Stress Parameters Research Articles

The effects of cadmium on selected oxidative stress parameters and the content of photosynthetic pigments in cucumber Cucumis sativus L.

BackgroundEnvironmental pollution by cadmium (Cd) is currently a common problem in many countries, especially in highly industrialised areas. Cd present in the soil can be absorbed by plants through the root system. AimThe aim of the present study was to investigate the effects of cadmium on the metabolic activity of cucumber plants (Cucumis sativus L.) and the accumulation and distribution of Cd in the organs of the plants. MethodsCucumber seeds (3 g) were exposed to 0.76, 1.58 or 4.17 mg Cd/L (applied as CdCl2 solutions). The activity of selected antioxidant enzymes - glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation and the content of photosynthetic pigments were determined in 6-week-old cucumber plants. In addition, intake of Cd has been determined by flame atomic absorption spectrometry (F-AAS). ResultsThe results show that the applied cadmium concentrations affected the activity of antioxidant enzymes. An increase in CAT activity and a decrease in SOD activity were observed in all cucumber organs analysed. GSH-Px activity increased in the roots and stems. Surprisingly, GSH-Px activity decreased in the leaves. The level of lipid peroxidation was usually unchanged (the only one statistically significant change was a decrease in the concentration of malondialdehyde in the leaves which was observed after exposure to the highest Cd concentration). The applied Cd concentrations had no effect on the content of photosynthetic pigments. The highest cadmium content was found in the roots of cucumber plants. Cd tends to accumulate in the roots and a small amount was translocated to the stems and leaves, which was confirmed with the translocation factor (TF). ConclusionsThe results indicate that the range of cadmium concentrations used, corresponding to the level of environmental pollution recorded in Europe, effectively activates the antioxidant enzyme system, without intensifying lipid peroxidation or reducing the content of photosynthetic pigments.

The Impact of Rubber Dam Association With Physiological Stress Parameters on Children of 7-10 Years Undergoing Pit and Fissure Sealant Treatment: An In-Vivo Study

The Impact of Rubber Dam Association With Physiological Stress Parameters on Children of 7-10 Years Undergoing Pit and Fissure Sealant Treatment: An In-Vivo Study

Protective effects of arbutin against doxorubicin-induced cardiac damage.

Doxorubicin is an effective antineoplastic agent but has limited clinical application because of its cumulative toxicities, including cardiotoxicity. Cardiotoxicity causes lipid peroxidation, genetic impairment, oxidative stress, inhibition of autophagy, and disruption of calcium homeostasis. Doxorubicin-induced cardiotoxicity is frequently tried to be mitigated by phytochemicals, which are derived from plants and possess antioxidant, anti-inflammatory, and anti-apoptotic properties. Arbutin, a natural antioxidant found in the leaves of the bearberry plant, has numerous pharmacological benefits, including antioxidant, anti-bacterial, anti-hyperglycemic, anti-inflammatory, and anti-tumor activity. The study involved male Wistar rats divided into three groups: a control group, a group treated with doxorubicin (20mg/kg) to induce cardiac toxicity, a group treated with arbutin (100mg/kg) daily for two weeks before doxorubicin administration. After treatment, plasma and heart tissue samples were collected for analysis. The samples were evaluated for oxidative stress parameters, including superoxide dismutase, malondialdehyde, and catalase, as well as for cardiac biomarkers, including CK, CK-MB, and LDH. The heart tissues were also analyzed using molecular (TNF-α, IL-1β and Caspase 3), histopathological and immunohistochemical methods (8-OHDG, 4 Hydroxynonenal, and dityrosine). The results showed that arbutin treatment was protective against doxorubicin-induced oxidative damage by increasing SOD and CAT activity and decreasing MDA level. Arbutin treatment was similarly able to reverse the inflammatory response caused by doxorubicin by reducing TNF-α and IL-1β levels and also reverse the apoptosis by decreasing caspase-3 levels. It was able to prevent doxorubicin-induced cardiac damage by reducing cardiac biomarkers CK, CK-MB and LDH levels. In addition to all these results, histopathological analyzes also show that arbutin may be beneficial against the damage caused by doxorubicin on heart tissue. The study suggests that arbutin has the potential to be used to mitigate doxorubicin-induced cardiotoxicity in cancer patients.

[Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen].

To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H2<4% in the gas mixture), the control group (n=17) didn't receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p<0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p<0.001), and the date in oxidative damage (p<0.001) and antioxidant activity (p=0.03) parameters in the blood serum. The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

Fatigue Crack Propagation of 51CrV4 Steels for Leaf Spring Suspensions of Railway Freight Wagons.

Leaf springs are critical components for the railway vehicle safety in which they are installed. Although these components are produced in high-strength alloyed steel and designed to operate under cyclic loading conditions in the high-cyclic fatigue region, their failure is still possible, which can lead to economic and human catastrophes. The aim of this document was to precisely characterise the mechanical crack growth behaviour of the chromium-vanadium alloyed steel representative of leaf springs under cyclic conditions, that is, the crack propagation in mode I. The common fatigue crack growth prediction models (Paris and Walker) considering the effect of stress ratio and parameters such as propagation threshold, critical stress intensity factor and crack closure ratio were also determined using statistical methods, which resulted in good approximations with respect to the experimental results. Lastly, the fracture surfaces under the different test conditions were analysed using SEM, with no significant differences to declare. As a result of this research work, it is expected that the developed properties and fatigue crack growth prediction models can assist design and maintenance engineers in understanding fatigue behaviour in the initiation and propagation phase of cracks in leaf springs for railway freight wagons.

Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats

Pirfenidone (PFD), one acceptable medication for treating idiopathic pulmonary fibrosis (IPF), is not well tolerated by patients at full doses. Hence, employing of some approaches such as combination therapy may be applicable for increasing therapeutic efficacy of PFD. Losartan (LOS), an angiotensin II receptor antagonist, could be a suitable candidate for combination therapy because of its stabilizing effect on the pulmonary function of IPF patients. Therefore, this study aimed to investigate the effects of LOS in combination with PFD on bleomycin (BLM)-induced lung fibrosis in rats. BLM-exposed rats were treated with LOS alone or in combination with PFD. The edema, pathological changes, level of transforming growth factor-β (TGF-β1), collagen content, and oxidative stress parameters were assessed in the lung tissues. Following BLM exposure, the inflammatory response, collagen levels, and antioxidant markers in rat lung tissues were significantly improved by PFD, and these effects were improved by combination with LOS. The findings of this in vivo study suggest that the combined administration of PFD and LOS may provide more potent protection against IPF than single therapy through boosting its anti-inflammatory, anti-fibrotic, and anti-oxidant effects. These results hold promise in developing a more effective therapeutic strategy for treating of lung fibrosis.

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: An animal study

AimThis study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. Materials and methodsEighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet + Metformin (300 mg/kg), 5) diabet + Forskolin (100 mg/kg), 6) diabet + Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC + Metformin (300 mg/kg), 8) HCC + Forskolin (100 mg/kg), 9) HCC + Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group + Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. ResultsThe average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin + Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P < 0.05). Although the rats treated with Forskolin + Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. ConclusionMetformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

Evaluation of Design Parameters (α and β) for Analysis and Design of Piles on Soft Clays

This paper presents the analyses of 12 prestressed concrete instrumented test piles (TPs) that were driven in different bridge construction projects of Louisiana as part of a load testing program. The 12 TPs were driven mainly in cohesive soils. Detailed soil characterizations including both laboratory and in situ tests were conducted to determine the different soil properties. The TPs were instrumented with vibrating wire strain gauges to be able to calculate the distribution of skin friction and end-bearing capacities separately. Static load tests and dynamic load tests were conducted on each TP after end of driving to calculate the ultimate load capacity. Fifty six soil layers exhibiting clayey soil behavior and sandy soil behavior dominated the remaining 15 soil layers. The total stress parameter (α) and the effective stress parameter (β) were back-calculated for each soil layer. The α values ranged from 0.22 to 1.80, and the β values ranged from 0.11 to 0.83. Regression analyses were performed on 42 soil layers (75% data) to develop an empirical model to predict α as a function of undrained shear strength. The remaining 25% of the data were used to verify the developed model, and good agreement was observed between the measured and predicted values.

