Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease.

ABSTRACT: The globus pallidus plays a pivotal role In the basal ganglia circuit. Parkinson's disease Is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico-striato-pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia-thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

High-Performance Ultraviolet Organic Light-Emitting Diodes Enabled by Double Boron-Oxygen-Embedded Benzo[m]tetraphene Emitters.

Ultraviolet organic light-emitting diodes (UV OLEDs) have attracted increasing attention because of their promising applications in healthcare, industry, and agriculture; however, their development has been hindered by the shortage of robust UV emitters. Herein, we embedded double boron-oxygen units into nonlinear polycyclic aromatic hydrocarbons (BO-PAHs) to regulate their molecular configurations and excited-state properties, enabling novel bent BO-biphenyl (BO-bPh) and helical BO-naphthyl (BO-Nap) emitters with hybridized local and charge-transfer (HLCT) characteristics. They could be facilely synthesized in gram-scale amounts via a highly efficient two-step route. BO-bPh and BO-Nap showed strong UV and violet-blue photoluminescence in toluene with full width at half-maximum values of 25 and 37 nm, along with quantum efficiencies of 98 and 99%, respectively. A BO-bPh-based OLED showed high color purity UV electroluminescence peaking at 394 nm with Commission Internationale de l'Eclairage (CIE) coordinates of (0.166, 0.021). Moreover, the device demonstrated a record-high maximum external quantum efficiency (EQE) of 11.3%, achieved by successful hot exciton utilization. This work demonstrates the promising potential of double BO-PAHs as robust emitters for future UV OLEDs.

Evaluation of sustained drug release performance and osteoinduction of magnetron-sputtered tantalum-coated titanium dioxide nanotubes.

Modifying the drug-release capacity of titanium implants is essential for maintaining their long-term functioning. Titanium dioxide nanotube (TNT) arrays, owing to their drug release capacity, are commonly used in the biomaterial sphere. Their unique half open structure and arrangement in rows increase the drug release capacity. However, their rapid drug release ability not only reduces drug efficiency but also produces excessive local and systemic deposition of antibiotics. In this study, we designed a tantalum-coated TNT system for drug-release optimization. A decreased nanotube size caused by the tantalum nanocoating was observed through SEM and analyzed (TNT: 110 nm, TNT-Ta1: 80 nm, TNT-Ta3: 40 nm, TNT-Ta5: 20 nm, TNT-Ta7: <5 nm). XPS analysis revealed the distribution of the chemical components, especially that of the tantalum element. In vitro experiments showed that the tantalum nanocoating enhanced cell proliferation; in particular, TNT-Ta5 possessed the best cell viability (about 1.18 of TNT groups at 7d). It also showed that the tantalum nanocoating had a positive effect on osteogenesis (especially TNT-Ta5 and TNT-Ta7). Additionally, hydrophilic/hydrophobic drug (vancomycin/raloxifene) release results indicated that the TNT-Ta5 group possessed the most desirable sustained release capacity. Moreover, in this drug release system, the hydrophobic drug showed more sustained release capacity than the hydrophilic drug (vancomycin: sustained release for more than 48 h, raloxifene: sustained release for more than 168 h). More importantly, TNT-Ta5 is proved to be an appropriate drug release system, which possesses cytocompatibility, osteogenic capacity, and sustained drug release capacity.

Fabrication and evaluation of silver modified micro/nano structured titanium implant.

