Effect Of Combined Treatment Research Articles

AB029. Mitochondrial dysfunction and impaired growth of glioblastoma cell lines caused by antimicrobial agents inducing ferroptosis.

Glioblastoma, a malignant tumor, has no curative treatment. Mitochondria have been reported to be involved in tumorigenesis and drug resistance in various cancers. Recently, mitochondria have been considered a potential target for treating glioblastoma. We are developing a new treatment for glioblastoma targeting mitochondria. The microenvironment of glioblastoma is reported to be a low-nutrition and hypoxic condition. We focused our research on how mitochondria work under tumor circumstances. In this research, we used cell lines including U87, LN229, U373, T98G, and two patient-derived stem-like cells. First, we investigated the efficacy of mitochondria-targeted glioblastoma therapy in cell lines under glucose-starved conditions and the mechanism of cell death caused by mitochondria-targeted therapy. Second, we developed a treatment effective for cells with more glucose, because we believe that there is some lesion with higher glucose concentration in the tumor considering the heterogeneity of the tumor. We discovered that under glucose-starved conditions, mitochondria-related proteins and oxidative phosphorylation activity increased in glioblastoma cells, and in this condition, glioblastoma cells strongly depended on mitochondria. Administration of agents causing mitochondrial dysfunction including chloramphenicol was very effective and it led to cell death. The mechanism of cell death was not apoptosis but ferroptosis which is a recently discovered type of cell death caused by iron accumulation. In normoglycemic conditions, the effect of chloramphenicol was poor for the short term, however, for the long term, it was effective and caused cell death. Although both chloramphenicol alone and combined treatment using 2-DG (glycolysis inhibitor) and chloramphenicol had poor effects on cells in glucose-sufficient conditions, combined treatment was very effective for the short term under normal glucose conditions. These results suggest the importance of controlling glucose concentration. The effect of combined treatment was also confirmed in hypoxic conditions and for patient-derived neurosphere cells. And the mechanism of cell death was ferroptosis, too. Our mitochondria-targeted treatment was effective for cells with both glucose-starved conditions and normoglycemic conditions. It is necessary to investigate its effectiveness in vivo in the future. However, chloramphenicol has already been used, and therefore, this treatment can be used for humans safely. This discovery is expected to make a major contribution to the development of treatments for glioblastomas.

The effects of cryogenic treatment and impact-oscillatory loading on changes in the mechanical properties and structural condition of stainless steel 12Kh18N10T

Research findings are presented dealing with the combined effect of cryogenic treatment + impact-oscillatory loading applied in different sequences on changes in the mechanical properties of stainless steel 12Kh18N10T. One-hour long cryogenic treatment and impact-oscillatory loading (IOL) applied at room temperature were shown to be practically unable to change the mechanical properties of the steel. At the same time, IOL pre-applied at a temperature of liquid nitrogen followed by static tensioning at room temperature proved to cause significant changes in the mechanical properties of the steel. Under further static tensioning, when IOL εimp = 2.7 … 12.5 % (assigned intensity range of introducing impulse energy into steel) or, more specifically, when εimp = 9.69 %, the ultimate strength of the steel was found to reach its maximum value, increasing by 32,2 % compared to baseline, while ductility decreased by 26 %. Specific physical investigations using the TEM microscope were conducted. The analysis of the steel structure of a specimen pre-subjected to IOL in liquid nitrogen at εimp = 9.63 % indicates that under such complex loading conditions the well-known mechanism of plastic deformation by sliding changes into plastic deformation by twinning upon further static tensioning, and the strength of the steel increases.

Biofertilizer and biostimulant potentials of phosphate-solubilizing Bacillus subtilis subsp. subtilis M1 strain and silicon in improving low phosphorus availability tolerance in rosemary.

