Escape Phenomenon Research Articles

Dependence of Metrics and Noise Intensity on Escape Dynamics:Mean First Exit Time and Escape Probability

Abstract This paper focuses on analyzing two deterministic quantities of the dynamics of stochastic 
systems, mean first exit time and escape probability. Through a detailed exploration of the escape phenomenon, we have successfully fitted the complex dynamics of the mean first exit time as a function of interval length (area size) and noise intensity, respectively.
We have found that the mean first exit time tends to increase monotonically with the interval length (area size).
Meanwhile, we also accurately captured the dynamical behavior of the minimum escape probability under various parameter cases. 
The relationship between them displays a range of patterns when we observed different intervals.
Our research highlights the importance of noise effects when considering escape processes, especially in the context of interaction of interval length (area size) and noise intensity.
A concrete error analysis is conducted to ensure the accuracy and generalization ability of the model's predictions.

Fluorescent Aerolysin (FLAER) Binding Is Abnormally Low in the Clonal Precursors of Acute Leukemias, with Binding Particularly Low or Absent in Acute Promyelocytic Leukemia.

Flow cytometry plays a fundamental role in the diagnosis of leukemias and lymphomas, as well as in the follow-up and evaluation of minimally measurable disease after treatment. In some instances, such as in the case of acute promyelocytic leukemia (APL), rapid diagnosis is required to avoid death due to serious blood clotting or bleeding complications. Given that promyelocytes do not express the glycophosphatidylinositol (GPI)-anchored protein CD16 and that deficient CD16 expression is a feature of some CD16 polymorphisms and paroxysmal nocturnal hemoglobinuria (PNH), we included the GPI anchor probe FLAER aerolysin in the APL flow cytometry probe panel. Initial tests showed that FLAER binding was absent in pathological promyelocytes from APL patients but was consistently detected with high intensity in healthy promyelocytes from control bone marrow. FLAER binding was studied in 71 hematologic malignancies. Appropriate control cells were obtained from 16 bone marrow samples from patients with idiopathic thrombocytopenic purpura and non-infiltrated non-Hodgkin's lymphoma. Compared with the positive FLAER signal in promyelocytes from healthy bone marrow, malignant promyelocytes from APL patients showed weak or negative FLAER binding. The FLAER signal in APL promyelocytes was also lower than that in control myeloid progenitors and precursors from patients with other forms of acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia, or myelodysplastic syndrome. Minimal measurable disease studies performed in APL patients after treatment found normal promyelocyte expression when minimal measurable disease was negative and FLAER-negative promyelocytes when disease relapse was detected. The inclusion of FLAER in the flow cytometry diagnosis and follow-up of APL could be very helpful. Decreased FLAER binding was found in all cases of APL, confirmed by the detection of the PML-RARA fusion transcript and, to a lesser extent, in the other AMLs studied. This study also revealed FLAER differences in other acute leukemias and even between different precursors (myeloid and lymphoid) from healthy controls. However, the reason for FLAER's non-binding to the malignant precursors of these leukemias remains unknown, and future studies should explore the possible relation with an immune escape phenomenon in these leukemias.

A Calculation Study on the Escape of Incident Solar Radiation in Buildings with Glazing Facades

More and more modern buildings are using glass curtain walls as their building envelope. The large area of window leads to a significant increase in solar heat gain, resulting in an increase in the cooling load and energy consumption of the building envelope. In the calculation of building cooling load, the thermal performance parameter of windows, the solar heat gain coefficient, is used to calculate the solar radiation heat gain of the windows. The window-to-wall ratio of buildings with glazing facades is large, and the phenomenon of escape of incident solar radiation cannot be ignored. In order to calculate the solar radiation escape rate, a dynamic model of solar radiation escape rate incorporating the solar path tracking model is developed in this research, which can achieve big data simulation analysis based on actual meteorological conditions. The model is programmed and simulated using MATLAB R2024a software. Five representative cities from different climate regions in China are selected and the variation rule of solar radiation escape rate are analyzed on three different time scales: day, month, and year. The influence of building orientation was also calculated and analyzed. The numerical calculation results indicate that the escape solar radiation rate varies with the incident angle of solar radiation at different times. It was found that the smaller the solar azimuth angle and solar altitude angle, the smaller the escape rate of solar radiation. The latitude of a city has a significant impact on the solar radiation escape rate. The weighted average of the solar radiation escape rates for each city were calculated for both summer and winter. Regardless of the season, the city’s location, and the orientation of the room, the value of solar radiation escape rate varies from 8.64% to 10.33%, which indicates that the solar radiation escape phenomenon cannot be ignored in glass curtain wall buildings. The results can be used as a reference value of solar radiation escape rate for the correction of actual solar heat gain of buildings in different climate regions.

