Performance evaluation of rhamnolipid biosurfactant produced by Pseudomonas aeruginosa and its effect on marine oil-spill remediation.

This study aimed to reveal that the effect of biosurfactant on the dispersion and degradation of crude oil. Whole genome analysis showed that Pseudomonas aeruginosa GB-3 contained abundant genes involved in biosurfactant synthesis and metabolic processes and had the potential to degrade oil. The biosurfactant produced by strain GB-3 was screened by various methods. The results showed that the surface tension reduction activity was 28.6 mN·m-1 and emulsification stability was exhibited at different pH, salinity and temperature. The biosurfactant was identified as rhamnolipid by LC-MS and FTIR. The fermentation conditions of strain GB-3 were optimized by response surface methodology, finally the optimal system (carbon source: glucose, nitrogen source: ammonium sulfate, C/N ratio:16:1, pH: 7, temperature: 30-35 °C) was determined. Compared with the initial fermentation, the yield of biosurfactant increased by 4.4 times after optimization. In addition, rhamnolipid biosurfactant as a dispersant could make the dispersion of crude oil reach 38% within seven days, which enhanced the bioavailability of crude oil. As a biostimulant, it could also improve the activity of indigenous microorganism and increase the degradation rate of crude oil by 10-15%. This study suggested that rhamnolipid biosurfactant had application prospect in bioremediation of marine oil-spill.

Pollution characteristics of groundwater in an agricultural hormone-contaminated site and implementation of Fenton oxidation process.

The groundwater polluted by an agricultural hormone site was taken as the research object, and a total of 7 groundwater samples were collected at different locations in the plant. The main pollutants in the research area were determined to be extractable petroleum hydrocarbons (C10-C40); 1,2-dichloroethane; 1,1,2-trichloroethane; carbon tetrachloride; vinyl chloride, and chloroform; the maximum content of these pollutants can reach 271 mg/L, 1.68 × 107 µg/L, 1.56 × 104 µg/L, 9.53 × 104 µg/L, 6.58 × 104 µg/L, and 4.81 × 104 µg/L, respectively. Aiming at the problems of groundwater pollution in this area, two sets of oxidation experiments have been carried out. The addition of NaHSO3 modified Fenton oxidation system was used in this contaminated water, which enhanced (2.2 ~ 46.7%) chemical oxygen demand (COD) removal rate. The highest removal rate of extractable petroleum hydrocarbons (C10-C40) can reach 99%. And the degradation rate of chlorinated hydrocarbon pollutants can reach 99% to 100%, which almost achieved the purpose of complete removal. In the NaHSO3 modified Fenton oxidation system, the addition of NaHSO3 accelerates the cycle of Fe3+/Fe2+ and ensures the continuous existence of Fe2+ in the reaction system, thereby producing more ·OH and further oxidizing and degrading organic pollutants. Our work has provided important insights for this economically important treatment of this type water body and laid the foundation for the engineering of this method.

Flux-assisted synthesis of bismuth nanoparticle decorated carbon nitride for efficient photocatalytic degradation of endocrine disrupting compound.

Traditional approaches to synthesizing bismuth nanoparticle decorated carbon nitride (C3N4) materials suffer from the complex synthesis process and the addition of a surfactant, which is not conducive to environmental protection. To address these problems, we adopted a simple and green flux-assisted approach for the first time to fabricate metallic bismuth nanoparticle decorated C3N4 (BiCCN). Electron microscopy results suggested that bismuth vanadate was converted into small bismuth nanoparticles via the flux-assisted approach. Highly dispersed Bi nanoparticles dramatically intensify light absorption, facilitate spatial charge separation as electron acceptors, shorten the charge diffusion length, and reserve more active sites for generating reactive species via surface photo-redox reactions. Consequently, the derived optimized photocatalyst BiCCN-15 rendered around 26 times higher photocatalytic degradation efficiency toward an endocrine disrupting compound (bisphenol A) than C3N4. This work provides a novel approach for developing non-precious metal decorated photocatalytic materials for sustainable water decontamination.

