Analysis of protein expression for hypoxia-inducible factor-1 (HIF-1), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) was performed via Western blotting. Employing reverse transcription-polymerase chain reaction (RT-PCR), the mRNA expressions of HIF-1, NLRP3, and interleukin-1 (IL-1) were assessed. Apoptotic renal cells were identified using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. By employing a transmission electron microscope, the morphological alterations in renal tubular epithelial cells and mitochondria were observed.
The ARDS model group displayed kidney oxidative stress and inflammatory responses, leading to a substantial increase in serum NGAL levels. Activation of the NF-κB/NLRP3 inflammasome pathway, augmented kidney tissue cell apoptosis, and renal tubular epithelial damage along with mitochondrial disruption observed by transmission electron microscopy, confirmed successful induction of kidney injury compared to the control group. The rats given curcumin experienced a significant decrease in the injury to renal tubular epithelial cells and mitochondria, along with a notable reduction in oxidative stress, the suppression of the NF-κB/NLRP3 inflammasome pathway, and a substantial reduction in the rate of kidney tissue cell apoptosis, reflecting a dose-dependent pattern. Compared with the ARDS model, the high-curcumin dose treatment markedly reduced serum NGAL and kidney tissue levels of MDA and ROS (NGAL: 13817 g/L vs. 29627 g/L, MDA: 11518 nmol/g vs. 30047 nmol/g, ROS: 7519 kU/L vs. 26015 kU/L; all P < 0.05).
The mRNA levels of NLRP3 in groups 290039 and 949187 differed substantially.
Comparing 207021 and 613132, the IL-1 mRNA (2) level is noteworthy.
A comparison of 143024 versus 395051 revealed a statistically significant difference (P < 0.05), along with a decrease in kidney tissue cell apoptosis rate from 436092% to 2775831% (P < 0.05), and a significant increase in superoxide dismutase (SOD) activity, with values of 64834 kU/g versus 43047 kU/g (P < 0.05).
In ARDS rats, curcumin's beneficial impact on kidney injury potentially stems from elevated SOD activity, reduction in oxidative stress, and inhibition of NF-κB/NLRP3 inflammasome activation.
Rats with ARDS exhibiting kidney injury may find curcumin beneficial, potentially due to elevated superoxide dismutase activity, reduction in oxidative stress, and inhibition of the NF-κB/NLRP3 inflammasome signaling complex.
To ascertain the prevalence and contributing factors of hypothermia in acute kidney injury (AKI) patients receiving continuous renal replacement therapy (CRRT), and to compare the impact of different heating approaches on the development of hypothermia in CRRT patients.
A prospective study design was employed. From January 2020 to December 2022, patients with acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) treatment, admitted to the critical care medicine department of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), were selected for this study. By way of a randomized numerical table, patients were grouped, specifically into a dialysate heating group and a reverse-piped heating group. To account for each patient's individual circumstance, the bedside physician customized treatment strategies and parameter settings for both groups. The dialysis solution's temperature was raised to 37 degrees Celsius by the dialysis heating group, utilizing the AsahiKASEI dialysis machine's heating panel. The Barkey blood heater from the Prismaflex CRRT system's reverse-piped heating group was responsible for heating the dialysis solution to a temperature of 41 degrees Celsius. A continuous monitoring process was then employed for the patient's temperature. A temperature below 36 degrees Celsius, or a decrease exceeding 1 degree Celsius from baseline core body temperature, was considered hypothermia. Examining both groups, a comparison was made concerning the frequency and duration of hypothermia. Within the context of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT), a binary multivariate logistic regression analysis was conducted to evaluate factors associated with hypothermia.
Seventy-three patients with AKI, undergoing CRRT, were recruited, comprising 37 in the dialysate heating cohort and 36 in the reverse-piped heating group. The dialysis heating group exhibited a significantly lower rate of hypothermia (405% [15/37]) compared to the reverse-piped heating group (694% [25/36]), with a statistically significant difference (P < 0.005). The hypothermia also emerged later in the dialysis heating group (540092 hours) than in the reverse-piped heating group (335092 hours), which was also statistically significant (P < 0.001). Hypothermic patients (n = 40) and non-hypothermic patients (n = 33) were compared based on the presence or absence of hypothermia. A univariate analysis of all parameters displayed a significant decrease in mean arterial pressure (MAP) in the hypothermic group. The statistical significance (P < 0.001) was observed with MAP values of 77451247 mmHg (1 mmHg = 0.133 kPa) for hypothermic patients and 94421451 mmHg for non-hypothermic patients, indicating shock and the administration of medium and high doses of vasoactive drugs (0.2-0.5 g/kg).
min
Patients receive a high dosage, greater than 0.5 grams per kilogram.
min
CRRT treatment significantly increased in the study group, a rise of 450% (18/40) patients compared to 61% (2/33) in the control group.
h
Analysis of 5150938 and 38421097 revealed significant differences (P < 0.05) in CRRT heating types. The hypothermia group displayed a strong preference for infusion line heating, comprising 625% of cases (25 out of 40), in contrast to the non-hypothermia group, where dialysate heating was the main method (667%, 22 of 33). This difference also demonstrated statistical significance (P < 0.05). A binary multivariate Logistic regression, with the given factors incorporated, linked shock (OR= 17633, 95%CI= 1487-209064), mid-to-high vasoactive drug doses (OR= 24320, 95%CI= 3076-192294), reverse-piped CRRT heating (OR= 13316, 95%CI= 1485-119377), and CRRT treatment dose (OR= 1130, 95%CI= 1020-1251) to hypothermia in AKI patients undergoing CRRT (all p < 0.005). MAP, conversely, was protective (OR= 0.922, 95%CI= 0.861-0.987, p < 0.005).
CRRT treatment for AKI patients often results in hypothermia, which can be considerably lessened by warming the CRRT treatment fluids. Risk factors for hypothermia during continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients include shock, the use of vasoactive drugs at medium and high dosages, the type of CRRT heating employed, and the treatment dose administered. A protective factor is identified in the mean arterial pressure (MAP).
A common observation in AKI patients undergoing CRRT is the occurrence of hypothermia, and this can be addressed by warming the CRRT treatment fluids. In acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT), shock, the use of medium and high doses of vasoactive drugs, the type of CRRT heating, and the CRRT treatment dose are all potential contributors to hypothermia risk. Mean arterial pressure (MAP), in contrast, acts as a protective factor.
To determine the effect of the phosphate and tension homology (PTEN) and its impact on PINK1/Parkin pathway activation in relation to hippocampal mitophagy and cognitive function in a mouse model of sepsis-associated encephalopathy (SAE), and understanding the associated mechanisms.
A total of 80 male C57BL/6J mice were randomly separated into groups of sixteen mice each, these groups consisting of Sham, cecal ligation puncture (CLP), PINK1 plasmid transfection pretreatment (p-PINK1+Sham, p-PINK1+CLP), empty vector plasmid transfection control (p-vector+CLP). To reproduce SAE models, mice in the CLP groups were subjected to CLP treatment. PGE2 supplier The mice in the Sham groups experienced only the operation of laparotomy. 24 hours before the surgical procedure, animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid via lateral ventricle injection, whereas mice in the p-vector+CLP group received the empty plasmid. Seven days after the CLP procedure, the Morris water maze experiment was performed. To analyze hippocampal tissues for pathological changes, a light microscope with hematoxylin-eosin (HE) staining was employed. Furthermore, transmission electron microscopy, employing uranyl acetate and lead citrate staining, allowed visualization of mitochondrial autophagy. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1) and microtubule-associated protein 1 light chain 3 (LC3) were quantified through Western blotting.
In the Morris water maze experiment, compared to the Sham group, CLP group mice demonstrated a prolonged escape latency, a reduced target quadrant residence time, and a decreased number of platform crossings during the 1-4 day period. A light microscopic examination of the mouse's hippocampal structure displayed an injured structure, with its neuronal cells arranged in a disordered manner and its nuclei exhibiting pyknosis. synthesis of biomarkers The bilayer or multilayer membrane structures enclosed swollen, round mitochondria, as determined by electron microscope observation. Research Animals & Accessories Significant differences were noted in hippocampal expression of PINK1, Parkin, Beclin1, the LC3II/LC3I ratio, IL-6, and IL-1 between the CLP group and the Sham group, with the CLP group exhibiting higher expression levels. This indicates that CLP-induced sepsis prompted an inflammatory response and stimulated PINK1/Parkin-mediated mitophagy. The p-PINK1+CLP group showed faster escape latencies, a greater proportion of time spent within the target quadrant, and a larger number of crossings compared with the CLP group from day 1 through day 4. Upon light microscopic examination of mice hippocampal structures, the neurons displayed a disorderly pattern, and the nuclei exhibited pyknosis, with the structures themselves exhibiting destruction.