The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway

Ethnopharmacological relevanceXihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor-suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well-explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. Aim of the studyTumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. Materials and methodsThrough in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor-associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity-related axis. ResultsXihuang Pill has a regulatory effect on the tumor immune microenvironment. ConclusionsThe results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL-6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein.

PIV experimental analysis of the escape phenomenon of air spraying jet in factories

Inefficient air spraying can release a large amount of paint particles from a spraying jet, which can seriously endanger the health of operators. The flow field characteristics of air atomizing spray guns have a significant influence on spraying efficiency. To investigate the reasons for the escape of paint particles during air spraying, improve efficiency at the source and curb the escape of pollutants into a factory building, this study measured the whole flow field of an air spray gun via a 2D particle image velocimetry (PIV) system. The results showed that the spraying jet velocity reached a maximum of 28 m/s near the spray nozzle with a Reynolds number of 3000 and subsequently decayed rapidly due to the strong momentum exchange with the surrounding air. The radial velocity at the junction of paint mist and air first increases and then decreases (maximum 0.5 m/s). The turbulence intensity was relatively high at the spraying jet boundary. In addition, the spay flow at the nozzle and the jet boundary showed high intermittency. The turbulence structures were studied by proper orthogonal decomposition (POD). The results indicated that the radial velocity of spray was the major source underlying the development of spraying jet radial diffusion. Finally, the spraying efficiency was calculated to be between 53 % and 58 %. For air spraying, suppressing radial movement can improve spraying efficiency by up to 40 %, which is essential to controlling the escape of paint mist and improving the working environment in spray booths.

Oxeiptosis core genes and their multi-omics analysis in hepatocellular carcinoma.

Oxeiptosis is a recently discovered caspase-independent, non-inflammatory programmed cell death modality. Current studies suggest that oxeiptosis has crucial effects on biological processes in a variety of diseases. However, the mechanism of oxeiptosis in hepatocellular carcinoma (HCC) remains unclear and no relevant studies have been published. Therefore, this study is intended to investigate the mechanism and prognostic role of oxeiptosis-related genes in HCC. We explored the mechanisms and molecular phenotypes underlying the role of oxeiptosis in HCC through multi-omics analysis. Firstly, we obtained RNA-sequencing and clinical data from public database and divided the samples into trial and validation cohorts in subsequent analyses. We then screened oxeiptosis core genes (OCGs) and screened prognosis-related genes. Based on different molecular markers, we identified the molecular phenotypes of HCC, and the potential OCGs molecular mechanisms were explored. Subsequently, we construct a prognostic prediction system for HCC. Finally, we analyzed the tumor microenvironment and the immune escape phenomenon. We screened a total of 69 OCGs, most of which were prognostic risk factors for HCC. A majority of OCGs were enriched in cell cycle regulation and mitotic processes, which were related to both tumor cell proliferation and death. We identified 2 different molecular typing options with significant differences in prognosis, function, and signaling pathway enrichment between different molecular subtypes. The prognostic prediction model combined with molecular phenotypes and had a good predictive effect. Finally, we found CD4 + T-cell exhaustion in samples with specific molecular phenotypes. Through multi-omics analysis of OCGs, we not only revealed the possible molecular mechanisms of OCGs in HCC but also provided a prognostic prediction system for clinical application through molecular typing and risk scoring model. Meanwhile, we found immune escape mechanisms in HCC.