Degradation characteristics of crude oil by a consortium of bacteria in the existence of chlorophenol.

In order to enhance the degradation effect of microorganisms on crude oil in the existence of chlorophenol compounds, oil-degrading bacteria C4 (Alcaligenes faecails), C5 (Bacillus sp.) and 2,4-dichlorophenol (2,4-DCP) degrading bacteria L3 (Bacillus marisflavi), L4 (Bacillus aquimaris) were isolated to construct a highly efficient consortium named (C4C5 + L3L4). When the compound bacteria agent combination by VC4: VC5: VL3: VL4 = 1:2:2:1, the crude oil degradation efficiency of 7 days was stable at 50.63% ~ 55.43% under different conditions. Degradation mechanism was analyzed by FTIR, GC-MS and IC technology and the following conclusions showed that in the system of adding consortium (C4C5 + L3L4), the heavy components were converted into saturated and unsaturated components. The bacterial consortium could first degrade medium and long chain alkanes into short chain hydrocarbons and then further degrade. And the dechlorination efficiency of 2,4-DCP in the degradation system reached 73.83%. The results suggested that the potential applicability and effectiveness of the selected bacteria consortium for the remediation of oil-contaminated water or soil with the existence of chlorophenol compound.

Evidence for 5-HT1A receptor-mediated antiallodynic and antihyperalgesic effects of apigenin in mice suffering from mononeuropathy.

BACKGROUND AND PURPOSE: Neuropathic pain places a devastating health burden, with very few effective therapies. We investigated the potential antiallodynic and antihyperalgesic effects of apigenin, a natural flavonoid with momoamine oxidase (MAO) inhibitory activity, against neuropathic pain and investigated the mechanism(s). EXPERIMENTAL APPROACH: The neuropathic pain model was produced by chronic constriction injury of sciatic nerves in male C57BL/6J mice, with pain-related behaviours being assayed by von Frey test and Hargreaves test. In this model the role of 5-HT and 5-HT1A receptor-related mechanisms were investigated in vivo/in vitro. KEY RESULTS: Apigenin repeated treatment (p.o., once per day for 2 weeks), in a dose-related manner (3, 10 and 30 mg·kg-1 ), ameliorated the allodynia and hyperalgesia in chronic nerve constriction injury in mice. These effects seem dependent on neuronal 5-hydroxytryptamine, because (i) the antihyperalgesia and antiallodynia were attenuated by depletion of 5-HT with p-chlorophenylalanine and potentiated by 5-hydroxytryptophan and (ii), apigenin-treated chronic constriction injury mice caused an increased level of spinal 5-HT, associated with diminished MAO activity. In vivo administration, spinally or systematically, of the 5-HT1A antagonist WAY-100635 inhibited the apigenin-induced antiallodynia and antihyperalgesia. In vitro, apigenin acted as a positive allosteric modulator to increase the efficacy (stimulation of [35 S]GTPγS binding) of the 5-HT1A agonist 8-OH-DPAT. Apigenin attenuated neuronal changes caused by chronic constriction of the sciatic nerve in mice, without causing a hypertensive crisis. CONCLUSION AND IMPLICATIONS: Apigenin antiallodynic and antihyperalgesic actions against neuropathic pain crucially involve spinal 5-HT1A receptors and indicate it could be used to treat neuropathic pain.

