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1.
Sci Rep ; 13(1): 10119, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37344501

RESUMEN

Cerebral ischemic stroke is a high-risk disease and imposes heavy burdens on patients in china. Acupuncture has been used for thousands of years to treat motor dysfunction, cognitive disorder and language barrier caused by cerebral ischemic stroke. Acupoint lines, vertex middle line and anterior oblique line of vertex temple, are always employed to treat cerebral ischemic stroke. However, the mechanism of the two acupoint lines in relieving cerebral ischemic stroke needs further exploration. In the present study, scalp acupuncture treatment alleviated the motor dysfunction, brain damage, and cell death induced by middle cerebral artery occlusion (MCAO) in rats. Proteomics analysis and ultrastructure observation indicated that endoplasmic reticulum and lysosomes might involve in the mechanism of the scalp acupuncture treatment in suppressing MCAO-triggered neural deficits. Effect of the scalp acupuncture treatment on ER stress was then investigated and found that the activation of ER stress mediators, including PERK, IRE1, and ATF6, was downregulated after the scalp acupuncture treatment. Co-localisation analysis of KDEL and CD63 showed that the engulfment of ER fragments by lysosomes was accelerated by the scalp acupuncture treatment. Moreover, expression of pro-apoptotic protein CHOP, phosphorylated-JNK, cleaved capases-3 and -9 also decreased after the scalp acupuncture. In conclusion, the present study showed that scalp acupuncture of vertex middle line and anterior oblique line of vertex temple may alleviate cerebral ischemic stroke by inhibiting ER stress-accelerated apoptosis.


Asunto(s)
Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratas , Animales , Cuero Cabelludo/metabolismo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/metabolismo , Estrés del Retículo Endoplásmico , Autofagia
2.
Int J Cosmet Sci ; 44(6): 614-624, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35979727

RESUMEN

OBJECTIVE: A critical and often-overlooked factor that may give rise to dandruff and oily hair is the intrinsic quality of the scalp stratum corneum (SC), which is often unbalanced and susceptible to external aggressions. Addressing the inflammation element of unhealthy scalp plays an important role in promoting healthy-looking and feeling hair. Although specialized pro-resolving lipid mediators (SPMs) have been studied in the skin to end the inflammation process and promote tissue regeneration, no studies have been provided in the scalp. This study aims to investigate SPMs expression and its role in improving scalp integrity and consequently improving hair appearance using an Anetholea anisita extract. METHODS: The effect of Anetholea anisita extract was investigated in vitro on human follicle dermal papilla cells (HFDPC), evaluating its antioxidant and anti-inflammatory properties by fluorescence staining and ELISA, respectively. Ex vivo measurement of the volume of human scalp sebaceous glands was performed using X-ray microtomography (micro-CT). The extract was then clinically tested on a population of dandruff sufferers presenting oily hair. Volunteers' sebum was collected on the scalp and analysed by LC-MS/MS or ELISA to identify SPMs and pro-inflammatory markers. Scalp integrity was assessed by measuring the pH and the TEWL. Sebum production, dandruff and hair gloss were also evaluated. RESULT: Anetholea anisita extract reduced IL-8 and reactive oxygen species (ROS) generation in HFDPC. Interestingly, this extract also decreased the volume of sebaceous glands as revealed by micro-CT. This result was confirmed in vivo by a decrease in sebum production in volunteers. Moreover, SPMs were analysed and detected in the scalp for the first time. An increase in Lipoxin B4 (LxB4) and Resolvin D1 and D2 (RvD1 and RvD2) was observed after Anetholea anisita treatment as well as decrease in pro-inflammatory sebum mediators expression such as PGE2, LTB4 and IL-8. Consequently, the scalp barrier was reinforced as observed through improved transepidermal water loss (TEWL) and skin surface pH, reducing dandruff and improving hair health. CONCLUSION: The present results suggest the potential of cosmetic applications of Anetholea anisita extract to improve scalp health by targeting inflammation pathways to decrease dandruff and improve hair condition.


