Lemon-derived carbon dots as antioxidant and light emitter in fluorescent films applied to nanothermometry.

The design of luminescent nanomaterials for the development of nanothermometers with high sensitivity and free of potentially toxic metals has developed in several fields, such as optoelectronics, sensors, and bioimaging. In addition, luminescent nanothermometers have advantages related to non-invasive measurement, with their wide detection range and high spatial resolution at the nano/microscale. Our study is the first, to our knowledge, to demonstrate a detailed study of a fluorescent film (Film-L) thermal sensor based on carbon dots derived from lemon bagasse extract (CD-L). The CD-L properties were explored as an antioxidant agent; their cytotoxicity was evaluated by using a human non-tumoral skin fibroblast (HFF-1) cell line from an MTT assay. The CD-L were characterized by HRTEM, DLS, FTIR, UV-VIS, and fluorescence spectroscopy. These confirmed their particle size distribution below 10 nm, graphitic structure in the core and surface organic groups, and strong blue emission. The CD-L showed cytocompatibility behavior and scavenging potential reactive species of biological importance: O2•- and HOCl, with IC50 of 276.8 ± 4.0 and 21.6 ± 0.7, respectively. The Film-L emission intensities (I425 nm) are temperature-dependent in the 298 to 333 K range. The Film-L luminescent thermometer shows a maximum relative thermal sensitivity of 2.69 % K-1 at 333 K.

LQM10, a guanylhydrazone derivative, reduces nociceptive and inflammatory responses in mice.

In the present study, we examined the antinociceptive and anti-inflammatory activities of a guanylhydrazone derivative, (E)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-guanylhydrazone hydrochloride (LQM10), in mice. The antinociceptive effect was determined by assessing behavioural responses in different pain models, while anti-inflammatory activity was examined in carrageenan-induced pleurisy. Intraperitoneal LQM10 administration reduced the acetic acid-induced nociceptive behaviour, a phenomenon that was unaltered by pretreatment with yohimbine, atropine, naloxone or glibenclamide. In the formalin assay, LQM10 reduced nociceptive behaviour only in the second phase, indicating an inhibitory effect on inflammatory pain. LQM10 did not alter the pain latency in the hot plate assay and did not impact the locomotor activity of mice in the rotarod assay. In the carrageenan-induced pleurisy assay, LQM10 treatment inhibited critical events involved in inflammatory responses, namely, leucocyte recruitment, plasma leakage and increased inflammatory mediators (tumour necrosis factor Like Properties of Chalchones and Flavonoid Derivatives [TNF]-α and interleukin [IL]-1ß) in the pleural exudate. Overall, these results indicate that LQM10 exhibits antinociceptive effects associated with peripheral mechanisms and anti-inflammatory activity mediated via a reduction in leucocyte migration and proinflammatory mediators, rendering this compound a promising candidate for treating pain and inflammatory process.

Synthesis of newly functionalized 1,4-naphthoquinone derivatives and their effects on wound healing in alloxan-induced diabetic mice.

Naphthoquinone derivatives have various pharmacological properties. Here, we describe the synthesis of new 1,4-naphthoquinone derivatives inspired by lawsone and ß-lapachone and their effects on both migration of fibroblasts in vitro and dermal wound healing in diabetic mice. NMR and FTIR spectroscopy aided characterization of chemical composition and demonstrated the molecular variations after the synthesis of four different derivatives, namely 2-bromo-1,4-naphthoquinone (termed derivative S3), 2-N-phenylamino-1,4-naphthoquinone (derivative S5), 2-N-isonicotinoyl-hydrazide-1,4-naphthoquinone (derivative S6), and 1-N-isonicotinoyl-hydrazone-[2-hydroxy-3-(3-methyl-2-butenyl)]-1,4-naphthoquinone (derivative S7). Our results indicate that derivatives S3, S5, S6 and S7 were non-toxic to the 3T3 fibroblast cell line. In scratch assays, derivatives S3 and S6, but not S5 or S7, stimulated the migration of fibroblasts. Compared with untreated diabetic mice, S3, S6 and S7 treatments accelerated wound closure. However, derivative S3 was optimal for the stimulation of epithelization, thereby increasing the number of keratinocyte layers and blood vessels, and reducing diffuse cellular infiltration, compared to derivatives S6 and S7. Our results suggest that novel 1,4-naphthoquinone derivatives promote fibroblast migration and accelerate wound closure under diabetic conditions.