Neurovascular decoupling in type 2 diabetes mellitus without mild cognitive impairment: Potential biomarker for early cognitive impairment.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for mild cognitive impairment (MCI) and the acceleration of MCI to dementia. The high glucose level induce disturbance of neurovascular (NV) coupling is suggested to be one potential mechanism, however, the neuroimaging evidence is still lacking. To assess the NV decoupling pattern in early diabetic status, 33 T2DM without MCI patients and 33 healthy control subjects were prospectively enrolled. Then, they underwent resting state functional MRI and arterial spin labeling imaging to explore the hub-based networks and to estimate the coupling of voxel-wise cerebral blood flow (CBF)-degree centrality (DC), CBF-mean amplitude of low-frequency fluctuation (mALFF) and CBF- mean regional homogeneity (mReHo). We further evaluated the relationship between NV coupling pattern and cognitive performance (false discovery rate corrected). T2DM without MCI patients displayed significant decrease in the absolute CBF-mALFF, CBF-mReHo coupling of CBFnetwork and in the CBF-DC coupling of DCnetwork. Besides, networks which involved CBF and DC hubs mainly located in the default mode network (DMN). Furthermore, less severe disease and better cognitive performance in T2DM patients were significantly correlated with higher coupling of CBF-DC, CBF-mALFF or CBF-mReHo, especially for the cognitive dimensions of general function and executive function. Thus, coupling of CBF-DC, CBF-mALFF and CBF-mReHo may serve as promising indicators to reflect NV coupling state and to explain the T2DM related early cognitive impairment.

Serotonergically dependent antidepressant-like activity on behavior and stress axis responsivity of acacetin.

Acacetin, a natural flavonoid, possesses broad spectrum of pharmacological and biochemical activities, such as neuroprotection, antinociception and inhibition of monoamine oxidase. The current work aimed to investigate the antidepressant-like activity of acacetin in mice and explore the underlying mechanism(s). Chronic, but not acute, acacetin treatment (5, 15 or 45 mg/kg, p.o., once per day for three weeks) exerted in mice dose-dependently antidepressant-like activity, assessed by forced swim test (FST) and tail suspension test (TST). Although acacetin-treated mice showed normal circadian hypothalamo-pituitary-adrenal (HPA) axis activity, their endocrine responsivity to both acute restraint stress and intracerebroventricular injection of corticotropin-releasing factor (CRF) was buffered. The acacetin-triggered antidepressant-like activities are serotonergically dependent, since its impacts on behavior and stress responsivity were totally abolished by chemical depletion of brain serotonin by PCPA. Consistently, acacetin-treated mice showed escalated levels of brain monoamines especially serotonin and depressed activity of monoamine oxidase. Moreover, the acacetin-evoked anti-depression was preferentially counteracted by co-administration of 5-HT1A receptor antagonist WAY-100635, but potentiated by 5-HT1A receptor agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine, suggesting a pivotal engagement of 5-HT1A related serotonergic system. In vitro, acacetin (1-100 nM) increased the Emax of 8-OH-DPAT. Collectively, these findings confirm that chronic acatetin administration to mice engenders antidepressant-like efficacy on both behavior and stress axis responsivity, with serotonergic system that preferentially couples with 5-HT1A receptors being critically involved.

Chronic itch impairs mood and HPA axis function in mice: modulation by CRFR1 antagonist.

Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. We subjected mice to chronic itch by repetitive cutaneous treatment with acetone and diethylether followed by water (AEW) that models "dry skin." After 3 to 4 weeks AEW treatment, the mice developed behavioral phenotypes of anxiety and depression assessed by a battery of behavioral paradigms, such as light-dark box and forced swim test. These behavioral symptoms of mood disturbance were independent of cutaneous barrier disruption, but correlated well with the degree of the irritating itch sensation. Although AEW mice showed normal circadian hypothalamic-pituitary-adrenal (HPA) axis activity, their neuroendocrine functionality was dampened, including impaired endocrine stress responsivity, altered neuroendocrine-immune interaction, and blunted corticosterone response to both dexamethasone and CRF. Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.

Chemical properties and antioxidant activity of a water-soluble polysaccharide from Dendrobium officinale.

