The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Perfil molecular de cáncer de endometrio en mujeres de Bogotá D.C., Colombia

Introducción: El cáncer de endometrio ocupa el sexto lugar en incidencia del cáncer en mujeres. La caracterización molecular de este cáncer permite optimizar la estratificación de riesgo para mejorar el tratamiento de las pacientes. Objetivo: Determinar el perfil molecular TCGA de pacientes con cáncer de endometrio en Bogotá, D.C., Colombia. Método: Estudio descriptivo en una cohorte de pacientes con cáncer de endometrio. Las mutaciones en los exones 9 a 14 del gen POLE fueron identificadas mediante amplificación por reacción en cadena de la polimerasa, seguida de secuenciación Sanger y análisis bioinformático. La expresión de las proteínas MMR y p53 se identificó mediante inmunohistoquímica. Resultados: Se incluyeron 40 pacientes con una mediana de edad de 66 años. El 15% presentaron mutaciones en el dominio exonucleasa de POLE. El 32% de las pacientes que no presentaron mutaciones manifestaron deficiencia en el sistema MMR. El 43,47% de las pacientes sin mutaciones en POLE ni alteración del sistema MMR presentaron alteración de la proteína p53. Conclusiones: La población de cáncer de endometrio analizada presenta un perfil molecular TCGA similar a lo reportado para otras poblaciones.

Introduction: Endometrial cancer ranks sixth in cancer incidence among women. Its molecular characterization allows for a more precise risk stratification with the aim of improving patient treatment. Objective: To determine the TCGA molecular profile of patients with endometrial cancer in Bogota, Colombia. Method: A descriptive study of a cohort of patients with endometrial cancer. The expression of MMR proteins and p53 was identified through immunohistochemistry. Mutations in exons 9 to 14 of the POLE gene were identified through polymerase chain reaction amplification, followed by Sanger sequencing and bioinformatic analysis. Results: Forty patients were included in the study, with a median age of 66 years, 15% of them exhibited mutations in the exonuclease domain of POLE, while 32% of patients without mutations showed deficiency in the MMR system. Forty three percent of patients without mutations in POLE or MMR alterations showed aberrant p53 protein expression. Conclusions: The analyzed population of endometrial cancer presents a TCGA molecular profile similar to that reported for other populations.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

Effect of Gandou Fumu Decoction on Autophagy in Mice with Liver Fibrosis in Wilson's Disease by Regulating Expression of miR-29b-3p/ULK1 / 中国实验方剂学杂志

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg-1. In the penicillamine group， 0.1 g·kg-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Effects of alfentanil on myocardial fibrosis in rats with acute myocardial infarction by regulating the SphK1/S1P signaling pathway / 中国药房

OBJECTIVE To explore the effects of alfentanil （ALF） on myocardial fibrosis in rats with acute myocardial infarction （AMI） by regulating sphingosine kinase 1 （SphK1）/sphingosine 1-phosphate （S1P） signaling pathway. METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery. The successfully modeled rats were randomly divided into AMI model group （Model group）， ALF low-dose group （ALF-L group， 0.25 mg/kg ALF）， ALF high-dose group （ALF-H group， 0.5 mg/kg ALF）， high dose of ALF+SphK1 activator group （ALF-H+K6PC-5 group， 0.5 mg/kg ALF+1 μg/g K6PC-5）. At the same time， a sham operation group （Sham group） was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery， with 15 rats in each group. Rats in each drug group were intraperitoneally injected with the corresponding drug solution， once a day， for 4 consecutive weeks. Twelve hours after the last medication， cardiac function indicators [left ventricular systolic pressure （LVSP）， left ventricular ejection fraction （LVEF）， left ventricular systolic diameter （LVSD）， left ventricular fractional shortening （LVFS）] of rats were detected in each group； the condition of myocardial infarction， pathological changes in myocardial tissue， and degree of fibrosis were observed； serum levels of brain natriuretic peptide （BNP） and cardiac troponin Ⅰ （cTnⅠ） in rats were detected. The protein expressions of collagen Ⅰ ， collagen Ⅲ ， matrix metalloproteinase-2 （MMP-2）， SphK1 and S1P were alsodetected in the myocardial tissue of rats. RESULTS Compared with the Sham group， the arrangement of myocardial cells in the Model group was disordered， with a large number of inflammatory cells infiltrating. The levels of LVSP， LVFS and LVEF in the Model group were significantly reduced （P＜0.05）； LVSD level， myocardial infarction area， collagen volume fraction， serum levels of BNP and cTnⅠ， the protein expressions of collagen Ⅰ， collagen Ⅲ， MMP-2， SphK1 and S1P in myocardial tissue were significantly increased or enlarged （P＜0.05）. Compared with the Model group， the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved， while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group （P＜0.05）. K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats （P＜0.05）. CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats， and the effect may be related to the inhibition of the SphK1/S1P signaling pathway.

