MicroRNA-155 inhibition up-regulates LEPR to inhibit osteoclast activation and bone resorption via activation of AMPK in alendronate-treated osteoporotic mice.

Osteoporosis is characterized by a progressive increase in bone fragility, leading to low bone mass and structural deterioration of bone tissue. MicroRNA-155 (miR-155) is highly expressed in osteoporosis. Thus, the current study aimed to investigate the effect of miR-155 on the inhibition of osteoclast activation and bone resorption by targeting leptin receptor (LEPR) through the adenosine monophosphate activated protein kinase (AMPK) pathway in alendronate-treated osteoporotic mice. An osteoporosis mouse model was established to examine the bone tension and bone density and the expression of miR-155 in osteoclasts. Binding sites between miR-155 and LEPR were verified. Osteoclasts in the treatment group were transfected with different mimic, inhibitor, vector, or siRNA for subsequent experiments. The expression of miR-155, LEPR, AMPK, p-AMPK, RANKL, OPG, M-CSF, RANK, TRAP, Bax, Bcl-2, and the contents of TNF-α and IL-1ß were all examined. The proliferation and bone resorption of osteoclasts were also detected. Mice with osteoporosis exhibited decreased bone density and bone tension, along with elevated expression of miR-155. LEPR was verified as a target gene of miR-155. Down-regulated miR-155 was found to increase the expression of LEPR, AMPK, p-AMPK, OPG, Bax, decrease expression of TNF-α, IL-1ß, RANKL, M-CSF, RANK, TRAP, Bcl-2, inhibit the cell proliferation and bone resorption of osteoclasts. Taken together, decreased miR-155 up-regulated LEPR via activation of AMPK, which ultimately repressed osteoclast activation and bone resorption of osteoclasts in alendronate-treated osteoporotic mice.

Monosialoganglioside protects against bupivacaine-induced neurotoxicity caused by endoplasmic reticulum stress in rats.

BACKGROUND: Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has a therapeutic effect on bupivacaine-induced neurotoxicity. The aim of this study was to determine the underlying mechanisms of bupivacaine-induced neurotoxicity and the potential neuroprotective role of GM1. MATERIALS AND METHODS: A rat spinal cord neurotoxicity model was established by injecting bupivacaine (5%, 0.12 µL/g) intrathecally. The protective effect of GM1 (30 mg/kg) was evaluated by pretreating the animals with it prior to the bupivacaine regimen. The neurological and locomotor functions were assessed using standard tests. The histomorphological changes, neuron degeneration and apoptosis, and endoplasmic reticulum stress (ERS) relevant markers were analyzed using immunofluorescence, quantitative real-time PCR, and Western blotting. RESULTS: Bupivacaine resulted in significant neurotoxicity in the form of aberrant neurolocomoter functions and spinal cord histomorphology and neuronal apoptosis. Furthermore, the ERS specific markers were significantly upregulated during bupivacaine-induced neurotoxicity. These neurotoxic effects were ameliorated by GM1. CONCLUSION: Pretreatment with GM1 protects against bupivacaine-induced neurotoxicity via the inhibition of the GRP78/PERK/eIF2α/ATF4-mediated ERS.

Addition of dexmedetomidine to ropivacaine improves cervical plexus block.

OBJECTIVE: To investigate the sensory block onset time, duration time, and side effects of adding dexmedetomidine to ropivacaine for cervical plexus block. METHODS: Forty American Society of Anesthesiologists (ASA) Class I or II adult patients who were scheduled to undergo thyroid surgery were randomly allocated to the following groups to receive cervical plexus block: 30 mL of 0.375% ropivacaine combined with 1 µg kg(-1) of dexmedetomidine; 30 mL of 0.375% ropivacaine combined with saline (control). The sensory block onset time, duration of analgesia, mean arterial pressure (MAP), heart rate (HR), and the incidences of side effects, such as hypotension, bradycardia, and hypoxemia were recorded. RESULTS: The addition of dexmedetomidine to ropivacaine (Group D) shortened the sensory block onset time compared with the ropivacaine group (Group C) (95% confidence interval [CI] 4.18-5.26; p < 0.05). The duration of analgesia of cervical plexus block in Group D was significantly longer than that in Group C (95% CI 295.96-311.12; p < 0.05). The Ramsay sedation score at 5, 10, 20, 40, 60, 90, and 120 minutes after local anesthetic administration in Group D was significantly higher than that in Group C (p < 0.05). MAP level and HR level in Group D were significantly lower than that in Group C (p < 0.05). CONCLUSION: The addition of 1 µg kg(-1) dexmedetomidine to ropivacaine for cervical plexus block could shorten the sensory block onset time and extend the duration of analgesia, and increased the quality of analgesia, with the patients being sedated and arousable.

[Effect of Coflex interspinous stabilization and vertebral arch pedicle screw implantation on the stability of three-dimensional motions of the lumbar spine].

OBJECTIVE: To evaluate the effect of Coflex interspinous stabilization and vertebral arch pedicle screw implant on the stability and motion of the lumbar spine. METHODS: The range of motion (ROM) of 6 fresh adult human cadaver lumbar spine specimens (L(1) approximately S(1)) was biomechanically tested in forward flexion/extension stretch, left/right lateral bending and left/right axial rotation. The ROM and neutral zone (NZ) of the segments L(2/3), L(3/4), and L(4/5) were measured and compared in 3 conditions, namely intact condition (a), rigid fixation of the segment L(4/5) with vertebral arch pedicle screw (b), and condition b plus L(3/4) stabilization with Coflex device (c). RESULTS: The ROM of segment L(4/5) was significantly smaller in conditions b and c than in condition a in all the directions (P<0.05). The ROM of segment L(3/4) was significantly smaller in conditions a and c than in condition b in extension stretch (P<0.01), smaller in condition a than in conditions b and c in left/right lateral bending (P<0.01), and decreased significantly in the order of a0.05). CONCLUSIONS: The ROM of the segment superior to the lumbar spine with rigid fixation increases in all the directions, but can be reduced with Coflex device implanted in the superior segment, which results in only increased ROM of the segment superior to Coflex device in extension stretch.

[Determination of the concentrations of interleukin-18 and other cytokines in the synovial fluid in patients with osteoarthritis].

OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18), IL-6, IL-8, and prostaglandin E2 (PGE2) in the synovial fluid in patients with osteoarthritis (OA), and explore the role of IL-18 in the pathogenesis of OA. METHODS: The synovial fluid was collected from 30 patients with knee OA, and the concentrations of IL-18 and the other cytokines were measured using enzyme-linked immunosorbent assay (ELISA). A linear regression was performed between IL-18 and the other cytokines. RESULTS: The average IL-18 and PGE2 concentrations were 220-/+304 pg/ml and 89-/+104 pg/ml in the synovial fluid, respectively, and the two cytokines showed a positive correlation in the synovial fluid (r=0.628, P=0.001). The IL-18 concentration was also correlated to the concentrations of IL-6 (1200-/+1587 pg/ml, n=22; r=0.590, P=0.008) and IL-8 (5190-/+6024 pg/ml, n=9; r=0.776, P=0.014). CONCLUSION: IL-18 can promote PGE2 production, which causes cartilage degradation in OA, thus therapies targeting this cytokine may prove an effective approach to early OA treatment.