Correlation Between Soft Tissue Injury and the Type of Nasal Fracture Based on Stranc-Robertson Classification.

Nasal fractures are the most common facial bone fractures, and soft tissue injuries are frequently accompanied. This study intends to make a deep analysis on the relationship between the 2.Patients diagnosed with nasal fracture between 2015 and 2017 were included. Patients younger than 17 years and those with previous facial fractures or aesthetic surgeries were excluded. Nasal fractures were classified according to the Stranc-Robertson (S-R) classification, and the severity of soft tissue injury was evaluated by length and depth. The authors compared the frequency of soft tissue injury between frontal and lateral groups. Second, the authors investigated whether the incidence of soft tissue injuries increases as a function of the increase in the S-R classification both in frontal and lateral group (from plane I to III). The authors also analyzed the difference in severity of soft tissue injuries in each group. Pearson chi-square analysis, linear by linear and Jonckheere-Terpstra tests were used for statistical analysis.Of 621 patients, 296 were frontal plane and 325 were lateral plane. The frontal group had a higher incidence of soft tissue injury than the lateral group (P = 0.004). The incidence of soft tissue injury and severity by depth increased as a function of the increase in the S-R classification only in the frontal group (P = 0.046, 0.019).In nasal fractures, frontal impact is more associated with frequency and severity of soft tissue injury than lateral impact. This seems to be related to the anatomical characteristics of nasal area and mechanism of injuries in each group.

Falcarindiol inhibits LPS-induced inflammation via attenuating MAPK and JAK-STAT signaling pathways in murine macrophage RAW 264.7 cells.

Falcarindiol (FAD) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Previously, we isolated FAD from the rhizome of Cnidium officinale Makino, which belongs to the Umbelliferae family and found it to have a significant inhibitory effect on lipopolysaccharide (LPS)-induced production of nitric oxide, a pro-inflammatory molecule in murine macrophage RAW 264.7 cells. In this study, we investigated its effect on the expression of other major pro-inflammatory molecules as well as the mechanism underlying these effects. Pre-treatment of RAW 264.7 cells with FAD suppressed LPS-stimulated mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) and thereby reduced the respective protein levels. Mechanistic studies demonstrated that FAD attenuated the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules. Moreover, we found that FAD did not influence LPS-induced activation of p38 and NFκB signaling pathways. Collectively, this study provides evidence that FAD inhibits the production of major pro-inflammatory molecules in LPS-challenged murine macrophages via suppression of JNK, ERK, and STAT signaling pathways.

Anti-inflammatory activity of Ternstroemia gymnanthera stem bark extracts in bacterial lipopolysaccharide-stimulated RAW264.7 murine macrophage cells.

CONTEXT: Ternstroemia gymnanthera Sprague (Theaceae) possesses various known pharmacological properties. However, its anti-inflammatory activity has not been reported. OBJECTIVE: The anti-inflammatory activity of Ternstroemia gymnanthera stem bark aqueous extract (TGSBE) was evaluated using LPS-stimulated RAW264.7 macrophages. MATERIALS AND METHODS: Cytotoxicity was assessed by MTT assay after 24 h with TGSBE (25-200 µg/mL). Further testing used TGSBE at 100 and 200 µg/mL. Griess and ELISA methods after 24 h with TGSBE determined NO and cytokine levels, respectively; then, mRNA levels (iNOS & cytokines) were analyzed by Quantitative-PCR after 12 h. NF-κB and MAPK were assessed by immunoblotting after TGSBE treatment for 12 h, followed by LPS for 30 min. Immunofluorescence assay was also performed for NF-κB. ROS and MMP, after 12 h with TGSBE, were determined by flow cytometry. The antioxidant potential of TGSBE was analyzed by ABTS assay. The Folin-Ciocalteu method determined the total phenolic content of TGSBE. LPS concentration was 0.5 µg/mL. RESULTS: TGSBE at 200 µg/mL showed about 96.2% viability while suppressing the production of NO (88.99%), TNFα (24.38%), IL-6 (61.70%) and IL-1ß (55.12%) and gene expression by 67.88, 45.24, 65.84, and 70.48%, respectively. TGSBE decreased ROS (79.26%) and improved MMP (48.01%); it inhibited translocation of NF-κB and MAPK activation. Radical scavenging activity was 50% at 402.17 µg/mL (ascorbic acid standard: 88.8 µg/mL). Total phenolic content was 240.9 mg GAE/g. DISCUSSION AND CONCLUSION: TGSBE suppresses the inflammatory response by inhibiting the NF-κB and MAPK cascades exhibiting therapeutic potential to treat inflammatory diseases associated with increased activation of macrophages.

Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells.

In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE-induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells.

Primary Infraorbital Foramen Decompression for the Zygomaticomaxillary Complex Fracture: Is It Essential?

PURPOSE: The frequency of zygomaticomaxillary fracture is second only to nasal bone fracture. Up to 30% to 80% of zygomaticomaxillary fracture patients complain of sensory disturbance results from infraorbital nerve injury. The objective of this study was to detect what factors are related to infraorbital nerve recovery and specifically to investigate decompression of infraorbital foramen improves sensory recovery. PATIENTS AND METHODS: A total of 257 patients were assessed with unilateral zygomaticomaxillary complex fracture, treated with open reduction and internal fixation with orbital floor reconstruction. Of these, 166 patients followed up over 6 months were included in this study. The data collected included age, sex, pre, and postoperative sensory score measured by visual analogue scale (range: 0-10). Sensory score was measured at the infraorbital nerve innervation. The impact of decompression operation on the change of sensory score was compared. Statistical analysis was performed using SPSS 18.0 software (SPSS Inc, Chicago, IL). RESULTS: In patients with preoperative hypoesthesia, difference between postoperative and preoperative sensory score was 3.2 (decompression group), 4.4 (nondecompression group), respectively, but not significant (P > 0.05). In patients without preoperative hypoesthesia, difference between postoperative and preoperative sensory score was -0.2 (decompression group), -0.3 (nondecompression group), respectively, and did not show significant association (P > 0.05). DISCUSSION: Based on this result, in patients with preoperative hypoesthesia, infraorbital decompression operation is not useful for sensory recovery. This result indicates infraorbital sensory disturbance occurs from not only pinched nerve injury at the infraorbital foramen but also traction nerve injury at the other part of the nerve.

The effect of botulinum neurotoxin type A on capsule formation around silicone implants: the in vivo and in vitro study.

This study confirms that botulinum neurotoxin type A (BoNT-A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT-A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT-A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor-beta1 (TGF-ß1) expression in cultured fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha-smooth muscle actin (α-SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF-ß1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT-A did not significantly affect fibroblast viability. Western blot analysis showed that α-SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF-ß1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT-A (P < 0·001). This study confirms that BoNT-A prevents capsular formation around silicone implants, possibly by blocking TGF-ß1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.

Surgical management of severe cherubism persisting into early adulthood: a case report and literature review.

Cherubism is a rare fibro-osseous condition characterized by bilateral expansion of the mandible and maxilla. Due to its rarity, treatment guidelines for cherubism have not been clearly established. Observation without surgical intervention is typically recommended, as cherubism often regresses spontaneously after puberty. However, a surgical intervention may be necessary if aggressive lesions lead to severe complications. In this report, we present a case involving surgical management of cherubism that did not spontaneously regress until early adulthood. An 18-year-old man was diagnosed with cherubism, presenting characteristic upward-looking eyes and a swollen face. He strongly desired surgical management. Gross contouring of the mandible was performed using an osteotome. Subsequently, delicate contouring was performed by bone burring and curettage. The remaining multiple locular bony defects were filled with demineralized bone matrix. No major complications, including infection and hematoma, occurred during the 8-month follow-up period. The facial contour remained stable without the aggravation of cherubism. The patient was satisfied with the cosmetic results. Considering that cherubism is a rare disease globally, with few reported cases in Korea, and that treatment guidelines are not clearly established, we anticipate that the results of this case will contribute to the development of future protocols for treating cherubism.

Simultaneous diagnosis and resection of orofacial rhabdomyosarcoma with frozen section biopsy: a case report.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for 4.5% of all cases of cancer in childhood. Although the head and neck are the most common sites of rhabdomyosarcoma, oral lesions are relatively rare and account for only 10% to 12% of head and neck rhabdomyosarcoma cases. This is a case report of a girl aged 2 years and 1 month who initially presented with an upper lip mass that invaded the oral mucosa, oral skin, and nostril skin, causing narrowing of the airway. Through our case, we show that rapidly growing small round cell malignancies, especially rhabdomyosarcoma, can be effectively diagnosed and treated at the same time using primary resection with intraoperative frozen section biopsy and that the time spent waiting for the results of preoperative biopsy can be saved in this way, particularly when the patient's symptoms are intensifying rapidly and require immediate operation.

