Involvement of SIRT1 and SIRT3 in Effects of Hypoxic Hypobaric Preconditioning on Hippocampal Damage Induced by Chronic Cerebral Hypoperfusion in C57/6j and a7nAchRs(-/-) Mice / Participación de SIRT1 y SIRT3 en los Efectos del Precondicionamiento Hipobárico Hipóxico sobre el Daño del Hipocampo Inducido por Hipoperfusión Cerebral Crónica en Ratones C57/6j y a7nAchRs (-/-)

SUMMARY: Hypoxic preconditioning is known to induce neuroprotection, but its effects and pathways in chronic brain pathology still unknown. The aim was to establish an involvement of a7 subunit of nicotinic acetylcholine receptors (a7nAchRs), and sirtuins of 1 (SIRT1) and 3 (SIRT3) types in the effects of hypoxic hypobaric preconditioning on brain damage in mice with chronic cerebral hypoperfusion caused by the left common carotid artery occlusion. The male C57/6j (C57, wild type) and a7nAchRs(-/-) mice were divided to six experimental groups (10 mice per group): sham-operated C57, C57 with chronic cerebral hypoperfusion, C57 with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion, sham-operated a7nAchRs(-/-) mice, a7nAchRs(-/-) with chronic cerebral hypoperfusion, a7nAchRs(-/-) with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion. For preconditioning, mice were exposed to hypoxia by "lifting" in barochamber to simulated altitude of 5600 m a.s.l. for 1 h/day on 3 consecutive days before surgical manipulation. Expressions of SIRT1, SIRT3 in brain tissue, and histopathological changes of the hippocampi were examined. It was shown that 8-week chronic hypoperfusion of the brain, caused by unilateral occlusion of the common carotid artery, was accompanied by injury to the neurons of the hippocampi of both hemispheres, which was more pronounced on the side of the occlusion. This damage, as well as the mechanisms of neuroprotection induced by hypoxic preconditioning, were maintained for at least 8 weeks by mechanisms mediated through a7nAChRs. Deficite of a7nAChRs was accompanied with reduction of neuronal damage caused CCH in 8 weeks, as well as preconditioning effects, and lead to compensatory activation of regulatory and protective mechanisms mediated by SIRT1, in normal conditions and in CCH. In wild-type (C57) mice, protective mechanisms in CCH were realized to a greater extent by increased expression of SIRT3 in both hemispheres of the brain.

Se sabe que el precondicionamiento hipóxico induce neuroprotección, pero aún se desconocen sus efectos y vías en la patología cerebral crónica. El objetivo fue establecer la participación de la subunidad a7 de los receptores nicotínicos de acetilcolina (a7nAchR) y las sirtuinas de tipo 1 (SIRT1) y 3 (SIRT3) en los efectos del precondicionamiento hipóxico hipobárico sobre el daño cerebral en ratones con hipoperfusión cerebral crónica causada por la oclusión de la arteria carótida común izquierda. Los ratones macho C57/6j (C57, tipo salvaje) y a7nAchRs(-/-) se dividieron en seis grupos experimentales (10 ratones por grupo): C57 con operación simulada, C57 con hipoperfusión cerebral crónica, C57 con precondicionamiento hipobárico hipóxico y crónica. hipoperfusión cerebral, ratones a7nAchRs(-/-) operados de forma simulada, a7nAchRs(-/-) con hipoperfusión cerebral crónica, a7nAchRs(-/-) con precondicionamiento hipobárico hipóxico e hipoperfusión cerebral crónica. Para el preacondicionamiento, los ratones fueron expuestos a hipoxia "levantándolos" en una cámara de barro a una altitud simulada de 5600 m s.n.m. durante 1 h/día durante 3 días consecutivos antes de la manipulación quirúrgica. Se examinaron las expresiones de SIRT1, SIRT3 en tejido cerebral y los cambios histopatológicos de los hipocampos. Se demostró que la hipoperfusión cerebral crónica de 8 semanas, causada por la oclusión unilateral de la arteria carótida común, se acompañaba de lesión de las neuronas del hipocampo de ambos hemisferios y que era más pronunciada en el lado de la oclusión. Este daño, así como los mecanismos de neuroprotección inducidos por el precondicionamiento hipóxico, se mantuvieron durante al menos 8 semanas mediante mecanismos mediados por a7nAChR. El déficit de a7nAChR se acompañó de una reducción del daño neuronal causado por CCH en 8 semanas, así como de efectos de precondicionamiento, y condujo a una activación compensatoria de mecanismos reguladores y protectores mediados por SIRT1, en condiciones normales y en CCH. En ratones de tipo salvaje (C57), los mecanismos de protección en CCH se realizaron en mayor medida mediante una mayor expresión de SIRT3 en ambos hemisfe- rios del cerebro.

Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Neural and Neural Crest-Derived Stem Cell Distribution in the Adult Human Dental Pulp / Distribución de Células Madre Neurales y Derivadas de la Cresta Neural en la Pulpa Dental Humana Adulta

SUMMARY: Despite comprehensive studies and reports about the properties of dental pulp stem cells (DPSCs) in vitro, we still need to confirm whether these in vitro characteristics coincide with the nature of DPSCs in situ. The anatomical location of DPSCs populations in the dental pulp has yet to be investigated. Moreover, the mesenchymal DPSCs have been much more studied than the neural crest-derived DPSCs. In this study, well-recognized neural/neural crest stem cell markers NCAM1, Nestin, SNAIL/SLUG, SOX9, and S100 are being investigated by immunohistochemistry to localize the precise location of these populations of DPSCs within the human adult dental pulp.All previously mentioned markers were expressed in the dental pulp, and their intensity and location of expression were reported.

A pesar de estudios e informes exhaustivos sobre las propiedades de las células madre de la pulpa dental (DPSC) in vitro, todavía necesitamos confirmar si estas características in vitro coinciden con la naturaleza de las DPSC in situ. La ubicación anatómica de las poblaciones de DPSC en la pulpa dental aún no se ha investigado. Además, las DPSC mesenquimales han sido mucho más estudiadas que las DPSC derivadas de la cresta neural. En este estudio, se están investigando mediante inmunohisto química marcadores de células madre de la cresta neural/ neural NCAM1, Nestin, SNAIL/SLUG, SOX9 y S100 para localizar la ubicación precisa de estas poblaciones de DPSC dentro de la pulpa dental humana adulta. Todos los marcadores mencionados anteriormente se expresaron en la pulpa dental y se informó su intensidad y ubicación de expresión.

Expression and Clinical Significance of CLCA2 in Pan-Cancer / Expresión y Significado Clínico de CLCA2 en Pan-Cáncer

SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.

El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.

Physicochemical properties, metabolomic analysis, antioxidant and lipid - lowering activity of a functional beverage based on cocona (Solanum sessiliflorum Dunal) / Propiedades fisicoquímicas, análisis metabolómico, actividad antioxidante e hipolipemiante de una bebida funcional a base de cocona (Solanum sessiliflorum Dunal)

The physicochemical, microbiological and metabolomics analysis, antioxidant and lipid - lowering effect, and shelf life prediction of a functional beverage based on cocona pul p of SRN9 ecotype was to carry out. According to the results obtained, the beverage complies with all the characteristics of the Peruvian technical standard for juices, nectars and fruit beverages NTP 203.110:2009 and is within the limits established by th e sanitary technical standard NTS N° 071 - MINSA/DIGESA - V.01, with a shelf - life period of 4 months and 1 day. The metabolome regarding bioactive compounds showed the presence of 30 compounds, including several glycosylated flavonols, two flavanols, and two s permidines. Likewise, showed a lipid - lowering effect statistically significant (p < 0.05) about the serum levels of total cholesterol and triglycerides, with a mean reduction of 41.52 mg/dL for total cholesterol levels and 130.80 mg/dL for triglyceride lev els. This beverage could be an alternative for the treatment of atherosclerosis and prevention of cardiovascular diseases.