The present study aimed to evaluate the single and combined effects of Si exogenous treatment and Bacillus subtilis subsp. subtilis M1 strain inoculation on rosemary tolerance to low phosphorus (P) availability. Hence, rosemary plants were fertilized with 250µmol Ca3HPO4 (stressed plants) or 250µmol KH2PO4 (control plants) under Si treatment and B. subtilis M1 strain inoculation. P starvation negatively affected rosemary growth and its P nutrition. However, exogenous Si supply or B. subtilis M1 strain inoculation significantly (P<0.001) alleviated the deficiency-induced effects and significantly improved rhizogenesis, acid phosphatase activity, P uptake, and eventually dry weight of shoot and root. Moreover, Si-treatment and/or B. subtilis M1 strain inoculation significantly (P<0.001) reduced the oxidative damage, in terms of malondialdehyde and hydrogen peroxide accumulation. This was found positively correlated with the higher superoxide dismutase activity, and the elevated non-enzymatic antioxidant molecules accumulation, including total polyphenols in Si-treated and inoculated P-deficient plants. Taken together, Si supplementation and/or B. subtilis M1 strain inoculation could be a good strategy to sustain rosemary plant growth under P starvation conditions.

Is freeze-dried superfood kale supplementation healthier than common green peas? Outcomes of a cross-over trial.

Kale (Brassica oleracea species) is considered a functional food whose macronutrient and phytochemical contents are considered beneficial and widely considered as a superfood. In the present 6-week cross-over trial with a 2-week washout period, we compared the beneficial effects of freeze-dried kale over peas among Arab women with obesity. A total of 124 Saudi women with obesity were allocated to receive either freeze-dried kale (n = 62) or freeze-dried peas (n = 62) given in the form of 3-gram sachets thrice daily for 2 weeks, followed by a 2-week washout period and a cross-over of 4 weeks. Anthropometric measurements, glucose, lipids and markers of gut barrier function were assessed at baseline and post-intervention. Participants who took kale supplementation first resulted in significant weight reduction (p = 0.02) which was not observed among those who took peas first. Participants receiving pea supplementation first experienced a significant decline in Hba1c (p = 0.005) and CD14 (p = 0.03), but C-peptide increased (p = 0.05). Crossover analysis revealed significant carryover effects in most variables with non-significant combined treatment effects. Among the variables with no carryover effect with significant combined treatment effect include HbA1c which was in favor of the pea group (p = 0.005) and C-peptide which was modestly in favor of the kale group (p = 0.05). While both freeze dried kale and pea supplementation appear beneficial, supplementation of freeze-dried pea appears to be more effective in terms of acute glycemic control than kale. The study suggests that common but less-hyped vegetables such as pea maybe equally, if not more beneficial than the more expensive promoted superfoods such as kale. Longer clinical trials using a parallel design instead of cross-over are recommended to strengthen present findings.

STUDY OF THE COMBINED EFFECT OF POST-SYNTHETIC ALKALINE TREATMENT AND NICKEL MODIFICATION OF MFI ZEOLITE ON THE DYNAMICS OF ITS DEACTIVATION IN THE PROCESS OF REFINING STRAIGHT-RUN GASOLINE

To determine the combined effect of post-synthetic treatments on the catalytic properties of MFI type zeolite (other names ZSM-5 or pentasil) during the upgrading of straight-run gasoline fraction of oil, MFI zeolite was synthesized and on its basis a sample was obtained, treated with an alkaline solution, as well as a nickel-containing sample after alkaline treatment of the zeolite. Modification of zeolite powder treated with an alkaline solution with nanosized nickel powder was carried out by dry mechanical mixing of the original powders in a vibrating mill. The activity and dynamics of deactivation of the obtained zeolite catalysts during the upgrading of straight-run gasoline fraction of oil were studied. Along with determining the characteristics of the target reaction products - high-octane gasoline, an analysis of the resulting gaseous hydrocarbons was carried out and the amount of carbon compaction products was determined. It has been shown that post-synthetic treatments of zeolite have a positive effect on the qualitative composition and yield of catalysates and reduce the rate of deactivation of zeolite catalysts. Post-synthetic alkaline treatment of MFI zeolite significantly reduces its aromatizing and cracking activity, resulting in an increased yield of high-octane gasoline with improved environmental characteristics. The introduction of nickel nanopowder into alkali-treated zeolite further enhances this tendency. Carrying out post-synthetic treatments of zeolite increases the time of stable operation of the resulting zeolite systems in the process of upgrading straight-run gasoline and reduces the amount of carbon compaction products formed. The state, location and dimensions of the zeolite carrier, nickel particles and carbon compaction products were determined using the transmission electron microscopy method. It has been shown that oxidative regeneration of a carbonized catalyst makes it possible to almost completely remove the resulting carbon deposits from the surface of both the active component and the zeolite support. For citation: Velichkina L.M., Gerasimov E.Yu., Vosmerikov A.V. Study of the combined effect of post-synthetic alkaline treatment and nickel modification of MFI zeolite on the dynamics of its deactivation in the process of refining straight-run gasoline. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 8. P. 103-112. DOI: 10.6060/ivkkt.20246708.10t.