Components of rhizome extract of Cnidium officinale Makino and their in vitro biological effects.

The anti-inflammatory and anticancer activities of a methanol extract of the rhizome of Cnidium officinale were investigated. Four compounds, namely falcarindiol (1), 6-hydroxy-7-methoxy-dihydroligustilide (2), ligustilidiol (3), and senkyunolide H (4) were isolated from the extract of the rhizome of Cnidium officinale and their structures were elucidated by analysis of their spectroscopic data and by comparison with previously reported data. These compounds showed anti-inflammatory activities, measured as inhibition of nitric oxide (NO) release in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, with IC(50) values of 4.31 ± 5.22, 152.95 ± 4.23, 72.78 ± 5.13, and 173.42 ± 3.22 µM, respectively. They also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expression induced by LPS. Among these compounds, falcarindiol (1) was found to have anti-proliferative effect against MCF-7 human breast cancer cells by induction of a G(0)/G(1) cell cycle block of the cells, with an IC(50) value of 35.67 µM. Typical apoptotic effects were observed by phase contrast microscopy and were also exhibited in fluorescence microscopy with Hoechst 33342 staining. In addition, falcarindiol induced apoptosis through strongly increased mRNA expression of Bax and p53, and slightly reduced Bcl-2 mRNA levels in a dose dependent manner. This study suggested that C. officinale extract and its components would be valuable candidates in therapeutic applications for anti-inflammatory and anti-cancer agents.

Three-dimensional analysis of facial asymmetry after zygomaticomaxillary complex fracture reduction: a retrospective analysis of 101 East Asian patients.

BACKGROUND: The zygomaticomaxillary complex (ZMC) has a protruded, convex shape and plays a vital role in determining the contour by affecting the width of the middle face. This study aimed to evaluate the efficiency of ZMC fracture reduction and explore detailed directions for outcome improvement. METHODS: We conducted a retrospective study of patients diagnosed with unilateral ZMC fracture who underwent ZMC reduction surgery at a single hospital between January 2015 and May 2020. The primary outcome variable was facial asymmetry using the difference in the bilateral malar eminence (ME) position measured by computed tomography scan. The 3-dimensional distance (IA, asymmetry index) and the distance in each dimension, Dx (anteroposterior distance), Dy (mediolateral distance), and Dz (superoinferior distance) were compared. RESULTS: A total of 101 patients with ZMC fractures and 54 non-fracture patients were enrolled in the study. The mean age of the study sample was 43.49 years (control sample, 43.35 years), and the male-to-female ratio was 66.3:33.7 (control sample, 64.8:35.2). There were 53 and 48 patients with right and left ZMC fractures, respectively. The IA was not statistically different between the two groups. In terms of position in each dimension, only Dx was significantly different between the two groups. CONCLUSION: The results show that overall facial asymmetry was recovered after ZMC reduction, but in certain dimension significant difference in ME position has still remained. For further improvement, treatment should be performed to relieve malar depression in the anteroposterior dimension.

Qualitative and Quantitative Analyses of Donor Site Morbidity Following a Graft of the Acellular Dermal Matrix Versus Primary Fascial Repair After ALT Flap Harvesting.

BACKGROUND: The anterolateral thigh (ALT) flap is one of the most useful flaps in reconstruction because of its reliability, large skin flap territory, and versatility. The relatively small number of side effects is a common reason for preferring this flap. Primary repair is usually performed at the donor site closure; however, this requires substantial tension and causes many donor site morbidities, including pain. We attempted to use acellular dermal matrix graft to overcome these problems. METHODS: We analyzed a total of 41 cases (41 flaps) in this study. Among these flaps, we conducted donor fascia suture with artificial dermis in 20 cases (study group) and primary fascial suture in 21cases (control group). Post-operative ambulation recovery times, pain scores, drainage removals, and wound problems of the donor site were recorded. RESULTS: There were no serious complications, including infection, at the donor sites of all 41 cases. Of 20 cases using the acellular dermal matrix, seroma occurred in 2 cases and partial skin necrosis occurred in 2 cases. In 1 case of skin necrosis, the acellular dermal matrix was removed. However, in comparison to the control group, the group using the artificial dermis recovered ambulatory ability 3.9 days earlier and had a 1.8-point lower visual analogue scale score 5 days post-operatively. CONCLUSIONS: Our study suggested that, if used selectively, the acellular dermal matrix may play an effective role in donor site closure in cases with procedures involving the ALT flap.