OBJECTIF: Un facteur important et peu étudié pouvant mener à l'apparition des pellicules ou des cheveux gras est la qualité intrinsèque du stratum corneum (SC) du cuir chevelu, souvent déséquilibré et susceptible aux agressions. L'inflammation joue un rôle clé dans l'état de santé du cuir chevelu et par conséquent du cheveu. Les médiateurs lipidiques pro-résolution (SPMs) ont été étudiés dans la peau pour mettre fin au processus inflammatoire et promouvoir la régénération des tissus. Cependant, aucune étude n'avait été réalisée sur le cuir chevelu. Cette étude vise donc à étudier l'expression des SPMs et leurs rôles dans l'amélioration de l'intégrité du cuir chevelu et de l'apparence des cheveux en utilisant un extrait de Anetholea anisita. MÉTHODES: Les propriétés antioxydantes et anti-inflammatoires de l'Anetholea anisita ont été étudiées in vitro sur les cellules papillaires folliculaires dermiques humaines (HFDPC) par fluorescence et ELISA. La mesure ex vivo du volume des glandes sébacées du cuir chevelu humain a été réalisée par microtomographie à rayons X (micro-CT). L'extrait a ensuite été cliniquement testé sur des volontaires présentant des pellicules et des cheveux gras. Le sébum des volontaires a été prélevé sur le cuir chevelu et analysé par LC-MS/MS ou ELISA pour identifier les SPMs et les marqueurs pro-inflammatoires. L'intégrité du cuir chevelu a ensuite été évaluée en mesurant le pH et la perte en eau transépidermique. La production de sébum, les pellicules et la brillance des cheveux ont également été évalués. RÉSULTATS: L'extrait d'Anetholea anisita a réduit la production d'IL-8 et d'espèces réactives oxygénées sur HFDPC. Cet extrait a également diminué le volume des glandes sébacées. Ce résultat a été confirmé in vivo avec une diminution de la production de sébum chez les volontaires. De plus, les SPMs ont été analysés et détectés pour la première fois sur le cuir chevelu. Une augmentation de la Lipoxine B4 (LxB4) ainsi que des Resolvines D1 et D2 (RvD1 et RvD2) a été observée après le traitement par Anetholea anisita en plus d'une diminution de l'expression des médiateurs pro-inflammatoires tels que PGE2, LTB4 et IL-8. Par conséquent, la barrière du cuir chevelu a été renforcée comme observé avec une diminution de la PIE et un ajustement pH de la surface du scalp, réduisant les pellicules et améliorant la santé des cheveux. CONCLUSION: Les résultats obtenus montrent qu'un extrait d'Anetholea anisita permet d'améliorer la santé du cuir chevelu en ciblant les voies de l'inflammation et de la résolution permettant ainsi de renforcer la barrière du cuir chevelu, pour diminuer les pellicules et améliorer l'état des cheveux.


Asunto(s)
Caspa , Dermatitis Seborreica , Humanos , Cuero Cabelludo/metabolismo , Cromatografía Liquida , Interleucina-8/metabolismo , Espectrometría de Masas en Tándem , Inflamación/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Extractos Vegetales/farmacología
3.
Int J Cosmet Sci ; 44(2): 154-165, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35133683

RESUMEN

OBJECTIVE: Hair loss and greying affect men and women of all ages, often causing psychosocial difficulties. Dickkopf-1 (DKK1), a major hair loss factor secreted from dermal papilla (DP) cells in response to the secretion of dihydrotestosterone (DHT), has been reported to induce and accelerate androgenetic alopecia (AGA). In addition, DKK1 acts as a potent suppressor of melanogenesis and is closely related to hair colour. R-spondin 1 (RSPO1) is a secretory agonist of Wnt signalling known to antagonize the effects of DKK1, including DKK1-mediated hair follicle suppression. In this study, we investigated the effect of watercress extract (WCE) on the secretion of RSPO1 and DKK1 from DP cells as well as its anti-hair loss effect in human hair follicles and patients. METHODS: The in vitro secretion of RSPO1 and DKK1 was measured by ELISA. Human hair follicles were collected from the scalp of a female donor and used for ex vivo organ culture to investigate the effects of WCE on human hair loss. Finally, a 6-month human clinical trial was conducted to examine the effect of WCE-containing lotion on hair growth in a male panel. RESULTS: WCE significantly upregulated RSPO1 secretion and suppressed DKK1 secretion in a dose-dependent manner, even in the presence of DHT. WCE-treated hair follicles elongated 1.6-fold compared with the control, and the level of RSPO1 production in DP as well as RSPO1 bound to the outer root sheath (ORS) increased. In the clinical trial, the hair lotion containing 2% WCE increased hair thickness and density to improve against hair loss symptoms. CONCLUSION: WCE exhibited a strong anti-androgenic effect through its ability to suppress DKK1 secretion and antagonize DKK1 via RSPO1. These findings highlighted the potential use of WCE for the treatment of hair loss.