Targeting Angiotensinogen With N-Acetylgalactosamine-Conjugated Small Interfering RNA to Reduce Blood Pressure.

Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or the so-called RAS escape phenomenon, elicited by the compensatory renin elevation upon RAS blockade. Recently, evidence points toward targeting hepatic AGT (angiotensinogen) as a novel approach to block the RAS pathway that could circumvent the RAS escape phenomenon. Removing AGT, from which all angiotensins originate, should prevent further angiotensin generation, even when renin rises. Furthermore, by making use of a trivalent N-acetylgalactosamine ligand-conjugated small interfering RNA that specifically targets the degradation of hepatocyte-produced mRNAs in a highly potent and specific manner, it may be possible in the future to manage hypertension with therapy that is administered 1 to 2× per year, thereby supporting medication adherence. This review summarizes all current findings on AGT small interfering RNA in preclinical models, making a comparison versus classical RAS blockade with either ACE (angiotensin-converting enzyme) inhibitors or AT1 (angiotensin II type 1) receptor antagonists and AGT suppression with antisense oligonucleotides. It ends with discussing the first-in-human study with AGT small interfering RNA.

Structural optimization and flow field simulation of gas distribution device in desulfurization tower

AbstractIn order to comply with ultra‐low emission requirements and further reduce the concentration of SO2 emissions from coal‐fired power plants, a novel distributor has been proposed to enhance the uniformity of fluid distribution in the desulfurization tower. The distributor ensures that the inlet flue gas comes into even contact with the slurry droplets ejected from the nozzle, thereby improving the removal efficiency of SO2. The research focuses on a circular desulfurization tower using ammonia‐based desulfurization. To study the enhancement of non‐empty tower desulfurization efficiency, a CFD‐DPM model based on the Euler–Lagrange method has been established. The accuracy of the model has been verified through comparison with experimental or validated data, ensuring its reliability in predicting the performance of the proposed distributor in enhancing desulfurization efficiency in the circular desulfurization tower. The simulation results demonstrate that the addition of the new inflow gas distributor leads to a significantly thinner flue gas escape zone in the circular desulfurization tower. The flue gas flow velocity at the wall side of the tower, above the distributor, increases by only about 1 m/s with the rise of the horizontal cross section, and there is hardly any flue gas escape zone observed. The addition of the distributor increases the pressure drop in the local area, while optimizing the flow field in other areas and reducing the turbulent dissipation energy, which in turn reduces the full tower pressure drop from 701 to 474 Pa. Additionally, the flue gas at the outlet of the distributor is uniformly dispersed, with gas velocity distribution unevenness values of 0.558, 0.587, and 0.601, respectively, which are 15.9%, 14.0%, and 14.0% lower than the unevenness value of the empty tower spraying, at a depth of 1 m below each spray layer. These improvements in gas flow distribution and pressure drop contribute to better control of ammonia escape and aerosol phenomenon, while also enhancing the desulfurization efficiency.

Effect of different ammonia mixing methods for diesel ignition on combustion and emission performance of high pressure common rail engine

Ammonia is a zero-carbon fuel. Diesel/ammonia dual-fuel combustion mode can solve the problem of difficult compression ignition of pure ammonia. This article aims to explore the best mixing method and mixing ratio of ammonia fuel. The research results show that with the increase of the ammonia mixing ratio in the intake duct, the fuel consumption rate decreases by 7.71%. However, the serious ammonia escape phenomenon reaches a maximum of 37.35%, resulting in a serious decrease in power output. The cylinder temperature dropped by 197.12K, CO2 emissions decreased by 49.34%, NOx emissions decreased by 16.84%, and emissions significantly improved. When using direct injection ammonia mixing in the cylinder, as the ammonia mixing ratio increases, the explosion pressure in the cylinder decreases by 8.32%, the temperature in the cylinder decreases by 127.37K, the maximum ammonia escape is only 6.89%, CO2 emissions decreased by 88.10%, NOx emissions decrease by 75.90%, and CO2 and NOx emissions significantly decrease. Compared with the two ammonia blending methods, the direct injection ammonia blending method in the cylinder is obviously better. When the direct injection ammonia blending ratio in the cylinder is 70%, compared to the original engine, the diesel engine has the best working performance, increased power, and improved economy by 7.52%, and the proportion of ammonia escape is small. CO2 emissions are reduced by 69.05%, and NOx emissions are reduced by 29.22%. The research results of this article provide data support for achieving energy-saving, emission reduction, and low-carbon environmental protection of diesel engines.

