A novel lncRNA GM15416 regulates osteoblast apoptosis and differentiation through the c-Fos/Fas axis and mitigates osteoporosis.

Osteoporosis (OP) is a common systemic bone disorder, and the programmed cell death of osteoblasts is closely linked to the development of osteoporosis. Previous studies have shown that c-fos can cause osteoblast apoptosis. Furthermore, it has been demonstrated that long non-coding RNA (lncRNA) plays a pervasive role in regulating the biology of osteoblasts. Nevertheless, the precise role and mechanism of long non-coding RNA (lncRNA) in relation to c-Fos at the transcriptional level in osteoblast cell death remain uncertain. Compared with normal osteoblasts, serum deprivation resulted in significant upregulation of the transcription factor c-Fos and apoptosis-related Fas proteins in osteoblasts. In addition, the expression of lncRNA GM15416 related to c-Fos was significantly increased. The results showed that overexpression of c-Fos leads to an increase in downstream Fas protein, which subsequently leads to osteoblast apoptosis and hinders osteogenesis. On the contrary, a decrease in lncRNA GM15416 expression leads to a decrease in c-Fos/Fas expression, which hinders osteoblast apoptosis and promotes osteogenesis. Our results suggest that lncRNA GM15416 exerts inhibitory effects on osteoblast apoptosis and acts as a preventive factor against osteoporosis. As a result, GM15416 emerges as an important lncRNA associated with osteoporosis and holds potential as a future therapeutic target.

Wireless, Smart Hemostasis Device with All-Soft Sensing System for Quantitative and Real-Time Pressure Evaluation.

The properly applied pressure between the skin and hemostasis devices is an essential parameter for preventing bleeding and postoperative complications after a transradial procedure. However, this parameter is usually controlled based on the subjective judgment of doctors, which might cause insufficient hemostatic effect or thrombosis. Here this study develops a compact and wireless sensing system for continuously monitoring the pressure applied on the radial artery and wrist skin in clinical practice. A liquid metal (LM)-based all-soft pressure sensor is fabricated to enable conformal attachment between the device and skin even under large deformation conditions. The linear sensitivity of 0.007 kPa-1 among the wide pressure range of 0-100 kPa is achieved and the real-time detection data can be wirelessly transmitted to mobile clients as a reference pressure value. With these devices, detailed pressure data can be collected, analyzed, and stored for medical assistance as well as to improve surgery quality.

Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix.

Many clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.

miR-30c-5p Reduces Renal Ischemia-Reperfusion Involving Macrophage.

BACKGROUND Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. MATERIAL AND METHODS Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. RESULTS MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. CONCLUSIONS We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.

CTCF regulates the FoxO signaling pathway to affect the progression of prostate cancer.

The present research focuses on the influence of CCCTC-binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP-seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT-qPCR and Western blot. Inhibition of CTCF could lead to the up-regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down-regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.

Ketamine induces reactive oxygen species and enhances autophagy in SV-HUC-1 human uroepithelial cells.

This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor ÐºB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.

Comparison of OnabotulinumtoxinA versus sacral neuromodulation for refractory urinary urge incontinence: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIM: Both intradetrusor OnabotulinumtoxinA (BTX) and Sacral neuromodulation (SNM) as third-line therapies for urgency urinary incontinence (UUI) are increasingly being utilized. However, there are differences in preference between patients and medical personnel in clinical practice. This meta-analysis was designed to compare BTX versus SNM in treatment of UUI. METHODS: We searched the Cochrane Library, PubMed, EMBASE and Web of Science from January 1, 1992 to April 22, 2018. Mean differences (MDs) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare the outcomes of the groups. All the MDs were after subtracting OnabotulinumtoxinA data from Sacral neuromodulation data. RRs were acquired from comparing OnabotulinumtoxinA data to Sacral neuromodulation data. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. This work has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. RESULTS: Seven randomized controlled trials and two retrospective studies (N = 1649 participants) were identified for the present analysis. In change from baseline in UUI episodes (UUIE) per day, comparing BTX groups with SNM groups, the effects were observed through 1, 2, 4, 5 and 6 month, with pooled MDs of -0.62, -0.55, -0.38, -1.02 and -0.50 respectively. In UUIE reduction post treatment, the pooled RRs of complete UUIE reductions through 4 and 6 months respectively were 5.13 and 6.63. Significant results were observed through overall times in more than 75% UUIE reduction. No significance was found in more than 50% UUIE reduction. Significant results were observed in urinary tract infection. More treatment satisfaction were found in BTX groups than that in SNM groups (RR 1.14, 95% CI 1.01-1.29; P = 0.004). CONCLUSIONS: Generally, BTX seems superior to SNM in treatment of UUI but inferior regarding safety. Patients receiving BTX experienced a higher treatment satisfaction.

