A Colormetric and Fluorescence Probe for Highly Specific Cu2+ and its Application in Live Cell Imaging.

Fluorescent probes are intriguing material for ion detection. In this study, 4,4-difluoro-4-bora3a,4a-diaza-s-indacene (BODIPY) containing a dipicolylethylenediamine unit was developed as a colorimetric and fluorescence "turn-off" probe for Cu2+. The probe exhibited higher selectivity for Cu2+ than other common metal ions with a detection limit of 8.49 µM. With increasing Cu2+ concentration, the probe showed a red-shift in the absorption spectrum as well as fluorescence quenching, possibly due to the intramolecular charge transfer effect of the probe-Cu(II) complex. Furthermore, the probe was used for imaging Cu2+ in living cells based on confocal fluorescence imaging. The results show that the probe is an effective tool for detection copper ions.

Pulse perfusion index for predicting intrapartum fever during epidural analgesia.

STUDY OBJECTIVE: To assess whether pulse perfusion index (PI) values could be employed to predict intrapartum fever and to provide a cut-off PI value for predicting intrapartum fever occurrence. DESIGN: We conducted a single-center, prospective, observational study. SETTING: Delivery room at the Department of Obstetrics, Affiliated Hospital of Jiangsu University. PATIENTS: 117 parturients who intended to have a vaginal delivery. INTERVENTIONS: Each parturient received epidural analgesia. MEASUREMENTS: We checked each parturient's tympanic temperature before analgesia (T0), at 1 h (T1) and 2 h (T2) after analgesia, immediately at the end of the second (T3) and third (T4) stages of labor, and at 1 h postpartum (T5). A temperature of ≥38°C was defined as fever. PI, measured on the right second toe, was recorded before analgesia (PI0) and at 10 min (PI10), 20 min (PI20), and 30 min (PI30) after analgesia. The PI change rate was calculated as the incremental change in PI30 from PI0, divided by the PI0. Receiver operating characteristic (ROC) curves were used to verify the utility of the PI30 and PI change rate values for predicting intrapartum fever. MAIN RESULTS: We found that peak temperature (TP) occurred at the end of the second or the third stage of labor. Within 30 min after analgesia, the PI showed a significant increase over time and there was a linear correlation between PI30 and TP values (P < 0.001, r = 0.544). The PI10, PI20, PI30 and PI change rate in febrile parturients were higher than those in afebrile parturients (P < 0.001). The area under the ROC (AUROC) for PI30 was 0.818 (P < 0.001) with a cut-off of 9.30. The AUROC of the PI change rate was 0.738 (P < 0.001) with a cut-off of 3.45. CONCLUSIONS: PI30 and PI change rate values could be used to predict intrapartum fever in parturients after epidural analgesia.

Liquid chromatography-mass spectrometry method for discovering the metabolic markers to reveal the potential therapeutic effects of naringin on osteoporosis.

The pharmacological effects and therapeutic targets of naringin (NG) against osteoporosis (OP) is still unclear. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) based non-targeted metabonomics has been used to explore the differentiated metabolites and potential biological pathways of NG in the pathological process of OP. Using network pharmacology analysis, the key protein targets of NG against OP were also screened. By the metabonomics analysis, a total of 33 differentiated metabolites in serum were discovered, of which 21 were significantly regulated by NG treatment. These metabolites majorly associated with to amino acid metabolism,polyunsaturated fatty acid metabolism, pyruvate metabolism and glycerophospholipidmetabolism. Using the network pharmacology prediction analysis, NG was related to the expression changes of 13 important protein targets. It showed that high-throughput metabonomics strategy integrated with network pharmacology could insight into molecular mechanisms of natural products.

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats.

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 µg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.

Stimulation of osteogenic differentiation in bone marrow stromal cells via Wnt/ß-catenin pathway by Qili Jiegu-containing serum.