Comparative efficacy of platelet-rich plasma (PRP) injection versus PRP combined with vitamin C injection for partial-thickness rotator cuff tears: a randomized controlled trial

BackgroundThe optimal approach for managing partial-thickness rotator cuff tears (PTRCT) remains controversial. Recent studies related to PTRCTs have shown that platelet-rich plasma (PRP) injection might be an effective treatment option. Despite the role of vitamin C in collagen synthesis and its antioxidant properties, the effects of combined PRP and vitamin C treatment on rotator cuff repair are not well understood. This study investigated the effect of combined treatment of PRP and vitamin C treatment on PTRCTs.MethodsOne hundred-ten patients with PTRCTs were randomly allocated to two groups and underwent subacromial injections of either (A) normal saline and platelet-rich plasma or (B) vitamin C and platelet-rich plasma. The Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analog scale were used to evaluate the outcomes before, 1 month after, and 3 months after injection.ResultsAt the 3-month follow-up, no statistically significant differences were observed between the two groups in terms of ASES and Constant scores. Although a slight difference favoring group B was noted in functional scores and pain reduction, this difference was not statistically significant. However, both groups demonstrated significant pain reduction over time (p-value < 0.001). Additionally, the enhancement of ASES and Constant scores in both groups was statistically significant (p-value < 0.001).ConclusionsIn conclusion, both PRP injection alone and PRP combined with vitamin C led to significant reductions in pain and enhancements in function scores over time (p < 0.001), suggesting the effectiveness of PRP as a non-surgical treatment for PTRCTs within 3 months. While PRP alone showed significant benefits, further research is required to ascertain if the combination therapy offers statistically significant advantages over PRP alone.Trial registrationClinical trial registration code: IRCT20230821059205N1.

A study on combination of alkaline treatment and PLA/f-CNTs composite coating on corrosion, biocompatibility and antibacterial activity of Mg alloy

The present study explores the effect of combined alkaline treatments (NaOH) and the incorporation of functionalized carbon nanotubes (f-CNTs) into poly(lactic acid) (PLA) composite coatings on the corrosion resistance, biocompatibility, and antibacterial efficacy of AZ31 magnesium (Mg) alloy. Various pretreatment techniques and coating layers have been found to exert considerable influence on the phase composition, morphology, thickness, wettability, as well as corrosion resistance, and biological characteristics of the Mg alloy. The formation of an Mg(OH)2 layer on alkaline-treated Mg alloy has proven to enhance hydrophilicity, corrosion resistance, and biocompatibility. Moreover, the findings highlight that incorporating f-CNTs into PLA improves the corrosion resistance, cytocompatibility, and antibacterial activity of Mg alloy in physiological solutions and the extent of these improvements is related to the quantity of f-CNTs present in the composite coating. Additionally, the outcomes have shown that the inclusion of f-CNTs promotes the formation of carbonate based precipitates during a 14-day immersion in Ringer's solution. Overall, the combination of alkaline treatments and the PLA/f-CNTs composite coating is showcased as a promising surface modification approach for orthopedic applications.

Are there any benefits from prescribing a cardiac cytoprotector to enhance the quality of life in patients with coronary heart disease and chronic heart failure?