Research progress on the role of cytochrome P450 in plant sesquiterpene biosynthesis / 药学学报

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

Meta-analysis of the efficacy of invisible orthodontic appliances for maxillary molar distalization in adult patients / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of invisible orthodontic appliances without brackets for the distal movement of maxillary molars to improve the ability of orthodontists to predict treatment outcomes.@*Methods@#Web of Science, Cochrane Library, Embase, PubMed, Wanfang Database, CNKI Database, and VIP Database were searched for studies investigating the efficacy of invisible orthodontic appliances for distal movement of maxillary molars in adult patients and published from database inception to August 1, 2023. A total of three researchers screened the studies and evaluated their quality and conducted a meta-analysis of those that met quality standards.@*Results@#This study included 13 pre- and postcontrol trials with a total sample size of 281 patients. The meta-analysis revealed no significant differences in the sagittal or vertical parameters of the jawbone after treatment when compared with those before treatment (P>0.05). The displacement of the first molar was MD=-2.34, 95% CI (-2.83, -1.85); the displacement was MD=-0.95, 95% CI (-1.34, -0.56); and the inclination was MD=-2.51, 95% CI (-3.56, -1.46). There was a statistically significant difference in the change in sagittal, vertical, and axial tilt of the first molar before and after treatment. After treatment, the average adduction distance of the incisors was MD=-0.82, 95% CI (-1.54, -0.09), and the decrease in lip inclination was MD=-1.61, 95% CI (-2.86, -0.36); these values were significantly different from those before treatment (P<0.05).@*Conclusion@#Invisible orthodontic appliances can effectively move the upper molars in a distal direction and control the vertical position of the molars. When the molars move further away, there is some degree of compression and distal tilt movement, which is beneficial for patients with high angles. The sagittal movement of incisors is beneficial for improving the patient's profile.

Etiological characteristics of viral gastroenteritis in pediatric inpatients under five years old in Shanghai， 2021‒2022 / 上海预防医学

ObjectiveTo investigate the changes in the pathogen spectrum of viral diarrhea in local pediatric inpatients as well as any variations in genotypes of major pathogens during the COVID-19 control period. MethodsFecal samples were collected from the children <5 years who were hospitalized due to acute gastroenteritis in a pediatric hospital in Shanghai. PCR test was carried out to detect rotavirus， norovirus， sapovirus， astrovirus and enteric adenovirus， and then genotyping was performed for major pathogens. ResultsOut of 546 samples， 37.55% tested positive for virus with the following positive rate ranking： norovirus GⅡ （22.16%）， group A rotavirus （16.12%）， astrovirus （2.93%）， enteric adenovirus （2.38%）， sapovirus （0.92%） and norovirus GⅠ （0.18%）. The predominant genotype within norovirus GⅡ were GⅡ.4［P31］ and GⅡ.4［P16］ with a proportion of 24.79% and 14.05% respectively. The detection rate of GⅡ.4［P31］ dropped significantly over the 2-year period （χ2＝16.140，P<0.001）. In addition， an emerging rotavirus genotype G8P ［8］， which was rarely found nationally， was discovered for the first time locally with an increasing proportion， accounting for 7.95% of all rotavirus positive cases. Phylogenic analysis demonstrated that the representative strains of this genotype were genetically closer to the DS-1-like G8P ［8］ strain found in Southeast Asia. ConclusionThe changes in the prevalence of various norovirus genotypes together with the emergence of rare rotavirus genotype in the local area illustrate the importance of continuous monitoring of viral diarrhea and genotyping of key pathogens. Increased local activity of the rare genotype also adds new parameters in the efficacy evaluation of marketed vaccines and development of potential new vaccines in near future.

Effect and Mechanism of Action of Epimedii Folium Polysaccharides on Mice with Exercise-induced Fatigue Based on p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group， model group， vitamin C group， and low， medium， and high dose groups of Epimedii Folium polysaccharides， with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming， the Epimedii Folium polysaccharide groups were given 100， 200， 400 mg∙kg-1 of Epimedii Folium polysaccharides by gavage， and the vitamin C group was given 200 mg∙kg-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period， the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen （BUN）， lactic acid （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidation （GSH-Px）， myoglycogen （MG） in skeletal muscle， hepatic glycogen （HG） in the liver were detected by kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylation （p）-p38 MAPK， extracellular signal-regulated kinase1/2 （ERK1/2）， nuclear factor-κB （NF-κB）， p-NF-κB， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in muscle tissue. The immunofluorescence （IF） method was used to detect the expression of tumor necrosis factor-α （TNF-α） in skeletal muscle tissue of mice in each group. ResultCompared with the control group， the body mass of mice in the model group decreased， and the time of last swimming due to exhaustion decreased （P<0.01）. In addition， there were significantly higher serum levels of the fatigue metabolites LA， LDH， BUN， and lipid peroxidation product MDA （P<0.01） and decreased levels of MG， HG， SOD， and GSH-Px （P<0.01）. The protein expressions of p-p38 MAPK， ERK1/2， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue were significantly higher than those of the control group （P<0.01）. Compared with the model group， the body mass and time of last swimming due to exhaustion of the mice in the low， medium， and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased （P<0.05， P<0.01）， and the contents of LA， LDH， BUN， and MDA were significantly decreased （P<0.05， P<0.01）. The levels of MG， HG， SOD， and GSH-Px increased （P<0.05， P<0.01）， and the protein expression levels of p-p38 MAPK， ERK， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue decreased （P<0.05， P<0.01）. ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway， thereby reducing the accumulation of metabolites， improving the activity of antioxidant enzymes， increasing the glycogen content of the body， and reducing inflammation in skeletal muscle.

