Astragaloside IV attenuates renal tubule injury in DKD rats via suppression of CD36-mediated NLRP3 inflammasome activation.

Background: In recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated. Purpose: The primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß). Methods: The DKD rat model was created by administering streptozotocin along with a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinations were conducted. The levels of CD36, ROS, NLRP3, Caspase-1, and IL-1ß were detected using western blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments. Results: In vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1ß, TNF-α, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1ß secretion in PA-induced HK-2 cells. Conclusion: AS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation.

Field observations of C2 and C3 organosulfates and insights into their formation mechanisms at a suburban site in Hong Kong.

Organosulfates (OSs) are formed from volatile organic compounds (VOCs) and their oxidation products in the presence of sulfate particles. While OSs represent an important component in secondary organic aerosol, the knowledge of their formation driving force, mechanisms, and environmental impact remain inadequately understood. In this study, we report ambient observations of C2-3 oxygenated VOCs derived OSs (C2-3 OSs) at a suburban location of Hong Kong during autumn 2016. The C2-3 OSs, including glycolaldehyde sulfate (GS), hydroxyacetone sulfate (HAS), glycolic acid sulfate (GAS), and lactic acid sulfate (LAS), were quantified/semi-quantified using offline liquid chromatography-mass spectrometry analysis of aerosol filter samples. The average sum concentration of C2-3 OSs was 36 ng/m3. Correlation analysis revealed that sulfate, surface area, and liquid water content were important factors influencing C2-3 OS formation. Online measurement with an iodide High-Resolution Time-of-Flight Chemical-Ionization Mass Spectrometer (HR-ToF-CIMS) coupled with the Filter Inlet for Gases and AEROsols (FIGAERO) was also conducted to monitor C2-3 OSs, and their potential oxygenated VOC precursors in both gas- and particle-phase, and aerosol acidity tracer simultaneously. Our measurements support that glycolaldehyde/glyoxal, hydroxyacetone, glycolic acid/glyoxal, and lactic acid/methylglyoxal are likely precursors for GS, HAS, GAS, and LAS, respectively. Additionally, we found strong correlation between C2-3 OSs and H3S2O8-, a marker for aerosol acidity, providing field observational evidence for acid-catalyzed formation of small OSs. Based on both online and offline measurements, acid-catalyzed formation mechanisms in particle/aqueous phase are proposed. Specifically, the unique structure of adjacent carbonyl and hydroxyl groups in the C2-3 oxygenated VOC precursors can facilitate the formation of (1) a five-member ring intermediate via intramolecular hydrogen bond to react with sulfur trioxide through heterogenous reaction or (2) cyclic sulfate intermediate via particle-phase reaction with sulfuric acid to generate C2-3 OSs. These proposed mechanisms provide an alternative pathway for the liquid-phase production of C2-3 OSs.

Interaction behaviors of sulfamethoxazole and microplastics in marine condition: Focusing on the synergistic effects of salinity and temperature.

Microplastics and antibiotics are two common pollutants in the ocean. However, due to changes of salinity and temperature in the ocean, their interaction are significantly different from that of fresh water, and the mechanism remains unclear. Here, the interactions of sulfamethoxazole (SMZ) and microplastics were studied at different temperatures and salinities. The saturation adsorption capacity of SMZ in polypropylene (PP), polyethylene (PE), styrene (PS), polyvinyl chloride (PVC), and synthetic resins (ABS) were highest at the temperature of 20 °C, with 0.118 ± 0.002 mg·g-1, 0.106 ± 0.004 mg·g-1, 0.083 ± 0.002 mg·g-1, 0.062 ± 0.007 mg·g-1 and 0.056 ± 0.003 mg·g-1, respectively. The effect of temperature reduction is more significant than temperature rise. The intraparticle diffusion model is appropriate to PP, when film diffusion model suited for PS. The salinity has a more significant effect than temperature on different microplastics, due to the electrostatic adsorption and iron exchange. With the increase in salinity from 0.05% to 3.5%, the adsorption capacity of microplastics on SMZ fell by 53.3 ± 5%, and there was no discernible difference of various microplastics. The hydrogen bond and π-π conjugation of microplastics play an important role in the adsorption of SMZ. These findings further deepen the understanding of the interaction between microplastics and antibiotics in the marine environment.