In order to enhance the antibacterial property of titanium implant without inducing obvious cytotoxicity, the combination of Ag nanolayer and micro/nano surface structure was conducted by magnetron sputtering and hot-alkali treatment in this study. A series of specimens (AH-Ti, AH-Ti/Ag0.25, AH-Ti/Ag1, AH-Ti/Ag2, and AH-Ti/Ag5) were prepared with different sputtering durations (0 min, 0.25 min, 1 min, 2 min, 5 min), respectively, all realizing long-term release of Ag+. In vitro experiments indicated that AH-Ti/Ag1 group possessed good cytocompatibility, nice osteogenic ability, and excellent antibacterial efficiency as well. In addition, AH-Ti/Ag0.25 showed good biocompatibility, while the reduction of S.aureus (78.5%) was not enough compared with AH-Ti/Ag1. Although the AH-Ti/Ag2 and AH-Ti/Ag5 group showed superior antibacterial activity, their obvious cytotoxicity caused low ALP and mineralization level. Therefore, the design of suitable Ag nanolayer coating combined with micro/nano surface structure (AH-Ti/Ag1) might be a promising strategy to enhance osteogenic property and maintain excellent antibacterial ability at the same time.

Double boron-oxygen-fused polycyclic aromatic hydrocarbons: skeletal editing and applications as organic optoelectronic materials.

An efficient one-pot strategy for the facile synthesis of double boron-oxygen-fused polycyclic aromatic hydrocarbons (dBO-PAHs) with high regioselectivity and efficient skeletal editing is developed. The boron-oxygen-fused rings exhibit low aromaticity, endowing the polycyclic aromatic hydrocarbons with high chemical and thermal stabilities. The incorporation of the boron-oxygen units enables the polycyclic aromatic hydrocarbons to show single-component, low-temperature ultralong afterglow of up to 20 s. Moreover, the boron-oxygen-fused polycyclic aromatic hydrocarbons can also serve as ideal n-type host materials for high-brightness and high-efficiency deep-blue OLEDs; compared to single host, devices using boron-oxygen-fused polycyclic aromatic hydrocarbons-based co-hosts exhibit dramatically brightness and efficiency enhancements with significantly reduced efficiency roll-offs; device 9 demonstrates a high color-purity (Commission International de l'Eclairage CIEy = 0.104), and also achieves a record-high external quantum efficiency (28.0%) among Pt(II)-based deep-blue OLEDs with Commission International de l'Eclairage CIEy < 0.20; device 10 achieves a maximum brightnessof 27219 cd/m2 with a peak external quantum efficiency of 27.8%, which representes the record-high maximum brightness among Pt(II)-based deep-blue OLEDs. This work demonstrates the great potential of the double boron-oxygen-fused polycyclic aromatic hydrocarbons as ultralong afterglow and n-type host materials in optoelectronic applications.

Altered frontoparietal activity in acoustic startle priming tasks during reticulospinal tract facilitation: An fNIRS study.

Background: Because it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood. Objectives: To explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks. Methods: Twenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30-130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The ß values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses. Results: Separate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed. Conclusion: The right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.

Toward a BT.2020 green emitter through a combined multiple resonance effect and multi-lock strategy.

Color-saturated green-emitting molecules with high Commission Internationale de L'Eclairage (CIE) y values have great potential applications for displays and imaging. Here, we linked the outer phenyl groups in multiple-resonance (MR)-type blue-emitting B (boron)-N (nitrogen) molecules through bonding and spiro-carbon bridges, resulting in rigid green emitters with thermally activated delayed fluorescence. The MR effect and multiple interlocking strategy greatly suppressed the high-frequency vibrations in the molecules, which emit green light with a full-width at half-maximum of 14 nm and a CIE y value of 0.77 in cyclohexane. These were the purest green molecules with quantum efficiency and color purity that were comparable with current best quantum dots. Doping these emitters into a traditional green-emitting phosphorescence organic light-emitting diode (OLED) endowed the device with a Broadcast Service Television 2020 color-gamut, 50% improved external quantum efficiency, and an extremely high luminescence of 5.1 × 105 cd/m2, making it the greenest and brightest OLED ever reported.

Fused 6/5/6 Metallocycle-Based Tetradentate Pt(II) Emitters for Efficient Green Phosphorescent OLEDs.