OBJECTIF: La perte de cheveux et le grisonnement touchent des hommes et des femmes de tous âges, ce qui entraîne souvent des difficultés psychosociales. Selon des rapports, Dickkopf-1 (DKK1), un facteur de perte de cheveux majeur sécrété par les cellules de la papille dermique (PD) en réponse à la sécrétion de dihydrotestostérone (DHT), induit et accélère l'alopécie androgénétique (AAG). En outre, DKK1 agit comme un puissant suppresseur de la mélanogenèse et est étroitement lié à la couleur des cheveux. La protéine R-spondin 1 (RSPO1) est un agoniste sécrétoire de la voie de signalisation Wnt connue pour antagoniser les effets de DKK1, notamment la suppression des follicules pileux médiée par DKK1. Dans cette étude, nous avons étudié l'effet de l'extrait de cresson sur la sécrétion de RSPO1 et de DKK1 à partir des cellules de la PD, ainsi que son effet anti-perte de cheveux sur les follicules pileux humains et chez les patients. MÉTHODES: La sécrétion in vitro de RSPO1 et de DKK1 a été mesurée à l'aide de la méthode ELISA. Des follicules pileux humains ont été prélevés sur le cuir chevelu d'une femme et utilisés pour une culture d'organes ex vivo afin d'étudier les effets de l'extrait de cresson sur la perte de cheveux humains. Enfin, un essai clinique de 6 mois chez l'être humain a été mené pour examiner l'effet d'une lotion contenant de l'extrait de cresson sur la croissance des cheveux au sein d'un panel d'hommes. RÉSULTATS: L'extrait de cresson a significativement régulé à la hausse la sécrétion de RSPO1 et a supprimé la sécrétion de DKK1 de manière dose-dépendante, même en présence de DHT. Les follicules pileux traités avec de l'extrait de cresson ont été multipliés par 1,6 par rapport au groupe témoin, et le niveau de production de RSPO1 dans la PD ainsi que le taux de RSPO1 lié à la gaine externe de la racine ont augmenté. Dans l'essai clinique, la lotion pour cheveux contenant 2 % d'extrait de cresson a augmenté l'épaisseur et la densité des cheveux, améliorant ainsi les symptômes de perte de cheveux. CONCLUSION: La capacité de l'extrait de cresson à supprimer la sécrétion de DKK1 et à antagoniser DKK1 via la protéine RSPO1 lui a conféré un effet anti-androgénique puissant. Ces résultats ont mis en évidence le potentiel de l'extrait de cresson pour le traitement de la perte de cheveux.


Asunto(s)
Alopecia , Folículo Piloso , Alopecia/tratamiento farmacológico , Femenino , Cabello , Humanos , Masculino , Extractos Vegetales/farmacología , Cuero Cabelludo/metabolismo
4.
Zhongguo Zhen Jiu ; 42(10): 1137-44, 2022 Oct 12.
Artículo en Chino | MEDLINE | ID: mdl-37199205

