Sepsis is a life-threatening organ dysfunction caused by the host's dysregulated response to infection, with a complex pathogenesis and high mortality rate. Currently, there are no clear and effective treatment drugs available. Epigenetic modification serves as a major mechanism regulating gene expression under pathological and physiological conditions, and it has been shown to play a critical role in regulating the occurrence and development of sepsis. Histone acetylation modification, as a sophisticated epigenetic modification mechanism, plays a crucial regulatory role in many aspects of life. It can jointly regulate the acetylation status of histones through histone acetyltransferase (HAT) and histone deacetylase (HDAC), thereby changing DNA expression and dynamically regulating sepsis related gene expression at the epigenetic level. Previous studies have shown that histone acetylation can participate in the progression of sepsis by regulating inflammatory mediators, nuclear factor-ΚB (NF-ΚB) signaling pathway, autophagy, efferocytosis, ferroptosis, pyroptosis. These mechanisms are promising targets for novel sepsis treatments. In addition, with the deepening of research, it has been found that various selective/non selective histone deacetylase inhibitors (HDACI) can regulate histone acetylation status by acting on different HDAC targets, which has been shown to alleviate organ damage caused by sepsis and improve prognosis in septic animal models. This article further summarizes the role and potential applications of histone acetylation in sepsis, providing new ideas for the treatment of sepsis.
Sepsis/metabolism* ; Acetylation ; Humans ; Histones/metabolism* ; Histone Acetyltransferases/metabolism* ; Histone Deacetylase Inhibitors ; Epigenesis, Genetic ; Histone Deacetylases/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Animals

We searched the literature related to sarcopenia to retrieve information on modeling method and model-evaluation schemes using sarcopenic mice.Here,we review the operation method,advantages and disadvantages,and application scopes of the four modeling method,including drug injection,aging,muscle atrophy,and transgenic mice,and summarize the method used to evaluate muscle function,muscle strength,and muscle endurance.We then compare their advantages and disadvantages,to provide a reference for subsequent research into sarcopenia.

Cardiac arrest most commonly occurs outside of the hospital, known as out-of-hospital cardiac arrest (OHCA), and is an important global health problem. Approximately 40% of cardiac arrest has no clear cause. Hereditary arrhythmias and cardiomyopathies factors contribute to cardiac arrest. The identification of genetic factors for cardiac arrest after its occurrence is of great value not only for the individual, but also for relatives who may be at risk for the disease in their family. In the United States, there are over 350?000 cases of OHCA and over 200?000 cases of in-hospital cardiac arrest (IHCA) each year, and in Western Europe, cardiac arrest accounts for 15%-20% of all adult natural deaths and 50% of all cardiovascular deaths. In order to reduce the burden caused by cardiac arrest within society, it is essential to further understand its etiological factors, such as incidence in different regions, risk factors, and populations at higher risk. For each individual, cardiac arrest is the result of a complex interaction of genetic and acquired factors. Understanding the complex interplay of pathogenic factors in cardiac arrest and the development of individualized prevention and treatment approaches requires the collection of clinical data from cardiac arrest populations and multimodal analysis in order to identify epidemiological features and risk factors for cardiac arrest. Recently, cardiac arrest-related data are being collected and integrated in Europe in different regions and populations. As a result of the commitment to the creation of large datasets of clinical information on cardiac arrest populations, the knowledge of the pathology of cardiac arrest pathogenesis as well as risk factors is steadily increasing. This article reviews the epidemiologic data of cardiac arrest in recent years and the associated risk factors, thus providing ideas for developing better strategies for the prevention and treatment of cardiac arrest.

