Myrtus communis leaves: source of bio - actives, traditional use, their biological properties, and prospects / Hojas de Myrtus communis: fuente de bioactivos, uso tradicional, sus propiedades biológicas y perspectivas

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times, the inhabitant s of this area have been using it for its cultural and medicinal properties. Because of the vast diversity of biomolecules in its aerial parts, it exhibits several biological properties, including antioxidant, antimicrobial, and anticancer properties. This review retrospect the research on the source, biological activities with empirical evidence, chemical composition, applications, and cellular targets of extracts and essential oils obtained from M. communis leaves, which provides a perspective for further studies on the applications and formulations of extract and EO of M. communis leaves. The efficacy of constituents' individually, in association with other bioactive constituents, or in combination with available commercial drugs would provide insights in to the development of these bio - actives as future drugs and their evolving future potential applications in the pharmaceutical, food, and aroma industries.

Myrtus communis L., comúnmente conocido como arrayán verdadero, es una planta medicinal originaria de la zona mediterránea. Desde la antigüedad, los habitantes de esta zona lo utilizan por sus propiedades culturales y medicinales. Debido a la gran div ersidad de biomoléculas en sus partes aéreas, exhibe varias propiedades biológicas, incluidas propiedades antioxidantes, antimicrobianas y anticancerígenas. Esta revisión retrospectiva de la investigación sobre la fuente, las actividades biológicas con evi dencia empírica, la composición química, las aplicaciones y los objetivos celulares de los extractos y aceites esenciales obtenidos de las hojas de M. communis , lo que brinda una perspectiva para futuros estudios sobre las aplicaciones y formulaciones de l os extractos y EO de M. communis . La eficacia de los componentes individualmente, en asociación con otros componentes bioactivos o en combinación con medicamentos comerciales disponibles proporcionaría información sobre el desarrollo de estos bioactivos co mo medicamentos futuros y sus futuras aplicaciones potenciales en las industrias farmacéutica, alimentaria y aromática

The evolution and application progress of non-modified drug target discovery CETSA technology / 药学学报

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Role of Histone Methyltransferase in Fibrosis and Traditional Chinese Medicine Treatment： A Review / 中国实验方剂学杂志

Fibrosis， a tumor-like lesion between benign tissue and malignant tumor， mostly occurs in the liver， kidney， heart， lung， bone marrow and other organs and tissues. It can affect almost every organ and eventually induce multiple organ failure and cancers， seriously endangering human life. It will be of great importance to prevent cancer if the disease can be opportunely blocked in the fibrotic stage. The pathogenesis of fibrosis is still not completely clear. It is of great clinical significance to study the occurrence， development， and mechanism of fibrosis as well as to screen new therapeutic targets. Enhancer of zeste homolog 2 （EZH2） is mainly located in the nucleus and involved in the formation of the polycomb repressive complex 2. EZH2 is a methyltransferase which makes the lysine on position 27 of histone H3 （H3K27me3） undergo trimethyl modification induces gene silencing through classical or nonclassical actions， so as to inhibit or activate transcription. EZH2 plays a critical role in cell growth， proliferation， differentiation， and apoptosis， which is regulated by different targets and signaling pathways. EZH2 regulates the transformation of myofibroblasts and participates in the fibrosis of multiple organs. Recent studies have shown that EZH2 plays a role in fibrosis-related pathophysiological processes such as epithelial-mesenchymal transition， oxidative stress， and inflammation. EZH2 as the target of fibrosis， EZH2 inhibitors， and EZH2-related traditional Chinese medicine （TCM） formula and active compounds have gradually become hot research directions. EZH2 may be a powerful target for organ fibrosis. Exploring the structure， function， and distribution of EZH2， the role of EZH2 in fibrosis， the EZH2 inhibitors， and TCM formulas and active components targeting EZH2 has great meanings. This paper reviews the research progress in EZH2 and fibrosis， providing new ideas for the diagnosis， treatment， and drug development of fibrosis.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P® / Effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®