Introduction. Type 2 diabetes (T2D) increases the risk of developing cardiovascular diseases, which leads to a high mortality in this category of patients. Issues regarding the prevention of the onset and progression of coronary heart disease (CHD) and chronic heart failure (CHF) in patients with T2D and/or metabolic syndrome (MS) are still not fully understood. The use of metabolic drugs with cardioprotective effects, in particular Mildronate®, is one of the possibilities to improve the effectiveness of combination treatment of CHD and CHF.Aim. To study the effect of Mildronate® on the quality of life (QoL) of patients with CHD and CHF, suffering from T2D and/or MS.Materials and methods. A total of 2.084 patients with co-occurring two (or more) disorders: obesity, type 2 diabetes, angina pectoris, CHT, and CHF were included in the INDICOR observational study conducted in real-life clinical practice settings. Group 1 received therapy with disease-modifying agents prescribed due to CHD and T2D; Group 2 received Mildronate® at a dose of 1000 mg per day in addition to the same therapy. The studied lab test results were assessed at baseline and 42 days of therapy.Results. A 42-day course of therapy in patients receiving Mildronate® at a dose of 1000 mg per day in addition to disease-modifying therapy (DMT) contributed to a percentage increase in the number of patients with CHD, FC (functional class) I angina pectoris (Δ,% + 63%, p &lt; 0.001 ) as compared to the control group with no significant changes (Δ,% + 7%, p &gt; 0.5). A significant increase in the number of patients with FC I CHF was recorded in Group 2 (from 23.5 to 42.1%, Δ,% + 79%) as compared to Group 1, where no significant changes were detected (22.7 to 23.7%, Δ,% + 4%). The QoL in patients with CHF based on data collected using the Minnesota Questionnaire and QoL in patients with CHD based on data collected using the Seattle Questionnaire significantly improved in the groups that received Mildronate® in addition to DMT, as compared with the group of patients who were only on DMT.Conclusion. Results from the Seattle and Minnesota questionnaires showed that the use of Mildronate® as part of combination therapy in patients with CHD and CHF, suffering from T2D and/or MS, contributed to a significant reduction in the frequency of angina attacks and lowering angina FC, CHF FC, and also enhanced the quality of life in this category of patients.

Citicoline: A Cholinergic Precursor with a Pivotal Role in Dementia and Alzheimer's Disease.

Citicoline is a naturally occurring compound with pleiotropic effects on neuronal function and cognitive processes. Based on previous studies, which shed light on the positive effects of citicoline 1 g when combined with acetylcholinesterase inhibitors (AChEIs) and/or memantine, we further investigated the benefits of citicoline in combination therapy in Alzheimer's disease and mixed dementia. We integrated the datasets of CITIMEM and CITIDEMAGE, increasing the overall sample size to enhance statistical power. We analyzed data from these two investigator-initiated studies involving 295 patients. The primary outcome was the assessment over time of the effects of combined treatment versus memantine given alone or AChEI plus memantine on cognitive functions assessed by Mini-Mental State Examination (MMSE). The secondary outcomes were the influence of combined treatment on daily life functions, mood, and behavioral symptoms assessed by activities of daily life (ADL) and instrumental ADL, Geriatric Depression Scale, and Neuropsychiatric Inventory Scale. One-hundred-forty-three patients were treated with memantine and/or AChEI (control group), and 152 patients were treated with memantine and/or AChEI plus citicoline 1 g/day orally (Citicoline group). A significant difference in MMSE score was found in the average between the two groups of treatment at 6 and 12 months. This study confirmed the effectiveness of combined citicoline treatment in patients with mixed dementia and Alzheimer's disease, with a significant effect on the increase of MMSE score over time. The treated group also showed a significant reduction in the Geriatric Depression Scale and a significant increase in the instrumental ADL scale.

The combined effect of acid and mild heat treatment on the shelf-life and quality of fresh wet noodles

In this research, changes in microbial shelf-life and quality characteristics of fresh wet noodles (FWNs) were analyzed under acid and different mild heat treatment conditions. Acid combined with heat treatment at 50 °C for 30 min extended the shelf-life of FWNs by 30–40 d and effectively delayed the color deterioration of FWNs. The water absorption of FWNs was reduced by the mild heat treatment. Meanwhile, the cooking loss of the noodles and hardness significantly (p < 0.05) increased. Differential scanning calorimetry (DSC) analysis showed that the gelatinization enthalpy of the starch in FWNs decreased and the gelatinization temperature increased. The X-ray diffraction (XRD) results showed that the crystallinity of the starch decreased from 27.51% to 24.2% after mild heat treatment. In addition, it was observed by confocal laser scanning microscope that the mild heat treatment made the gluten networks more continuous. The free sulfhydryl content of noodles showed a decreasing trend, while the sodium dodecyl sulfate-extractable protein (SDS-EP) value was also significantly (p < 0.05) reduced. Overall, the combination of mild heat treatment with acid extended the shelf-life of FWNs and had less impact on their quality.