In this report, a water-soluble polysaccharide was obtained from the dried stems of Dendrobium officinale Kimura et Migo by hot-water (70-75°C) extraction and 85% ethanol precipitation, and successively purification by DEAE-cellulose anion-exchange chromatography and gel-permeation chromatography. The D. officinale polysaccharide (DOP) has a molecular weight of 8500Da. Monosaccharide composition analysis reveals that DOP is composed of mannose, glucose, and arabinose with a trace of galacturonic acid in a molar ratio of 6.2:2.3:2.1:0.1. Periodate oxidation-smith degradation and 1D and 2D NMR spectroscopy analysis suggest the predominance of mannose and glucose, and it contains a 2-O-acetylglucomannan and (1→4)-linked-ß-d-mannopyranosyl and (1→4)-linked-ß-d-glucopyranosyl residues. Atomic force microscope shows that DOP mainly exists as rod-shaped chains, supporting high degrees of polymerization. The antioxidant activities of the polysaccharide in vitro assay indicate that DOP has good scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, higher scavenging activity of hydroxyl radical, and metal chelating activities.

Kaempferol inhibits the growth and metastasis of cholangiocarcinoma in vitro and in vivo.

Kaempferol is a flavonoid that has been reported to exhibit antitumor activity in various malignant tumors. However, the role of kaempferol on cholangiocarcinoma (CCA) is largely unknown. In this article, we found that kaempferol inhibited proliferation, reduced colony formation ability, and induced apoptosis in HCCC9810 and QBC939 cells in vitro. Results from transwell assay and wound-healing assay demonstrated that kaempferol significantly suppressed the migration and invasion abilities of HCCC9810 and QBC939 cells in vitro. Kaempferol was found to decrease the expression of Bcl-2 and increase the expressions of Bax, Fas, cleaved-caspase 3, cleaved-caspase 8, cleaved-caspase 9, and cleaved-PARP. In addition, kaempferol also downregulated the levels of phosphorylated AKT, TIMP2, and MMP2. In vivo, it was found that the volume of subcutaneous xenograft (0.15 cm(3)) in the kaempferol-treated group was smaller than that (0.6 cm(3)) in the control group. Kaempferol also suppressed the number and volume of metastasis foci in the lung metastasis model, with no marked effects on body weight of mice. Immunohistochemistry assay showed that the number of Ki-67-positive cells was lower in the kaempferol-treated group than that in the control group. We further confirmed that the changes of apoptosis- and invasion-related proteins after kaempferol treatment in vivo were similar to the results in vitro. These data suggest that kaempferol may be a promising candidate agent for the treatment of CCA.

Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity.

Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer.

AIM: To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer. METHODS: MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibition and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry. RESULTS: Apoptosis of BGC-823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence intensity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05). CONCLUSION: Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.

Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system.

Fisetin, a natural flavonoid, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential antinociceptive efficacies of fisetin against neuropathic pain and explore mechanism(s). We subjected mice to chronic constriction injury (CCI) by loosely ligating the sciatic nerves, and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic fisetin treatment (5, 15 or 45 mg/kg, p.o.) ameliorated thermal hyperalgesia (but not mechanical allodynia) in CCI mice, concomitant with escalated levels of spinal monoamines and suppressed monoamine oxidase (MAO)-A activity. The antihyperalgesic action of fisetin was abolished by chemical depletion of spinal serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. Moreover, intraperitoneal (i.p.) or intrathecal (i.t.) co-treatment with 5-HT7 receptor antagonist SB-258719 completely abrogated fisetin's antihyperalgesia. These findings confirm that chronic fisetin treatment exerts antinociceptive effect on thermal hyperalgesia in neuropathic mice, with spinal serotonergic system (coupled with 5-HT7) being critically involved. Of special benefit, fisetin attenuated co-morbidly behavioral symptoms of depression and anxiety (evaluated in forced swim test, novelty suppressed feeding test and light-dark test) evoked by neuropathic pain.

Procoagulant role of neutrophil extracellular traps in patients with gastric cancer.