Introducción: Los diabéticos muestran una disminuida función del sistema inmune. Su complicación más temida es la aparición de las úlceras del pie. El Heberprot-P® tiene efectos beneficiosos en la curación de estas úlceras. Objetivo: Evaluar el efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P®. Métodos: Se realizó un estudio observacional, prospectivo, de serie de casos, en 30 pacientes con úlcera de pie diabético, ingresados en el Instituto Nacional de Angiología y Cirugía Vascular. Se administraron 75 µg de Heberprot-P®, tres veces por semana, a través de vías peri- e intralesional, durante ocho semanas. Se evaluaron las variables edad, sexo, glucemia en ayunas, creatinina, urea, ácido úrico, prueba de hipersensibilidad retardada, porcentaje de granulación, tiempo de cierre de la lesión y localización de la úlcera, antes de comenzar el tratamiento, a las 4 y 8 semanas. Resultados: Se precisó un predominio del 60 por ciento en el sexo femenino y del color de piel blanca. Los niveles de glucemia y creatinina se comportaron más elevados en los anérgicos; la urea fue similar tanto en anérgicos como en reactivos; y el ácido úrico resultó mayor en hombres reactivos y en mujeres anérgicas. Hubo mayor proporción de reactivos (63,6 por ciento), que en la cuarta semana presentaron un tejido de granulación igual o mayor al 50 por ciento; y a la octava, igual o mayor al 70 por ciento. Conclusiones: La condición en los pacientes diabéticos de ser reactivo a las pruebas de hipersensibilidad retardada con úlcera de pie diabético de tipo neuropática, tratados con Heberprot-P®, está asociada directamente con una mejor respuesta en la cicatrización de sus lesiones, mediante la formación del tejido de granulación, que favorece el cierre total o parcial de la lesión. Esto no ocurrió con los pacientes anérgicos a dicha prueba(AU)

Introduction: Diabetics show decreased immune system function. Its most feared complication is the appearance of foot ulcers. Heberprot-P® has beneficial effects in healing these ulcers. Objective: To assess the effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®. Methods: An observational, prospective, case series study was conducted in 30 patients with diabetic foot ulcer admitted to the National Institute of Angiology and Vascular Surgery. 75 µg of Heberprot-P®, three times a week, were administered through peri- and intralesional routes, during eight weeks. The variables age, sex, fasting blood glucose, creatinine, urea, uric acid, delayed hypersensitivity test, percentage of granulation, time of closure of the lesion and location of the ulcer, before starting treatment, at 4 and 8 weeks were evaluated. Results: A predominance of 60 % in females and white skin color were specified. Blood glucose and creatinine levels behaved higher in the anergics; urea was similar in both anergics and reagents; and uric acid was higher in reactive men and anergic women. There was a higher proportion of reagents (63.6 por ciento), which in the fourth week presented a granulation tissue equal to or greater than 50 por ciento; and at the eighth week, it was equal to or greater than 70 por ciento. Conclusions: The condition of being reactive to delayed hypersensitivity tests in diabetic patients with diabetic foot ulcer of neuropathic type, treated with Heberprot-P® is directly associated with a better response in the healing of their lesions, through the formation of granulation tissue, which favors the total or partial closure of the lesion. This did not occur with patients who were anergic to this test(AU)

Senescence in oral lichen planus as assessed by the immunohistochemical evaluation of senescence marker protein-30 (Regucalcin)

Background: Oral lichen planus is a T-cell-mediated chronic inflammatory disease affecting approximately 1% to 2% of the population, the etiology of which is currently unknown. The objectives of this study were to observe if senescence occurs in oral lichen planus, through the assessment of the immunohistochemical expression of a novel marker for senescence called Senescence marker protein-30 or regucalcin, and compare the expression to that in oral lichenoid reaction and non-specific inflammation. Subjects and Methods: The study material consisted of 30 cases of oral lichen planus, 15 cases of oral lichenoid reaction and 15 cases of non-specific inflammation. The number of positive cells in ten randomly selected high power fields were counted in the epithelium and the connective tissue separately and the mean was determined. Results: Mann–Whitney U test was used to statistically analyze if there was any significant difference in the expression of Senescence marker protein-30 between oral lichen planus, oral lichenoid reaction and non-specific inflammation. Even though a greater expression was seen in the oral lichen planus cases than oral lichenoid reaction, the difference in both the epithelium and connective tissue was not statistically significant. Conclusion: This study shows that in addition to the already known mechanisms like apoptosis and increased cell proliferation rates, the activated T-lymphocytes may also trigger a senescent change in the cells of oral lichen planus. As with the other mechanisms, this is also seen only in a small proportion of the cases.

Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts

Abstract Background Oxidative stress is strongly associated with cellular senescence. Numerous studies have indicated that microRNAs (miRNAs) play a critical part in cellular senescence. MiR-181a was reported to induce cellular senescence, however, the potential mechanism of miR-181a in hydrogen peroxide (H2O2)-induced cellular senescence remains obscure. Objective The aim of this study is to investigate the role and regulatory mechanism of miR-181a in H2O2-induced cellular senescence. Methods Human foreskin fibroblasts (HFF) transfected with miR-181a inhibitor/miR-NC with or without H2O2 treatment were divided into four groups: control + miR-NC/miR-181a inhibitor, H2O2 + miR-NC/miR-181a inhibitor. CCK-8 assay was utilized to evaluate the viability of HFF. RT-qPCR was used to measure the expression of miR-181a and its target genes. Protein levels of protein disulfide isomerase family A member 6 (PDIA6) and senescence markers were assessed by western blotting. Senescence-associated β-galactosidase (SA-β-gal) staining was applied for detecting SA-β-gal activity. The activities of SOD, GPx, and CAT were detected by corresponding assay kits. The binding relation between PDIA6 and miR-181a was identified by luciferase reporter assay. Results MiR-181a inhibition suppressed H2O2-induced oxidative stress and cellular senescence in HFF. PDIA6 was targeted by miR-181a and lowly expressed in H2O2-treated HFF. Knocking down PDIA6 reversed miR-181a inhibition-mediated suppressive impact on H2O2-induced oxidative stress and cellular senescence in HFF. Study limitations Signaling pathways that might be mediated by miR-181a/PDIA6 axis were not investigated. Conclusion Downregulated miR-181a attenuates H2O2-induced oxidative stress and cellular senescence in HFF by targeting PDIA6.

Research progress on the role and mechanism of premature cellular senescence on wound healing in radiation-induced skin injury / 中华放射医学与防护杂志

Radiation skin injury can be induced by medical exposure, occupational exposure, and emergency exposure. Many relevant studies focused on the prevention and treatment of radiation-induced skin injury, but the underlying molecular mechanisms have not been fully clarified. It has been demonstrated that radiation-induced premature cellular senescence is involved in radiation skin injury. To discuss the relationship between radiation-induced premature cellular senescence and radiation-induced skin injury, this paper reviewed the mechanism of radiation-induced skin injury, the promotion of premature cellular senescence and related signal pathways, and the role of premature cellular senescence in wound healing.

Correlation between anti-C1q antibody and disease activity and cellular immune function in patients with systemic lupus erythematosus / 中国医师杂志

Objective:To evaluate the correlation between anti-C1q antibody and disease activity and cellular immune function in patients with systemic lupus erythematosus (SLE).Methods:The clinical data and test indexes of 134 patients with SLE and 90 healthy people who were admitted to Henan Provincial People′s Hospital from June 2017 to February 2018 were collected. The level of anti-C1q antibody was measured by enzyme-linked immunosorbent assay (ELISA), and lymphocyte subsets were measured by flow cytometry. According to the score of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, SLE patients were divided into active and inactive groups, and SLE patients were divided into LN group and non-LN group according to the presence or absence of kidney involvement. The levels of anti-C1q antibodies and lymphocyte subsets were compared among the three groups, and correlations between anti-C1q antibodies and disease activity and lymphocytes were analyzed. The predictive value of anti-C1q antibodies and anti double stranded DNA (dsDNA) antibodies for SLE disease activity was evaluated.Results:The anti-C1q antibody level, percentage of T cells and Ts cells in SLE group were higher than those in control group, while the percentage of Th cells, percentage of NK cells, T cell count, Th cell count, B cell count and NK cell count in SLE group were lower than those in control group (all P<0.05); The anti-C1q antibody level in the active group was higher than that in the inactive group, and the counts of T cells, Ts cells, Th cells, B cells and NK cells were lower than those in the inactive group (all P<0.05); The anti-C1q antibody level in LN group was higher than that in non-LN group, and the T cell count, Ts cell count, Th cell count, B cell count, NK cell count were lower than that in non-LN group, with statistically significant difference (all P<0.05). Correlation analysis showed that age, hemoglobin (HB), C3, C4, T cell count, Th cell count, B cell count and NK cell count were negatively correlated with anti-C1q antibody, while SLEDAI-2K, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-dsDNA antibody were positively correlated with anti-C1q antibody (all P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of anti-C1q antibody alone in predicting SLE disease activity was 0.702, with a sensitivity of 0.547 and a specificity of 0.827. The combination of anti-C1q and anti ds-DNA antibodies resulted in an AUC of 0.761, a sensitivity of 0.756, and a specificity of 0.691. The combined detection value of the two antibodies predicting SLE disease activity was better than the single detection. Conclusions:Anti-C1q antibody is closely related to disease activity and cellular immune dysfunction, and has certain predictive value in SLE disease activity.