HISTORIQUE: Le lambeau antérolatéral de la cuisse est l'un des plus utiles pour la reconstruction à cause de sa fiabilité, de son grand territoire et de sa polyvalence. Le relativement petit nombre d'effets secondaires est une raison courante pour le préférer. La réparation primaire est généralement effectuée à la fermeture du site du donneur, mais il faut une tension importante, ce qui entraîne de nombreuses morbidités au site du donneur, y compris la douleur. Les chercheurs ont tenté d'utiliser une greffe de la matrice dermique acellulaire pour vaincre ces problèmes. MÉTHODOLOGIE: Les chercheurs ont analysé un total de 41 cas (41 lambeaux) dans cette étude. De ce nombre, ils ont effectué une suture du fascia du donneur à l'aide de derme artificiel dans 20 cas (groupe d'étude) et une suture fasciale primaire dans 21 cas (groupe témoin). Ils ont également pris note de la durée de convalescence ambulatoire postopératoire, des scores de douleur, de la désinstallation du drainage, et des problèmes de plaie au site du donneur. RÉSULTATS: Il n'y a pas eu de complications graves, y compris l'infection, aux sites des donneurs des 41 cas. On a observé un sérome dans deux des 20 cas faisant appel à la matrice dermique acellulaire, et une nécrose cutanée partielle dans également deux cas. Dans l'un des cas de nécrose cutanée, la matrice dermique acellulaire a dû être retirée. Cependant, comparativement au groupe témoin, le groupe qui a utilisé le derme artificiel a récupéré sa capacité ambulatoire 3,9 jours plus rapidement et présentait un score de 1,8 point de moins à l'échelle analogique visuelle cinq jours après l'opération. CONCLUSIONS: Selon la présente étude, la matrice dermique acellulaire utilisée sélectivement peut jouer un rôle efficace à la fermeture du site du donneur dans les cas d'intervention faisant appel au lambeau antérolatéral de la cuisse.

Compounds from Viburnum sargentii Koehne and evaluation of their cytotoxic effects on human cancer cell lines.

Compounds were isolated from a methanol extract of the dried stem barks of Viburnum sargentii Koehne. The structures of the compounds, namely 9'-O-methylvibsanol (3), furcatoside A (4) and lareciresinol (5) were elucidated by analysis of spectroscopic data and comparison with values for previously known analogues. In addition, (+)-catechin (1), (+)-epicatechin (2) were also isolated. This work also examined the cytotoxic effects of three compounds 3-5 (25-100 microM) in MCF-7 and A549 cells after 24, 48 and 72 h of exposure. Our results showed that 9'-O-methylvibsanol (3) exhibited strong concentration-dependent anticancer effects according to the MTT assay and produced morphological changes consistent with apoptosis, as confirmed by Ho3342 staining analysis revealed that more apoptotic cells were observed after 9'-Omethylvibsanol (3) treatment.

Patterns of wrist cutting: A retrospective analysis of 115 suicide attempts.

BACKGROUND: Rosenthal et al. classified female, habitual, non-suicidal wrist cutters as a group and introduced the concept of wrist-cutting syndrome. We investigated the characteristics of wrist-cutting patients at our institution in comparison with results reported previously. METHODS: We conducted a retrospective study involving 115 patients who had cut their wrists and been examined at the emergency department of a single hospital in Seoul, Korea, between March 2014 and August 2018. RESULTS: There were more women (73 patients; 63.5%) than men (42 patients; 36.5%), and the women (mean age, 34.42 years) were significantly younger than the men (mean age, 50.07 years). The patients who had cut their wrists repeatedly were mainly women (22 of 26 patients; 84.6%); however, men caused more severe damage than women. Substance use before a suicide attempt did not significantly increase the severity of wrist cutting. Our institution planned and implemented a suicide prevention intervention program to improve the continuity of outpatient care. The number of patients who continued psychiatric treatment increased significantly after program completion. CONCLUSIONS: We confirmed that most patients were young women who were not suicidal in the true sense because their wounds were not severe. Our study showed a protective role of the barrier tendons (flexor carpi radialis, palmaris longus, flexor carpi ulnaris), and we suggest careful repair of the barrier tendons to protect neurovascular structures against subsequent cutting events. We found that it was possible to improve the continuity of patient counseling by managing patients through a psychiatric treatment program.

Effect of an extraction solvent on the antioxidant quality of Pinus densiflora needle extract.