RESUMEN

OBJECTIVE: To observe the impact of electro-scalp acupuncture (ESA) on the neural function and inflammatory response of ischemic cortex in the model rats with ischemic stroke and explore the anti-inflammation mechanism of ESA in treatment of ischemic stroke from the perspective of modulating the interleukin 12 (IL-12) mediated JAK (Janus kinase)/STAT (signal transduction and transcription activator) signal pathway. METHODS: Ninety male SD rats were randomized into a normal group (n =16) and a model preparation group (n=74). In the model preparation group, the model of middle cerebral artery occlusion (MCAO) was duplicated with suture-occlusion method. After modeled successfully, 48 rats with neurological deficit score of 1-3 were divided into a model group, an inhibitor group and an ESA group, 16 rats in each one. In the inhibitor group, IL-12 inhibitor (apilimod, 5 mg/kg) was used via intragastric administration. In the ESA group, the anterior oblique line of vertex-temporal (MS6) was stimulated bilaterally with electric acupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in current intensity. The needles were retained for 30 min. The treatment was given once daily and for 7 days in above two intervention groups. Before and after intervention, the neurological deficit score (NDS) and neurobehavioral score (NBS) were assessed in each group. HE staining method was adopted to observe the morphological manifestations of ischemic cortical lesion; the concentrations of IL-12 and IL-12R of the brain tissue in the ischemic cortical lesion were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA expression levels of STAT4 and Tbx21 were detected by real-time PCR technique; and the protein expression of IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-4 were detected using immunohistochemistry. RESULTS: NDS and NBS in the model group, the inhibitor group and the ESA group were all higher than those in the normal group before intervention (P<0.01). After intervention, NDS and NBS in the model group were higher than the normal group (P<0.01); the two scores were all reduced when compared with those before intervention in the inhibitor group and the ESA group (P<0.01), and lower than those of the model group (P<0.01). NDS in the ESA group was lower than the inhibitor group (P<0.05). In the model group, the cells were shrunk and vacuolated in the ischemic cortical lesion. Many normal cells were visible in the ESA group and the inhibitor group. Compared with the normal group, the concentrations of IL-12 and IL-12R , the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in brain tissue of ischemic cortical lesion were all increased in the model group (P<0.01), while the protein expression level of IL-4 decreased (P<0.01). The concentrations of IL-12 and IL-12R, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ were all reduced (P<0.01), while the protein expression level of IL-4 increased (P<0.01) in the ESA group and the inhibitor group when compared with the model group. The concentration of IL-12, the mRNA expression levels of STAT4 and Tbx21 and the protein expression levels of IL-2, TNF-α and IFN-γ in the ESA group were all higher than those of the inhibitor group (P<0.05); while the concentration of IL-12R and the protein expression level of IL-4 were lower than the inhibitor group (P<0.05). CONCLUSION: Electro-scalp acupuncture may improve the neurological function of the rats with ischemic stroke. The modulation to IL-12 mediated JAK/STAT signaling pathway is the potential molecular mechanism of this therapy for the inflammatory response in ischemic cortical lesion.


Asunto(s)
Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Cuero Cabelludo/metabolismo , Interleucina-2 , Interleucina-4 , Quinasas Janus/genética , Quinasas Janus/metabolismo , Transducción de Señal , Interleucina-12 , ARN Mensajero
5.
J Mol Neurosci ; 72(1): 82-96, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34405366

RESUMEN

Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin-eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH.


Asunto(s)
Terapia por Acupuntura , Ferroptosis , Animales , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/terapia , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Cuero Cabelludo/metabolismo , Transducción de Señal
6.
Exp Dermatol ; 29(3): 259-264, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31997403

RESUMEN

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.


Asunto(s)
Alopecia Areata/radioterapia , Hormonas/metabolismo , Fototerapia/métodos , Cuero Cabelludo/metabolismo , Rayos Ultravioleta , alfa-MSH/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Adulto , Alopecia Areata/metabolismo , Biopsia , Hormona Liberadora de Corticotropina/metabolismo , Folículo Piloso/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/patología , Inmunohistoquímica , Persona de Mediana Edad , Sistema Hipófiso-Suprarrenal/metabolismo , Receptor de Melanocortina Tipo 2/metabolismo , Estudios Retrospectivos , Transducción de Señal , Piel/metabolismo
7.
BMC Anesthesiol ; 19(1): 91, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31153358