Understanding thermal induced escape mechanism of optically levitated sphere in low vacuum

The escape phenomenon, mainly caused by thermal effects, is known as an obstacle to the further practical application of optical levitation system in vacuum. Even though thermal effects have been mentioned in many works, the escape mechanism of heated particle remains unclear. Irregular photophoresis induced by thermal effects can act as an “amplifier” of Brownian motion. Studies on this topic provide interpretation for particle escape phenomenon during vacuum pumping, as well as valuable insights into the micro- and nanoscale thermal effects in optical trap in vacuum. In this paper, we derive and test a dynamic model for the motion of an optically levitated particle in a non-equilibrium state and demonstrate the escape mechanism. The result of theoretical investigations is consistent with experimental escape at 0.1 mBar.

Adenosine Methylation Level of miR-125a-5p Promotes Anti-PD-1 Therapy Escape through the Regulation of IGSF11/VSIG3 Expression.

Despite encouraging anti-tumour activity in lung cancer, anti-PD-1 therapy has encountered increasing resistance to treatment. Several companion diagnostic assays have been performed to identify patients who may benefit from this immunotherapy and to adapt this therapy in case of acquired resistance. A large panel of methods was used for the analysis of expression and methylation levels of miRNAs (qPCR, MemiRIP, …), protein/miRNA interactions (CLIP, oligo pull-down, …), and protein-protein interactions (CoIP) in cells and/or blood samples. Our work highlights that the saturation of PD-1 by anti-PD1 therapies induces an immune escape phenomenon due to the overexpression of IGSF11 following adenosine methylation of miR-125a-5p. Mechanistically, we identify METTL3/KHDRBS3 and HuR as two crucial players in the methylation and the loss of the repressive function of this miRNA. Finally, our work shows that the adenosine methylation of miR-125a-5p is analyzable from EVs/exosomes from longitudinal blood samples and that such EVs/exosomes modulate the IGSF11/VSIG3 expression in lung cancer cells to promote an immune escape phenomenon. Our data provide a biomarker (m6A-miR-125a-5p level) and two therapeutic solutions (anti-IGSF11 antibody and METTL3 inhibitor) that could potentially address the anti-PD1 therapy failure in the context of precision and personalized medicine.

The Spontaneous Escape Behavior of Silver from Graphite-like Carbon Coatings and Its Effect on Corrosion Resistance.

Silver-doped graphite-like carbon (Ag-GLC) coatings were prepared on the surface of aluminum alloy and single-crystal silicon by magnetron sputtering under different deposition parameters. The effects of silver target current and deposition temperature, as well as of the addition of CH4 gas flow, on the spontaneous escape behavior of silver from the GLC coatings were investigated. Furthermore, the corrosion resistance of the Ag-GLC coatings were evaluated. The results showed that the spontaneous escape phenomenon of silver could take place at the GLC coating, regardless of preparation condition. These three preparation factors all had an influence on the size, number and distribution of the escaped silver particles. However, in contrast with the silver target current and the addition of CH4 gas flow, only the change in deposition temperature had a significant positive effect on the corrosion resistance of the Ag-GLC coatings. The Ag-GLC coating showed the best corrosion resistance when the deposition temperature was 500 °C, which was due to the fact that increasing the deposition temperature effectively reduced the number of silver particles escaping from the Ag-GLC coating.

Add fuel to the fire: Inflammation and immune response in lung cancer combined with COVID-19.

