The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications.

Changes in lifestyle induce an increase in patients with hyperuricemia (HUA), leading to gout, gouty arthritis, renal damage, and cardiovascular injury. There is a strong inflammatory response in the process of HUA, while dysregulation of immune cells, including monocytes, macrophages, and T cells, plays a crucial role in the inflammatory response. Recent studies have indicated that urate has a direct impact on immune cell populations, changes in cytokine expression, modifications in chemotaxis and differentiation, and the provocation of immune cells by intrinsic cells to cause the aforementioned conditions. Here we conducted a detailed review of the relationship among uric acid, immune response, and inflammatory status in hyperuricemia and its complications, providing new therapeutic targets and strategies.

Impact of leptin or melatonin on Sema4D overexpression-related bone metabolism.

PURPOSE: The current study aims to investigate the regulatory impact of leptin or melatonin on bone metabolism as well as the underlying mechanism in conjunction with Sema4D (monoclonal antibody to semaphorin 4D). METHODS: Rats were used to create the osteoporosis model utilizing the OVX (OVariectomize) technique. Rat tibial specimens from each side were collected for three-dimensional reconstruction and Micro-CT scanning examination. The Hematoxylin-osinstaining (HE) staining technique was used to determine the pathological condition of bone tissues. The ELISA (Enzyme-Linked Immunosorbent Assay) assay was used to measure the amount of estradiol present in the serum. In the current study, there were six groups: control, OVX, OVX + NL (no load group), OVX + Sema4D, OVX + Sema4D + leptin, and OVX + Sema4D + MT (melatonin). Rats were given injections of the Sema4D or leptin overexpressing vectors via the tail vein in accordance with the aforementioned classification. By using a high-resolution micro-CT technology, 3D bone structure was discovered. The activity of tartrate-resistant acid phosphatase-5b (TRAP-5b) and bone-derived alkaline phosphatase (BALP) in serum was assessed using an ELISA. The number of osteoclasts in the metaphysis of the upper tibia was determined using TRAP (tartrate-resistant acid phosphatase) staining. Immunohistochemistry was used to find leptin and bone morphogenetic protein-2 (BMP-2) expressions in bone tissue. RESULTS: The BV/TV (Bone volume/Tissue volume), Tb.N (Trabecular number), BMD (Bone Mineral Density), and BMC (Bone Mineral Content) levels were significantly higher in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups compared to OVX + NL, while Tb.Sp (Trabecular separation) levels were significantly lower. In contrast to the OVX group, the bone trabeculae in the OVX + Sema4D + leptin and OVX + Sema4D + MT groups had a relatively complete structure and tended to be organized closely. The amount of bone trabeculae grew drastically, whereas the proportion of TRAP-positive osteoclasts declined dramatically. BMP-2 and leptin were also elevated, while BALP and TRAP-5b activity was reduced. CONCLUSION: Leptin or melatonin improved Sema4d's role in trabecular bone microstructure, bone production, and repairment of trabecular bone loss in osteoporosis rats.

Development of Inhalable Chitosan-Coated Oxymatrine Liposomes to Alleviate RSV-Infected Mice.

Human respiratory syncytial virus (RSV) infection is the most important cause of acute lower respiratory tract infection in infants, neonates, and young children, even leading to hyperinflation and atelectasis. Oxymatrine (OMT), originating from natural herbs, possessed potential antivirus activity against influenza A virus, Coxsackie B3 virus, and RSV, whereas the absence of an in vivo study indicated the difficulties in overcoming the physiological obstacles. Since RSV basically replicated in lung tissue, in this study, we fabricated and characterized a chitosan (CS)-coated liposome with OMT loaded for the treatment of lethal RSV infection via inhalation. The results uncovered that OMT, as a hydrophilic drug, was liable to diffuse in the mucus layer and penetrate through the gas-blood barrier to enter systemic circulation quickly, which might restrict its inhibitory effect on RSV replication. The CS-coated liposome enhanced the distribution and retention of OMT in lung tissue without restriction from mucus, which contributed to the improved alleviative effect of OMT on lethal RSV-infected mice. Overall, this study provides a novel inhalation therapy for RSV infection, and the CS-coated liposome might be a potential inhalable nanocarrier for hydrophilic drugs to prevent pulmonary infections.

Short-interval exposure to ambient fine particulate matter (PM2.5) exacerbates the susceptibility of pulmonary damage in setting of lung ischemia-reperfusion injury in rodent: Pharmacomodulation of melatonin.