BACKGROUND: Patients with gastric cancer (GC) commonly exhibit a hypercoagulable state that results in significant morbidity and mortality. Recent studies have shown that neutrophil extracellular traps (NETs) trigger coagulation through an intrinsic pathway and contribute to thrombus initiation and progression. In this study, we aimed to determine the procoagulant activity (PCA) of NETs in patients with GC. METHODS: NET formation and their PCAs were assessed in 48 patients with GC and 36 healthy controls using immunofluorescence microscopy of neutrophil markers and extracellular DNA as well as a modified capture ELISA technique, and thrombin-antithrombin complex and clot (fibrin) spectroscopic detection, respectively. RESULTS: Here we showed that neutrophils isolated from patients with GC displayed significantly enhanced NET formation compared with those from healthy controls; furthermore, plasma or platelets obtained from patients with GC induced control neutrophils to release NETs. In addition, NETs released by GC neutrophils significantly increased the potency of control plasma to generate thrombin and fibrin. Notably, these procoagulant effects were dramatically attenuated by application of DNase I. We further found that spontaneous NET formation in patients with GC was significantly higher than that in controls, increased with tumor- node-metastasis stage elevation, and positively correlated with thrombin-antithrombin complex levels and D-dimers. Additionally, the effect of DNase I on cell-free plasma generation of fibrin was dependent on the concentration of NET formation. CONCLUSION: These results suggest that GC creates a systemic environment that primes neutrophils to release procoagulant NETs. Thus, targeting NETs might improve the coagulopathy of patients with GC.

[Mechanism of the dentino-enamel junction on the resist-crack propagation of human teeth by the finite element method].

OBJECTIVE: This study aims to identify the crack tip stress intensity factor of the propagation process, crack propagation path, and the changes in the shape of the crack tip by the finite element method. METHODS: The finite element model of dentino-enamel junction was established with ANSYS software, and the length of the initial crack in the single edge was set to 0.1 mm. The lower end of the sample was fixed. The tensile load of 1 MPa with frequency of 5 Hz was applied to the upper end. The stress intensity factor, deflection angle, and changes in the shape of the crack tip in the crack propagation were calculated by ANSYS. RESULTS: The stress intensity factor suddenly and continuously decreased in dentino-enamel junction as the crack extended. A large skewed angle appeared, and the stress on crack tip was reduced. CONCLUSION: The dentino-enamel junction on human teeth may resist crack propagation through stress reduction.

Effect of trichostatin a on SGC-7901 gastric cancer cells.

AIM: To explore Trichostatin A (TSA) effect on SGC-7901 gastric cancer cells. METHODS: MTT, fluorescence microscopy, and flow cytometry were used to assess TSA effect on cell growth and apoptosis in SGC-7901. Immunocytochemistry was used to evaluate the expression of acetylated histone H4 in SGC-7901 cells.Gene expression profile was determined by microarray assays. Glycoprotein hormones alpha subunit (CGA) gene and protein expressions in SGC-7901 cells were evaluated by Real-time PCR and Western blot, respectively. In addition, CGA protein levels in gastric adenocarcinoma and normal adjacent tissues were assessed by immunohistochemistry. RESULTS: TSA inhibited SGC-7901 cell growth. In addition, cell proliferation was significantly decreased (P = 0.02) in TSA treatment groups (0.93 ± 0.07) compared with controls (1.15 ± 0.07). Apoptosis related morphological changes, including nuclear chromatin condensation and fluorescence strength, were observed by fluorescence microscopy. These findings corroborated the increased expression of acetylated histone H4 observed in TSA treated cells compared to controls, as determined by immunocytochemistry. Interestingly, treatment of SGC-7901 cells with TSA (75 ng/ml) resulted in CGA gene down-regulation (P = 0.0381). Accordingly, CGA protein levels were decreased in TSA treated SGC-7901 cells. Finally, immunohistochemistry analysis showed that CGA expression was significantly higher in gastric adenocarcinoma tissues than normal adjacent tissues (P = 0.001). CONCLUSION: TSA induces cell apoptosis and increases the levels of acetylated histone H4 in SGC-7901 cells. In addition, TSA treatment decreases the expression in gastric cancer cells of the CGA gene, which is upregulated in gastric adenocarcinoma tissues.