Iron-modified biochar boosts anaerobic digestion of sulfamethoxazole pharmaceutical wastewater: Performance and microbial mechanism.

The accumulation of volatile fatty acids (VFAs) caused by antibiotic inhibition significantly reduces the treatment efficiency of sulfamethoxazole (SMX) wastewater. Few studies have been conducted to study the VFAs gradient metabolism of extracellular respiratory bacteria (ERB) and hydrogenotrophic methanogen (HM) under high-concentration sulfonamide antibiotics (SAs). And the effects of iron-modified biochar on antibiotics are unknown. Here, the iron-modified biochar was added to an anaerobic baffled reactor (ABR) to intensify the anaerobic digestion of SMX pharmaceutical wastewater. The results demonstrated that ERB and HM were developed after adding iron-modified biochar, promoting the degradation of butyric, propionic and acetic acids. The content of VFAs reduced from 1166.0 mg L-1 to 291.5 mg L-1. Therefore, chemical oxygen demand (COD) and SMX removal efficiency were improved by 22.76% and 36.51%, and methane production was enhanced by 6.19 times. Furthermore, the antibiotic resistance genes (ARGs) such as sul1, sul2, intl1 in effluent were decreased by 39.31%, 43.33%, 44.11%. AUTHM297 (18.07%), Methanobacterium (16.05%), Geobacter (6.05%) were enriched after enhancement. The net energy after enhancement was 0.7122 kWh m-3. These results confirmed that ERB and HM were enriched via iron-modified biochar to achieve high efficiency of SMX wastewater treatment.

Astragaloside IV attenuates myocardial dysfunction in diabetic cardiomyopathy rats through downregulation of CD36-mediated ferroptosis.

Diabetic cardiomyopathy (DCM), one of the major complications of type 2 diabetes, is a leading cause of heart failure and death in advanced diabetes. Although there is an association between DCM and ferroptosis in cardiomyocytes, the internal mechanism of ferroptosis leading to DCM development remains unknown. CD36 is a key molecule in lipid metabolism that mediates ferroptosis. Astragaloside IV (AS-IV) confers various pharmacological effects such as antioxidant, anti-inflammatory, and immunomodulatory. In this study, we demonstrated that AS-IV was able to recover the dysfunction of DCM. In vivo experiments showed that AS-IV ameliorated myocardial injury and improved contractile function, attenuated lipid deposition, and decreased the expression level of CD36 and ferroptosis-related factors in DCM rats. In vitro experiments showed that AS-IV decreased CD36 expression and inhibited lipid accumulation and ferroptosis in PA-induced cardiomyocytes. The results demonstrated that AS-IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in DCM rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.

Stimulating Anaerobic Degradation of Butyrate via Syntrophomonas wolfei and Geobacter sulfurreducens: Characteristics and Mechanism.

Anaerobic digestion (AD) has been widely applied for the degradation of organic wastewater due to its advantages of high-load operation and energy recovery. However, some challenges, such as low treatment capacity and instability caused by the accumulation of volatile fatty acids, limit its further application. Here, S. wolfei and G. sulfurreducens were initially co-cultured in the anaerobic anode of bio-electrochemical system for degrading butyric acid. Butyrate degradation characteristics in different conditions were quantitatively described. Moreover, G. sulfurreducens simultaneously strengthened the consumption of H2 and acetic acid via direct interspecies electron transfer, thereby strengthening the degradation of butyric acid via a co-metabolic process. During butyrate degradation, the co-culture of S. wolfei and G. sulfurreducens showed more advantages than that of S. wolfei and methanogens. This present study provides a new perspective of butyrate metabolism, which was independent of methanogens in an AD process.

Two-stage hybrid microalgal electroactive wetland-coupled anaerobic digestion for swine wastewater treatment in South China: Full-scale verification.