Se rea lizó el análisis fisicoquímico, microbiológico y metabolómico, efecto antioxidante e hipolipemiante, y vida útil de una bebida funcional a base de cocona ecotipo SRN9. De acuerdo a los resultados, la bebida cumple con las características de la norma técnic a peruana para jugos, néctares y bebidas de frutas NTP 203.110:2009 y se encuentra dentro de los límites establecidos por la norma técnica sanitaria NTS N° 071 - MINSA/DIGESA - V.01, con una vida útil de 4 meses y 1 día. Del perfil metabolómico se identificaro n 30 compuestos, entre ellos varios flavonoles glicosilados, dos flavanoles y dos espermidinas. Asimismo, mostró un efecto hipolipemiante estadísticamente significativo (p < 0,05) sobre los niveles séricos de colesterol total y triglicéridos, con una reduc ción media de 41,52 mg/dL y de 130,80 mg/dL para los niveles de colesterol total y de triglicéridos, respectivamente. Esta bebida podría ser una alternativa para el tratamiento de la aterosclerosis y prevención de enfermedades cardiovasculares.

Dyslipidemic effect of aqueous and ethanolic extracts of raw and roasted xoconostle (Opuntia joconostle) peel / Efecto dislipidémico de extractos acuosos y etanólicos de cáscara cruda y asada de xoconostle (Opuntia joconostle)

The aim of the present study was to assess the impacts of roasting and the type of extraction solvent (ethanol or water) on the hypolipidemic act ivity of xoconostle fruit peel extracts in a tyloxapol - induced model of hyperlipidemia. Water and ethanol extracts from raw and roasted Opuntia joconostle peels were obtained to quantify the phytochemicals contained within and assess their hypolipidemic ac tivity in rats (n=5) against tyloxapol - induced dyslipidemia (400 mg/kg). The raw ethanol and water extracts, as well as the roasted water extract (200 mg/kg), showed hypolipidemic activity in the tyloxapol - treated group ( p <0.05). In contrast, the roasted s ample extracted with ethanol did not show this effect. The concentrations of phenolic compounds (39.80 mg GAE/g) and flavonoids (16.42 ± 0.14 mg QE/g) were higher in the ethanolic extracts than in the aqueous extracts. Conversely, the concentration of beta lains (115.51 ± 1.66 mg/100 g) was higher in the water extracts than in the ethanol extracts. It was concluded that the roasting process modified the concentration of some phytochemicals and their antioxidant capacity in vitro , producing a hypolipidemic ef fect in tyloxapol - induced hyperlipidemic rats

El objetivo del presente estudio fue evaluar el impacto del tostado y del tipo de disolvente de e xtracción (etanol o agua) sobre la actividad hipolipidémica de los extractos de cáscara de frutos de xoconostle en un modelo de hiperlipidemia inducido por el tyloxapol. Se obtuvieron extractos acuosos y etanólicos de cáscara cruda y asada de Opuntia jocon ostle para cuantificar los fitoquímicos que contienen y evaluar su actividad hipolipidémica en ratas (n=5) contra la dislipidemia inducida por el tyloxapol (400 mg/kg). Los extractos acuosos y etanólicos crudos, así como el extracto acuoso tostado (200 mg/ kg), mostraron actividad hipolipidémica en el grupo tratado con tiloxapol ( p <0,05). En cambio, la muestra asada y extraída con etanol no mostró este efecto. Las concentraciones de compuestos fenólicos (39,80 mg GAE/g) y flavonoides (16,42 ± 0,14 mg QE/g) f ueron mayores en los extractos etanólicos que en los acuosos. Por el contrario, la concentración de betalaínas (115,51 ± 1,66 mg/100 g) fue mayor en los extractos acuosos que en los etanólicos. Se concluyó que el proceso de asado modificó la concentración de algunos fitoquímicos y su capacidad antioxidante in vitro , produciendo un efecto hipolipidémico en ratas hiperlipidémicas inducidas por el tyloxapol.