Objective To investigate the correlation between the expression of serum 25hydroxyvitamin D[25(OH)D]and growth differentiation factor 15(GDF-15)levels and the risk of malignancy in patients with metabolic syndrome(MS)and the development of combined thyroid nodules(TN).Methods From August 2019 to August 2023,185 MS patients who visited the First Affiliated Hospital of Xinjiang Medical University were regarded as the study subjects,according to the results of thyroid ultrasound examination,they were separated into MS group(n=73)and MS+TN group(n=112).According to the malignant grading of thyroid nodules,MS+TN patients were separated into benign group(n=89)and malignant group(n=23).Another 68 healthy individuals who underwent physical examinations were regarded as control group.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the levels of serum 25(OH)D and GDF-15 in each group.Pearson was applied to analyze the correlation between serum 25(OH)D and GDF-15 levels and clinical indicators in MS in TN patients.Multivariate Logistic regression was applied to analyze the influencing factors of malignant TN in patients with MS combined with TN.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic value of serum 25(OH)D and GDF-15 levels in MS with malignant TN.Results Comparison of serum 25(OH)D(30.41±6.73 ng/ml,27.23±6.15 ng/ml,24.67±4.38 ng/ml)and GDF-15(167.99±22.56 ng/L,239.75±25.92 ng/L,286.63±26.04 ng/L)levels in control,MS and MS+TN groups,the differences were statistically significant(F=22.219,472.113,all P<0.05).Compared with the benign group,the serum 25(OH)D(26.28±4.53 ng/ml vs 18.44±3.79 ng/ml)level in the malignant group was obviously reduced,while the GDF-15(276.93±24.53 ng/L vs 324.17±31.89 ng/L)level was obviously increased,the differences were statistically significant(t=7.631,7.718,all P＜0.05).The BMI,age,FPG,TG,TSH and TGAb levels of patients in the malignant group were obviously higher than those in the benign group,the difference were statistically significant(t=2.868,3.523,3.542,3.603,4.581,5.516,all P＜0.05).Pearson correlation analysis,and the serum 25(OH)D level in MS patients with TN was negatively correlated with FPG,TSH,TG and TGAb levels(r=-0.302,-0.482,-0.524,-0.546,all P<0.001),while GDF-15 level was positively correlated with TG,TSH,TGAb and FPG levels(r=0.467,0.541,0.578,0.623,all P<0.05).Multivariate logistic regression analysis,GDF-15(OR=1.673,95%CI:1.146～2.442)was a risk factor for the occurrence of malignant TN in MS patients(P<0.05),and 25(OH)D(OR=0.744,95%CI:0.604～0.916)was a protective factor for the occurrence of malignant TN,the AUC values of serum 25(OH)D and GDF-15 levels in the diagnosis of MS combined with malignant TN were 0.813,0.799 and 0.930,respectively,and the combination was superior to the single diagnosis(Z=2.088,2.021,P=0.037,0.043).Conclusion The levels of serum 25(OH)D and GDF-15 in patients with MS combined with TN are obviously correlated with nodular nature.The decrease in serum 25(OH)D level and the increase in GDF-15 level are risk factors for malignant TN in MS patients.

BACKGROUND/OBJECTIVES: Benign prostatic hyperplasia (BPH) is the most common prostate disease and one of the most common chronic diseases caused by aging in men. On the other hand, there has been no research on BPH using Abeliophyllum distichum Nakai (A.distichum). Therefore, this study investigated the effects of A. distichum on BPH.MATERIALS/METHODS: A. distichum leaves were extracted with distilled water, 70% ethanol, and 95% hexane as solvents. Subsequently, the inhibitory effects of each A. distichum extract on androgen receptor (AR) signaling were evaluated in vitro. The testosterone-induced BPH model was then used to confirm the efficacy of A. distichum leaves in 70% ethanol extract (ADLE). RESULTS: ADLE had the strongest inhibitory effect on AR signaling. A comparison of the activity of ADLE by harvest time showed that the leaves of A. distichum harvested in autumn had a superior inhibitory effect on AR signaling to those harvested at other times. In the BPH rat model, the administration of ADLE reduced the prostate size and prostate epithelial cell thickness significantly and inhibited AR signaling. Subsequently, the administration of ADLE also reduced the expression of growth factors, thereby inactivating the PI3K/AKT pathway. CONCLUSIONS An analysis of the efficacy of ADLE to relieve BPH showed that the ethanol extract grown in autumn exhibited the highest inhibitory ability of the androgen-signaling related factors in vitro. ADLE also inhibited the expression of growth factors by inhibiting the expression of the androgen-signaling related factors in vivo. Overall, ADLE is proposed as a functional food that is effective in preventing BPH.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Objective:To investigate the effects and mechanisms of anti-cancer by bacailein combined with U0126 on human breast cancer in vitro. Methods: The human breast cancer cell line MCF-7 was treated by baicalein,U0126 and baicalein combined with U0126 respectively. CCK8 assay measured cell proliferation of MCF-7;flow cytometry tested the cell cycle and apoptosis of MCF-7;microscopy observed the amount;TUNEL assay evaluated the apoptosis of MCF-7;Western blot detected the protein level of proliferation and apoptosis related protein;scratch assay measured the ability of migration. Results: Human breast cancer cell line MCF-7 was treated by baicalein or U0126 at different concentration for 24 h, CCK8 assay suggested that both of them can dramatically inhibit MCF-7 proliferation in a dose-dependent way (P<0. 05). Compared to the blank and DMSO groups,the human breast cancer cell line MCF-7 was treated with baicalein for 24 h,the cellular rate at G0-G1 phase increased a lot (91%) (P<0. 05),while the cellular rate at S phase reduced dramatically (P<0. 05),cell apoptosis increased dramatically by microscopy and TUNEL assay(P<0. 05),the level of ERK1/2,CyclinD1 and JNK reduced quickly (P<0. 05). Compared to the baicalein group,MCF-7 was treated by baicalein combined with U0126,the cellular rate at S phase decreased remarkably (P<0. 05),apoptosis was much obvious (P<0. 05),the phosphorylation level of ERK1/2 and JNK reduced a lot (P<0. 05),and the proliferation accelerator CyclinD1 highly decreased (P<0. 05);the scratch assay demonstrated that cell migration was dramatically inhibited when MCF-7 was treated by 20 μmol/L baicalein ( P<0. 05 ) . Conclusion:Both of baicalein and U0126 can inhibit the proliferation and migration,induce the apoptosis of human breast cancer cell line MCF-7 through decreasing the level of ERK, JNK and CyclinD1. Baicalein and U0126 can provide some novel avenues to treat breast cancer in clinic.

Objective:To investigate the role of Baicalein combined with U0126 resisting human bladder cancer T-24 cells in vitro and mechanism.Methods: T-24 cells were dealt with Baicalein combined with U0126,flow cytometry was used to detect cell cycle and cell apoptosis,microscope to count cell number,TUNEL method to detects cell apoptosis index,and Real time quantitative PCR and Western blot to measure extracellular signal regulating kinase 1/2 (ERK1/2), CyclinD1, GSK-3β and AKT RNA level, protein level of T-24 cells respectively.Effect of Baicalein and U0126 on apoptosis and proliferation of bladder cancer cell was analyzed.Results: Cell apoptosis rate was significantly increased after T-24 cells dealt with various concentrations of Baicalein.Cell proportion of G0/G1 phase was significantly increased,while cell percentage of S phase was obviously decreased and cell count was decreased,after T-24 cells were dealt with Baicalein for 24 h.After T-24 cells were dealt with Baicalein combined with U0126 for 24 h,cell proportion of S phase was evidently decreased.T-24 cells were dealt with Baicalein or U0126 obviously promoted cell apoptosis,which was more obvious with Baicalein combined with U0126.Phosphorylation level of GSK-3β,ERK1/2,and AKT was significantly reduced and expression of ERK1/2 and CyclinD1 mRNA was evidently lower after Baicalein or U0126 or Baicalein combined with U0126,and combined application had more remarkable effect.Conclusion: Baicalein and U0126 can induce apoptosis of T-24 cells,increase cell proportion in G0/G1 phase,reduce cell proportion of S phase,and Baicalein combined with U0126 effect has more remarkable effect.

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph⁺ patients, MLL⁺ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

High expression of Fightless I (FLII) is associated to multiple tumors. Based on our previous study that FLII might be involved in the nuclear export, we assessed the possible interaction of FLII with the nuclear envelop associating proteins Importin β and Nup88. We first constructed GST-FLII, GST-LRR recombinant plasmids and transformed them into the Rosetta strain to produce GST-FLII, GST-LRR fusion protein. After purification of these proteins, GST-pull down, as well as co-immunoprecipitation, were used to test the interaction of FLII with Importin β and Nup88. FLII interacted with Importin β and Nup88, and FLII LRR domain is responsible for these interactions. Thus, FLII may play a role in nuclear export through interaction with Importin β and Nup88.
Humans ; Microfilament Proteins ; metabolism ; Nuclear Pore Complex Proteins ; metabolism ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Recombinant Fusion Proteins ; metabolism ; beta Karyopherins ; metabolism