Constructed wetlands have been widely used for organic wastewater treatment owing to low operating costs and simple maintenance. However, there are some disadvantages such as unstable efficiency in winter. In this study, a microalgal electroactive biofilm-constructed wetland was coupled with anaerobic digestion for full-scale treatment of swine wastewater. In a 12-month outdoor trial, the overall removal efficiencies of chemical oxygen demand, ammonium, nitrate, total nitrogen, total phosphorus, and nitrite reached 98.26%/95.14%, 97.96%/92.07%, 85.45%/66.04%, 95.07%/91.48%, 91.44%/91.52%, and 85.45%/84.67% in summer/winter, respectively. Hydrolytic bacteria were dominant in the anaerobic digestion part, and Cyanobium, Shewanella, and Azoarcus were enriched in the microalgal electroactive biofilm. The operating cost of the entire system was approximately 0.118 $/m3 of wastewater. These results confirm that the microalgal electroactive biofilm significantly enhances the efficiency and stability of constructed wetlands. In conclusion, the anaerobic digestion-microalgal electroactive biofilm-constructed wetland is technically and economically feasible for the treatment of swine wastewater.

Novel insights into the anaerobic digestion of propionate via Syntrophobacter fumaroxidans and Geobacter sulfurreducens: Process and mechanism.

The accumulation of volatile fatty acids, particularly propionic acid, significantly inhibits the efficiency of the anaerobic digestion system. In propionate degradation metabolism, the unfavorable thermodynamics of syntrophic reactions, strict ecological niche of syntrophic priopionate oxidizing bacteria, and slow metabolic rate of methanogens are regarded as major limitations. In this study, Geobacter sulfurreducens was co-cultured with Syntrophobacter fumaroxidans in bioelelectrochemical cells to analyze the propionate degradation process, impact factor, mechanism metabolic pathways, and electron transfer comprehensively. The results revealed that the syntroph S. fumaroxidans and syntrophic partner G. sulfurreducens achieved more efficient propionate degradation than the control group, comprising S. fumaroxidans and methanogens. Moreover, the carbon resource concentration and pH were both significantly correlated with propionate degradation (P < 0.01). The results further confirmed that G. sulfurreducen strengthened the consumption of H2 and acetate via direct interspecific electron transfer in propionate degradation. These findings indicate that G. sulfurreducens plays an unidentified functional role in propionate degradation.

Quantitative evaluation of dexamethasone treatment effects in renal ischemia-reperfusion injury using contrast enhanced ultrasonography in rats.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury often occurs in various clinical events, and its incidence and mortality have been increasing. OBJECTIVE: To investigate the value of contrast enhanced ultrasonography (CEUS) in the monitoring of dexamethasone in the improvement of renal I/R injury in rats. METHODS: Eighteen healthy male Sprague-Dawley rats were randomly divided into sham-operated, I/R, and I/R surgery plus dexamethasone treatment (Dexa) groups. In the I/R group 45-minute renal ischemia with 24 h reperfusion period was monitored. Time-intensity curve (TIC)-derived parameters, which included peak value, time to peak (TP), area under the curve (AUC), and mean transit time (MTT) were compared to the blood creatinine, urea, Caspase-1, and NLRP3 levels. RESULTS: The I/R group showed an increased peak value, prolonged TP and MTT, and greater AUC (P < 0.05). The Dexa group showed shorter TP and MTT, and smaller AUC (P < 0.05). Results show that the associations between (i) TP, AUC, and MTT and (ii) creatinine, urea, Caspase-1, and NLRP3 levels were significant (P < 0.05). CONCLUSION: Dexamethasone can alleviate renal I/R injury in rats, which may be related to the inhibition of NLRP3 and caspase-1. CEUS can quantitatively measure this change, in which the changes in TP, AUC and MMT values have considerable reference values.

Monoterpene and Sesquiterpene α-Hydroxy Organosulfates: Synthesis, MS/MS Characteristics, and Ambient Presence.