Morin Mediates Protective Effects on Bone in Aged Rats by Inhibiting ERK1/2-p38 Signaling Pathway / 中山大学学报(医学科学版)

ObjectiveTo investigate the effects of morin treatment on bone metabolism and bone mass in aged rats， and to clarify the possible mechanism. MethodsTen young female Sprague-Dawley rats （3 months old） and 20 old female Sprague-Dawley rats （24 months old） were randomly divided into three groups： Control group （CON， 10 young rats）； Model group （MOD， 10 young rats）； 10 old rats and SangHuangSu Group （SSS， 10 old rats）. During the experiment， the SSS group received intraperitoneal injection of morin （10 mg / kg） daily. The treatment lasted for 12 weeks. After treatment， Micro-CT， HE stained sections， serological tests and Western blot were used to observe the treatment effect and possible mechanism. ResultsAfter 12 weeks of treatment， compared with MOD group， the number and density of bone trabeculae in SSS group were significantly improved. The BMD， Conn. D， Tb. N， Tb.Th and Tb.Sp of the left femur in the SSS group were significantly better than those in the MOD group（P <0.05）. After 12 weeks of treatment， the levels of CTX-1， osteocalcin， TRACP-5b and PINP in SSS group were significantly lower than those in MOD group（P <0.05）. Compared with the MOD group， the ERK1/2-p38 signal pathway was significantly inhibited and the levels of ERK1/2 and p38 were significantly decreased in the SSS group（P <0.05）. ConclusionMorin pigment mediates the protective effect on the bones of aged rats by inhibiting the ERK1/2-p38 signaling pathway and reducing bone turnover.

Mechanism of Ruanmai decoction in treating atherosclerosis based on YWHAZ/p38MAPK/CASP3 signaling pathway / 中国药理学通报

Aim To explore the mechanism of action of Ruanmai decoction in treating atherosclerosis through network pharmacology. Methods The chemical components and targets of Ruanmai decoction were queried using TCMSP. Relevant targets for atherosclerosis were retrieved from DrugBank, GeneCards, OMIM, and TTD databases. The " Drug-Active Ingredient-Target" PPI network was constructed using Cyto-scape software. GO and KEGG enrichment analysis were performed using the David database. Molecular docking verification of key components with core targets was conducted using the Seesar software. Atherosclerosis mouse models were established by feeding ApoE mice with a high-fat diet, and Ruanmai decoction granules were administered orally. Aortic pathological sections were stained, blood lipids were measured, and immunofluorescence was used to detect Mac2 and YWHAZ protein expression. Western blot was used to detect p-p38MAPK and C-CASP3 protein expression. Results Ruanmai decoction screened a total of 72 active drug components corresponding to 168 target genes for the treatment of atherosclerosis. The targets were primarily enriched in biological processes related to lip-id metabolism, inflammation and immunity, oxidative stress, vascular endothelial function, cell proliferation and apoptosis, glycolysis, and ubiquitination. Signaling pathways such as МАРК, TNF, PDK-Akt, and IL-17 were also involved. Animal experiments verified that RMJ could regulate the p38MAPK signaling pathway by down-regulating key targets YWHAZ, p-p38MAPK, and C-CASP3, thereby reducing AS inflammation and inflammation-induced apoptosis. Conclusions Ruanmai decoction can inhibit the expression of YWHAZ and activate the p38MAPK signaling pathway, potentially improving vascular inflammation, lipid metabolism, oxidative stress, and other pathological processes by regulating the МАРК, TNF, PDK-Akt, and IL-17 signaling pathways, thus preventing and treating atherosclerosis.

Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes / 中国药理学通报

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway / 中国药理学通报

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways / 中国药理学通报

Aim To investigate the effect of benzyl iso-thiocyanate (BITC) on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis. Methods The effect of BITC on U14 cell activity was detected by MTT, nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope, cell cycle and apoptosis were determined by flow cytometry, and the transcriptome database of U14 cells before and after BITC (20 μmol · L

Effect of Qingshen granules on miR-23b and PINKl/Parkin pathway in rat NRK-52E cell transdifferentiation model / 中国药理学通报

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.