BMP8B mediates the survival of pancreatic cancer cells and regulates the progression of pancreatic cancer.

Pancreatic cancer has become one of the most common types of cancer. It is believed that inhibiting the apoptosis of tumor cells as well as overgrowth of tumor cells accelerate the progression and development of cancer. However, the detailed mechanisms of pancreatic cancer progression remain to be fully elucidated. Although bone morphogenetic protein (BMP) families are crucial mediators in some types of cancer, whether BMP8B is involved in regulating the growth and apoptosis of pancreatic cancer cells and the progression of pancreatic cancer is not clear. In the present study, we found that the expression of BMP8B was downregulated in pancreatic cancer tissue compared with the normal tissue adjacent to the tumors. Moreover, the overexpression of BMP8B inhibited cell growth and promoted activation of caspase-3 and -9, the decrease of mitochondrial membrane potential and cell apoptosis in PANC-1, while silencing the BMP8B gene expression with BMP8B shRNA exerted anti-apoptotic effects and boosted the growth of pancreatic cancer cells in BxPC-3. Therefore, we concluded that BMP8B mediates the survival of pancreatic cancer cells and regulates the progression of pancreatic cancer, making it a potential therapeutic target for pancreatic cancer.

Effect of a novel synthesized sulfonamido-based gallate-SZNTC on chondrocytes metabolism in vitro.

The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not only potent anti-inflammatory effect but also favorable biological properties to restore cartilage function. Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1]. However, GA has much weaker antioxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5-trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed its chondro-protective and pharmacological effects. Comparison of SZNTC with GA and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce the progression of OA. SZNTC can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of the collagen I gene was effectively down-regulated, revealing the inhibition of chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC ranges from 3.91µg/ml to 15.64µg/ml, among which the most profound response was observed with 7.82µg/ml. In contrast, its source products of GA and ST-Na have a weak effect in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed SZNTC as a promising novel agent in the treatment of chondral and osteochondral lesions.

Chronic resveratrol treatment exerts antihyperalgesic effect and corrects co-morbid depressive like behaviors in mice with mononeuropathy: involvement of serotonergic system.

Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. This work aimed to investigate the effects of resveratrol, a phenolic monomer enriched in red wine and grapes, on pain-related and depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). Mice received chronic constriction injury (CCI) of sciatic nerves, and sequentially developed pain-related and depressive-like behaviors, as evidenced by sensory hypersensitivity (thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test) and behavioral despair (prolonged immobility time in forced swim test). Chronic treatment of neuropathic mice with resveratrol (30 mg/kg, p.o., twice per day for three weeks) normalized their thermal hyperalgesia (but not mechanical allodynia) and depressive-like behaviors, and these actions were abolished by chemical depletion of central serotonin (5-HT) but potentiated by co-treatment with 5-HTP, a precursor of 5-HT. The anti-hyperalgesia and anti-depression exerted by resveratrol may be pharmacologically segregated, since intrathecal (i.t.) and intracerebroventricular (i.c.v.) injection of methysergide, a non-selective 5-HT receptor antagonist, separately abrogated the two actions. Furthermore, the antihyperalgesic action of resveratrol was preferentially counteracted by co-administration of the 5-HT7 receptor antagonist SB-258719, while the anti-depression was abrogated by 5-HT1A receptor antagonist WAY-100635. These results confirm that chronic resveratrol administration exerts curative-like effects on thermal hyperalgesia and co-morbid depressive-like behaviors in mice with mononeuropathy. Spinal and supraspinal serotonergic systems (coupled with 5-HT7 and 5-HT1A receptors, respectively) are differentially responsible for the antihyperalgesic and antidepressant-like properties of resveratrol.