Organosulfates (OSs) derived from biogenic volatile organic compounds are important compounds signifying interactions between anthropogenic sulfur pollution and natural emission. In this work, we substantially expand the OS standard library through the chemical synthesis of 26 α-hydroxy OS standards from eight monoterpenes (i.e., α- and ß-pinene, limonene, sabinene, Δ3-carene, terpinolene, and α- and γ-terpinene) and two sesquiterpenes (i.e., α-humulene and ß-caryophyllene). The sulfation of unsymmetrically substituted 1,2-diol intermediates produced a regioisomeric mixture of two OSs. The major regioisomeric OSs were isolated and purified for full NMR characterization, while the minor regioisomers could only be determined by liquid chromatograph-mass spectrometer (MS). The tandem mass spectra of the molecular ion formed through electrospray ionization confirmed the formation of abundant bisulfate ion fragments (m/z 97) and certain minor ion fragments characteristic of the carbon backbone. A knowledge of the MS/MS spectra and chromatographic retention times for authentic standards allows us to identify α-hydroxy OSs derived from six monoterpenes and ß-caryophyllene in ambient samples. Notably, among two possible regioisomers of α-hydroxy OSs, we only detected the isomers with the sulfate group at the less substituted carbon position derived from α-pinene, limonene, sabinene, Δ3-carene, and terpinolene in the ambient samples. This observation sheds light on the atmospheric OS formation mechanisms.

Research on a Novel Fabry⁻Perot Interferometer Model Based on the Ultra-Small Gradient-Index Fiber Probe.

A novel Fabry⁻Perot (F⁻P) interferometer model based on the ultra-small gradient-index (GRIN) fiber probe is investigated. The signal arm of the F⁻P interferometer is organically combined with the ultra-small GRIN fiber probe to establish the theoretical model of the novel F⁻P interferometer. An interferometer experimental system for vibration measurements was built to measure the performance of the novel F⁻P interferometer system. The experimental results show that under the given conditions, the output voltage of the novel interferometer is 3.9 V at the working distance of 0.506 mm, which is significantly higher than the output voltage 0.48 V of the single-mode fiber (SMF) F⁻P interferometer at this position. In the range of 0.1⁻2 mm cavity length, the novel interferometer has a higher output voltage than an SMF F⁻P interferometer. Therefore, the novel F⁻P interferometer is available for further study of the precise measurement of micro vibrations and displacements in narrow spaces.

CD36 Enhances Vascular Smooth Muscle Cell Proliferation and Development of Neointimal Hyperplasia.

Objective- Dysregulated proliferation of vascular smooth muscle cells (VSMC) plays an essential role in neointimal hyperplasia. CD36 functions critically in atherogenesis and thrombosis. We hypothesize that CD36 regulates VSMC proliferation and contributes to the development of obstructive vascular diseases. Approach and Results- We found by immunofluorescent staining that CD36 was highly expressed in human vessels with obstructive diseases. Using guidewire-induced carotid artery injury and shear stress-induced intima thickening models, we compared neointimal hyperplasia in Apoe-/-, Cd36-/- /Apoe-/-, and CD36 specifically deleted in VSMC (VSMC cd36-/-) mice. CD36 deficiency, either global or VSMC-specific, dramatically reduced injury-induced neointimal thickening. Correspondingly, carotid artery blood flow was significantly increased in Cd36-/- /Apoe-/- compared with Apoe-/- mice. In cultured VSMCs from thoracic aorta of wild-type and Cd36-/- mice, we found that loss of CD36 significantly decreased serum-stimulated proliferation and increased cell populations in S phase, suggesting that CD36 is necessary for VSMC S/G2-M-phase transition. Treatment of VSMCs with a TSR (thrombospondin type 1 repeat) peptide significantly increased wild-type, but not Cd36-/- VSMC proliferation. TSR or serum treatment significantly increased cyclin A expression in wild-type, but not in Cd36-/- VSMCs. STAT3 (signal transducer and activator of transcription), which reportedly enhances both VSMC differentiation and maturation, was higher in Cd36-/- VSMCs. CD36 deficiency significantly decreased expression of Col1A1 (type 1 collagen A1 chain) and TGF-ß1 (transforming growth factor beta 1), and increased expression of contractile proteins, including calponin 1 and smooth muscle α actin, and dramatically increased cell contraction. Conclusions- CD36 promotes VSMC proliferation via upregulation of cyclin A expression that contributes to the development of neointimal hyperplasia, collagen deposition, and obstructive vascular diseases.

