[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

Association between obstructive sleep apnea and low bone mass in adults: a systematic review and meta-analysis.

Introduction: This study aimed to synthesize existing evidence on the potential association between obstructive sleep apnea (OSA) and low bone mass in adults. Methods: Electronic searches of four main databases were performed. The inclusion criteria consisted of observational studies investigating the relationship between OSA and bone mass, osteoporosis, fractures, or bone metabolism markers in adult population. Bone mineral density (BMD) and T score of lumbar and femur neck, incidence of osteoporosis and fractures, bone metabolism marker levels were extracted as primary outcomes. Results: Among the 693 relevant publications, 10 studies consisting of 158,427 participants met with the inclusion and exclusion criteria. Meta-analysis showed a significant lower BMD of lumbar (mean difference (MD) = - 0.03; 95% CI - 0.05, - 0.01; I2 = 46%), femur neck (MD = - 0.06; 95% CI - 0.12, 0.00; I2 = 71%), and a significant lower T score of lumbar (MD = - 0.42; 95% CI - 0.79, - 0.05; I2 = 63%) in the OSA group. The results suggested that both male (odds ratio (OR) = 2.03; 95% CI 1.23, 3.35; I2 = 38%) and female (OR = 2.56; 95% CI 1.96, 3.34; I2 = 0%) had higher risk of osteoporosis in the OSA group. Besides, meta-analysis also showed that bone-specific alkaline phosphatase was significantly lower in OSA patients (MD = - 1.90; 95% CI - 3.48, - 0.32; I2 = 48%). Conclusions: A potential association between OSA and lower bone mass in adults is preliminarily proved. It also seems plausible that both male and female with OSA have a higher risk of osteoporosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00481-1.

Construction of 3D network aluminum sludge-based hydrogel beads: combination of macroization, amino functionalization, and resource utilization.

An aluminum sludge-based composite material was constructed against the problems of phosphorus pollution and the waste of aluminum sludge resources. Utilizing metal Ce doping and hydrogel microbeads with pore preparation, the adsorption performance of the original sludge was improved. Meanwhile, the macroscopic body was constructed, and on this basis, polyethyleneimine (PEI) was introduced to complete the amino functionalization further to enhance the adsorption of phosphorus by the adsorbent, and NH-CeAIS-10 microbeads were successfully prepared. In adsorption, microbeads with larger specific surface area and richer functional groups are better choice compared to original sludge. The results of SEM, BET, FT-IR, and XPS analyses indicate that the adsorption of phosphorus by the microbeads is mainly achieved through electrostatic interactions, ligand exchange, and the formation of inner-sphere complexes. According to the Langmuir model, the maximum phosphorus adsorption capacity of NH-CeAIS-10 was 29.56 mg g-1, which was four times higher compared to native aluminum sludge. This also confirms the significant enhancement of phosphorus adsorption through the modification of aluminum sludge. Besides, in dynamic adsorption column experiments, the material exhibited up to 99% removal in simulated wastewater for up to 30 days, demonstrating the great adsorption potential of NH-CeAIS-10 in engineering applications.

The Effects and Mechanisms of PBM Therapy in Accelerating Orthodontic Tooth Movement.

Malocclusion is one of the three major diseases, the incidence of which could reach 56% of the imperiled oral and systemic health in the world today. Orthodontics is still the primary method to solve the problem. However, it is clear that many orthodontic complications are associated with courses of long-term therapy. Photobiomodulation (PBM) therapy could be used as a popular way to shorten the course of orthodontic treatment by nearly 26% to 40%. In this review, the efficacy in cells and animals, mechanisms, relevant cytokines and signaling, clinical trials and applications, and the future developments of PBM therapy in orthodontics were evaluated to demonstrate its validity. Simultaneously, based on orthodontic mechanisms and present findings, the mechanisms of acceleration of orthodontic tooth movement (OTM) caused by PBM therapy were explored in relation to four aspects, including blood vessels, inflammatory response, collagen and fibers, and mineralized tissues. Also, the cooperative effects and clinical translation of PBM therapy in orthodontics have been explored in a growing numbers of studies. Up to now, PBM therapy has been gaining popularity for its non-invasive nature, easy operation, and painless procedures. However, the validity and exact mechanism of PBM therapy as an adjuvant treatment in orthodontics have not been fully elucidated. Therefore, this review summarizes the efficacy of PBM therapy on the acceleration of OTM comprehensively from various aspects and was designed to provide an evidence-based platform for the research and development of light-related orthodontic tooth movement acceleration devices.

Enhanced phosphate adsorption studies on several metal-modified aluminum sludge: preparation optimization, adsorption behavior, and mechanistic insight.

To solve the problems such as water eutrophication caused by excess phosphorus, the potential residual value of aluminum sludge was fully exploited and its phosphate adsorption capacity was further improved. In this study, twelve metal-modified aluminum sludge materials were prepared by co-precipitation method. Among them, Ce-WTR, La-WTR, Y-WTR, Zr-WTR, and Zn-WTR showed excellent adsorption capacity for phosphate. The adsorption performance of Ce-WTR on phosphate was twice that of the native sludge. The enhanced adsorption mechanism of metal modification on phosphate was investigated. The characterization results showed that the increase in specific surface area after metal modification was 9.64, 7.5, 7.29, 3, and 1.5 times, respectively. The adsorption of phosphate by WTR and Zn-WTR was in the accordance with Langmuir model, while the others were more following the Freundlich model (R2 > 0.991). The effects of dosage, pH, and anion on phosphate adsorption were investigated. The surface hydroxyl groups and metal (hydrogen) oxides played an important role in the adsorption process. The adsorption mechanism involves physical adsorption, electrostatic attraction, ligand exchange, and hydrogen bonding. This study provides new ideas for the resource utilization of aluminum sludge and theoretical support for preparing novel adsorbents for efficient phosphate removal.