Effects of probiotics on intestinal flora, intestinal function and T lymphocyte level in patients with cervical cancer after radiotherapy / 中国基层医药

Objective:To investigate the effects of probiotics on intestinal flora, intestinal function, and T lymphocyte level in patients with cervical cancer after radiotherapy.Methods:A total of 92 patients with cervical cancer who underwent pelvic radiotherapy in The Second Affiliated Hospital of Zhengzhou University from September 2020 to February 2022 were included in this study. They were randomly divided into control and experimental groups ( n = 46/group). The patients in the experimental group took probiotics during radiotherapy, while the patients in the control group did not take probiotics during radiotherapy. The amount of intestinal flora, D-lactic acid, diamine oxidase, and T lymphocyte subset levels pre- and post-radiotherapy were compared between the two groups. Urinary lactulose (L) and mannitol (M) concentrations were determined in each group. Urinary excretion ratios of L to M were calculated. Results:After 10, 15, and 20 times of radiotherapy and after all radiotherapies, the amount of Escherichia coli and Enterococcus in the experimental group was significantly lower than that in the control group ( F = 128.60, 224.99, all P < 0.05). The amount of Bifidobacteria and Lactobacilli in the experimental group was significantly higher than that in the control group ( F = 2 065.46, 948.23, both P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma D-lactic acid level in the experimental group was (9.34 ± 1.63) μg/L, (9.15 ± 1.36) μg/L, (8.68 ± 1.06) μg/L, and (8.05 ± 0.82) μg/L, respectively. After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma diamine oxidase level in the experimental group was (86.34 ± 20.25) μg/L, (84.28 ± 17.45) μg/L, (80.40 ± 13.35) μg/L, and (76.85 ± 10.87) μg/L, respectively, and urinary excretion ratio of L to M in the experimental group was (1.84 ± 0.16), (1.55 ± 0.12), (1.26 ± 0.09), (0.98 ± 0.06), respectively, all of which were significantly lower than those in the control group ( F = 121.60, 31.73, 417.84, all P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, CD4 + level in the experimental group was (39.80 ± 4.90)%, (40.92 ± 5.30)%, (42.52 ± 6.14)%, (43.83 ± 6.55)%, respectively, CD4 +/CD8 + was (1.52 ± 0.25), (1.63 ± 0.22), (1.71 ± 0.39), (1.83 ± 0.22), respectively, all of which were significantly higher than those in the control group ( F = 58.69, 31.07, all P < 0.05). Conclusion:Probiotics can improve the status of intestinal flora and intestinal barrier function in patients with cervical cancer after radiotherapy, and simultaneously improve the cellular immune function of patients.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication / 药物分析学报

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively character-izing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear time-invariant dynamical model.It is shown that the transition matrices of dynamical cell systems signifi-cantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Role of intrahepatic microenvironment induced-autophagy in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a series of abnormal liver lesions mainly characterized by excessive lipid deposition in hepatocytes, and it is also the most common chronic liver disease worldwide. Autophagy is a basic cellular process in which cells degrade their own components and participate in the maintenance of organ function and body homeostasis, and it is closely associated with the progression of NAFLD. High fat, hypoxia, and stress in human body may cause abnormal changes in extracellular microenvironment in the liver, and such abnormal microenvironment may promote the development and progression of NAFLD by inducing liver cell autophagy. This article reviews the role and mechanism of autophagy of liver cells such as hepatocytes, Kupffer cells, and hepatic stellate cells in the progression of NAFLD based on various microenvironment characteristics in the liver.