Biomechanically stimulated chondrocytes promote osteoclastic bone resorption in the mandibular condyle.

OBJECTIVE: Chondrocyte signaling is important in osteoclastic bone resorption in mice tibiae. The present study aimed to test whether biomechanically stimulated chondrocytes promote osteoclastic bone resorption in the mandibular condyle. METHODS: Primary chondrocytes isolated from rat condylar cartilage were stimulated by fluid flow shear stress (FSS) for 30, 60, 120 min at intensities of 10, 20, or 30 dynes/cm2. The levels of pro-osteoclastic factors and pro-osteoclastic function of FSS-stimulated chondrocytes were tested. Abnormal molar occlusion was established in rats, and the relationship between cartilage degeneration and osteoclastogenesis in the subchondral bone of the mandibular condyle, and the expression of pro-osteoclastic factors in condylar cartilage, were evaluated. RESULTS: The mRNA and protein levels of SDF-1 and TGFß-1 increased significantly in all FSS-treated groups; the levels of RANKL and RANKL:OPG increased in all intensities and in 60 and 120 min of FSS; and those of Wnt5 A increased in all time-points and in 20 and 30 dynes/cm2 of FSS-treated groups (all compared with their levels the controls; P < 0.05). The percent area of degenerative cartilage changes correlated positively with osteoclast number and osteoclast surface/bone surface in the mandibular condyles of abnormal occlusion rats (P < 0.05). Abnormal occlusion increased the immune-positive area and the mRNA expression levels of Sdf1, Tgfb1, Rankl, Wnt5a and the RANKL:OPG ratio in rat condylar cartilage compared with those in the controls (all P < 0.05). CONCLUSION: Chondrocytes under mechanical stimulation could express higher levels of pro-osteoclastic factors and induced condylar subchondral bone resorption by promoting osteoclastogenesis.

Aromatic formulas in ambient PM2.5 samples from Hong Kong determined using FT-ICR ultrahigh-resolution mass spectrometry.

Many aromatic compounds (e.g., polycyclic aromatic hydrocarbons (PAHs)) found in atmospheric aerosols are toxic and exist in both unsubstituted and substituted forms. Previous studies have mainly concentrated on investigating unsubstituted PAHs, leaving the substituted compounds largely uncharacterized. This study focuses on detection of both unsubstituted and substituted aromatics in ambient aerosol samples using ultrahigh-resolution mass spectrometry. Aerosol samples collected from roadside, urban, and suburban sites in Hong Kong were characterized by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) coupled with atmospheric pressure photoionization (APPI) or electrospray ionization (ESI). In the APPI+ mode, 166 aromatic CH formulas (i.e., formulas containing C and H only and with a double bond equivalent (DBE) of 4 or higher) were determined through molecular formula calculations based on an accurate m/z determination. Among the determined aromatic CH formulas, 141 are possible alkylated monocyclic aromatic hydrocarbon (MAH) or PAH formulas, and account for ≥ 45% of the total intensity by aromatic CH+ formulas. Both APPI+ and ESI+ are effective in detecting nitroaromatics (i.e., CHO2N1 formulas and DBE ≥ 5). The two ionization modes provide complementary formula coverage, with formulas determined by APPI+ extending to higher DBE and those by ESI+ covering higher carbon numbers. Alkylated nitrobenzene compounds are the most abundant among nitroaromatics, and they, together with alkylated nitro-PAHs, account for > 80% of the total intensity of aromatic CHO2N+ formulas, indicating the importance of these compounds in real aerosol samples. Aromatic CHN+ and CHO+ formulas are also determined, confirming the atmospheric presence of some previously reported O- and N-containing aromatic compounds and revealing new possible formulas. The determination of aromatic organic formulas in this study provides useful guidance for future quantitative analysis of hazardous aromatic compounds. Future work is needed to determine the abundance and to study the toxicity of alkylated MAHs and PAHs outside the 16 US EPA priority PAH compounds. Graphical abstract.

Selective and Cleavable Extraction of Sialo-glycoproteins by Disulfide-Linked Amino-oxy-Functionalized Fe3O4 Magnetic Nanoparticles.