This study tested the hypothesis that exposure to ambient fine particulate matter (PM2.5) pollution increased susceptibility of rat lung to damage from acute ischemia-reperfusion (IR) injury that was reversed by melatonin (Mel) treatment. Male-adult SD rats (n = 30) were categorized into group 1 (normal control), group 2 (PM2.5 only), group 3 (IR only at day 8 after PM2.5 exposure), group 4 (PM2.5 + IR) and group 5 (PM2.5 + IR + Mel), and all animals were sacrificed by day 10 after PM2.5 exposure. Oxygen saturation (%) was significantly higher in group 1 than in other groups and significantly lower in group 4 than in groups 2, 3 and 5 but it did not differ among the latter three groups (p < 0.01). Pulmonary protein expressions of inflammation (MMP-9/TNF-α/NF-kB), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (mitochondrial-Bax/caspase-3/PARP) and fibrosis were lowest in group 1, highest in group 4, significantly higher in group 5 than in groups 2 and 3 (all p < 0.0001), but they did not differ between groups 2 and 3. Inflammatory cell infiltration in lung parenchyma, specific inflammatory cell surface markers (CD14+, F4/88+), allergic inflammatory cells (IgE+, eosinophil+), number of goblet cells, thickness of tracheal epithelial layer and fibrotic area exhibited an identical pattern of protein expressions to inflammation among the five groups (all p < 0.0001). In conclusion, lung parenchymal damage and a rigorous inflammatory response were identified in rodent even with short-term PM2.5 exposure.

[Analysis of curative effect of traditional Chinese bone setting manipulation for the treatment of femoral neck fracture].

OBJECTIVE: To analysis the outcome of modified closure bone setting manipulation for the treatment of femoral neck fracture. METHODS: From January 2012 to December 2012, 47 cases of femoral neck fracture were treated and included 25 males and 22 females with an average age of (44.58±10.32) years old ranging from 23 to 61 years old. All patients had a history of trauma, hip pain and movement limited, limb shortening extorsion deformity, X-ray showed fracture between femoral head and femoral neck basic. Among them, 32 cases were Garden type III and 15 cases were type IV. Patients were performed surgical treatment at 2 to 5 days after admission with 45 degrees abduction and extension position, internal rotation reduction, and 3 guide pins were inverted in a equilateral triangular structure of upside down arrangement. The postoperative recovery quality, fracture healing, femoral head necrosis and hip function were observed. RESULTS: Operation time was 40 to 70 min, intraoperative bleeding was 20 to 50 ml. All patients received good reposition, and the intraoperative perspective was 12 to 25 times. Forty-five patients were followed up for 24 to 36 months, and 2 cases were lost. Fracture of 45 cases were got bony healing, 3 cases with partial necrosis of femoral head, both in the ARCO stage II. Twenty-four months after operation, Harris hip function score was 43.24±2.74 in pain, 42.82±1.95 in function, 3.72±0.45 in deformity, 2.77±0.52 in activity, 92.56±4.42 in total;the outcome was excellent in 39 cases, good in 4 cases, fair in 2 cases, without unbroken nails, infection, deep venous thrombosis, fracture and other complications. CONCLUSIONS: Treatment of femoral neck fracture with the modified bone setting manipulation has an advantages of good effect, postoperative hip function recovery, curative effect.

Optically excited nanoscale ultrasonic transducers.

In order to work at higher ultrasonic frequencies, for instance, to increase the resolution, it is necessary to fabricate smaller and higher frequency transducers. This paper presents an ultrasonic transducer capable of being made at a very small size and operated at GHz frequencies. The transducers are activated and read optically using pulsed lasers and without physical contact between the instrumentation and the transducer. This removes some of the practical impediments of traditional piezoelectric architectures (such as wiring) and allows the devices to be placed immediately on or within samples, reducing the significant effect of attenuation which is very strong at frequencies above 1 GHz. The transducers presented in this paper exploit simultaneous optical and mechanical resonances to couple the optical input into ultrasonic waves and vice versa. This paper discusses the mechanical and optical design of the devices at a modest scale (a few µm) and explores the scaling of the transducers toward the sub-micron scale. Results are presented that show how the transducers response changes depending on its local environment and how the resonant frequency shifts when the transducer is loaded by a printed protein sample.

Characterization of metal matrix composites by linear ultrasonics and finite element modeling.

Titanium metal matrix composites (TiMMCs) offer advantages over traditional materials for aerospace applications due to the increased mechanical strength of the materials. But the non-destructive inspection of these materials, especially with ultrasound, is in an infancy stage. If the manufacturing process of TiMMC is not correctly controlled, then disbonds and voids between the fibers can result. The effective microstructure of the composite makes difficulty to interpret results from traditional ultrasound techniques because of the scattering caused by fibers; the scattering prevents the ultrasound from penetrating far into the composite region and produces a background signal masking any reflections from voids. In this paper, relatively low frequency ultrasound is used to probe the composite region, and the state of the composite (porosity) is inferred from the velocity of the ultrasound traversing the composite. The relationship between the velocity and porosity is complex in this regime, so finite element (FE) analysis is used to model the composite regions and relate the velocity to the porosity. The FE simulated results are validated by ultrasound velocity measurements.

Lasing action and optical amplification in Nd3+ doped electrooptic lanthanum lead zirconate titanate ceramics.