Physiological and behavioral contagion/buffering effects of chronic unpredictable stress in a socially enriched environment: A preliminary study

Rodents are sensitive to the emotional state of conspecifics. While the presence of affiliative social partners mitigates the physiological response to stressors (buffering), the partners of stressed individuals show behavioral and endocrine changes indicating that stress parameters can be transmitted across the group members (contagion). In this study, we investigated the social contagion/buffering phenomena in behavior and neuroendocrine mechanisms after exposure to chronic stress, in groups of rats living in the PhenoWorld (PhW). Three groups were tested (8 stressed rats, 8 unstressed rats, and a mixed group with 4 and 4) and these were analyzed under 4 conditions: stressed (pure stress group, n = 8), unstressed (naive control group, n = 8), stressed from mixed group (stressed companion group, n = 8), unstressed from mixed group (unstressed companion group, n = 8. While naive control animals remained undisturbed, pure stress group animals were all exposed to stress. Half of the animals under the mixed-treatment condition were exposed to stress (stressed companion group) and cohabitated with their unstressed partners (unstressed companion group). We confirmed the well-established chronic unpredictable stress (CUS) effects in physiological, behavioral, and neuroendocrine endpoints; body weight gain, open arm entries and time in EPM, and oxytocin receptor expression levels in the amygdala decreased by stress exposure, whereas adrenal weight was increased by stress. Furthermore, we found that playing, rearing and solitary resting behaviors decreased, whereas huddling behavior increased by CUS. In addition, we detected significant increases (stress-buffering) in body weight gain and huddling behaviors between pure stress and stress companion animals, and significant stress contagion effects in emotional behavior and oxytocin receptor expression levels between naive control and control companion groups. Hence, we demonstrate buffering and contagion effects were evident in physiological parameters, emotional behaviors, and social home-cage behaviors of rats and we suggest a possible mediation of these effects by oxytocin neurotransmission. In conclusion, the results herein suggest that the stress status of animals living in the same housing environment influences the behavior of the group.

Renoprotective effect of diacerein in rats with partial unilateral ureteral obstruction model

Abstract Objectives We aimed to analyze the effects of diacerein in a rat model of partial unilateral ureteral obstruction (PUUO). Methods We randomly divided 24 female rats into three groups. Control group, PUUO group and PUUO + diacerein group. The PUUO group was subjected to the PUUO model for seven days. The PUUO + diacerein group received oral diacerein (80 mg/kg) for seven days. Spectrophotometric methods were employed to measure oxidative stress parameters, including malondialdehyde (MDA), protein carbonyl (PC) and antioxidant enzyme levels, including glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), while indicators of renal function, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinous-associated lipocalin (NGAL), along with inflammatory parameters interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were assessed using the ELISA method. Inflammatory parameters were measured in blood samples, and other parameters were analyzed in kidney tissue. Hematoxylin-eosin method examinations were used for histological analyses. Results IL-1beta, TNF-alpha, and IL-6 levels were found to be significantly decreased in the PUUO + diacerein group compared to the PUUO group (p=0.006, p=0.002 and p=0.001, respectively). In the PUUO + diacerein group, GSH-Px and SOD activities increased compared with the PUUO group (p=0.031 and p=0.037, respectively). We also observed a significant improvement in renal function parameters, such as KIM-1 and NGAL levels in the PUUO + diacerein group compared to PUUO (p=0.002 and p=0.012, respectively). The PC and MDA levels were highest in the PUUO group (p&lt;0.001). Similarly, the histopathologic tissue damage was the most prominent PUUO group (p&lt;0.001). Conclusions Our study found that diacerein is a highly effective pharmacologic agent in alleviating oxidative damage in PUUO model rats.

Assessing the impact of body composition, metabolic and oxidative stress parameters on insulin resistance as a prognostic marker for reactive hypoglycemia: a cross-sectional study in overweight, obese, and normal weight individuals.

Oxidative stress (OS) plays a pivotal role in the pathogenesis of insulin resistance (IR), particularly in its association with obesity. This study evaluate both the diagnostic and clinical significance of assessing oxidative status in patients affected by overweight and obesity displaying IR, especially with reactive hypoglycemic episodes (RH). A comprehensive examination of OS biomarkers was carried out, encompassing measurements of total oxidative capacity (TOC) and total antioxidant capacity (TAC). Our analysis results reveal noteworthy connections between OS levels and the severity of IR in overweight and obese patients. Moreover, in the study, we demonstrated the diagnostic utility of serum concentrations of TAC and TOC as indicators of the risk of RH, the occurrence of which, even at the stage of overweight, may be associated with increased OS and further development of obesity. Our findings imply that the evaluation of oxidative status could serve as a crucial diagnostic and prognostic tool for patients observed with IR and overweight and obesity. In conclusion, our study underscores the potential utility of assessing oxidative status in the context of IR and highlights the possibility of identifying novel therapeutic targets for the treatment of overweight and obese patients.

Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI],26.5 ± 2.3 kg m-2) or obese (OBBMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OBgroup showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a β-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-βRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients: a double-blinded randomized clinical trial.

The present study investigated the effect of curcumin and eicosapentaenoic acid, as one the main components of omega-3 polyunsaturated fatty acids, on anthropometric, glucose homeostasis, and gene expression markers of cardio-metabolic risk in patients with type 2 diabetes mellitus. This clinical trial was conducted at the Endocrinology Clinic of Imam Reza Hospital in Tabriz. It aimed to determine the impact of Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), and curcumin supplements on various health indicators in patients with Type 2 Diabetes Mellitus (DM2) from 2021.02.01 to 2022.02.01. The study was a randomized double-blinded clinical trial and conducted over 12 weeks with 100 participants randomly divided into four groups. Stratified randomization was used to assign participants to two months of supplementation based on sex and Body Mass Index (BMI). The study comprised four groups: Group 1 received 2 capsules of 500 mg EPA and 200 mg DHA, along with 1 nano-curcumin placebo; Group 2 received 1 capsule of 80 mg nano-curcumin and 2 omega 3 Fatty Acids placebos; Group 3 received 2 capsules of 500 mg EPA and 200 mg DHA, and 1 capsule of 80 mg nano-curcumin; Group 4, the control, received 2 omega 3 Fatty Acids placebos and 1 nano-curcumin placebo. After twelve weeks of taking EPA + Nano-curcumin supplements, the patients experienced a statistically significant reduction in insulin levels in their blood [MD: -1.44 (-2.70, -0.17)]. This decrease was significantly greater than the changes observed in the placebo group [MD: -0.63 (-1.97, 0.69)]. The EPA + Nano-curcumin group also showed a significant decrease in High-Sensitivity C-Reactive Protein (hs-CRP) levels compared to the placebo group (p < 0.05). Additionally, the EPA + Nano-curcumin group had a significant increase in Total Antioxidant Capacity (TAC) levels compared to the placebo group (p < 0.01). However, there were no significant differences in Fasting Blood Sugar (FBS), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, Quantitative Insulin Sensitivity Check Index (QUICKI), or Hemoglobin A1c (HbA1C) levels between the four groups (all p > 0.05). There were significant differences between the Nano-curcumin and EPA groups [MD: -17.02 (-32.99, -1.05)], and between the Nano-curcumin and control groups [MD: -20.76 (-36.73, -4.79)] in terms of lowering the serum cholesterol level. The difference in Triglycerides (TG) serum levels between the EPA + Nano-curcumin and placebo groups were not statistically significant (p = 0.093). The Nano-curcumin group showed significant decreases in Low-Density Lipoprotein (LDL) levels compared to the EPA group [MD: -20.12 (-36.90, -3.34)] and the control group [MD: -20.79 (-37.57, -4.01)]. There was a near-to-significant difference in High-Density Lipoprotein (HDL) serum levels between the EPA + Nano-curcumin and EPA groups (p = 0.056). Finally, there were significant differences in the decrease of serum Vascular Endothelial Growth Factor (VEGF) levels between the EPA and Nano-curcumin groups [MD: -127.50 (-247.91, -7.09)], the EPA and placebo groups [MD: 126.25 (5.83, 246.66)], the EPA + Nano-curcumin and Nano-curcumin groups [MD: -122.76 (-243.17, -2.35)], and the EPA + Nano- curcumin and placebo groups [MD: 121.50 (1.09, 241.92)]. The findings of the present study suggest that 12-week supplementation with EPA and Nano-curcumin may positively impact inflammation, oxidative stress, and metabolic parameters in patients with diabetes. The supplementation of EPA and Nano-curcumin may be a potential intervention to manage diabetes and reduce the risk of complications associated with diabetes. However, further research is needed to validate the study's findings and establish the long-term effects of EPA and Nano-curcumin supplementation in patients with diabetes.