The low abundance of sialo-glycoprotein hampered the separation, enrichment, and analysis of sialo-glycoproteins, which are critical for studying their functions. Here, we designed cleavable amino-oxy functionalized magnetic materials and employed to fast and selective isolate sialo-glycoproteins. This includes the ligation of disulfide-linked amino-oxy-functionalized magnetic nanoparticles with periodate-treated glycoproteins or cells, followed by magnetic separation. A reductive reagent could release the sialo-glycoproteins with small molecular fragments on the terminal of glycan chains, and the sialo-glycoproteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. On-bead digestion of the peptides were analyzed by tandem mass spectrometry. The results indicated that this method could selectively separate the majority of cell-surface sialo-glycoproteins.

Imaging features for diffuse-type tenosynovial giant cell tumor of the temporomandibular joint: A case report.

RATIONALE: The tenosynovial giant cell tumor (TGCT) is a benign but locally aggressive tumor that arises from the synovial membrane of joints, tendon sheaths, and bursae. Although any joint can be affected, involvement of the temporomandibular joint (TMJ) was reported very rarely, and there is no relevant report on F-FDG PET/computerized tomography (CT). PATIENT CONCERNS AND DIAGNOSES: We present here a rare case of diffuse-type of TGCT (D-TGCT) arising from the right TMJ in a 74-year-old woman. The patient was discovered a mass of the right temporal fossa during a head CT scan. However, she did not receive any treatment and was discharged from the hospital. She visited our institution again after 4 years with worsening headache and swelling of the right preauricular area. An enhanced CT demonstrated a 6.0 × 3.4 × 5.0 cm mass of mixed density involving the right TMJ, with evident enhancement and extensive erosion of adjacent bones. Magnetic resonance imaging (MRI) showed hypointensity in the solid part of the mass but high signal intensity in the cystic part or necrosis on T2-weighted images (T2WI). In F-FDG PET/CT images, the solid portion of the mass had increased FDG uptake with a SUVmax of 19.8. It was then diagnosed as D-TGCT by postoperative pathology. LESSONS: The case report shows the imaging features of the TGCT, including CT, MRI, and F-FDG PET/CT, especially the typical hypointensity on T2WI. Careful preoperative examination and complete resection are the factors that lead to the optimal treatment of the TGCT.

Response of mandibular condyles of juvenile and adult rats to abnormal occlusion and subsequent exemption.

OBJECTIVE: The adaptation capacities of the mandibular condyle in response to mechanical stimuli might be different between juveniles and adults, but has not been compared. This study aimed to investigate whether abnormal molar occlusion and subsequent molar extraction could lead to different remodeling responses in the mandibular condyles of juvenile and adult rats. METHODS: Abnormal molar occlusion (AMO) was established in the 5- and 16-wk old rats by moving their maxillary left and mandibular right third molars distally. AMO was removed in the molar extraction group at 4 weeks but remained in the AMO group. All rats were sacrificed at 8 weeks. Micro-computed tomography, histomorphology, immunohistochemistry and real-time PCR were adopted to evaluate the remodeling of condylar subchondral bone. RESULTS: Condylar subchondral bone loss and increased osteoclastic activities were observed in both juvenile and adult AMO groups, while increased osteoblastic activities were only seen in the juvenile AMO group. Decreased bone mineral density, bone volume fraction and trabecular thickness, but increased trabecular separation, number and surface of osteoclasts and mRNA levels of TRAP, cathepsin-K, RANKL in the juvenile AMO group were all reversed after molar extraction (all P<0.05). However, these parameters showed no difference between adult AMO and extraction groups (all P>0.05). CONCLUSIONS: Abnormal molar occlusion led to degenerative remodeling in the mandibular condyles of both juvenile and adult rats, while exemption of abnormal occlusion caused significant rescue of the degenerative changes only in the juvenile rats.

Reactive Oxygen Species Production Mediated by Humic-like Substances in Atmospheric Aerosols: Enhancement Effects by Pyridine, Imidazole, and Their Derivatives.