The corona virus disease 2019 (COVID-19) global pandemic has had an unprecedented and persistent impact on oncological practice, especially for patients with lung cancer, who are more vulnerable to the virus than the normal population. Indeed, the onset, progression, and prognosis of the two diseases may in some cases influence each other, and inflammation is an important link between them. The original chronic inflammatory environment of lung cancer patients may increase the risk of infection with COVID-19 and exacerbate secondary damage. Meanwhile, the acute inflammation caused by COVID-19 may induce tumour progression or cause immune activation. In this article, from the perspective of the immune microenvironment, the pathophysiological changes in the lungs and whole body of these special patients will be summarised and analysed to explore the possible immunological storm, immunosuppression, and immune escape phenomenon caused by chronic inflammation complicated by acute inflammation. The effects of COVID-19 on immune cells, inflammatory factors, chemokines, and related target proteins in the immune microenvironment of tumours are also discussed, as well as the potential role of the COVID-19 vaccine and immune checkpoint inhibitors in this setting. Finally, we provide recommendations for the treatment of lung cancer combined with COVID-19 in this special group.

Obstructive sleep apnea syndrome and cardiovascular risk factors in the antihypertensive therapy "escape" phenomenon

To assess the role of obstructive sleep apnea and other cardiovascular (CV) risk factors in the development of the antihypertensive therapy (AHT) efficacy "escape" phenomenon in patients with arterial hypertension (AH). The data of 75 patients with AH stage I-II, grades 1-3 were proceeded. All patients included in the study underwent night respiratory monitoring. After AHT prescription, blood pressure (BP) was monitored by three measurement methods (office, daily monitoring and self-control of blood pressure) - initially, in 1, 3 and 6 months after the inclusion - in order to confirm the initial therapy efficacy and to identify or exclude the "escape" phenomenon. In 36.0% of patients, the "escape" phenomenon was diagnosed in 1 or 3 months of observation. When comparing the group with the "escape" phenomenon, an initially higher level of systolic BP was revealed according to office measurements, 24-hour monitoring and self-control BP monitoring (134.0±4.7 mmHg vs 126.0±8.5 mmHg; 129.0±2.3 mmHg vs 121.0±7.7 mmHg; 131.0±8.2 mmHg vs 121.5±6.2 mmHg resp.; р<0,05). There were no differences in sleep apnea and CV risk factors between the groups. However in patients with a minimal SpO2≤85% during sleep, there were a higher levels of office systolic BP both before the AHT prescription, and during its use (157.6±10.4 mmHg vs 152.4±8.1 mmHg resp., р<0,05; 132.0±6.8 vs 127.1±8.9 mmHg resp.; р<0,05), and mean 24-hour systolic BP (125.7±5.9 vs 121.6±8.2 mmHg resp.; р<0,05) - compared with patients with a minimum SpO2>85%. The higher BP level in patients with lover nocturnal hypoxemia does not allow us to exclude the delayed negative impact of obstructive sleep apnea, especially severe, on the BP profile in case of initially successful AH control.

Central retina plays a decisive role in the suppression of pupillary escape

PurposeTo explore the pupil redilation during persistent light exposure (pupillary escape phenomenon) at the macula and periphery with monochromatic light stimuli.MethodsForty healthy subjects aged 18–64 years (24 females) were examined by chromatic pupil campimetry (CPC) using red and blue 4-s stimuli of 10° radius at the center and 20°-peripheral locations one per quadrant. One glaucoma patient and one achromatopsia patient served as disease models. For statistical analyses, linear mixed-effects models were performed followed by post hoc t-tests.ResultsA distinct pupillary escape could be demonstrated peripherally (blue 0.099%*s, red 0.153%*s); at the central healthy retina, there was no relevant escape, neither for blue nor red stimulation. Comparing central versus peripheral stimulation revealed highly significant differences in the escape (difference blue 0.100 ± 0.013, red 0.144 ± 0.013, < 0.0001, respectively). In the periphery, the escape was significantly more pronounced for red compared with blue stimulation (difference 0.054 ± 0.013; p = 0.0001). Enhanced pupillary escape outside of the 95% confidence interval of the linear mixed-effects model of the healthy population could be exemplarily shown in a patient with glaucomatous ganglion cell damage. In the achromatopsia example, no relevant escape was found for blue stimulation, but for red stimulation in the periphery in a comparable range to healthy controls.ConclusionThe results emphasize that an intact inner retinal network of nerve fibers arising from the central macular region is necessary for maintaining pupillary constriction during a bright 4-s light stimulus and preventing increase of pupillary escape. Increasing receptive field sizes towards the periphery on the level of retinal ganglion cells and less input from central 1:1 connections could be one of the driving mechanisms for pupillary escape.