Importancia biológica de los telómeros / Biological importance of telomeres

Se exponen los hallazgos históricos y la importancia biológica de los telómeros en la vida celular y en los aspectos genéticos del ADN humano. (AU)

The discovery and the biological importance of the telomeres are exposed. (AU)

Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

Identification of cancer inhibitors from Hystrix brachyura bezoar extracts using LC - MS multivariate data analysis and in silico evaluation on Bcl - 2, cyclin B/CDK1, VEGF and NM23 - H1 / Identificación de inhibidores de cáncer a partir de extractos de bezoar de Hystrix branchyura usando análisis multivariado LC - MS y evaluación in silico en Bcl - 2, cyclin B/CDK1, VEGF, y NM23 - H1

Hystrix brach yura bezoar is calcified undigested material found in the gastrointestinal tract known for various medicinal benefits including as an anticancer agent. However, the H. brachyura population has been declining due to its demand and is under Malaysian law pro tection. Therefore, present study aimed to identify bezoar anticancer active compounds through metabolomics and in - silico approaches. Five replicates of bezoar powder were subjected to extraction using different solvent ratios of methanol - water (100, 75, 5 0, 25, 0% v/v). Cytotoxicity and metabolite profiling using liquid chromatography - mass spectrometry were conducted. Putative compounds identified were subjected to in - silico analysis with targeted anticancer proteins namely, Bcl - 2, Cyclin B/CDK1 complex, V EGF and NM23 - H1. The correlation of LC - MS and cytotoxicity profile pinpointed two compounds, mangiferin and propafenone. In - silico study showed both compounds exerted good binding scores to all proteins with hydrophobic interaction dominating the ligand - pr otein complex binding, suggesting the ligands act as hydrophobes in the interactions.

El bezpar de Hystrix branchyura es material calcificado sin digerir encontr ados en el tracto gastrointestinal, conocido por sus variados beneficios médicos, incluyendo propiedades anticancerosas. De todas formas, la población de H. Branchyura ha ido declinando debido a su demanda y está bajo la protección de la ley de Malasia. Po r esto, este estudio busca identificar los componentes activos anticancerosos del bezoar mediante abordajes metabolómico e in silico. Cinco réplicas de polvo de bezoar fueron sometidos a extracción usando solventes con diferentes proporciones metanol - agua (100, 75, 50, 25, 0% v/v). Se hicieron perfiles de citotoxicidad y de metabolitos usando cromatografía líquida - espectrometría de masa ( LC - MS ). Se identificaron compuestos putativos yse sometieron a a nálisis in silico, buscando las proteínas anticancerosas B cl - 2, complejo Cyclin B/CDK1, VEGF, y NM23 - H1. La correlación LC - MS y el perfil de citotoxicidad identificaron dos compuestos: mangiferina y propafenona. El estudio in silico mostró que ambos compuestos tenían buenos índices de enlace con todas las proteín as con interacción hidrofóbica dominando el enlace complejo proteína - ligando, sugeriendo que los ligandos actúan como hidrófobos en las interacciones

Oxytocin neuron activation by acute infusion of Montanoa genus plants in the Wistar rats / Activación de neuronas de oxitocina por la infusión aguda de plantas del género de Montanoa en la rata Wistar

In tradition al Mexican medicine, plants from the Montanoa genus, family Asteraceae ( Montanoa tomentosa , Montanoa grandiflora , and Montanoa frutescens ) have been used to induce labor owing to their uterotonic properties like those produced by oxytocin (OXT). However, w hether infusions of these plants can activate hypothalamic OXT - producing neurons is unknown. To test this possibility, five independent groups of Wistar rats (n=4) were included: intact, vehicle, and three groups that received 50 mg/kg p.o. of M. tomentosa , M. grandiflora , and M. frutescens infusions, respectively. Ninety min after treatment, the brains were obtained and processed using double - labeled immunohistochemistry for Fos protein and oxytocin (Fos/OXT - ir). Rats that received Montanoa infusions had s ignificantly greater number of Fos/OXT - ir cells in the paraventricular (PVN) and supraoptic (SON) nuclei, with respect to intact and vehicle groups. These findings demonstrate that Montanoa infusions activated OXT neurons, an effect that may be related to the reported pharmacological properties.