Microneedle combined with iontophoresis and electroporation for assisted transdermal delivery of goniothalamus macrophyllus for enhancement sonophotodynamic activated cancer therapy

The underlying study was carried out aiming at transdermal drug delivery (TDD) of Goniothalamus macrophyllus as sono-photo-sensitizer (SPS) using microneedle (MN) arrays with iontophoresis (MN-IP), electroporation (MN-EP) in conjunction with applying photodynamic therapy (PDT), sonodynamic therapy (SDT) and sono-photodynamic therapy (SPDT) as an up-to-date activated cancer treatment modality. Study was conducted on 120 male Swiss Albino mice, inoculated with Ehrlich ascites carcinoma (EAC) divided into 9 groups. We employed three different arrays of MN electrodes were used (parallel, triangular, and circular), EP, IP with different volts (6, 9, 12 V), an infrared laser and an ultrasound (pulsed and continuous wave) as our two energy sources. Results revealed that parallel 6 V TDD@MN@IP@EP can be used as effective delivery system for G. macrophyllus from skin directly to target EAC cells. In addition MN@IP@EP@TDD G. macrophyllus is a potential SPS for SPDT treatment of EAC. With respect to normal control mice and as opposed to the EAC untreated control mice, MN@EP@IP TDD G. macrophyllus in the laser, ultrasound, and combination activated groups showed a significant increase in the antioxidant markers TAC level and the GST, GR, Catalase, and SOD activities, while decrease in lipid peroxidation oxidative stress parameter MDA levels. In addition significantly increased apoptotic genes expressions (p53, caspase (3, 9), Bax, and TNF alpha) and on the other hand decreased anti- apoptotic (Bcl-2) and angiogenic (VEGF) genes expressions. Moreover significantly ameliorate liver and kidney function decreasing ALT, AST, urea and creatinine respectively. Furthermore MN@IP@EP@TDD G. macrophyllus combined with SPDT was very effective at reducing the growth of tumors and even causing cell death according to microscopic H&E stain results. This process may be related to a sono- and/or photochemical activation mechanism. According to the findings, MN@IP@EP@TDD G. macrophyllus has a lot of potential as a novel, efficient delivery method that in combination with infrared laser and ultrasound activation SPDT demonstrated promising anticancer impact for treating cancer.

Advancements in stress‐based multiaxial fatigue prediction: A data‐driven approach and a new criterion

AbstractA highly accurate iteration of the Liu &amp; Zenner multiaxial fatigue criterion is presented and validated against the FatLim dataset. The proposed criterion modifies the mean stress parameters of the original criterion while keeping the amplitude parameters unchanged. The investigation of the best‐performing stress amplitude parameters revealed that existing multiaxial fatigue criteria that rely on dimensional weight parameters exhibit a notable prediction bias. This bias leads to inaccurate fatigue assessments. The paper sheds light on the extent of this bias and its implications for common engineering practices. By introducing the refined criterion, the study addresses these limitations and provides a more reliable framework for multiaxial fatigue analysis. The comprehensive validation against the FatLim dataset demonstrates the superiority of the proposed criterion in accurately predicting fatigue behavior under diverse loading conditions. The findings underscore the significance of considering both amplitude and mean stress parameters in multiaxial fatigue criteria, offering valuable insights for enhancing the accuracy of fatigue assessments in engineering applications.

Discovery of a new class of potent pyrrolo[3,4-c]quinoline-1,3-diones based inhibitors of human dihydroorotate dehydrogenase: Synthesis, pharmacological and toxicological evaluation

Twenty N-substituted pyrrolo[3,4-c]quinoline-1,3-diones 3a-t were synthesized by a cyclization reaction of Pfitzinger's quinoline ester precursor with the selected aromatic, heteroaromatic and aliphatic amines. The structures of all derivatives were confirmed by IR, 1H NMR, 13C NMR and HRMS spectra, while their purity was determined using HPLC techniques. Almost all compounds were identified as a new class ofpotent inhibitors against hDHODH among which 3a and 3 t were the most active ones with the same IC50 values of 0.11 μM, about seven times better than reference drug leflunomide. These two derivatives also exhibited very low cytotoxic effects toward healthy HaCaT cells and the optimal lipophilic properties with logP value of 1.12 and 2.07 respectively, obtained experimentally at physiological pH. We further evaluated the comparative differences in toxicological impact of the three most active compounds 3a, 3n and 3 t and reference drug leflunomide. The rats were divided into five groups and were treated intraperitoneally, control group (group I) with a single dose of leflunomide (20 mg/kg) group II and the other three groups, III, IV and V were treated with 3a, 3n and 3 t (20 mg/kg bw) separately. The investigation was performed in liver, kidney and blood by examining serum biochemical parameters and parameters of oxidative stress.