Status quo and influencing factors of computer vision syndrome among college freshmen in Tianjin / 中国学校卫生

Objective@#To investigate the current situation and associated factors of computer vision syndrome (CVS) among college freshmen in Tianjin during the COVID-19 epidemic, and to provide a reference for visual comfort of college students.@*Methods@#A total of 868 college freshmen from one university in Tianjin were administered with CVS qualitative analysis questionnaire, eye health status questionnaire and eye health examination during Oct to Dec 2021. Chi square test and multivariate Logistic regression were used for data analysis.@*Results@#The detection rate of CVS among the included students was 68.5% ( n =595) and was higher in females (72.2%) than in males (61.7%). The CVS detection rate in girls, students without myopia, >30 min sleep onset, >1 h mobile phone usage, and ≤8 h sleep duration (72.2%, 70.4%, 81.1%, 72.7%, 71.2%) were significantly higher than boys, students with low grade myopia, sleep onset required ≤30 min, use mobile phone for ≤1 h, and sleep duration >8 h(61.7%, 63.3 %, 67.4%, 65.9%, 61.1%) ( χ 2=10.08, 3.94, 5.89, 4.40, 7.94, P ＜0.05). Differences in CVS detection rates varied significantly by daily electronic device usage and academic stress students ( χ 2=22.03, 21.24, P ＜0.05). Multivariate Logistic regression analysis showed that daily use of electronic devices 4-6, 7-9, ≥10 h, sleep onset required >30 min, moderate to higher academic pressure were positively associated with CVS ( OR=1.95, 2.94, 2.30, 2.39, 3.51, 4.41, P ＜0.05), boys, low grade myopia, night sleep time >8 h were negatively associated with CVS ( OR=0.65, 0.70, 0.65, P ＜0.05).@*Conclusion@#The detection rate of CVS among freshmen in a university in Tianjing is high. Attention should be paid to the CVS situation of students with e learning, and general public should also be educated to reduce the time of unnecessary electronic product use and ensure night sleep to reduce the prevalence of CVS.