Pt(II) complexes are promising phosphorescent materials for organic light-emitting diode (OLED) applications in the fields of display, lighting, healthcare, aerospace, and so on. A series of novel biphenyl (bp)-based tetradentate 6/5/6 Pt(II) emitters using oxygen or carbon as a linking atom was designed and developed. The intermolecular interactions in crystal packing, electrochemical, and photophysical properties of the bp-based Pt(II) emitters and also their excited-state properties were systematically studied, which could be effectively regulated by ligand modification through linking group control; however, their emission spectra nearly showed no change. All the bp-based Pt(II) emitters exhibited vibronically featured emission spectra with dominant peaks at 502-505 nm and photoluminescent quantum yields of 24-34% in dichloromethane solution. Green OLED using Pt(bp-12) as an emitter achieved a maximum brightness (Lmax) of 16,644 cd/m2.

Tetradentate Platinum(II) and Palladium(II) Complexes Containing Fused 6/6/6 or 6/6/5 Metallocycles with Azacarbazolylcarbazole-Based Ligands.

A series of novel tetradentate Pt(II) and Pd(II) complexes containing fused 6/6/6 or 6/6/5 metallocycles employing azacarbazolylcarbazole (ACzCz)-based ligands was developed. Systematic experimental and theoretical studies suggest that both the ligand structures and the central metal ions have great influences on the electrochemical and photophysical properties of the complexes. The time-dependent density functional theory (TD-DFT) calculations and natural transition orbital (NTO) analyses reveal that the Pt(II) complexes possess 10.8-15.2% metal-to-ligand charge transfer (3MLCT) mixed with ligand-centered (3LC) characters, by contrast, the Pd(II) complexes exhibit significantly decreased 4.2-7.1% 3MLCT characters and enhanced 3LC compositions. All of the Pt(II) and Pd(II) complexes possess various channels for the intersystem crossing (ISC) on the basis of small energy gaps ΔES1-Tn and matching transition orbital compositions; moreover, Pd(ACzCz-1) and Pd(ACzCz-2) also possess efficient reverse intersystem crossing (RISC) to show both delayed fluorescence (DF) and phosphorescence in PMMA films at room temperature (RT). Pt(ACzCz-3) has ΦPL values of 57% with a τ of 5.1 µs in dichloromethane at RT and 50% with 3.9 µs in PMMA at RT. Notably, Pd(ACzCz-1) exhibits ultralong low-temperature phosphorescence with a τ of 1307 µs. Pt(ACzCz-2)-based green OLED employing 26mCPy as the host demonstrated a peak EQE of 8.2% and a Lmax of 24065 cd/m2.

Magnetron sputtering of strontium nanolayer on zirconia implant to enhance osteogenesis.

The zirconia implants have a wide range of clinical applications, however, the biological inertness and lack of osteoinductive properties limit these applications. Strontium possesses superior biocompatibility and excellent osteogenic properties. To take advantage of these, the strontium titanate-coated zirconia implants were prepared in this study by sandblasting, acid etching, and magnetron sputtering, followed by the analysis of the biological behavior. Briefly, the zirconia sheets were polished and subjected to sandblasting and acid etching. Subsequently, a nano­strontium titanate coating was developed on the sheets by magnetron sputtering. The specimens were characterized by scanning electron microscopy (SEM), water contact angle measurement (WCA) and EDS mapping, which confirmed the physical alternation and successful deposition of the strontium titanate coating. The in vitro experiments indicated that the majority of the filopodia and actin fibers of the MC3T3-E1 cells on SA-ZrO2/Sr possessed an optimal osteogenic property to promote the osteogenic differentiation. Moreover, the RT-PCR results revealed that SA-ZrO2/Sr significantly up-regulated the gene expression of Runx2, COL-1, ALP, OPG, OPN and OCN. Further, the in vivo evaluation confirmed that the SA-ZrO2/Sr implants promoted the bone-implant osseointegration to the greatest extent as compared to SA-ZrO2 and ZrO2 implant. Overall, the SA-ZrO2/Sr system was confirmed to be a promising implant, thus, providing new pathways for an effective implant design.

Urinary N-Acetyl-ß-d-Glucosaminidase (NAG) Levels and Risk of Cardiovascular Events in Diabetic Patients.