S-19-4: ANGIOTENSINOGEN SIRNA FOR HYPERTENSIVE PATIENTS

Multiple types of renin-angiotensin system (RAS) blockers exist, allowing interference with the system at the level of renin, angiotensin-converting enzyme or the angiotensin II receptor. Yet, in particular for the treatment of hypertension, the number of patients with uncontrolled hypertension continues to rise, either due to patient non-compliance, or because of the significant renin rises that may, at least partially, overcome the effect of RAS blockade (RAS escape). New approaches to target the RAS are either direct antisense oligonucleotides (ASO) that inhibit angiotensinogen RNA translation, or small interfering ribonucleic acids (siRNA) that function via the RNA interference pathway. Since all angiotensins stem from angiotensinogen, lowering angiotensinogen has the potential to circumvent the RAS escape phenomenon. Moreover, ASO and siRNA require injections only every few weeks to months, which might reduce non-compliance. Of course, angiotensinogen suppression also poses a threat in situations where the RAS is acutely needed, for instance in women becoming pregnant during treatment, or in cases of emergency, when severe hypotension occurs. This presentation discusses all preclinical data on angiotensinogen suppression, as well as the limited clinical data that are currently available. It concludes that it is an exciting new tool to target the RAS with high specificity and a low side effect profile. Its long-term action might revolutionize pharmacotherapy, as it could overcome compliance problems. Preclinical and clinical programs are now carefully investigating its efficacy and safety profile, allowing an optimal introduction as a novel drug to treat cardiovascular and renal diseases in due time.

Dissimilar welding of high nitrogen stainless steel and low alloy high strength steel under different shielding gas composition: Process, microstructure and mechanical properties

Ar–N2-O2 ternary shielding gas is employed in dissimilar welding between high nitrogen steel and low alloy steel. The effect of O2 and N2 is investigated based on the systematical analysis of the metal transfer, nitrogen escape phenomenon, weld appearance, nondestructive detection, nitrogen content distribution, microstructure and mechanical properties. There are two nitrogen sources of the nitrogen in the weld: high nitrogen base material and shielding gas. The effect of shielding gas is mainly reflected in these two aspects. The change of the droplet transfer mode affects the fusion ratio, N2 in the shielding gas can increase nitrogen content and promote the nitrogen uniform distribution. The addition of 2% O2 to Ar matrix can change the metal transfer from globular transfer to spray transfer, high nitrogen base material is thereby dissolved more to the molten pool, making nitrogen content increase, ferrite decrease and the mechanical properties improve. When applying N2-containing shielding gas, arc stability becomes poor and short-circuiting transfer frequency increases due to the nitrogen escape from droplets and the molten pool. Performance of the joints is improved with N2 increasing, but internal gas pores are easier to appear because of the poor capacity of low alloy steel to dissolve nitrogen, The generation of pores will greatly reduce the impact resistance. 4–8% N2 content in shielding gas is recommended in this study considering the integrated properties of the dissimilar welded joint.

The therapeutic effect of an autologous and allogenic mixed glioma cell lysate vaccine in a rat model.