Yiqi Wenyang Huwei Decoction Regulates PI3K/Akt/mTOR Pathway to Treat Bronchial Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo observe the regulatory effects of Yiqi Wenyang Huwei decoction （YWHD） on autophagy and phosphatidylinositol 3-kinase （PI3K）/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway in asthmatic rats and bronchial epithelial cells （16HBE） and further reveal the mechanism of YWHD in treating bronchial asthma （BA）. MethodForty-eight rats were randomly assigned into normal group， model group， dexamethasone group， and low-， medium-， and high-dose YWHD groups， with 8 rats in each group. The rat model of BA was established by intraperitoneal injection with ovalbumin （OVA） + aluminum hydroxide suspension and atomizing inhalation with OVA for 2 weeks. The normal group was administrated with an equal dose of normal saline. The bronchial maximum airway resistance （Max Rrs） induced by methacholine chloride （Mch） was determined by an animal lung function evaluation system. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin （IL）-4， IL-13， IL-6， IL-33， IL-25， tumor necrosis factor-α （TNF-α）， and immunoglobulin E （IgE） in the bronchial alveolar lavage fluid. Hematoxylin-eosin （HE） and Masson staining were used for observation of the pathological changes of bronchi in the lung tissue. The immunofluorescence assay was employed to measure the levels of the autophagy-associated proteins LC3B and Beclin1. The IL-13-induced autophagy of 16HBE cells exposed to the YWHD-containing serum was observed， and the autophagy level was traced by mRFP-GFP-LC3 adenovirus infection. The protein levels of LC3Ⅱ/Ⅰ， p-PI3K， p-Akt and p-mTOR were determined by Western blot. ResultCompared with the normal group， the model group showed increased Max Rrs （P<0.01） and elevated levels of IL-4， IL-13， IL-6， IL-33， IL-25， TNF-α， and IgE in the bronchial alveolar lavage fluid （P<0.05，P<0.01）. The modeling caused focal infiltration of inflammatory cells and lymphocytes around bronchus and blood vessels， epithelial goblet cell metaplasia， and increased subepithelial collagen deposition. Furthermore， it up-regulated the protein levels of LC3B and Beclin1 （P<0.01）， promoted the autophagy flux of GFP to mRFP in 16HBE cells induced by IL-13， down-regulated the protein levels of p-PI3K， p-Akt， and p-mTOR， and increased the LC3Ⅱ/Ⅰ ratio （P<0.01）. Compared with the model group， medium- and high-dose YWHD decreased Max Rrs （P<0.01）， lowered the levels of IL-4， IL-13， IL-6， IL-33， IL-25， TNF-α， and IgE in the bronchial alveolar lavage fluid （P<0.05， P<0.01）， and reduced lymphocyte and granulocyte infiltration in bronchi of the lung tissue， epithelial goblet cell metaplasia， and subepithelial collagen deposition. Moreover， they down-regulated the protein levels of LC3B and Beclin1 （P<0.05， P<0.01）， decreased the autophagy flux of GFP to mRFP， up-regulated the protein levels of p-PI3K， p-Ak， and p-mTOR， and decreased the LC3Ⅱ/Ⅰ ratio （P<0.05， P<0.01）. ConclusionYWHD ameliorates airway hyperresponsiveness and airway inflammation and inhibits the autophagy of airway epithelial cells in the lung tissue of BA rats by activating the PI3K/Akt/mTOR signaling pathway.

The relationship between mobile phone dependence and academic burden among junior middle school students in Guizhou Province / 中国学校卫生

Objective@#To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD.@*Methods@#From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students.@*Results@#The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05).@*Conclusion@#The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.

Role of non-coding RNA on immune cells in tumor microenvironment of hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is a common malignant tumor of the liver characterized by a high incidence rate, rapid progression, and poor prognosis. In recent years, it has been found that non-coding RNA (ncRNA) participates in the regulation of tumor immunity in tumor microenvironment (TME) and in turn affects the biological behavior of HCC. This article briefly describes the regulatory effect of ncRNA on immune cells in TME and introduces the potential value of ncRNA in the diagnosis and treatment of HCC, in order to provide potential diagnostic and treatment strategies for HCC.

GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma / 医学前沿

Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

Expression and clinical significance of stanniocalcin-2 and cellular-mesenchymal epithelial transition factor in tumor tissues in patients with cervical cancer / 中国医师进修杂志

Objective:To investigate the expression of stanniocalcin-2 (STC-2) and cellular-mesenchymal epithelial transition factor (C-met) in tumor tissues of cervical cancer patients and their clinical significance.Methods:A total of 110 cervical cancer patients were selected in Foshan First People′s Hospital from January 2014 to December 2018. Patients′ cancer tissue samples and normal tissue samples were collected during modified radical resection to determine and compare the expression levels of STC-2 mRNA and C-met mRNA in the two tissues, and to analyze the correlation between the expression levels of STC-2, C-met and the clinicopathological characteristics of the patients as well as the multivariate analysis of tumor metastasis and recurrence in the patients. The correlation between the expression of STC-2 and C-met and the time of postoperative tumor metastasis and recurrence in cervical cancer patients were analyzed after 24 months of follow-up.Results:The expression levels of C-met mRNA and STC-2 mRNA in cancer tissues were higher than those in adjacent normal tissues: 4.51 ± 1.21 vs. 3.97 ± 1.14, 2.57 ± 0.21 vs. 2.12 ± 0.24, there were statistical differences ( t = 3.41, 14.80, P<0.05). The expression of STC-2 and C-met in cancer tissues had no significant difference with age, pathological type, federation international of gynecology and obstetrics (FIGO) stage and tumor size ( P>0.05), but had significant difference with tumor recurrence or metastasis ( P<0.05). The results of Logistic multivariate analysis showed that vascular emboli, lymph node metastasis, TNM stage, depth of tumor invasion, C-met expression and STC-2 expression were independent risk factors affecting the prognosis of cervical cancer patients ( P<0.05). The expression of STC-2 and C-met were negatively correlated with the time of tumor metastasis in patients with cervical cancer ( r = - 0.663, P<0.001; r = - 0.747, P<0.001). Conclusions:The expression levels of STC-2 and C-met in cancer tissues of cervical cancer patients are higher than those in adjacent normal tissues, and the expression levels of STC-2 and C-met are negatively correlated with the time of metastasis. The expression of C-met, the expression of STC-2, vascular emboli, lymph node metastasis, TNM stage, and the depth of tumor invasion are all independent risk factors affecting the prognosis of cervical cancer patients.

