Clinical Features and Influencing Factors of Acute Kidney Injury in Patients with Intestinal Obstruction: A Meta-Analysis.

Background: Intestinal obstruction frequently leads to acute kidney injury (AKI), yet understanding the specific clinical features and influencing factors in these patients remains limited. Objective: This study aims to comprehensively evaluate the clinical features and affecting factors of AKI in patients with intestinal obstruction. Methods: We conducted a systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service platform, VIP, and China Biology Medicine Literature Database from 2010 to the present. Relevant literature addressing the clinical features or affecting factors of AKI in patients with intestinal obstruction was retrieved. The study group (SG) comprised patients with intestinal obstruction complicated by AKI, while the control group (CG) included patients without AKI after intestinal obstruction. Meta-analysis was performed to investigate the clinical features of both patient groups and funnel plots were employed to assess publication bias. Results: This study included 5 articles with a total of 7583 patients (1472 in the SG and 6111 in the CG). Meta-analysis results indicated a higher prevalence of hypertension (OR=1.80, 95% CI: 1.59-2.04, P < .00001), cardiovascular disease (OR=1.60, 95% CI: 1.06-2.41, P = .03), and diabetes (OR=1.61, 95% CI: 1.35-1.91, P < .00001) in both groups. Additionally, factors such as infection rate (OR=4.03, 95% CI: 2.10-7.73, P < .0001), age (OR=2.90, 95% CI: 1.07-7.90, P = .04), and BMI (OR=1.31, 95% CI: 1.15-1.48, P < .0001) significantly influenced AKI occurrence. No significant difference was observed in the history of pelvic surgery between both groups (OR=0.91, 95% CI: 0.53-1.55, P = .73). Funnel plot analysis suggested minimal publication bias. Conclusions: Age, BMI, hypertension, cardiovascular disease, diabetes mellitus, and infection emerge as primary influencing factors for AKI in patients with intestinal obstruction. Our findings advocate for early interventions to mitigate the global incidence of AKI in this patient population.

Neurofibromatosis type 1 with multiple gastrointestinal stromal tumors: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is characterized by café-au-lait patches on the skin and the presence of neurofibromas. Gastrointestinal stromal tumor (GIST) is the most common non-neurological tumor in NF1 patients. In NF1-associated GIST, KIT and PDGFRA mutations are frequently absent and imatinib is ineffective. Surgical resection is first-line treatment. CASE SUMMARY: A 56-year-old woman with NF1 was hospitalized because of an incidental pelvic mass. Physical examination was notable for multiple café-au-lait patches and numerous subcutaneous soft nodular masses of the skin of the head, face, trunk, and limbs. Her abdomen was soft and nontender. No masses were palpated. Digital rectal examination was unremarkable. Abdominal computed tomography was suspicious for GIST or solitary fibrous tumor. Laparoscopy was performed, which identified eight well-demarcated masses in the jejunum. All were resected and pathologically diagnosed as GISTs. The patient was discharged on day 7 after surgery without complications. No tumor recurrence was evident at the 6-mo follow-up. CONCLUSION: Laparoscopy is effective for both diagnosis and treatment of NF1-associated GIST.

Role of the MAPK pathway in human lung epithelial-like A549 cells apoptosis induced by paraquat.

This study aims to investigate the value of mitogen-activated protein kinases (MAPKs) for paraquat (PQ)-induced apoptosis in human lung epithelial-like A549 cells and the specific mechanism. A549 cell apoptosis were induced by PQ. These cells were divided into six groups: control group (cells were cultured in RPMI-1640 medium); SP600125 group (cells were preconditioned with SP600125); SB203580 group (cells were preconditioned with SB203580); PQ group (cells were treated with PQ); SP600125+PQ group (cells were preconditioned with SP600125 following PQ); SB203580+PQ group (cells were preconditioned with SB203580 following PQ). The cell survival rate, apoptosis rate, and activities of caspase-3 and -9 were detected. When compared with the control group, both SP600125 and SB203580 groups had no significant difference in the detected indicators. When compared with PQ group, the cells in both SP600125+PQ group and SB203580+PQ group had significantly increased viability and level of anti-apoptotic protein Bcl-2; and had decreased apoptotic rates, decreased levels of caspase-3 and -9, and decreased level of pro-apoptotic protein Bax. The ratio of p-JNK/JNK protein expression in the SP600125+PQ group significantly decreased, while the ratio of the p-P38/P38 protein expression in the SB203580+PQ group decreased. PQ induced A549 cell apoptosis through the MAPKs pathway.

Effect of endoplasmic reticulum calcium on paraquat­induced apoptosis of human lung type II alveolar epithelial A549 cells.