RESUMEN

BACKGROUND: The purpose of this study was to compare the effects of scalp nerve block (SNB) and local anesthetic infiltration (LA) with 0.75% ropivacaine on postoperative inflammatory response, intraoperative hemodynamic response, and postoperative pain control in patients undergoing craniotomy. METHODS: Fifty-seven patients were admitted for elective craniotomy for surgical clipping of a cerebral aneurysm. They were randomly divided into three groups: Group S (SNB with 15 mL of 0.75% ropivacaine), group I (LA with 15 mL of 0.75% ropivacaine) and group C (that only received routine intravenous analgesia). Pro-inflammatory cytokine levels in plasma for 72 h postoperatively, hemodynamic response to skin incision, and postoperative pain intensity were measured. RESULTS: The SNB with 0.75% ropivacaine not only decreased IL-6 levels in plasma 6 h after craniotomy but also decreased plasma CRP levels and increased plasma IL-10 levels 12 and 24 h after surgery compared to LA and routine analgesia. There were significant increases in mean arterial pressure 2 and 5 mins after the incision and during dura opening in Groups I and C compared with Group S. Group S had lower postoperative pain intensity, longer duration before the first dose of oxycodone, less consumption of oxycodone and lower incidence of PONV through 48 h postoperatively than Groups I and C. CONCLUSION: Preoperative SNB attenuated inflammatory response to craniotomy for cerebral aneurysms, blunted the hemodynamic response to scalp incision, and controlled postoperative pain better than LA or routine analgesia. TRIAL REGISTRATION: Clinicaltrials.gov NCT03073889 (PI:Xi Yang; date of registration:08/03/2017).


Asunto(s)
Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Craneotomía/tendencias , Aneurisma Intracraneal/cirugía , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Anestésicos Locales/metabolismo , Craneotomía/efectos adversos , Femenino , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/sangre , Aneurisma Intracraneal/sangre , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Manejo del Dolor/tendencias , Dolor Postoperatorio/sangre , Cuero Cabelludo/efectos de los fármacos , Cuero Cabelludo/inervación , Cuero Cabelludo/metabolismo , Resultado del Tratamiento
8.
Genome Med ; 8(1): 116, 2016 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-27799065

RESUMEN

BACKGROUND: Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. METHODS: We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient's tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. RESULTS: WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. CONCLUSIONS: This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/genética , Genómica/métodos , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/genética , Adolescente , Animales , Carboplatino/efectos adversos , Carcinoma/diagnóstico por imagen , Análisis Mutacional de ADN , Etopósido/efectos adversos , Resultado Fatal , Humanos , Masculino , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Paclitaxel/efectos adversos , Enfermedades Raras/diagnóstico por imagen , Cuero Cabelludo/efectos de los fármacos , Cuero Cabelludo/metabolismo , Cuero Cabelludo/patología , Ensayos Antitumor por Modelo de Xenoinjerto
9.
PLoS One ; 10(4): e0122142, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25856388

RESUMEN

BACKGROUND: Epidemiological studies have suggested a possible role of trace elements (TE) in the etiology of several neurological diseases including Multiple Sclerosis (MS). Hair analysis provides an easy tool to quantify TE in human subjects, including patients with neurodegenerative diseases. OBJECTIVE: To compare TE levels in scalp hair from patients with MS and healthy controls from the same geographic area (Sicily). METHODS: ICP-MS was used to determine the concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn) in scalp hair of 48 patients with relapsing-remitting Multiple Sclerosis compared with 51 healthy controls. RESULTS: MS patients showed a significantly lower hair concentration of aluminum and rubidium (median values: Al = 3.76 µg/g vs. 4.49 µg/g and Rb = 0.007 µg/g vs. 0.01 µg/g;) and higher hair concentration of U (median values U: 0.014 µg/g vs. 0.007 µg/g) compared to healthy controls. The percentages of MS patients showing hair elemental concentrations greater than the 95th percentile of controls were 20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the percentages of MS patients showing hair elemental concentrations lower than the 5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19% for Fe, and 16% for Pb. No significant association was found between levels of each TE and age, disease duration or Expanded Disability Status Scale (EDSS) score. After stratification by gender, healthy subjects did not show any significant difference in trace element levels, while MS patients showed significant differences (p<0.01) for the concentrations of Ag, Cr, Fe, Ni and Sr. No significant differences were also found, at p<0.01, in relation to the use of cigarettes, consume of water, vegetables and place of living. CONCLUSION: The different distributions of TE in hair of MS patients compared to controls provides an additional indirect evidence of metabolic imbalance of chemical elements in the pathogenesis of this disease. The increase in U and decrease in Al and Rb levels in MS compared to controls require further assessments as well as the observed different distributions of other elements.