A capsule of Qili Jiegu, a traditional Chinese medicine with numerous biological activities, may exert a protective eff ;ect against postmenopausal bone loss. However, it remains unclear whether Qili Jiegu-containing serum regulates the osteogenic diff ;erentiation of bone marrow stromal cells (BMSCs) in vitro. In this study, BMSCs were treated with medium and Qili Jiegu-containing serum over a 14-day period. We found that Qili Jiegu-containing serum promoted the BMSC proliferation and alkaline phosphatase (ALP) activities, as well as stimulated the expression of osteogenic markers and Wnt/ß-catenin pathway-related genes, i.e., runt-related transcription factor 2 (Runx2), osteocalcin (OCN), ß-catenin and Wnt4a, in BMSCs. Finally, we found that Qili Jiegu-containing serum activated the Wnt/ß-catenin pathway. An addition of Dickkopf-related protein-1 (an inhibitor of the Wnt/ß-catenin signaling pathway) to the Qili Jiegu-containing serum could decrease the stimulatory osteogenic effect of Qili Jiegu-containing serum on BMSCs. Therefore, Qili Jiegu-containing serum could promote the osteogenic diff ;erentiation of BMSCs, and the potential mechanism may involve regulation of Wnt/ß-catenin signaling.

Bu-Shen-Jian-Pi-Yi-Qi Therapy Prevents Alcohol-Induced Osteoporosis in Rats.

Bu-Shen-Jian-Pi-Yi-Qi therapy, which refers to reinforcing kidney, regulating qi, and invigorating spleen, is a traditional Chinese medicine, and we investigated its efficacy in treatment of alcohol-induced osteoporosis and its underlying mechanism. Forty adult male Sprague-Dawley rats were randomly assigned into alcohol-supplemented group, JIAN-GU-LING (JGL) group, calcium D3 + alfacalcidol group, and sham-treated group. Bone mineral density (BMD), bone mineral content (BMC), and bone biomechanical properties were assessed. Biochemical analyses of serum and urine specimens were detected. Reverse transcription-polymerase chain reaction was used to detect the mRNA level of vitamin D receptor (VDR). There were markedly lower bone metabolic markers and biomechanical properties in alcohol-supplemented group compared with sham-treated group (all P < 0.05). BMD, BMC, 25(OH)D3, and 1,25(OH)2D3 were elevated in JGL group relative to calcium D3 + alfacalcidol group (all P < 0.05). U-Ca/Cr and U-P/Cr in JGL group were higher than those in the calcium D3 + alfacalcidol group (all P < 0.05). VDR mRNA level in the JGL group was elevated markedly in comparison with alcohol + calcium D3 + alfacalcidol group (P < 0.05). Based on our results, Bu-Shen-Jian-Pi-Yi-Qi therapy inhibits bone loss, promotes bone formation, and effectively improves bone metabolism in rats with experimental alcoholic osteoporosis. The disease reversal is evidenced by increased BMD and BMC, improved biomechanical properties, elevated VDR mRNA level, enhanced response sensitivity of 1, 25(OH)2D3, and reduced S-Ca/P.

Morroniside promotes bone marrow mesenchymal stem cell proliferation in rats.

The aim of this study was to explore the mechanism underlying the promotive effect of morroniside on rat mesenchymal stem cell (RMSC) proliferation and to provide an experimental basis for the development of potential new drugs. RMSCs were obtained from the bone marrow of Sprague-Dawley rats aged 3-4 months. The proliferation of primary and subcultured RMSCs in the high­, medium­ and low­concentration morroniside intervention and blank control groups was observed using light microscopy. Cell proliferation and survival conditions were detected using methyl thiazolyl tetrazolium (MTT) colorimetric tests. Light microscopy and the MTT assay revealed that RMSC adherence time in the morroniside groups was shorter compared with that of the control group. Twelve hours after the media of primary RMSCs were changed, the number of adherent cells in the morroniside groups increased and an elongated cell morphology was observed. The cells at the fourth passage in the morroniside groups fused completely 12­16 h after inoculation and then rapidly entered into the logarithmic phase. The primary RMSCs of the morroniside intervention groups grew into typical bone marrow mesenchymal stem cell (BMSC) colonies after 4 days of morroniside treatment and their fusion rate had reached 80% after 9­11 days. By contrast, the cell fusion rate of the control group only reached 75-80% after 14 days of morroniside treatment. Morroniside exhibited a similar promotive effect on proliferation in primary and subcultured RMSCs. Morroniside may promote RMSC proliferation through secreted factors, cell-to-cell interactions and/or the interactions between cellular adhesion molecules and extracellular matrices (ECMs). However, the specific mechanism underlying this effect remains to be fully elucidated.