Cadmium uptake by Carpobrotus rossii (Haw.) Schwantes under different saline conditions.

Plants used for phytoextraction of heavy metals from contaminated soils with high levels of salinity should be able to accumulate heavy metals and also be tolerant to salinity. Australian native halophyte species Carpobrotus rossii has recently been shown to tolerate and accumulate multiple heavy metals, especially cadmium (Cd). This study examined the effects of salt type and concentration on phytoextraction of Cd in C. rossii. Plants were grown in contaminated soil for 63 days. The addition of salts increased plant growth and enhanced the accumulation of Cd in shoots up to 162 mg kg(-1) which almost doubled the Cd concentration (87 mg kg(-1)) in plants without salt addition. The increased Cd accumulation was ascribed mainly to increased ionic strength in soils due to the addition of salts and resultantly increased the mobility of Cd. In comparison, the addition of Cl(-) resulted in 8-60 % increase in Cd accumulation in shoots than the addition of SO4 (2-) and NO3 (-). The findings suggest that C. rossii is a promising candidate in phytoextraction of Cd-polluted soils with high salinity levels.

Enhanced Fenton-like removal of nitrobenzene via internal microelectrolysis in nano zerovalent iron/activated carbon composite.

The efficiency of Fenton-like catalysis using nano zerovalent iron (nZVI) is limited by nZVI aggregation and activity loss due to inactive ferric oxide forming on the nZVI surface, which hinders electron transfer. A novel iron-carbon composite catalyst consisting of nZVI and granular activated carbon (GAC), which can undergo internal iron-carbon microelectrolysis spontaneously, was successfully fabricated by the adsorption-reduction method. The catalyst efficiency was evaluated in nitrobenzene (NB) removal via the Fenton-like process (H2O2-nZVI/GAC). The results showed that nZVI/GAC composite was good for dispersing nZVI on the surface of GAC, which permitted much better removal efficiency (93.0%) than nZVI (31.0%) or GAC (20.0%) alone. Moreover, iron leaching decreased from 1.28 to 0.58 mg/L after reaction of 240 min and the oxidation kinetic of the Fenton-like reaction can be described well by the second-order reaction kinetic model (R2=0.988). The composite catalyst showed sustainable catalytic ability and GAC performed as a medium for electron transfer in internal iron-carbon microelectrolysis to promote Fe2+ regeneration and Fe3+/Fe2+ cycles. Therefore, this study represents an important method to design a low cost and high efficiency Fenton-like catalyst in practical application.

Influence of nitrogen form on the phytoextraction of cadmium by a newly discovered hyperaccumulator Carpobrotus rossii.

Using hyperaccumulator plants is an important method to remove heavy metals from contaminated land. Carpobrotus rossii, a newly found Cd hyperaccumulator, has shown potential to remediate Cd-contaminated soils. This study examined the effect of nitrogen forms on Cd phytoextraction by C. rossii. The plants were grown for 78 days in an acid soil spiked with 20 mg Cd kg(-1) and supplied with (NH4)2SO4, Ca(NO3)2, urea, and chicken manure as nitrogen (N) fertilizers. Nitrification inhibitor dicyandiamide (DCD) was applied to maintain the ammonium (NH4(+)) form. Nitrogen fertilization increased shoot biomass but decreased root biomass with the highest shoot biomass occurring in the manure treatment. Compared to the no-N control, urea application did not affect shoot Cd concentration, but increased Cd content by 17% due to shoot biomass increase. Chicken manure significantly decreased CaCl2-extractable Cd in soil, and the Cd concentration and total Cd uptake in the plant. Rhizosphere pH was the highest in the manure treatment and the lowest in the NH4(+) treatments. The manure and nitrate (NO3(-)) treatments tended to have higher rhizosphere pH than their respective bulk soil pH, whereas the opposite was observed for urea and NH4(+) treatments. Furthermore, the concentrations of extractable Cd in soil and Cd in the plant correlated negatively with rhizosphere pH. The study concludes that urea significantly enhanced the Cd phytoaccumulation by C. rossii while chicken manure decreased Cd availability in soil and thus the phytoextraction efficiency.

Australian native plant species Carpobrotus rossii (Haw.) Schwantes shows the potential of cadmium phytoremediation.