BACKGROUND: Cardiovascular diseases (CVDs) have a high incidence rate in population with diabetic patients. Studies on the association between urinary N-acetyl-ß-d-glucosaminidase (NAG) levels, the biomarker of renal tubular damage, with cardiovascular (CV) events diabetic patients was still few. METHODS: The relationship between urinary NAG levels and CV events was analyzed in a prospective cohort including 357 patients with type 2 diabetes mellitus at a follow-up of 5 years. RESULTS: Twenty-six (7.3%) patients have CV events. Kaplan-Meier analysis suggested that diabetic patients with urine NAG levels ≥37.5 IU/L had a higher rate of CV events than those with urine NAG levels <37.5 IU/L (Log rank test, P = 0.021). Cox analysis revealed that elevated urine NAG levels significantly contributed to increased risk of CV events (HR = 1.43, 95% CI 1.23-1.93, P < 0.001) after adjusting for clinical confounding factors. Interestingly, we also found that "abnormal renal function" has an effect modification on the association between urine NAG levels and CV events. ROC-AUC analysis suggested that the urine NAG (AUC = 0.81, P < 0.001) had a better predictive value than eGFR (AUC = 0.74, P = 0.012). CONCLUSION: Elevated urine NAG levels are associated with higher risk of CV events in patients with type 2 diabetes. These results might further suggested that urinary NAG is a value urinary biomarker for early detecting CV events among diabetic patients.

Phosphorescent Tetradentate Platinum(II) Complexes Containing Fused 6/5/5 or 6/5/6 Metallocycles.

A series of phenylpyridine (ppy)-based 6/5/5 N*C^N^O and biphenyl (bp)-based 6/5/6 N*C^C*N Pt(II) complexes employing tetradentate ligands with nitrogen or oxygen atoms as bridging groups have been developed. Ligand structural modifications have great influences on the electrochemical, photophysical, and excited-state properties, as well as photostabilities of the Pt(II) complexes, which were systematically studied by experimental and theoretical investigations. The time-dependent density functional theory calculations and natural transition orbital analyses reveal that Pt(bp-6), Pt(bp-7), and Pt(bp-8) have dominant ligand-centered (3LC) mixed with small metal-to-ligand charge-transfer (3MLCT) characters in T1 states, resulting in relatively low quantum efficiencies (ΦPL) of 5-33% and 12-32% in dichloromethane solution and PMMA film, respectively. By contrast, Pt(ppy-1) possesses much more 3MLCT character in the T1 state, enabling a high ΦPL of 95% in dichloromethane and 90% in DPEPO film, and large radiative decay rates. The strength of the Pt-N1 coordination bond plays a critical role in the photostability. Pt(ppy-1)- and Pt(bp-6)-doped polystyrene films demonstrate long photostability lifetimes of 150 min for LT97 and LT98.5, respectively. A Pt(ppy-1)-based green OLED using 26mCPy as host realized a peak EQE of 18.5%, which still maintained an EQE of 10.4% at 1000 cd/m2, and an Lmax of over 40 000 cd/m2 was achieved. This study should provide a valuable reference for the further development of efficient and stable phosphorescent Pt(II) complexes.

Efficient and Stable Organic Light-Emitting Diodes Employing Indolo[2,3-b]indole-Based Thermally Activated Delayed Fluorescence Emitters.