The present study aimed to explore the role of endoplasmic reticulum calcium (ER Ca2+) in the apoptosis of human lung type II alveolar epithelial A549 cells induced by paraquat (PQ) in vitro. PQ significantly elevated the intracellular Ca2+ concentration. Treatment with the Ca2+­ATPase inhibitor thapsigargin significantly increased PQ­induced cytotoxicity, elevated the intracellular level of Ca2+, and increased the apoptosis rate, the protein expression of glucose­regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), and the activities of caspase­7 and caspase­12 in PQ­treated cells. By contrast, treatment with heparin, an inositol 1,4,5­triphosphate receptor inhibitor, remarkably attenuated cytotoxicity and decreased the intracellular level of Ca2+, the apoptosis rate and the expression levels of GRP78, CHOP and Caspases. In conclusion, PQ impaired the regulating function of ER Ca2+ and resulted in an excessive increase of intracellular Ca2+. Therefore, influencing the Ca2+ signaling in the ER influenced the apoptosis of A549 cells via the ER stress pathway.

MnTMPyP inhibits paraquat-induced pulmonary epithelial-like cell injury by inhibiting oxidative stress.

OBJECTIVE: To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ)-induced lung alveolar epithelial-like cell injury. METHODS: Lung alveolar epithelial-like cells (A549) were pretreated with 10 µM MnTMPyP for 1.5 hr and then cultured with or without PQ (750 uM) for 24 hr. Cell survival was determined using the MTT assay. Apoptosis, mitochondrial transmembrane potential, reactive oxygen species (ROS) production, and Ca2+ levels were measured using flow cytometry. Glutathione reductase activity (GR activity) and caspase-3 activation were determined using spectrophotometry. Expression of the apoptosis proteins, Bcl-2 and Bax, and the endoplasmic reticulum (ER) stress proteins, glucose regulatory protein 78 (Grp78) and C/EBP homologous protein (CHOP), was measured using Western blot analysis. RESULTS: Cell viability, mitochondrial membrane potential, GR activity, and Bcl-2 expression were decreased, but apoptosis, ROS production, caspase-3 activity, cytoplasmic Ca2+ levels, and Bax, Grp78 and CHOP expression were all increased in the PQ group compared to the control group. There were no statistically significant changes in the MnTMPyP group. Cell viability, GR activity, mitochondrial membrane potential, and Bcl-2 protein expression were all increased, while apoptosis, ROS production, cytoplasmic Ca2+ levels, caspase-3 activity, and Bax, Grp78 and CHOP expression were all significantly reduced in the MnTMPyP group compared to PQ group. CONCLUSION: MnTMPyP effectively reduced PQ-induced lung epithelial-like cell injury, and the underlying mechanism is related to antagonism of PQ-induced oxidative stress.

Involvement of PINK1/Parkin-mediated mitophagy in paraquat- induced apoptosis in human lung epithelial-like A549 cells.

Paraquat (PQ) is one of the most popular herbicides and has been widely used all over the world over the past several decades. However, PQ exposure can cause multiple organ failure, especially acute lung injury in humans as well as in rodent animals. Mitochondrial dysfunction plays a crucial role in PQ-induced lung cell damage. Mitophagy, defined as the selective autophagic elimination process of mitochondria, is a significant mechanism controlling mitochondrial quality. In this study, we investigated PINK1/Parkin-mediated mitophagy activated in the process of the PQ-induced cell apoptosis by using human lung epithelial-like A549 cells. We showed that PQ inhibited cell viability and induced mitochondrial damage as well as cell apoptosis in A549 cells. During this process, PQ induced PINK1/Parkin-mediated mitophagy. Knocking down the expression of Parkin gene by the transient transfection of Parkin small interfering RNA mitigated PQ-induced mitophagy and worsened A549 cell apoptosis. On the contrary, overexpression of Parkin attenuated PQ-induced cell injury by promoting mitophagy. These results indicated PINK1/Parkin-mediated mitophagy played a protective role in PQ-induced A549 cell damage and provided a potential therapeutic strategy for enhancing mitophagy against PQ poisoning.

Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway.

Paraquat (PQ), as one of the most widely used herbicides in the world, can cause severe lung damage in humans and animals. This study investigated the underlying molecular mechanism of PQ-induced lung cell damage and the protective role of salubrinal. Human lung epithelial-like A549 cells were treated with PQ for 24h and were pre-incubated with salubrinal for 2h, followed by 500µM of PQ treatment. Silencing eIF2α gene of the A549 cells with siRNA interference method was conducted. Cell morphology, cell viability, apoptosis and caspase-3 activity were assessed by different assays accordingly thereafter. The expression of PERK, p-PERK, ATF6, c-ATF6, IRE1α, p-IRE1α, CHOP, GRP78, p-eIF2α and ß-actin was assayed by western blot. The data showed that PQ significantly reduced A549 cell viability, changed cell morphology, induced cell apoptosis and significantly upregulated the levels of GRP78, CHOP, p-PERK, c-ATF6 and p-IRE1α. However, 30µM salubrinal could attenuate the effects of PQ on damages to A549 cells through upregulating p-eIF2α. In contrast, knocking down eIF2α gene inhabited the effects of salubrinal. These results suggest that PQ-induced A549 cell apoptosis involved endoplasmic reticulum (ER) stress, specially the PERK-eIF2α pathway. Salubrinal attenuated A549 cells from PQ-induced damages through regulation of the PERK-eIF2α signaling.