Many polluted sites are typically characterized by contamination with multiple heavy metals, drought, salinity, and nutrient deficiencies. Here, an Australian native succulent halophytic plant species, Carpobrotus rossii (Haw.) Schwantes (Aizoaceae) was investigated to assess its tolerance and phytoextraction potential of Cd, Zn, and the combination of Cd and Zn, when plants were grown in soils spiked with various concentrations of Cd (20-320 mg kg(-1) Cd), Zn (150-2,400 mg kg(-1) Zn) or Cd + Zn (20 + 150, 40 + 300, 80 + 600 mg kg(-1)). The concentration of Cd in plant parts followed the order of roots > stems > leaves, resulting in Cd translocation factor (TF, concentration ratio of shoots to roots) less than one. In contrast, the concentration of Zn was in order of leaves > stems > roots, with a Zn TF greater than one. However, the amount of Cd and Zn were distributed more in leaves than in stems or roots, which was attributed to higher biomass of leaves than stems or roots. The critical value that causes 10% shoot biomass reduction was 115 µg g(-1) for Cd and 1,300 µg g(-1) for Zn. The shoot Cd uptake per plant increased with increasing Cd addition while shoot Zn uptake peaked at 600 mg kg(-1) Zn addition. The combined addition of Cd and Zn reduced biomass production more than Cd or Zn alone and significantly increased Cd concentration, but did not affect Zn concentration in plant parts. The results suggest that C. rossii is able to hyperaccumulate Cd and can be a promising candidate for phytoextraction of Cd from polluted soils.

Marrow stromal stem cell autologous transplantation in denervated fracture healing: an experimental study in rats.

OBJECTIVE: To investigate the influence of bone marrow stromal stem cell (BMSCs) transplantation on healing of fractures combined with central nerve injuries in rats. METHODS: Forty-eight healthy adult SD male rats were randomly divided into the following three groups (16 rats in each group): group A, simple (left) tibial fracture; group B, tibial fracture combined with T10 spinal cord transection (SCT); group C, tibial fracture combined with T10 SCT and BMSCs transplantation. The tibial fractures were stabilized with modular intramedullary nails and all operated hind limbs were further immobilized in plaster casts to prevent unequal load bearing. BMSCs were labeled with bromodeoxyuridine and implanted into the fractures of C group rats 2 days after creation of the model. The animals in B and C groups were evaluated by postoperative Tarlov scores. The fractured tibiae were evaluated separately radiographically (X-ray and CT) and immunohistochemically 1, 2, 3 and 4 weeks after injury to assess fracture healing. In addition, the wet weights of the left tibias were measured. RESULTS: All Tarlov score of the B and C group animals reached the requirements of the experiment. One, 2 and 3 weeks after surgery, the tibial callus widths in B and C group animals were significantly greater than those of group A rats (P < 0.05). At 4 weeks the tibial callus width in group C animals had decreased, but still differed significantly from that in group A rats (P < 0.05). One, 2, 3 and 4 weeks after surgery, the wet weights of B and C group tibias were significantly greater than those of group A (P < 0.05). Hematoxylin-eosin-stained sections showed bony union and increased bone trabecula in B and C groups and areas with particles positive for alkaline phosphatase staining were more abundant in groups B and C, especially in group C. CONCLUSION: Neural regulation plays an important role in fracture healing. Treatment with BMSCs has a positive effect on defective callus in rats that have been subjected to SCT.

[Reconstruciton of medial patellofemoral ligament (MPFL) for the treatment of recurrent patellar dislocation].

OBJECTIVE: To evaluate the middle term effectiveness of medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent patellar dislocation. METHODS: From February 2007 to January 2010, 65 patients including 6 males and 59 females with recurrent patellar dislocation received the MPFL reconstruction. The reconstruction was performed using ipsilateral semitendinosis tendon to restore the damaged MPFL. Patients were evaluated pre-operatively and post-operatively by physical and subjectively with the IKDC (International Knee Documentation Committee), Tegner, and Lysholm questionnaires and radiographic examination. RESULTS: The average follow-up duration was 20 months (ranged, 15 to 23 months). No recurrent episodes of dislocation or subluxation occurred. A firm endpoint to lateral patellar translation was noted in all patients at most recent follow-up. The Lysholm subjective knee evaluation score improved from (60.6 +/- 3.7) preoperatively to (89.8 +/- 4.6) postoperatively; and Tegner scores improved from (3.6 +/- 0.4) to (5.6 +/- 0.3), IKDC from (40.0 +/- 3.5) to (82.0 +/- 3.6). Radiographic evaluation demonstrated improvements in the congruence and sulcus femoral angles. CONCLUSION: MPFL reconstruction is an effective surgical procedure for the treatment of recurrent patellar dislocation.