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.

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.

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.

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.

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.

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.

Osteochondral angiogenesis in rat mandibular condyles with osteoarthritis-like changes.

OBJECTIVE: To investigate angiogenesis at the osteochondral junction and changes in expression of pro- and anti-angiogenic factors in rat mandibular condyles with osteoarthritis-like changes. METHODS: In order to evoke osteoarthritis-like lesions in mandibular condyles, disordered occlusion was created experimentally in rats. Osteochondral vascularity was assessed histologically at 20 and 24 weeks. Protein and mRNA levels of pro-angiogenic factors including vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and matrix metalloproteases 9 (MMP9), and anti-angiogenic factor chondromodulin-I (CHM-I) were investigated by means of immunohistochemical staining and real-time PCR. RESULTS: Osteochondral angiogenesis was demonstrated as increased numbers of vascular channels terminating in the calcified cartilage and non-calcified cartilage in 20- and 24-week experimental groups compared with controls (all P<0.05). In the experimental groups, VEGF, CTGF and MMP9 were highly expressed in the tissues adjacent to the osteochondral junction. However, CHM-I was more expressed in the superior but not deep hypertrophic chondrocytes. Compared to their age-matched controls, the protein levels of VEGF and CTGF were higher in 20-week experimental group, and the protein and mRNA levels of CTGF, MMP-9, and CHM-I increased in the 24-week experimental group (all P<0.05). CONCLUSION: In the present rat model, osteochondral angiogenesis was observed in mandibular condyles with osteoarthritis-like changes, accompanied with local upregulation of VEGF, CTGF and MMP9. Although the increase in CHM-I may moderate pro-angiogenic factors effects in the superior cartilage, the deficiency of deep hypertrophic chondrocytes to express CHM-I may permit vascular invasion into condylar cartilage.

Biologically active arborinane-type triterpenoids and anthraquinones from Rubia yunnanensis.

Twelve new arborinane-type triterpenoids (1-12) and four new anthraquinones (13-16), together with 50 known compounds, were isolated from the roots of Rubia yunnanensis. The structures of 1-16 were elucidated by spectroscopic data analysis and chemical methods. All compounds were evaluated for their cytotoxic, antibacterial, and antifungal activities. Rubiyunnanol C (5) is the first example of an arborinane-type triterpenoid with a double bond at C-8-C-9.

Antitumor cyclic hexapeptides from rubia plants: history, chemistry, and mechanism (2005-2011).

Rubiaceae-type cyclopeptides (RAs), cyclic hexapeptides from Rubia plants, have shown potential antitumor activity in vitro and in vivo. Based on the review about plant cyclopeptides (Chem. Rev., 2006, 106: 840), this mini-review will highlight new progress on the discovery, synthesis, and mechanism of RAs isolated during 2005 to 2011, covering recent work in our group.

Synthesis of 1,3,4-thiadiazole derivatives as aminopeptidase N inhibitors.

Aminopeptidase N (APN) is a zinc-dependent ectopeptidase which plays an important role in the invasion of metastatic tumors. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC50 values in the micromolar range.

[Immune regulating activity of a novel organoselenium compound ethaselen-1 in C57/BL mice].

OBJECTIVE: To detect the Immune regulating activity of ethaselen-1 (Eb1), a novel organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). METHODS: The LLC transplanted C57/BL mice models were established, and the mice was randomly divided into four groups, including high dose Eb1 group (25.0 mg/kg),low dose Eb1 group (12.5 mg/kg), positive control group (levamisole, LMS, 2.0 mg/kg) and negative control group(solvent). Intraperitoneal injections (ip.) of the four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth day after cancer was transplanted. On the eleventh day, six mice of each group were killed and relative weight of spleen, transforming activity of spleen lymphocytes, NK cell activity, LAK cell activity and percentage of CD4(+)CD8(+)T lymphocyte were detect. RESULTS: Compared with the control group, high dose Eb1 could obviously increase the relative weight of spleen (150.59% and 122.55%), transforming activity of spleen lymphocytes(162.25% and 561.98%), NK cell activity(78.60% and 219.42%) and percentage of CD4(-)/CD8(+) T lymphocyte(104.72% and 105.87%) in normal mice and LLC mice. Compared with the control group, high dose Eb1 could also increase LAK cell activity of LLC mice by 195.11%. CONCLUSION: The novel organoselenium compound Eb1 has immune regulating activity in vivo.