Asunto(s)
Cabello/metabolismo , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Cuero Cabelludo/metabolismo , Oligoelementos/metabolismo , Adulto , Anciano , Aluminio/metabolismo , Femenino , Cabello/química , Humanos , Masculino , Persona de Mediana Edad , Rubidio/metabolismo , Cuero Cabelludo/química , Uranio/metabolismo
10.
Med Hypotheses ; 82(4): 470-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24548755

RESUMEN

Trace metals play a significant role in neurological disorders. There is very limited information available on the role of macro and trace elements in bipolar disorders. The objective of this investigation was to identification, quantification of essential trace elements in the scalp hair samples of the patients and compare with those of normal subjects. We made a hypothesis about the role played by essential trace metals whose concentrations are significantly different to those of normals in the disease process. The analysis was carried out in the scalp hair samples of 26 male and 26 female patients suffering from bipolar disorder (BD) by Particle Induced X-ray Emission Technique (PIXE). The concentration of Cu (p < 0.002) was found to be higher in the hair samples of male bipolar disorder patients while the concentrations of Mn (p < 0.001), Fe (p < 0.005), Zn (p < 0.0001) and Se (p < 0.005) were found to be lower than those in normal subjects. The concentration of Cu (p < 0.0001) was higher in the hair samples of female bipolar patients but depressed levels of Fe (p < 0.005), Ni (p < 0.05), Zn (p < 0.00001) and Se (p < 0.05) were observed compared to controls. Cu/Zn ratio was found to be higher in the hair samples of male and female patients compared with normals. While the imbalance of certain trace elements leads to generation of more free radicals, the imbalance of some other trace elements causes changes in dopamine (neurotransmitter) activity. It is essential to monitor before and periodically during treatment the levels of essential trace elements for effective treatment of bipolar disorder.


Asunto(s)
Trastorno Bipolar/metabolismo , Cabello/metabolismo , Cuero Cabelludo/metabolismo , Oligoelementos/análisis , Adulto , Cobre/análisis , Dopamina/metabolismo , Femenino , Humanos , Hierro/análisis , Masculino , Persona de Mediana Edad , Selenio/análisis , Adulto Joven , Zinc/análisis
11.
Skin Pharmacol Physiol ; 26(2): 108-18, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23549137

RESUMEN

BACKGROUND/AIMS: Dry, itchy and inflamed scalp conditions are common and often associated with diseases such as atopic dermatitis or psoriasis. To improve these symptoms, we investigated the efficacy of a new tonic containing the active ingredients urea, lactate, polidocanol, and Glycyrrhiza inflata root extract, containing licochalcone A. STUDY DESIGN/METHODS: 30 subjects with dry and itchy scalp conditions underwent a randomized half-head study for 4 weeks, applying the leave-on tonic three times a week on one side of the scalp. Tonic effects on skin hydration, itching, lipids, microinflammation, and substantivity of tonic compounds were determined using corneometry, middle-infrared spectroscopy, direct analysis in real-time mass spectrometry, and enzyme-linked immunosorbent assay. Volunteers performed a self-assessment; changes in scalp condition were documented by in vivo microscopy. RESULTS: After tonic treatment, scalp moisture was significantly increased, whereas scalp itching and tautness were significantly reduced. Results also demonstrated a high substantivity of urea and lactate on the scalp, an increase in triglyceride, and a decrease in free fatty acid levels. The amount of total lipids was unchanged. Analyses of scalp wash-ups verified a significant reduction in important pro-inflammatory markers. CONCLUSION: Due to the actives urea, lactate, polidocanol, and the anti-inflammatory licochalcone A, the new scalp tonic exhibited excellent performance in alleviating scalp dryness, itching, microinflammation, and in normalizing disturbances of scalp lipids.


Asunto(s)
Chalconas/administración & dosificación , Ácido Láctico/administración & dosificación , Polietilenglicoles/administración & dosificación , Prurito/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Urea/administración & dosificación , Citocinas/metabolismo , Glycyrrhiza , Humanos , Metabolismo de los Lípidos , Extractos Vegetales/administración & dosificación , Raíces de Plantas , Polidocanol , Cuero Cabelludo/metabolismo
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