Research progress of cellular senescence in glaucoma / 中华实验眼科杂志

Cellular senescence is a response process in which cells are activated by ischemia, hypoxia, oxidative stress, DNA damage, reactive oxygen species deposition and other stimulations.Senescent cells markers include such as senescence-associated β-galactosidase (SA-β-gal) activation, P16INK4a upregualtion, senescence-associated heterochromatic foci (SAHF) accumulation, senescence-associated secretory phenotype (SASP) generation, telomere shortening and so on.P16INK4a/Rb and P19 ARF/P53/P21 Cip1 pathways are two classic cell senescence signaling pathways, which are interconnected and independent on each other.In recent years, glaucoma is considered as a blinding eye disease associated with cell senescence.Research on cell senescence in glaucoma mainly focuses on trabecular meshwork and Schlemm cannel endothelial cells senescence leading to increased resistance of aqueous humor outflow pathway, and the mechanism of retinal ganglion cells senescence and treatment in glaucoma.As an irreversible stage before cell death, deeper study on the mechanism of retinal ganglion cells senescence, and specific blocking of cell senescence will provide a new target for reducing the aqueous humor outflow resistance and protecting the optic nerve in glaucoma.This article reviewed characteristics, inducements, molecular signaling pathways of cellular senescence in glaucoma.

Effect of trichostatin A on lipopolysaccharide-induced injury and apoptosis of human microvascular endothelial cell / 中国小儿急救医学

Objective:To investigate the effect of histone deacetylase inhibitor trichostatin A(TSA) on the lipopolysaccharide(LPS)-induced injury and apoptosis of human microvascular endothelial cell(HMEC).Methods:HMECs were used as research cells to establish LPS-induced septic cell model, which were divided into three groups according to different treatments: control group (150 μL of phosphate buffer), LPS group (150 μL of 5 μg/mL LPS), LPS+ TSA group (150 μL of 5 μg/mL LPS and 500 μg/L TSA). After cells of each group were cultured for 24 h and 48 h, the concentration of lactate dehydrogenase(LDH)in the culture supernatant was detected by enzyme-linked immunosorbent assay and the apoptosis rate of HMECs was detected by Annexin V-FTTC/PI staining, then comparison between different groups were made.Results:Compared with the control group, LDH concentration in LPS group increased significantly at 24 h[(4.67±1.27) ng/L vs. (11.57±0.83) ng/L ] and 48 h[(7.93±0.80) ng/L vs. (12.72±0.89) ng/L ]; Compared with LPS group, LDH concentration in LPS + TSA group decreased significantly at 24 h[(6.01±0.29) ng/L ] and 48 h[(5.96±0.27) ng/L ], and the differences were statistically significant ( P<0.05). Compared with the control group, the apoptosis rates of HMEC cells in LPS group were significantly higher at 24 h[(0.92±0.89)% vs. (1.66±0.09)% ] and 48 h[(1.09±0.14)% vs. (5.01±0.16)%]; Compared with LPS group, the apoptosis rate of HMEC cells in LPS + TSA group significantly decreased at 24 h[(1.36±0.01)% ] and 48 h[(4.19±0.23)% ], the differences were statistically significant ( P<0.05). Conclusion:TSA has the protective effect of reducing cell injury and apoptosis in sepsis.