[Reconstruction of infected median sternotomy wound dehiscence after coronary artery revascularization].

OBJECTIVE: To introduce the experience about the reconstruction of median sternotomy wound dehiscence. METHODS: From February 2002 to October 2004, 10 patients with median sternotomy wound dehiscence due to coronary artery revascularization were treated. There were 7 males and 3 females, aging from 68 to 76 years. The sizes of defects ranged from 3 cm x 5 cm to 5 cm x 15 cm. After debridement of necrotic soft tissue, sternum and rib, infected median sternotomy wound was reconstructed with rectus abdominis myocutaneous flap, pectoralis major myocutaneous flap and latissimus dorsi flap or single muscle flap. The sizes of flaps ranged from 3 cm x 5 cm to 5 cm x 16 cm. RESULTS: All patients were followed up from 3 to 11 months with an average of 6 months. All the patients achieved healing by first intention with normal respiration and normal function of upper limbs. The wound of donor site healed well. No abdominal hernia and other complications occurred. The wound of donor site healed well. The results were satisfactory. CONCLUSION: According to different stages of the disease and different conditions of an operation, the surgical management should vary with each individual.

A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five cultured human carcinoma cell lines.

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) -ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on A549, HeLa, Bel-7402, BGC823 and KB cell lines. After treated with BBSKE, a good linear correlation coefficient (r>or=0.989) between TrxR activity and cell viability exists in each cell line together with cell growth/proliferation inhibition and apoptosis through Bcl-2/Bax and Caspase-3 pathways. These results suggest that there exists some relationship between TrxR inactivation and growth/proliferation inhibition or apoptosis in the investigated cell lines.

[The antitumor activity of Shuang-Xi-Zuo-Wan-1 in C57/BL mice].

OBJECTIVE: To detect the antitumor activity of Shuang-Xi-Zuo-Wan-1(Eb), a novel organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC). METHODS: The LLC transplanted C57/BL mice model was established,and the mice were randomly divided into four groups, including high dose Eb group (25.0 mg/kg), low dose Eb group (12.5 mg/kg), positive control group (DDP, 2.0 mg/kg) and negative control group (solvent). Each group had twelve mice. Intraperitoneal injections (ip.) of four pharmaceuticals were performed once a day through the abdominal wall separately, from the second to the eighth days after cancer was transplanted. On the eleventh day, six mice of each group were killed and the influences of Eb on growth speed, size, weight, invasion, inhibitory rate, proliferation index and apoptosis rate of LLC were observed and calculated. The remaining mice were fed till all of them died naturally and the average survival time of each group was calculated. RESULTS: Eb could inhibit the growth and infiltration of LLC (the cancer inhibitory rate of high does Eb was 80.31%) obviously and prolong the average survival time of these with mice cancer. After being given Eb, the nuclear of the cancer cell concentrated and the fission phase cells reduced. In addition,the number of apoptosis cancer cells increased. CONCLUSION: The novel organoselenium compound Eb has antitumor activity in vivo. It can inhibit the growth and infiltration of LLC in mice, and induce the apoptosis of cancer cells.

[Repair the infra-orbital defect with a rotation flap after basal cell carcinoma resection].

OBJECTIVE: To explore the method repairing the infra-orbital defect after basal cell carcinoma resection. METHOD: A facial rotation flap was applied to repair the infra-orbital defects from tumor resection in 28 cases. RESULT: All defects were repaired by this one-stage method, which avoided skin graft, shortened the operation time and minimized the operation trauma. The incision sears are inconspicuous. The facial contours are more satisfactory. CONCLUSION: This technique is simple and effective in repairing the infra-orbital defects, worthy of extensive application.