Protective effect and mechanisms of Weining granule on N-methyl-N'-nitro-N- nitrosoguanidine-induced gastric cancer in rats.

OBJECTIVE: To investigate the protective effect and molecular mechanisms of Weining granule on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer in rats. METHODS: A total of sixty healthy male wistar rats were randomly divided into five groups, including control group (CG), gastric cancer model group (MG), low-dose Weining granule treated group (LWT), medium-dose Weining granule treated group (MWT), and high-dose Weining granule treated group (HWT). Except the control group, the other groups were treated with MNNG to establish a rat model of gastric cancer. Low-dose Weining granule treated group, medium-dose Weining granule treated group, and high-dose Weining granule treated group were fed 9.0, 18.0 and 36.0 g/kg Weining granule, respectively. Histopathologic and molecular biologic technology were adopted to determine the protective effect of Weining granule on MNNG-induced gastric cancer in rats. The pathological changes of gastrointestinal tissue were observed. Meanwhile, the differential expression of proliferation, apoptosis and angiogenesis markers were determined, including proliferating cell nuclear antigen (PCNA), pokemon, cyclin D1, B-cell lymphoma-2 (Bcl-2), caspase-3, phosphatase and tensin homolog (PTEN) and vascular endothelial growth factor (VEGF). RESULTS: After the MNNG treated, the pathological changes of stomach tissue were improved noticeably, including the intestinal metaplasia and atypic hyperplasia. The experiment was completed in 58 rats (96.67%). As compared with gastric cancer model group, the general states of rats were improved significantly after treated with different dose Weining granule. Moreover, treatment with different doses of Weining granule could inhibit the protein and mRNA expression of PCNA, pokemon, cyclin D1, Bcl-2, and VEGF, while increase caspase-3 and PTEN (P < 0.01). CONCLUSION: Weining granule could improve gastric cancer by suppressing cell proliferation, promoting tumor cell apoptosis, and inhibiting angiogenesis.

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.

On-line two-dimensional countercurrent chromatography×high performance liquid chromatography system with a novel fragmentary dilution and turbulent mixing interface for preparation of coumarins from Cnidium monnieri.

This study describes a novel on-line two-dimensional countercurrent chromatography×high performance liquid chromatography (2D CCC×HPLC) system for one-step preparative isolation of coumarins from the fruits of Cnidium monnieri. An optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds. In order to address the solvent incompatibility problem between CCC and RP-HPLC, a novel fragmentary dilution and turbulent mixing (FD-TM) interface was successfully developed. In detail, the eluent from the first dimensional CCC column was divided into fractions to form 'sample-dilution' stripes in the two switching sample loops, by the dilution water from the makeup pump. Following this, a long, thin tube was applied to mix the CCC eluent with water by in-tube turbulence, to reduce the solvent effect. Each CCC fraction was alternately trapped on the two holding columns for further preparative HPLC separation. This nationally designed FD-TM strategy effectively reduced post-column pressure and allowed a higher water dilution ratio at the post end of CCC, leading to improved sample recovery and a robust 2D CCC×HPLC isolation system. As a result, in a single 2D separation run (6.5h), eight target compounds (1-8) were isolated from 0.5g crude extract of C. monnieri, in overall yields of 1.3, 2.0, 0.5, 0.5, 0.8, 1.5, 8.2, and 15.0%, with HPLC purity of 90.1, 91.1, 94.7, 99.1, 99.2, 98.2, 97.9, and 91.9%, respectively. We anticipate that this improved 2D CCC×HPLC system, based on the novel FD-TM interface, has broad application for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.

Two-dimensional countercurrent chromatography×high performance liquid chromatography with heart-cutting and stop-and-go techniques for preparative isolation of coumarin derivatives from Peucedanum praeruptorum Dunn.

Pure compounds isolated from complex natural plants are important for drug discovery. This study describes a novel two-dimensional hyphenation of counter-current chromatography and high-performance liquid chromatography (2D CCC×HPLC) with heart-cutting and stop-and-go techniques for preparative isolation of multiple targets components from Peucedanum praeruptorum Dunn (Umbelliferae) crude extracts in a single step. The CCC and HPLC were hyphenated via a 4-port valve equipped at the post-end of the CCC column, to heart cut the impure fractions to the 2nd dimensional HPLC for further separation. Furthermore, the stop-and-go flow scheme was applied in the 1st dimensional CCC to fit with the time constraints of the 2nd dimensional preparative HPLC. Last but not least, an optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds, resulting in the improvement of the CCC column efficiency. By taking the advantages of this rationally designed system, sixteen coumarins were isolated from 1.0g of P. praeruptorum crude extract, with HPLC purity from 90.1% to 99.5%, in a single 2D separation run. More interestingly, two minor linear coumarins and one angular coumarin were isolated from P. praeruptorum Dunn for the first time. As far as we known, this is the first report on the combination of heart-cutting technique and stop-and-go protocol in 2D CCC×HPLC system, by which good separations on comprehensive matrix were achieved. We expect that this approach may have broad applications for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.