Triplet excitons can be effectively harvested in organic light-emitting diodes employing thermally activated delayed fluorescence (TADF) molecules as the emitter and host. A design strategy for blue and green emitters with small S1-T1 splitting (ΔEST) is to construct a donor-acceptor (D-A) type molecule with moieties combining a high T1 level with a strong electron-donating/withdrawing character. Here, we report a new kind of TADF emitter with an indolo[2,3-b]indole (IDID) donor. In comparison to other reported indolocarbazole and indoloindole donors, IDID has a higher T1 level, which is comparable to that of the classical donor 9,9-dimethyl-9,10-dihydroacridine (DMAC) for blue TADF emitters. The sky-blue and green TADF emitters based on the IDID donor and a phenyltriazine acceptor exhibit high photoluminescence quantum yields (0.78-0.92) and short TADF lifetimes (1.1-1.7 µs) in doped films. Devices employing these IDID-based emitters offer an external quantum efficiency of 19.2%, which is comparable to that obtained for a device employing an analogous compound with a DMAC donor, while the stability of the former is higher than that of the latter owing to the just-right D-A twisting angles (∼59°) in the IDID-based emitters leading to a balance between ΔEST and the fluorescence rate. The utilization of host materials with a similar polarity to the emitter is found to be an effective strategy to improve device stability.

Metal-Assisted Delayed Fluorescent Pd(II) Complexes and Phosphorescent Pt(II) Complex Based on [1,2,4]Triazolo[4,3-a]pyridine-Containing Ligands: Synthesis, Characterization, Electrochemistry, Photophysical Studies, and Application.

The synthesis and photophysical characterization of a series of tetradentate cyclometalated M(tzpPh-O-CzPy-R) complexes and their analogues are reported, where M is palladium or platinum and a tetradentate cyclometalating ligand contains tzpPh (3-phenyl-[1,2,4]triazolo[4,3-a]pyridine) and CzPy (carbazolylpyridine) moieties linked with an oxygen atom. Variations of the σ-electron-donating group R on the ligand significantly affect the photophysical properties of the complexes. By using the strong electron-withdrawing tzp portion as an acceptor and the carbazole portion as a donor, a series of Pd(II)-based metal-assisted delayed fluorescence (MADF) materials was developed. Electrochemical analysis demonstrates the irreversible reduction process occurs on the tzp ring and the irreversible oxidation process mainly occurs on the metal-phenyl moiety. This is in agreement with the HOMO and LUMO distributions by the DFT calculations, which also shows that the Pt(II) complex has more metal orbital character than those of the Pd(II) complexes. Most of the Pd(II) complexes reported here are highly emissive at 77 K in 2-MeTHF with luminescent lifetimes in the millisecond range (τ = 1.96-2.36 ms) and λmax = 488-499 nm; however, the luminescent lifetimes are shortened to the microsecond range (τ = 26.7-152.9 µs in solution and 57.0-109.9 µs in thin film respectively) at room temperature. The quantum efficiency of the Pd(II) complexes can be increased by more than 8-fold through structure modification with σ-donating groups on the ligand. Especially, the Pd(tzp-3) has a small ΔEST of 0.228 eV and exhibits strong typical MADF in PMMA film. The Pt(II) complex Pt(tzp-2) exhibits high thermal stability (ΔT0.5% = 440 °C) and high quantum efficiency (Φ = 50.1%) in dichloromethane solution with τ of 15.8 µs. The Pt(tzp-2) based bright green OLED achieved a peak EQE of 8.7% and a maximum brightness of 28280 cd/m2 using an unoptimized device structure.

Difluoroboron-Enabled Thermally Activated Delayed Fluorescence.

A new series of tetracoordinated boron-enabled thermally activated delayed fluorescence (TADF) materials with a donor-acceptor BF2-type framework were designed and conveniently synthesized. Difluoroboron plays a critical role and acts as a key to coordinate with the latent acceptor of the 2-(4-phenylpyridin-2-yl)phenol (PPyPOH) moiety to realize TADF. TADF materials are air-stable and have a high photoluminescence quantum yield of up to 99%. NOBF2-Cz- and NOBF2-DPCz-doped blue OLEDs demonstrated EQEs of 11.0% with CIE coordinates of (0.14, 0.16) and 15.8% with (0.14, 0.28) and high brightness of 6761 and 19383 cd/m2 could be achieved, respectively. Moreover, the blue OLED doped with NOBF2-DPCz and the green OLED doped with NOBF2-DMAC achieved operational lifetimes at 50% of initial luminance (L0 = 500 cd/m2), LT50, of 54 and 920 h, respectively. This work indicates that these tetracoordinated difluoroboron molecules can act as efficient and stable TADF materials for OLED applications.

Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced arthritis in DBA/1 mice.

Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1ß and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted ß-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.

Cancer Chemopreventive Effects of Boswellia sacra Gum Resin Hydrodistillates on Invasive Urothelial Cell Carcinoma: Report of a Case.

A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia-derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics of major compounds, as well as long-term benefits and possible adverse effects will be needed to meet the guidelines of the US Food and Drug Administration for botanical drug development.

A Truncated IL-17RC Peptide Ameliorates Synovitis and Bone Destruction of Arthritic Mice.

Peptide-based therapy, such as modified peptides, has attracted increased attention. IL-17 is a promising therapeutic target for autoimmune diseases, and levels of circulating bioactive IL-17 are associated with rheumatoid arthritis severity. In this study, a modified truncated IL-17RC is generated to ameliorate inflammation and bone destruction in arthritis. The truncated IL-17RC binds to both IL-17A and IL-17F with higher binding capacity compared to nonmodified IL-17RC. In addition, the truncated IL-17RC reduces the secretion of inflammatory and osteoclastogenic factors induced by IL-17A/F in vitro. Moreover, the administration of truncated IL-17RC dramatically improves symptoms of inflammation and inhibited bone destruction in collagen-induced arthritis mice. Collectively, these data demonstrate that modified truncated IL-17RC peptide may be a more effective treatment strategy in the simultaneous inhibition of both IL-17A and IL-17F signaling, whereas the existing agents neutralize IL-17A or IL-17F alone. These suggest that the truncated IL-17RC may be a potential candidate in the treatment of inflammatory associated bone diseases.

Preparation and Characterization of Lanthanum-Incorporated Hydroxyapatite Coatings on Titanium Substrates.

Titanium (Ti) has been widely used in clinical applications for its excellent biocompatibility and mechanical properties. However, the bioinertness of the surface of Ti has motivated researchers to improve the physicochemical and biological properties of the implants through various surface modifications, such as coatings. For this purpose, we prepared a novel bioactive material, a lanthanum-incorporated hydroxyapatite (La-HA) coating, using a dip-coating technique with a La-HA sol along with post-heat treatment. The XRD, FTIR and EDX results presented in this paper confirmed that lanthanum was successfully incorporated into the structure of HA. The La-HA coating was composed of rod-like particles which densely compacted together without microcracks. The results of the interfacial shear strength test indicated that the incorporation of lanthanum increased the bonding strength of the HA coating. The mass loss ratios under acidic conditions (pH=5.5) suggested that the La-HA coatings have better acid resistance. The cytocompatibility of the La-HA coating was also revealed by the relative activity of alkaline phosphatase, cellular morphology and cell proliferation assay in vitro. The present study suggested that La-HA coated on Ti has promising potential for applications in the development of a new type of bioactive coating for metal implants.

In vivo evaluation of in situ polysaccharide based hydrogel for prevention of postoperative adhesion.

In this paper, the carboxymethyl chitosan/oxidized dextran hydrogel was developed and its potency application in the prevention of postoperative adhesion was investigated. The developed hydrogel showed porous and interconnected interior structure with pore size about 250 µm, which was sensitive to lysozymic solution (1.5 µg/ml) with almost complete degradation after 4 weeks of in vitro incubation. In vivo study suggested that the developed hydrogel showed the great capacity on the prevention of postoperative adhesions in rat model. According to the result of histopathological examination, it clearly showed that the mesothelial cell layer of abdominal wall and cecum were completely recovered after 7 days of surgery in 3% carboxymethyl chitosan/oxidized dextran hydrogel group, while obvious adhesion between abdominal wall and cecum was observed as treatment with saline solution or 3% carboxymethyl chitosan solution after 1 day of surgery. All these results suggested that the developed biodegradable hydrogel might have potential application in the prevention of postoperative adhesion.