Tumor immunotherapy has the advantages of high specificity, minimal damage to the patient's body, and a long-lasting anti-tumor effect. However, due to the existence of immune escape phenomenon, the effect of anti-tumor immunotherapy is still poor. Therefore, a cancer vaccine that reverses tumor-associated immunosuppression is a very promising approach for research and treatment. Vaccines were prepared using autologous and allogeneic tumor cells and their lysates to syngeneic tumor cell lysates as immunogens. The glioma cell proliferation, apoptosis and the secretion level of MCP-2, IFN-γ were detected to evaluate the efficacy of this treatment against glioma in vitro. In addition, a rat glioma model was established to investigate the anti-tumor effect in vivo, and evaluated its efficacy by observing the changes of CD4 + T cells, CD8 + T cells, NK cells, and the level of IL-2 and IL-10 in peripheral blood before and after treatment. The C6 + 9L glioma cell lysate vaccine (C6 + 9L-CL) not only inhibited the proliferation of glioma cells and promoted their apoptosis in vitro, but also significantly inhibited the tumor growth in vivo and improved the survival time of rats. In addition, the C6 + 9L-CL vaccine enhanced the anti-tumor immune response by promoting the secretion of T cell chemokines MCP-2, IFN-γ and IL-2, and by stimulating the proliferation of T cells and NK cells in peripheral blood and glioma tissues. Our findings demonstrate the inhibitory effect of molecular mimic vaccines on glioma and provided a theoretical basis for molecular mimic hybrid vaccines as a potential therapeutic approach.

Angiotensinogen Suppression: A New Tool to Treat Cardiovascular and Renal Disease.

Multiple types of renin-angiotensin system (RAS) blockers exist, allowing interference with the system at the level of renin, angiotensin-converting enzyme, or the angiotensin II receptor. Yet, in particular, for the treatment of hypertension, the number of patients with uncontrolled hypertension continues to rise, either due to patient noncompliance or because of the significant renin rises that may, at least partially, overcome the effect of RAS blockade (RAS escape). New approaches to target the RAS are either direct antisense oligonucleotides that inhibit angiotensinogen RNA translation, or small interfering RNA (siRNA) that function via the RNA interference pathway. Since all angiotensins stem from angiotensinogen, lowering angiotensinogen has the potential to circumvent the RAS escape phenomenon. Moreover, antisense oligonucleotides and small interfering RNA require injections only every few weeks to months, which might reduce noncompliance. Of course, angiotensinogen suppression also poses a threat in situations where the RAS is acutely needed, for instance in women becoming pregnant during treatment, or in cases of emergency, when severe hypotension occurs. This review discusses all preclinical data on angiotensinogen suppression, as well as the limited clinical data that are currently available. It concludes that it is an exciting new tool to target the RAS with high specificity and a low side effect profile. Its long-term action might revolutionize pharmacotherapy, as it could overcome compliance problems. Preclinical and clinical programs are now carefully investigating its efficacy and safety profile, allowing an optimal introduction as a novel drug to treat cardiovascular and renal diseases in due time.

Inflammation and Diabetic Kidney Disease: New Perspectives

Diabetic Kidney Disease (DKD) can occur in approximately 30-40% of the population with type 1 or 2 diabetes mellitus around the world. In the pathogenesis and progression the Diabetic Kidney Disease (DKD), three fundamental axes are distinguished: hemodynamic, metabolic and inflammatory. The primary purpose of the review is to describe the role and mechanisms related to inflammation in the course of this disease. The pathophysiological mechanisms involved in the development and progression of DKD include different pathways present long before the clinical diagnosis of the disease. Inflammation is a complex mechanism where innate and acquired immunity play an important role, in addition to other factors such as oxidative stress and end products of glycation that in one way or another would be linked to this process of inflammation. We cannot forget the contribution in this axis of inflammation of the well-known aldosterone escape phenomenon. The blockade of the Mineralocorticoid Receptor (MRA) inactivates the action of aldosterone and prevents the genomic and non-genomic response from interacting with the receptor, thus decreasing the degree of inflammation and remodeling in the heart and kidney. Finally, there are many territories to explore in this fascinating universe of inflammation as a mechanism of kidney damage in diabetic patients. Current management of DKD with innovative interventions point to this multitarget approach.