AI-Based Design With Data Trimming for Hybrid Phase Shift Modulation for Minimum-Current-Stress Dual Active Bridge Converter

Dual active bridge (DAB) topology has been recognized as the key circuit for the next generation of high-frequency-link power conversion systems. In order to realize desired operating performance, DAB modulation strategies need to be selected carefully. Different modulation strategies have been considered and combined into a hybrid one, which is able to fully optimize performance. However, to develop a hybrid modulation strategy, the conventional methods including harmonic model and piecewise model have difficulty in balancing modeling accuracy and manpower burden. Although recent data-driven modulation approaches can automate the design process, the accuracy of data-driven models decreases nontrivially with the existence of outliers and without sufficient data. Hence, to alleviate human-dependence and improve modeling accuracy, this paper proposes an AI-based design with data trimming (AI-DT) for hybrid phase shift modulation. Two two-degree-of-freedom modulation strategies are considered for the sake of optimal current stress performance. AI-DT firstly adopts the one-class support vector machine (SVM) to exclude outliers. Second, the state-of-the-art extreme gradient boosting (XGBoost), which is insensitive to training data size, is adopted to build data-driven current stress models for the DAB converter. After that, differential evolution (DE) algorithm helps to choose modulation strategy and optimize modulation parameters for optimal current stress. Generally, the proposed AI-DT is developed in an automated fashion, which largely relieves manual computational complexity while exhibiting satisfactory modulation accuracy. The effectiveness of the proposed AI-DT approach has been experimentally verified with a 1kW hardware prototype, realizing optimal current stress under full operating conditions with more than 96.5% as peak efficiency.

Thermal Fracture Simulation in Depleted Gas Field Carbon Capture and Storage: Implications for Injectivity and Flow Assurance

Summary CO2 injection into depleted gas fields causes long-term cooling of the reservoir. Therefore, even if injection pressure stays below the fracture initiation pressure, the cooled volume still creates an extensive stress disturbance that can induce the propagation of large fractures over time. The enhanced injectivity after the onset of this thermal fracturing might jeopardize injection operations due to the risk of hydrate plugging in the injection well caused by the combination of low pressure and low temperature, and large fractures may also increase the risk of loss of containment. Modeling the fracture evolution provides an estimate of the magnitude and timing of these effects. In this study, commercial compositional reservoir simulation software capable of modeling the physical phenomena associated with CO2 injection into depleted natural gas reservoirs has been used. These encompass CO2 mixing with natural gas, water vaporization, thermal effects, and geomechanics. The finite-element geomechanics module used “two-way” coupling, which computes pressure and temperature in the flow simulation module, transmits this information to the geomechanics module to update stress and strain parameters, and uses these parameters to adjust porosity and permeability, thereby enhancing the accuracy and reliability of the overall simulation results. The thermal fracture opening is simulated as increased permeability in the fracture domain by using a fracturing criterion based on the effective stress. The fracture simulations were developed in close relation with flow assurance modeling to determine the operational windows that avoid hydrate formation while maintaining the required injection target. Unlike matrix injection, thermal fracturing shows a substantial reduction in injection bottomhole pressure (BHP), reaching 26 000 kPa (260 bar) in a specific scenario. These findings underscore the crucial consideration of cooling effects and thermal fracturing in carbon capture and storage (CCS) operations, particularly in flow assurance studies where well injectivity significantly influences overall outcomes. Due to the intense cooling-induced stress reduction, thermal fractures may propagate uncontrollably, potentially reaching faults within the reservoir. Temperature distributions along boundary faults may differ markedly from matrix flow conditions, highlighting the need to incorporate these effects into geomechanical studies to mitigate risks associated with fault stability during cooling processes.

Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress.

Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 μg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.