Pinus densiflora needle extract (PDNE) is widely reported to have many pharmacological activities including antioxidant potential. However, the solvent system used for extraction greatly affects its antioxidant quality. Hence, in the present study, we investigated the effect of a different ratio (vol/vol) of ethanol to water (0-100%) in the extraction of PDNE with potent antioxidant capacity. The chemical assays, 2,2-diphenyl-1 picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), were conducted to assess the antioxidant potential of PDNE. Subsequently, the cytoprotective effect of PDNE was determined using tert-butyl hydroperoxide (TBHP)-challenged HepG2 cellular model. The needle extracts from 40% ethanol (PDNE-40) showed greater radical scavenging activity followed by 60%, 20%, 80%, 0% and 100% ethanol extracts. EC50 value of the most active extract, PDNE-40, was 8.56 ±â€¯0.51 µg/mL, relative to 1.34 ±â€¯0.28 µg/mL of the standard trolox (for ABTS radical), and 75.96 ±â€¯11.60 µg/mL, relative to 4.83 ±â€¯0.26 µg/mL of the standard trolox (for DPPH radical). Either PDNE-20 or PDNE-40 pretreatment remarkably decreased the levels of reactive oxygen species (ROS), lipid peroxides and protein carbonyls in TBHP-challenged HepG2 cells. In addition, both PDNE-20 and PDNE-40 significantly reversed the decreased ratio of reduced (GSH) to oxidized (GSSG) glutathione. Moreover, these two extracts showed a significant inhibitory effect on TBHP-induced nuclear damage and loss of cell viability. In summary, the inclusion of 40% ethanol in water for extraction of Pinus densiflora needle greatly increases the antioxidant quality of the extract.

Epidemiology of violence in pediatric and adolescent nasal fracture compared with adult nasal fracture: An 8-year study.

BACKGROUND: The epidemiology of nasal fractures varies according to factors such as the era and area of the study, as well as the age of the patient. We compared the characteristics and causes of pediatric nasal fractures. METHODS: A total of 2,321 patients with nasal fractures from 2010 to 2017 were examined. The patients were divided into age groups using the Korean school system of age classification. The causes of injury were divided into five groups: violence, fall or slip down, sports, road traffic accidents, and others. Fractures were classified using the Stranc and Robertson standard: vector of force and plane of fracture. RESULTS: Violence was the most common cause of nasal fracture in patients older than 12 years. Violence was a significantly less frequent cause among patients younger than 12 years old than among adolescent and adult patients. Nasal fractures due to violence were not observed in patients younger than 10 years. Plane 2 and lateral force fractures were the most common; however, in patients younger than 12 years, frontal force fractures were significantly more frequent than were lateral force fractures. CONCLUSION: As children may simply be injured due to a fall or slip down, it is important for the parents and guardians to ensure their safety. As they become older, children should abstain from violence and be monitored. It is therefore very important to ensure that the environment is free of violence in order to prevent such injuries.

Impact of Different Extraction Solvents on Phenolic Content and Antioxidant Potential of Pinus densiflora Bark Extract.

It is well established that various extraction factors, including the method, temperature, time, and solvent system, significantly influence the antioxidant quality of plant-derived products. Previously, we observed that extraction of Pinus densiflora bark (PDB) by the most common traditional Soxhlet method using water at two different temperature conditions 60°C and 100°C for 6-15 h noticeably altered their antioxidant quality. In this study, we examined the impact of different extraction solvents such as ethanol, methanol, isopropanol, acetonitrile, and acetone at a different percentage with water (vol/vol) on antioxidant efficiency as well as the total phenolic content (TPC) of PDB extracts. Among the fourteen different PDB extracts, the extracts obtained from 20% ethanol (E20), 40% ethanol (E40), and 20% acetonitrile (ACN20) showed more significant antioxidant potential, as well as high total phenol content (TPC). Extracts from other aqueous mixtures of organic solvents such as isopropanol, acetone, and methanol, as well as water, showed lesser antioxidant capacity and also had less TPC compared to these three most active extracts, E20, E40, and ACN20. Moreover, using ethanol at 100% for extraction significantly decreased the TPC and antioxidant capacity of PDB extracts. Data are implicating that an increased phenolic content in PDB extracts proportionally increases their antioxidant efficiency.

Pinus densiflora needle supercritical fluid extract suppresses the expression of pro-inflammatory mediators iNOS, IL-6 and IL-1ß, and activation of inflammatory STAT1 and STAT3 signaling proteins in bacterial lipopolysaccharide-challenged murine macrophages.