En la medicina tradicional mexicana, plantas del género Montanoa , familia Asteraceae ( Montanoa tomentosa , Montanoa grandiflora y Montanoa frutescens ), se han utilizado para inducir el parto debido a sus propiedades uterotónicas, aparentemente similares a las producidas por la hormona oxitocina (OXT). Sin embargo, se desconoce si las infusiones de estas plantas pueden activar neuronas hipotalámicas productoras de OXT. Para probar esta posibilidad, se incluyeron cinco grupos independientes (n=4): intacto, vehículo y tres grupos que recibieron 50 mg/kg p.o. de infusiones de M. tomentosa , M. grandiflora , y M. frute scens , respectivamente. Noventa minutos después del tratamiento, los cerebros fueron obtenidos y procesados por doble marcaje de inmunohistoquímica para la proteína Fos y oxitocina (Fos/OXT - ir). Las ratas que recibieron infusiones de Montanoa aumentaron si gnificativamente el número de células Fos/OXT - ir en los núcleos paraventricular (PVN) y supraóptico (SON), respecto a los grupos intacto y vehículo. Estos hallazgos demuestran que las infusiones de Montanoa activan neuronas de OXT, lo que podría estar rela cionado con sus propiedades farmacológicas

The infusion of Baccharis spicata (Lam. ) Baill (Asteraceae) has antiviral activity against hepatitis B virus without cytotoxic effects against several cell lines / La infusión de Baccharis spicata (Lam. ) Baill (Asteraceae) posee actividad antiviral contra el virus de la hepatitis B sin efectos citotóxicos contra varias líneas celulares

Medicinal plants are used to cure diseases, and their replacement is frequent and affects public health. The genus Baccharis has representatives within the medicinal flora of Argentina, although the replacement of the species of this genus known under the vulgar name of "carqueja" by Baccharis spicata has been detected i n herbalists or markets of herbal products. The genotoxic safety of this species has been established in previous work of our group. The aim of this study was to evaluate the antiviral activity of an infusion made from B. spicata leaves against hepatitis B virus with the HepG2.2.15 cellular system and to determine cytotoxicity in HepG2.2,15, A549 and Vero cell lines. Infusion of B. spicata was active to inhibit HBV replication with an EC 50 of 22.54 µg/mL and a CC 50 of 190 µg/mL.

Las plantas medicinales son empleadas para la cura de enfermedades, y su sustituc ión es frecuente y afecta a la salud pública. El género Baccharis posee representantes dentro de la flora medicinal de Argentina, aunque se ha detectado la sustitución de las especies de dicho género conocidas bajo el nombre vulgar de "carqueja" por Baccha ris spicata en herboristerías o mercados de productos herb arios . Se ha establecido la seguridad genotóxica de esta especie en trabajos previos de nuestro grupo. Este estudio buscó evaluar la actividad antiviral de una infusión elaborada a partir de hojas de B. spicata frente al virus de la hepatitis B con el sistema celular HepG2.2.15 y determinar la citotoxicidad en las líneas celulares HepG2.2.15, A549 y Vero. La infusión de B. spicata fue activa para inhibir la replicación del virus con un EC 50 de 22.54 µg/mL y un CC 50 de 190 µg/mL.

Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.@*METHODS@#The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.@*RESULTS@#For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.@*CONCLUSION@#It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway / 中华创伤杂志(英文版)

PURPOSE@#Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.@*METHODS@#C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference.@*RESULTS@#Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.@*CONCLUSIONS@#Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway.@*METHODS@#Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside.@*RESULTS@#Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05).@*CONCLUSION@#Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration / 中国结合医学杂志

OBJECTIVE@#To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism.@*METHODS@#B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR.@*RESULTS@#In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells.@*CONCLUSIONS@#Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes / 中国结合医学杂志

OBJECTIVE@#To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.@*METHODS@#Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.@*RESULTS@#TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).@*CONCLUSIONS@#TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.