Both single-pass gain and lasing action at 1064.4 nm were observed in ceramic gain media of neodymium doped lanthanum-modified lead zirconate titanate, which exhibits good electrooptic (EO) effect from visible through mid-wave IR band (400 nm to 5.5 µm). These works have removed roadblocks off the way leading to development of long envisioned multifunctional optical devices. The impact of the Nd3+ doping concentration on the EO effect in the Nd3+:PLZT ceramics was studied. The finding of the slowly trailing-off was satisfactorily explained with the rich vacancy-based carrier traps, which are responsible for the long persistent optoenergy storage.

A laser-activated MEMS transducer for efficient generation of narrowband longitudinal ultrasonic waves.

In this paper, we demonstrate an optically powered microelectromechanical system (MEMS) transducer. It was designed and fabricated using MEMS techniques, and can generate narrowband ultrasonic bulk waves from a broadband laser excitation pulse with high efficiency. The transducer is a two-mask-level MEMS device with a microdisk seated on a microstem. When a laser pulse is incident on the disk center, a resonant flapping motion of the disk is actuated because of the thermomechanical interaction between the absorbing and non-absorbing parts of the disk, coupling a narrowband longitudinal bulk wave propagating along the axis of the stem into the sample. Finite element (FE) methods were used to simulate the generated ultrasound; the results agree well with experimental measurements. Experiments with the fabricated transducers have shown that narrowband ultrasound with a high SNR/amplitude was generated successfully; compared with normal thermoelastic generation, ultrasound with at least 5 times higher amplitude can be achieved by an optimized MEMS transducer. The transducer is inexpensive, compact, and simple to use.

Design and experimental study of microcantilever ultrasonic detection transducers.

This paper presents the analysis, design, and experimental study of a microcantilever optically-activated ultrasonic detection transducer. An analytical model was derived using 1-D cantilever structural dynamics, leading to the optimization of the transducer design. Finite element modeling enabled dynamic simulation to be performed, with results in good agreement with the analytical model. Transducers were fabricated using MEMS (microelectromechanical systems) techniques. Experimental results are presented on remote noncontact detection of ultrasound using the fabricated transducers; high SNR is achieved for the detected signals, even for relatively low ultrasonic amplitudes. Both analysis and experimental study show that the transducer has a sensitivity approximately 1 to 2 orders of magnitude higher than that of conventional optical detection techniques. Furthermore, we show that the dominant factor in the increased sensitivity of the transducer is the resonant nature of the finger structure.

[Relationship between inflammation and neointimal proliferation after coronary stent implantation in porcine model].

OBJECTIVE: To study the relationship between inflammation and neointimal proliferation after coronary stent implantation in porcine model. METHODS: Twenty normal minipigs were randomly divided into group A (implanted with 316L bare metal stents), group B (implanted with 605L bare metal stents), group C (implanted with PLGA coating 605L stents), and group D (implanted with rapamycin-loaded PLGA coating 605L stents). Each minipig was implanted with two same stents in left anterior descending artery and right coronary artery. Four weeks later, the animals were sacrificed and histomorphometric measurements on the stent-segment coronary arteries were made to calculate the correlation between inflammation area and neointimal area. RESULTS: Group D had the smallest neointimal area [(0.64 +/- 0.38) mm2, P < 0. 001] and inflammation area (median 0.00 mm2, P = 0.009) among all the groups, while there were no statistical differences among group A, B, and C in neointimal area [(2.09 +/- 0.90), (2.11 +/- 1.07), and (1.42 +/- 0.35) mm2 respectively] and in inflammation area (0.22 , 0.21, and 0.09 mm2, respectively). Bivariate correlation analysis showed that the inflammation area was positively correlated with the neointimal area (P < 0.001, correlation coefficient = 0.719). When stent type, mean injury score, and EEL area were adjusted, partial correlations analysis showed that the inflammation area was still positively correlated with the neointimal area (P = 0.01, correlation coefficient = 0.498). CONCLUSION: Inflammation promotes the neointimal proliferation after coronary stent implantation. Sirolimus-eluting stent may reduce the inflammatory response.

Wavelength translation based on photoinduced broadband absorption in Nd3+ -doped lanthanum lead zirconate titanate ceramics.

A correlation between a photoinduced broadband absorption (BBA) and a strong long persistent optoenergy storage (LPOES), both evident in ceramic plates of neodymium-doped lanthanum-modified lead zirconate titanate (Nd:PLZT), has been proposed and verified experimentally. As a direct evidence of the suggested correlation, a 3.0 dB gain was obtained with a preilluminated Nd:PLZT plate by simply heating up the plate to 60 degrees C. Thermal history related gain profiles taken in an Nd:PLZT plate unveiled that the intrinsically rich carrier traps in the ceramics are highly responsible for the remarkable BBA and underlying LPOES, and hence thermal to near-IR wavelength translation.