BACKGROUND: Regulation of a persistently-activated inflammatory response in macrophages is an important target for treatment of various chronic diseases. Pine needle extracts are well known to have potent immunomodulatory effects. The current study was designed to evaluate the effects of Pinus densiflora needle supercritical fluid extract (PDN-SCFE) on bacterial lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 murine macrophages. METHODS: Cytotoxic effect of PDN-SCFE was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of nitric oxide (NO) and the corresponding enzyme, inducible nitric oxide synthase (iNOS), were quantified by Griess and immunoblotting methods, respectively. The levels of cytokines were quantified using commercial ELISA kits. Quantitative real-time PCR (qRT-PCR) analysis was performed to assess the mRNA expression of iNOS and cytokines. To elucidate the mechanism of action, the involvement of nuclear transcription factor-kappa B (NFκB), mitogen activated protein kinases (MAPKs) and Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways were examined by an immunoblotting method. In addition, the cellular localization of NFκB was analyzed by immunofluorescence staining. RESULTS: MTT assay results indicated that PDN-SCFE is non-toxic to RAW 264.7 cells up to a maximum assayed concentration of 40 µg/mL. The PDN-SCFE exhibited a concentration-dependent inhibitory effect on LPS-induced NO production by down regulating the expression of iNOS. In addition, the extract suppressed the LPS-induced expression of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) but not tumour necrosis factor-α (TNFα). Mechanistic studies revealed that PDN-SCFE does not influence the NFκB and MAPK pathways. However, it showed a significant inhibitory effect on LPS-induced activation of STAT1 and STAT3 proteins in macrophages. CONCLUSION: The present findings revealed that the anti-inflammatory activity of PDN-SCFE in LPS-challenged RAW 264.7 macrophages is probably caused by the suppression of the JAK-STAT signaling pathway.

Deoxyrhapontigenin, a Natural Stilbene Derivative Isolated From Rheum undulatum L. Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Human Breast Cancer Cells.

Although current chemotherapeutic agents are active at the beginning of therapy, the most common risk is the development of resistance during later stages in almost all cancer types including breast cancer. Hence, investigation of novel drugs is still a priority goal for cancer treatment. The objective of the present study is to investigate the anticancer effect of a derivative of stilbene, deoxyrhapontigenin (DR) isolated from Rheum undulatum L. root extracts against the chemoresistant MCF-7/adr and its parental MCF-7 human breast cancer cells. The morphological images indicate that DR induces an extensive cytoplasmic vacuolation in breast cancer cells. Mechanistic investigations revealed that DR treatment causes endoplasmic reticulum (ER) dilation and upregulated the expression of ER stress markers GRP78, IRE1α, eIF2α, CHOP, JNK, and p38. Subsequently, we also identified that DR increases the levels of apoptotic fragment of PARP (89 kDa) in breast cancer cells. Blocking the expression of one of the components of the ER stress-mediated apoptosis pathway, CHOP using siRNA significantly decreased DR-induced apoptotic cleavage of PARP. In summary, the present study suggests that the induction of ER stress-mediated apoptosis by DR may account for its cytotoxic effects in human breast cancer cells.

Treadmill exercise and methylphenidate ameliorate symptoms of attention deficit/hyperactivity disorder through enhancing dopamine synthesis and brain-derived neurotrophic factor expression in spontaneous hypertensive rats.

Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder of cognition. Behavioral symptoms of ADHD are inattention, hyperactivity, and impulsivity. We investigated the effects of treadmill exercise and methylphenidate (MPH) on activity and spatial learning memory in relation to dopamine synthesis and brain-derived neurotrophic factor (BDNF) expression using spontaneously hypertensive adult male rats. The rats in the MPH-treated group received 1mg/kg MPH orally once a day for 28days. The rats in the treadmill exercise group were made to run on a treadmill for 30min once a day, five times a week, for 28days. Activity was determined by an open-field test and spatial learning memory was evaluated by an 8-arm maze test. Immunohistochemistry and Western blotting were conducted to examine the levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, and BDNF. The rats in the ADHD group showed hyperactivity and spatial learning memory deficit. Reduction of TH in the striatum and substantia nigra and BDNF in the hippocampus was observed of the rats in the ADHD group. Treadmill exercise and MPH alleviated the ADHD-induced hyperactivity and spatial learning memory impairment. Expressions of TH and BDNF in the ADHD rats were also increased by both treadmill exercise and MPH. These findings provide a possibility that exercise may be used as an effective therapeutic intervention for ADHD patients as MPH treatment.