Gentamicin combination treatment is associated with lower mortality in patients with invasive listeriosis: a retrospective analysis.

Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01-0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.

Effects of combined treatment with chitosan, d-isoascorbate sodium and γ-aminobutyric acid on enzymatic browning and flavor quality of Paojiao

In this study, non-targeted metabolomics and GC-MS were used to investigate the effect of anti-browning treatment (adding 0.20% chitosan, 0.15% d-isoascorbate sodium and 0.10% γ-aminobutyric acid) on enzymatic browning and flavor of Paojiao, respectively. The results showed that compared with untreated Paojiao, the browning index of treated Paojiao was significantly reduced (P < 0.01), and the activities of phenylalanine ammonia lyase (PAL), peroxidase (POD), and polyphenol oxidase (PPO) were inhibited. In total, 944 metabolites were detected, including 59 differential metabolites. KEGG enrichment results showed that the anti-browning treatment mainly inhibited the browning of Paojiao through arachidonic acid metabolism and phenylpropanoid biosynthesis. Furthermore, the anti-browning treatment increased the richness of the flavor components of Paojiao, especially the esters. Overall, the anti-browning treatment could effectively inhibit the browning of Paojiao and improve its flavor, thereby providing a theoretical reference for the production and processing of high-quality Paojiao products.

Effects of combined treatment with hydrogen-rich electrolyzed water and tea polyphenols on oxidative stress, intestinal injury and intestinal flora disruption in heat-stressed mice

Heat stress (HS) can cause damage to the organism, especially the intestinal tract. In this paper, we investigated the effects of the combined action of tea polyphenols (TP) and hydrogen-rich electrolyzed water (HRW) on HS in mice. The combination of HRW feeding and TP of intraperitoneal injection was screened by in vitro antioxidant activity assay. The results revealed that the combined treatment was more helpful in alleviating the effects of HS on the behavior, growth performance, oxidative damage, and intestinal tract of mice compared with the respective treatments of TP and HRW (P < 0.05). Additionally, the combined treatment could repair HS-induced intestinal dysbiosis in mice, augmenting the number and abundance of bacteria, increasing the number of beneficial genera (Lachnospiraceae_NK4A136_group and Lactobacillus), and decreasing the number of harmful genera (Desulfovibrio and Enterorhabdus), and the effect was significantly better than that of individual treatment (P < 0.05). In conclusion, the combined treatment of TP and HRW effectively mitigates the adverse effects of HS on mouse behavior, growth performance, oxidative damage, and intestinal dysbiosis, surpassing the efficacy of individual treatments with TP or HRW alone.

Liposome co-delivery of quercetin and doxorubicin in inhibiting retinoblastoma by regulating epithelial-mesenchymal transition process

Regulating the process of epithelial-mesenchymal transition(EMT) is an essential strategy to inhibit tumor growth and metastasis. This study is based on the EMT process of retinoblastoma and constructs quercetin(QUE) and doxorubicin(DOX) co-loaded liposome(QD Lipo) to investigate the therapeutic effect and mechanisms of combined QUE and DOX treatment on retinoblastoma. Single-factor experiments were conducted to optimize the prescription process of QD Lipo. Eventually, spherical particles with a diameter of(108.87±1.93) nm, a PDI of 0.13±0.02, and a Zeta potential of(-34.83±1.92) mV were obtained. The encapsulation rates of QUE and DOX were 96.20%±4.40% and 91.17%±4.41%, respectively. Y79 human retinoblastoma cells were used as an in vitro cellular model, and confocal microscopy demonstrated that QD Lipo could enhance Y79 uptake efficiency. The CCK-8 assay confirmed that the optimal combination therapy effect of QUE and DOX occurred at a mass ratio of 1∶1 to 1∶2. Flow cytometry showed that QD Lipo enhanced the induction of apoptosis in Y79 cells. Western blot analysis revealed that QD Lipo significantly reduced the expression of EMT pathway-related proteins vimentin and α-SMA. Fluorescence assays detected a significant decrease in ROS levels in Y79 cells after treatment with QD. These results indicated that liposomal co-delivery of QUE and DOX can enhance drug delivery efficiency to retinoblastoma cells, inhibit the EMT process in retinoblastoma by downregulating ROS levels, and enhance the cytotoxicity of DOX against retinoblastoma.

Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists and cancer mortality. A real-world registry

Introduction and objectivesSodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD). MethodsWe conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome. ResultsWe included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively). ConclusionsInitiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.

Effect of combined treatment of curcumin and sodium bicarbonate on quality characteristics of refrigerated beef meatballs

In this study, we assessed the impact of curcumin (CC), sodium bicarbonate (SB), and their combination on the quality characteristics of refrigerated beef meatballs, aiming to ascertain the composite preservation effects of the combined use of CC and SB in meat products. Our findings revealed that, compared to the control group, CC, SB, and their combined treatment significantly reduced the levels of thiobarbituric acid reactive substances, total sulfhydryl losses, total survival counts, and total volatile basal nitrogen values of beef meatballs during storage (P < 0.05). Additionally, these treatments effectively delayed the colour and texture degradation of the meatballs and protected the structure of the meatball myofibrillar proteins. SB exhibited a significant reduction in cooking loss (P < 0.05) by enhancing the pH of beef meatballs and inducing the conversion of α-helix to β-sheet structure in myofibrillar proteins. Furthermore, beef meatballs treated with CC, SB, and their combination displayed dense microstructure and superior sensory quality through storage. The combined treatment of CC and SB yielded the most considerable improvement in the quality of refrigerated beef meatballs. Therefore, CC and SB can be used in combination in meat products to mitigate quality deterioration during storage.

Application of electron beam irradiation and mild thermal treatment of Bacillus cereus spores in Chinese braised beef cuisine

ABSTRACT The individual and combined effects of electron beam (EB) irradiation and thermal treatments were investigated on Chinese braised beef samples inoculated with Bacillus cereus spores. Log reductions of 1.19, 2.10, and 3.62 log CFU/g were recorded for B. cereus spores after 6, 9, and 12 kGy lone EB doses, respectively. An 85°C thermal treatment at 20 min (H) reduced the spores population by 1.03 log CFU/g. The combination of the thermal and EB irradiation treatments (HEB) of HEB-6 and HEB-9 achieved 1.69 and 2.89 log CFU/g reductions, respectively. The B. cereus spores population was depleted to below the detection limit following HEB-12 treatment. No significant pH change was observed in the treatments except for HEB-12. The hurdle treatment of HEB-12 caused marked changes in color, aroma, and overall acceptability. Although HEB irradiation improved microbial safety, careful selection of approved EB doses can effectively enhance food safety and maintain reasonable quality standards.

DIPG-87. TARGETING GENE-REPRESSIVE EPIGENETIC REGULATION TO INDUCE INTERFERON SIGNALING IN DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brainstem tumor with no known effective treatment. DIPG is driven by the H3K27M mutant histone, which promotes epigenetic dysregulation, leading to loss of gene-repressive H3K27me3 marks, global DNA hypomethylation, and a distinct gene expression profile. DIPG cells retain histone methylation at histone H3 lysine 9 (H3K9me2/3), suggesting that the tumor may rely on these marks to repress unwanted expression. Our prior work has demonstrated that treatment with the DNA hypomethylating agent decitabine (DAC) elicits expression of cancer-specific antigens and immune activation, including activation of interferon signaling, but modulating gene-repressive H3K9 methylation in DIPG has not been extensively investigated. METHODS We treated four primary patient-derived DIPG neurosphere cell lines with BIX01294 and UNC0642, inhibitors of H3K9 methyltransferases G9a/GLP, and analyzed gene expression changes by RNA-sequencing and Western blot. We assessed the effect of combination treatments on these four cell lines with both DAC and either BIX01294 or UNC0642 and evaluated impact on gene expression, innate immune signaling, and interferon pathway activation. RESULTS We found that treatment with either of the G9a/GLP inhibitors resulted in the upregulation of genes involved in immune signaling. Given the similarities in the immune signaling response elicited from treatment with DAC and the G9a/GLP inhibitors, we evaluated the effect of combination treatments with both DAC and either BIX01294 or UNC0642. These combinations resulted in an increased induction of genes involved in immune signaling, including STING. CONCLUSIONS Pharmacologic inhibition of DNA methylation and histone H3K9 methylation elicits immune activation in DIPG cells. Upregulation of interferon and STING signaling with this combination treatment may be significant in enhancing the immunogenicity of DIPG cells to allow effective immunotherapy.

Effects of combined radiotherapy with immune checkpoint blockade on immunological memory in luminal-like subtype murine bladder cancer model

ABSTRACT MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice. We first characterized the baseline tumor microenvironment and the effect of radiation, anti-PD-L1, and combinatorial treatments. Then, the mice were re-challenged with a second tumor (rechallenged tumor) in the contralateral flank of the first tumor to assess the immunological memory. Radiation slowed down the tumor growth. All treatments also decreased the neutrophil population and increased the T cell population. Anti-PD-L1 therapy was not able to synergize with radiation to further delay tumor growth. Furthermore, none of the treatments were able to generate immune memory. The treatments were not sufficient to induce a significant and lasting pool of memory cells. We show here that anti-PD-L1 treatment added to radiotherapy was not enough to achieve T cell-mediated memory in UPPL tumors. Stronger T cell activation signals may be required to enhance radiation efficacy in luminal-like bladder cancer.

The safety effect of increased pedestrian protection, autonomous emergency braking for pedestrians and bicyclists on passenger cars, and speed management

This was the first retrospective study to estimate the effect of increased pedestrian protection, autonomous emergency braking, and speed management to reduce serious injuries among pedestrians and bicyclists. More specifically, the aim was to estimate the injury mitigating effects of the following interventions: AEB with pedestrian and bicyclist detection, Euro NCAP pedestrian test score, active bonnet, traffic calming at pedestrian and bicycle crossings, and additionally, the combined effect of the above-mentioned treatments. The main source of data was the Swedish traffic data acquisition system (Strada), where information of road traffic crashes between passenger cars and pedestrians or bicyclists for the period 1 January 2003–31 December 2022 was obtained. Cars with optional fitment of AEB systems were identified, and the license registration number was used to access individual car equipment lists to identify whether the vehicle was equipped with AEB with pedestrian and/or cyclist detection. Information about traffic calming at pedestrian and bicycle crossings was obtained from the Swedish Transport Administration. The injury metric used was risk of permanent medical impairment (RPMI) of at least one percent and ten percent. RPMI captures the risk of long-term medical impairment based on a diagnosed injury location and Abbreviated Injury Severity (AIS) score. The relative difference between the mean values of RPMI (mRPMI1%+ and mRPMI10%+) was calculated and tested using an independent two sample t-test which was conducted for unequal sample sizes and variance. Although many results were found to be statistically non-significant, the following results were found to be significant at least at 90% level. Pedestrian mRPMI10%+ was reduced by 44% in speed zones ≤ 50 km/h comparing the group struck by cars equipped with AEB with pedestrian detection compared to the group struck by cars without the system. For cyclists, the mRPMI10%+ was reduced by 35% in speed zones ≤ 50 km/h. For crashes within ± 20 meters from a pedestrian or bicycle crossing, the AEB system reduced 60% of pedestrians mRPMI10%+ at crossings with good safety standard compared to crossings of poor safety standard. The comparison of cars with poor performance (1–9 points) in the NCAP pedestrian test and cars with a high score (28–36 points) showed that pedestrian mRPMI10%+ was reduced by 48% across all speed limits, and by 64% including only those aged ≤ 64 years. For bicyclists, a significant reduction of cyclist mRPMI10%+ was found comparing low scoring cars to high scoring cars in ≤ 30 km/h speed limit (-73%) and across all speed limits (-36%). Including only those aged ≤ 64 years, the reduction was 49%. For the active bonnet, a significant reduction of mRPMI1%+ by 24% was observed but given that the rate of helmet wearing was higher in the group struck by cars with active bonnet, this difference cannot be attributed to an effect of an active bonnet. The STA safety rating of pedestrian and bicycle crossings showed that overall pedestrian mRPMI1%+ was reduced by 15%, while cyclists mRPMI10%+ was reduced by 32% comparing crossings of high safety level to crossings of poor safety level. The analysis of combined interventions showed that the total reduction of pedestrians and cyclists mRPMI10%+ together was 69%, from 6.4% to 2%. This paper demonstrates that a road environment with adapted infrastructure and speed, combined with passenger car technologies that improve the safety for vulnerable road users, can create significant reductions of serious (long-term) injuries among pedestrians and bicyclists.