S in patients with SUI. METHODS: We searched PubMed databases from inception date to Jan 15, 2020 for RCTs that compared TVT-O and TVT-S in SUI patients. Two authors independently screened and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated for each outcome by fixed- or random-effects model. RESULTS: Seven RCTs with a total of 755 patients were identified, with 373 patients for TVT-O and 382 patients for TVT-S. TVT-O preceded TVT-S in the objective cure at 12 months (OR = 1.72, 95% CI 1.21-2.45), subjective cure (OR = 1.98, 95% CI 1.08-3.62); but TVT-S have more advantage in the incidence of postoperative thigh pain (OR = 18.94, 95% CI 7.01-51.15); no significant differences on the duration of operative procedure (OR = -1.09, 95% CI -2.37-0.18), urinary retention (OR = 0.77, 95% CI 0.36-1.62) and urinary infection (OR = 1.80, 95% CI 0.63-5.13) were found. CONCLUSIONS: TVT-O should be preferred for patients with SUI even though with higher risks of postoperative thigh pain when compared with TVT-S, more related studies are needed to identify the role of TVT-O and TVT-S for the treatment of SUI.

Recombinant Human Erythropoietin Restrains Oxidative Stress in Streptozotocin-induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury (RI/RI) is a common complication of diabetes mellitus (DM) in surgical practice. Oxidative stress plays a crucial role in this process. Recombinant human erythropoietin (rhEPO) is usually used to treat anemia resulting from several diseases. However, the functional involvement of rhEPO in diabetic RI/RI remains unclear. The present study was intended to investigate the antioxidant role of rhEPO on RI/RI in DM rats. METHODS: The bilateral renal arteries and veins of streptozotocin-induced diabetic rats were subjected to 45 minutes of ischemia followed by 1, 6, and 24 hours of reperfusion with or without rhEPO pretreatment at the beginning of an I/R procedure. The renal tissue pathomorphology, renal function, oxidative stress, and inflammatory response were evaluated by detection of a series of indices by hematoxylin-eosin staining, commercial kits, enzyme-linked immunosorbent assay, and spectrophotofluorometry, respectively. RESULTS: Compared to the I/R group, renal function was significantly advanced in the erythropoietin group, whose subjects were also subjected to renal tissue injury, oxidative stress, and inflammation. CONCLUSION: These results suggest that rhEPO preconditioning can attenuate diabetic RI/RI through regulating endogenous antioxidant activity.

microRNA221 is Involved in Human Placental Development by Targeting DDIT4.

BACKGROUND/AIMS: miR221 might have an important role in human embryo development. However, little is known about the function of miR221 in the human embryo. The aim of this study was to evaluate miR221 expression in human placental tissue, and to analyze the relationship between miR221 and target genes. METHODS: The human placentas tissue samples were collected from healthy pregnant women who were willing to terminate their pregnancy. The total RNA isolation and microRNA reverse transcription quantification were performed by TaqMan microRNA assay and qRT-PCR. RESULTS: The results showed that miR221 expression was significantly higher in 55- to 71-day placenta (mean value=0.1049) than that in 38- to 54- day (the mean value=0.0133) (p<0.001). miR221 targeting genes, such as PIK3R1, CDKN1B, CDKN1C, DDIT4, and FOS, were detected in human placenta tissue, but only DDIT4 was significantly decreased with development (mean value: 0.0101 for 38∼54 days, 0.0021 for 55∼71 days, p<0.001). Further analysis showed that only DDIT4 was negatively correlated with miR221 expression (DDIT4: r=-0.396, p=0.033; PI3KR: r=0.322, p=0.089; CDKN1B: r=0.298, p=0.128; CDKN1C: r=0.198, p=0.304; FOS: r=0.171, p=0.347). CONCLUSION: These findings indicate that miR221 might play an important role in human placental development by precisely regulating the DDIT4 expression.

Pharmacological Signatures of the Exenatide Nanoparticles Complex Against Myocardial Ischemia Reperfusion Injury.

BACKGROUND/AIMS: Myocardial ischemia/reperfusion (I/R) injury (MI/RI) is a critical cause of death in patients with heart disease. However, the pharmaco-therapeutical outcome for MI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering myocardial function in MI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of exenatide-loaded poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) nanoparticles (NPs) against MI/RI. METHODS: The size of PLL-PEG-PLL NPs and the loading and release rates of exenatide were determined. The in vitro NP cytotoxicity was evaluated using newborn rat cardiomyocytes. Rats pretreated with free exenatide or exenatide/PLL-PEG-PLL polyplexes were subjected to 0.5-h ischemia and 2-h reperfusion in the left anterior descending coronary artery. The histopathologic lesions were assessed using hematoxylin-eosin staining. The general physiological indices, including blood pressure (BP), heart rate (HR), the left ventricular ejection fraction (LVEF) and end-diastolic pressure (LEVDP), and the left ventricular pressure maximal rate of rising (dp/dtmax), were monitored using a non-invasive blood pressure analyzer and color Doppler echocardiography. The antioxidative activity in the myocardial tissue was measured. The myocardial enzymatic activity was further estimated by determining the serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and glucagon-like peptide-1 (GLP-1), as well as the expression of GLP-1R in the myocardial tissue. RESULTS: Exenatide preconditioning attenuated the oxidative stress injury and promoted the myocardial function in I/R-induced myocardial injury, while the application of block copolymer PLL-PEG-PLL as a potential exenatide nanocarrier with sustained release significantly enhanced the bioavailability of exenatide. CONCLUSION: The block copolymer PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting pharmacotherapy against MI/RI with unprecedented clinical benefits. Further study is needed to better clarify the underlying mechanisms.

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2.

BACKGROUND/AIMS: Liver progenitor cells (LPCs) were considered as a promising hepatocyte source of cell therapy for liver disease due to their self-renewal and differentiation capacities, while little is known about the mechanism of LPC differentiate into hepatocytes. This study aims to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from LPCs. METHODS: In this study, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation, then microRNAs were quantified by qPCR. Next, WB-F344 cell was transfected with miR-382 mimics, then hepatocyte cell trait was characterized by multiple experiments, including that periodic acid schiff staining and cellular uptake and excretion of indocyanine green to evaluate the hepatocellular function, qPCR and Western Blotting analysis to detect the hepatocyte-specific markers (ALB, Ttr, Apo E and AFP) and transmission electron microscopy to observe the hepatocellular morphology. Moreover, Luciferase reporter assay was used to determine whether Ezh2 is the direct target of miR-382. RESULTS: We found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. In addition, functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. CONCLUSIONS: This study demonstrates that miR-382 may be a novel regulator of LPCs differentiation by targeting Ezh2.

Lumbrokinase/paclitaxel nanoparticle complex: potential therapeutic applications in bladder cancer.

BACKGROUND: Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects. METHODS AND RESULTS: Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied. CONCLUSION: We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits.