C-X-C motif chemokine receptor 4 inhibition promotes the effect of plantamajoside in hepatocellular carcinoma.

BACKGROUND AND STUDY AIM: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide, and, more than half of these cases are diagnosed in China. However, effective treatment for HCC is still limited. MATERIAL AND METHODS: C-X-C motif chemokine receptor 4 (CXCR4) was first activated and inhibited in HepG2 cells using a pharmacological method. HepG2 cell proliferation was detected using the CCK-8 method. Metastasis and apoptosis of HepG2 cells were detected using wound healing and flow cytometry. The expression of each target molecule related to metastasis and invasion, such as MMPs, E-cadherin and the PI3K/AKT/Mcl-1/PARP signaling pathway was detected by western blotting. The secretion of molecular metastases was detected using competitive ELISA. RESULTS: This study constructed a CXCR4 activation and inhibition model in HepG2 cells. CXCR4 inhibition promoted the inhibitory effect of plantamajoside on the proliferation and metastasis of cells, which led to apoptosis. Furthermore, we found that the expression of apoptosis-related proteins was increased after treatment with plantamajoside combined with CXCR4 inhibition. In addition, the expression and secretion of pro-metastatic proteins, including MMPs and E-cadherin were decreased. We also noticed that this effect might be mediated by the PI3K/AKT/Mcl-1/PARP signaling pathway. CONCLUSION: CXCR4 inhibition may contribute to the treatment of HCC. Inhibition of CXCR4 expression contributes to the therapeutic effect of plantamajoside; the effect of plantamajoside might be mediated by the PI3K/AKT/Mcl-1/PARP signaling pathway; and CXCR4 might be a therapeutic target of HCC.

Safety and effectiveness of recombinant human erythropoietin coupled with different doses of Roxadustat for treatment of renal anemia in patients on maintenance hemodialysis.

OBJECTIVE: To investigate the safety and efficacy of recombinant human erythropoietin (rHuEPO) in combination with different doses of Roxadustat in treating renal anemia in patients on maintenance hemodialysis. METHODS: Eighty patients with renal anemia on maintenance hemodialysis treated in Shuyang Hospital of Traditional Chinese Medicine from January 2020 to December 2021 were selected as study subjects, and they were divided into a study group (n=40, high-dose Roxadustat + rHuEPO therapy) and a control group (Con) (n=40, low-dose Roxadustat + rHuEPO therapy) in accordance with different therapies. The effects of anemia therapy, changes in anemia indicators (hemoglobin (Hb), hematocrit (Hct)), changes in iron metabolism indicators (transferrin saturation (TSAT), serum ferritin (SF)), changes in oxidative stress indicators Malondialdehyde (MDA), Superoxide Dismutase (SOD), and changes in microinflammatory indicators IL6, CRP were compared between the two groups. The occurrences of adverse effects during therapy were counted and compared between the two groups. RESULTS: The therapy efficiency of the study group was 97.50% (39/40), which was higher than 85.00% (34/40) in the control group (P=0.048). The contents of Hb, Hct, TSAT, and SF were higher in the study group than the Con after therapy (all P<0.001 or P=0.001). The contents of MDA, IL6, and CRP were significantly lower in the study group than the Con after therapy (all P<0.001). The occurrence of adverse effects was 10.00% in the study group, which was higher than 5.00% in the Con, but the difference was not significant (P=0.396). CONCLUSION: The combination of rHuEPO and high-dose Roxadustat (120 mg/time) has a better effect on improving anemia symptoms in maintenance hemodialysis patients than in those who take low dose Roxadustat (100 mg/time). It can significantly improve anemia and iron metabolism indicators and alleviate patients' inflammation and oxidative stress levels.

Extending Precision Perturbative QCD with Track Functions.

Collider experiments often exploit information about the quantum numbers of final state hadrons to maximize their sensitivity, with applications ranging from the use of tracking information (electric charge) for precision jet substructure measurements, to flavor tagging for nucleon structure studies. For such measurements, perturbative calculations in terms of quarks and gluons are insufficient, and nonperturbative track functions describing the energy fraction of a quark or gluon converted into a subset of hadrons (e.g., charged hadrons) must be incorporated. Unlike fragmentation functions, track functions describe correlations between hadrons and therefore satisfy complicated nonlinear evolution equations whose structure has so far eluded calculation beyond the leading order. In this Letter, we develop an understanding of track functions and their interplay with energy flow observables beyond the leading order, allowing them to be used in state-of-the-art perturbative calculations for the first time. We identify a shift symmetry in the evolution of their moments that fixes their structure, and we explicitly compute the evolution of the first three moments at next-to-leading order, allowing for the description of up to three-point energy correlations. We then calculate the two-point energy correlator on charged particles at O(α_{s}^{2}), illustrating explicitly that infrared singularities in perturbation theory are absorbed by moments of the track functions and also highlighting how these moments seamlessly interplay with modern techniques for perturbative calculations. Our results extend the boundaries of traditional perturbative QCD, enabling precision perturbative predictions for energy flow observables sensitive to the quantum numbers of hadronic states.

Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway.

INTRODUCTION: Uremia could accelerate atherosclerosis (AS) formation involving Treg/Th17 imbalance. Losartan regulates the imbalance between regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). However, their interactions in uremia accelerated AS (UAAS) remained poorly understood. METHODS: UAAS mice model was established, and after losartan and VO-OHpic (VO, phosphatase and tensin homolog [PTEN] inhibitor) injection, biological indexes, and inflammatory cytokines (transforming growth factor-ß1, TGF-ß1; interleukin-10 [IL-10]; IL-17 and IL-6) levels were determined using enzyme-linked immunosorbent assay. Pathological changes on aorta were observed using hematoxylin-eosin staining. Percentages of Treg cells (CD4+CD25+Foxp3+) and Th17 cells (CD4+IL-17+) in total CD4+ T cells were determined using flow cytometry. PTEN expressions were measured using Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry staining as needed. RESULTS: After UAAS mice model construction, biological indexes (urea, cholesterol, and triglycerides) levels were increased, and aortic atherosclerotic plaque was formed. In UAAS mice, in total CD4+ T cells, Treg cells percentage was decreased yet Th17 cells percentage was increased, and TGF-ß1 and IL-10 levels were downregulated yet IL-17 and IL-6 levels were upregulated. An opposite effect was found after losartan treatment. PTEN was downregulated in UAAS mice, and suppressing PTEN reversed the alleviating effects of losartan in UAAS mice. CONCLUSION: Losartan attenuated UAAS in mice by regulating Treg/Th17 cells balance via mediating PTEN/PI3K/Akt pathway, providing possible therapeutic method for UAAS in clinical practice.

Effect of Pingan Fang, a Traditional Chinese Medicine compound, on behavioral sensitization and conditioned place preference induced by ethanol in mice.

OBJECTIVE: To observe the effect of Pingan Fang (PG) on behavioral sensitization and conditioned place preference (CPP) induced by ethanol in mice, and to determine the intervention mechanism of PG on alcohol addiction. METHODS: A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice. The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol. Concentrations of dopamine (DA), Glutamate (Glu), and ã-aminobutyric acid (GABA) in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay. RESULTS: Although PG did not alter spontaneous activity in mice, it reduced the growth of spontaneous activity stimulated by ethanol. The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased. CONCLUSION: Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system. This suggests that PG might be useful for the prevention and treatment of alcohol addiction.

Effect of ASF (a Compound of Traditional Chinese Medicine) on Behavioral Sensitization Induced by Ethanol and Conditioned Place Preference in Mice.

ASF composed by semen and epimedium herbal is a traditional plant compound that is widely used in the treatment of insomnia. Studies have shown that saponins and flavonoids contained in semen can significantly decrease the content of excitatory neurotransmitter Glu in mice. And the total flavone of YinYangHuo can increase the release of GABA in the anterior periventricular system of rat and increase the affinity of GABA for the receptors GABAA. It can be inferred that their synergism may have effect on the neurotransmitter that causes behavioral sensitization and conditioned place preference in experimental animals and affects their drinking behaviors, which is the starting point of this research. The present study found that ASF can inhibit development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. We demonstrate the inhibition of ASF on behavioral sensitization partly due to its effect on the mesolimbic neurotransmitter system, including decreasing level of DA and Glu and increasing the content of GABA. It suggested that the ASF may have pharmacological effects in the treatment of alcohol addiction.

Distribution of traditional Chinese medicine patterns in 324 cases with hepatitis B-related acute-on-chronic liver failure: a prospective, cross-sectional survey.

OBJECTIVE: To determine the distribution of Traditional Chinese Medicine (TCM) patterns in hepatitis B-related acute-on-chronic liver failure (HB-ACLF) in different stages for guiding clinical prescriptions and treatments. METHODS: A prospective, cross-sectional survey method was used in this study. A total of 324 cases with HB-ACLF in China were involved. RESULTS: The general frequency of TCM patterns in HB-ACLF were as follows: Heat Toxin Stagnation Pattern (134/324, 41.36%), Damp-heat Obstruction Pattern (66/324, 20.37%), Yang Qi Deficiency Pattern (52/324, 16.05%), and Liver and Kidney Yin Deficiency Pattern (26/324, 8.02%). In the early stage of HB-ACLF, there was a remarkably higher percentage of excessive patterns than those in the middle and late stage. The incidence of Heat Toxin Stagnation reached 58.57% (82/140) in the early stage, while it was 33.96% (36/106) in the middle stage and 20.51% (16/78) in the late stage. In the early stage of HB-ACLF, excessive patterns, such as the Heat Toxin Stagnation Pattern, were more prevalent than those in the middle and late stages (P < alpha' = 0.003). However, in the late stage of HB-ACLF, deficient patterns, such as the Yang Qi Deficiency Pattern, were more prevalent than those in the early and middle stages. The Yang Qi Deficiency Pattern had a higher rate of 41.03% (32/78) in the late stage compared with that of 20.75% (22/106) in the middle stage and 8.57% (12/140, P < alpha' = 0.003) in the early stage. The distribution of the other patterns was not significant between the three stages (P > 0.003). CONCLUSIONS: There are four major patterns of HB-ACLF, including the Heat Toxin Stagnation Pattern, the Damp-heat Obstruction Pattern, the Yang Qi Deficiency Pattern, and the Liver and Kidney Yin Deficiency Pattern. The Heat Toxin Stagnation and Yang Qi Deficiency Patterns are the representative patterns in the early and late stages of HB-ACLF. In the middle stage of HB-ACLF, the TCM patterns vary in a complicated manner, with no significant difference among the patterns. Treatment for HB-ACLF should vary with the different representative patterns in the early and late stages.