Ambient particulate matter (PM) can cause adverse health effects via their ability to produce reactive oxygen species (ROS). Humic-like substances (HULIS), a complex mixture of amphiphilic organic compounds, have been demonstrated to contain the majority of redox activity in the water-extractable organic fraction of PM. Reduced organic nitrogen compounds, such as alkaloids resulting from biomass burning emissions, are among HULIS constituents. In this study, we examined the redox activities of pyridine, imidazole and their alkyl derivatives using a cell-free dithiothreitol (DTT) assay under simulated physiological conditions (37 °C, pH = 7.40). These compounds were found to have little redox activity on their own as measured by the DTT assay, but they enhanced ROS generation catalyzed by 1,4-naphthoquinone (as a model quinone compound) and HULIS isolated from multiple aerosol samples. The enhancement effect by the individual nitrogen-containing bases was determined to be proportional to their amount in the assay solutions. It is postulated that the underlying mechanism involves the unprotonated N atom acting as a H-bonding acceptor to facilitate hydrogen-atom transfer in the ROS generation cycle. The enhancement capability was found to increase with their basicity (i.e., pKa of their conjugated acids, BH(+)), consistent with the proposed mechanism for enhancement. Among the imidazole homologues, a linear relationship was observed between the enhancement factors (in log scale) of the unprotonated form of the imidazole compounds (B) and the pKa of their conjugated acids (BH(+)). This relationship predicts that the range of alkylimidazole homologues (C6-C13) observed in atmospheric HULIS would be 1.5-4.4 times more effective than imidazole in facilitating HULIS-mediated ROS generation. Our work reveals that the ability of atmospheric PM organics to catalyze generation of ROS in cells could be affected by coexisting redox inactive organic constituents and suggests further work deploying multiple assays be conducted to quantify redox capabilities and enhancement effects of the HULIS components.

Synthesis and antiproliferative assay of norcantharidin derivatives in cancer cells.

Diels-Alder reaction between furan and maleic anhydride resulted in 5,6-dehydro norcantharidin, then norcantharidin was obtained by reduction. The substituted-carboxylic acid was condensed with N-aminothiourea in presence of phosphorus oxychloride, yielding 2-amino-1,3,4-thiadiazole derivatives. Novel norcantharidin derivatives were synthesized with acylation, then intramolecular condensation using norcantharidin (or 5,6-dehydro norcantharidin) and 2-amino- 1,3,4-thiadiazole derivatives. All the target compounds were confirmed by IR, (1)HNMR, ESI-MS and were reported for the first time. Norcantharidin derivatives antiproliferative assay was tested by MTT method against A549 and PC-3 cell lines. The results showed that all the norcantharidin derivatives displayed moderate inhibitory activities.

Combined degenerative and regenerative remodeling responses of the mandibular condyle to experimentally induced disordered occlusion.

INTRODUCTION: The purposes of this research were to investigate the long-term responses of mandibular condylar cartilage to experimentally induced disordered occlusion and to evaluate changes in the expression of the SDF-1/CXCR4 axis. METHODS: Experimentally induced disordered occlusions were created in 8-week-old female Sprague-Dawley rats by orthodontic methods. After 24 weeks, remodeling of the mandibular condylar cartilage was assessed by hematoxylin and eosin staining. Protein and mRNA expression of SDF-1, CXCR4, MMP9, IL6, OPG, and RANKL were investigated by means of immunohistochemical staining and real-time polymerase chain reaction. RESULTS: Obvious cartilage degenerative remodeling responses were observed; they appeared as uneven distributions of cellular disposition, loss of cartilage surface integrity, and cell-free areas. Regenerative responses presenting as thickening of the whole and the calcified cartilage layers in the experimental group were also observed. Compared with the age-matched controls, the protein and mRNA levels of SDF-1, CXCR4, MMP9, IL6, and OPG, but not RANKL, were increased in the experimental group (all, P <0.05). In addition, the mRNA level of RANKL/OPG showed a decreasing trend in the experimental group compared with the age-matched controls (P = 0.052). CONCLUSIONS: This study demonstrated that long-term experimentally induced disordered occlusion leads to a combined response in degeneration and regeneration of mandibular cartilage, accompanied by active interaction of the SDF-1/CXCR4 axis and local upregulation of MMP9, IL6, and OPG.