Topical Growth Hormone Accelerates Wound Healing in Mice.

OBJECTIVE: The aim of this study is to investigate the effects of topical growth hormone (GH) treatment on skin wound healing in mice. MATERIALS AND METHODS: An excisional wound healing model was established on male Swiss mice, and wound healing ability was evaluated by macroscopic and histologic analyses of mice treated with topical 10-8 M and 10-7 M of GH versus the mice receiving ve- hicle alone. Wound tissues were collected on post treatment days 3, 7, and 14. Skin fragments were subjected to hematoxylin and eo- sin and Masson's trichrome staining for morphological analyses. The expression of type I collagen and platelet endothelial cell adhesion molecule 1 (CD31) was detected by immunohistochemical analysis. RESULTS: Topical treatment with GH resulted in faster wound closure rates at all time points analyzed versus those observed in the control group (day 3: 18.3 ± 3.1 vs. 44.4 ± 7.4, 43.6 ± 0.6; day 7: 41.7 ± 6.3 vs. 73.8 ± 6.6, 71.3 ± 5.8; day 12: 94.3 ± 3.9 vs. 100 ± 0, 100 ± 0). Histological analysis of the wound on post treatment day 3 revealed a more diffused in ltration of in ammatory cells in the group treated with GH. After day 7, GH-treated animals began form- ing granulation tissue, and there was an increase in in ammatory cell in ltration. The GH signi cantly increased the expression of type I collagen (day 7: 57.4 ± 4.0 vs. 120.2 ± 9.7, 79.3 ± 7.9; day 14: 218.2 ± 10.4 vs. 301.5 ± 9.1, 235.0 ± 7.5) as well as the number of blood vessels (day 7: 10.0 ± 2.4 vs. 15.3 ± 2.0, 10.1 ± 2.2; day 14: 3.2 ± 0.8 vs. 5.6 ± 2.0, 6.2 ± 2.2) in the injured area. CONCLUSIONS: The GH accelerates the closure of skin wounds by resolving the in- ammatory phase faster, accelerating reepithelialization and collagen deposition, and stimulating angiogenesis.

The new supramolecular nano-aggregate curcumin-cucurbit[7]uril: synthesis, photophysical properties and biocompatibility evaluation.

The supramolecular nano-aggregate CUR-CB[7] (CUR = curcumin and CB[7] = cucurbit[7]uril) was efficiently prepared by mixing CUR and CB[7] at a molar ratio of 1 : 1 in ethanol at room temperature. The supramolecular aggregate formation was evidenced by mainly FTIR, 1H NMR, DOSY and spectroscopy experiments. The supramolecular arrangement promotes the increase in the solubility and stability of CUR without affecting the biological properties of the A549 cells. The luminescence properties of CUR and CUR-CB[7] show anti-Kasha's rule fluorescence, and their remarkable NIR emission enables this material to be used as a luminescent probe and marker for in vivo tracking and structural integrity monitoring of the supramolecular complex.

Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea.

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1ß, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 µg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

Synthesis and pharmacological evaluation of carvacrol propionate.

This study aimed at synthesizing the carvacrol propionate (CP) and evaluating its pharmacological profile. CP was obtained from carvacrol and propionyl chloride through an esterification reaction. Male Swiss mice were treated with CP (25, 50, or 100 mg/kg). We evaluated the analgesic effect, mechanical hyperalgesia, and anti-inflammatory effect. Pre-treatment with CP inhibited (p<0.01 and 0.001) the formalin-induced nociception in both phases. CP inhibited (p<0.05, 0.01, and 0.001) the development of mechanical hyperalgesia. CP was able to decrease the leukocyte recruitment (p<0.001) and the amount of TNF-α (p<0.001), IL-1ß (p<0.05), and protein leakage (p<0.01) into the pleural cavity. In addition, the paw edema was inhibited by CP (p<0.05, 0.01, and 0.001). The CP attenuates nociception, mechanical hyperalgesia, and inflammation, through an inhibition of cytokines.

Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent.

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.