The American journal of the medical sciences最新文献

Background: Ischemia-reperfusion injury (IRI) is a common pathophysiological mechanism of acute kidney injury (AKI). There is an urgent need for a more comprehensive analysis of its underlying mechanisms.

Materials and methods: The RNA-sequencing dataset GSE153625 was used to examine differentially expressed genes (DEGs) of kidney tissues in IRI-AKI mice compared with sham mice. We used 10 algorithms provided by cytohubba plugin and four external datasets (GSE192532, GSE52004, GSE98622, and GSE185383) to screen for hub genes. The IRI-AKI mouse model with different reperfusion times was established to validate the expression of hub gene in the kidneys. HK-2 cells were cultured in vitro under hypoxia/reoxygenation (H/R) conditions, via transfection with si-LIF or supplementation with the LIF protein to explore the function of the LIF gene.

Results: We screened a total of 1,540 DEGs in the IRI group compared with the sham group and identified that the LIF hub gene may play potential roles in IRI-AKI. LIF was markedly upregulated in the kidney tissues of IRI-AKI mice, as well as in HK-2 cells grown under H/R conditions. The knockdown of LIF aggravated apoptosis and oxidative stress (OS) injury under H/R conditions. Administration of the LIF protein rescued the effects of si-LIF, alleviating cellular apoptosis and OS.

Conclusion: These findings indicate an important role of the LIF gene in term of regulating apoptosis and OS in the early phases of IRI-AKI. Targeting LIF may therefore represent a promising therapeutic strategy for IRI-AKI.

Background: Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer (BC). Some potential molecular targets have been identified, and miR-105-5p was found to be abnormally expressed in TNBC tissues.

Objective: The objective of this study was to probe the effect of miR-105-5p on TNBC via FOXG1/HDAC2-mediated acetylation.

Methods: An animal model of TNBC was established by injecting BC cells into the axillary area of nude mice. The levels of miR-105-5p, FOXG1, HDAC2, Bcl-2, Bax, and Ki67 were detected via RT‒qPCR, Western blotting and immunohistochemistry. Flow cytometry, CCK-8, Transwell and colony formation assays were used to measure apoptosis, proliferation and migration, respectively. Total histone acetylation levels were measured by ELISA. The binding of FOXG1 to HDAC2 was detected by co-immunoprecipitation. The binding relationship between miR-105-5p and FOXG1 was verified using a dual-luciferase reporter gene assay.

Results: In this study, miR-105-5p and HDAC2 were highly expressed in the MDA-MB-231 and BT-549 BC cell lines, whereas FOXG1 was expressed at low levels. The inhibition of miR-105-5p inhibited the proliferation and migration of MDA-MB-231 and BT-549 cells and promoted their apoptosis. Bioinformatics analysis revealed that miR-105-5p and FOXG1 had a negative targeting regulatory relationship. FOXG1 overexpression had a similar effect on cancer cells as the inhibition of miR-105-5p. Moreover, experiments revealed that FOXG1 and HDAC2 could bind to each other and that HDAC2 overexpression or treatment with the histone acetyltransferase inhibitor Garcinol weakened the effect of FOXG1 overexpression. In addition, FOXG1 knockdown inhibited the effect of the miR-105-5p inhibitor, while Garcinol treatment further enhanced the effect of FOXG1 knockdown, inhibited histone acetylation, promoted the proliferation and migration of cancer cells, and inhibited apoptosis. Moreover, the in vivo results confirmed the in vitro results.

Conclusion: miR-105-5p promotes HDAC2 expression by reducing FOXG1, inhibits histone acetylation, and aggravates the malignant biological behavior of TNBC cells.

Rationale: Observations from our clinical practice indicate a notable occurrence of pleural complications post-percutaneous renal cryoablation (PRC).

Objective: To identify the incidence of pleural complications following PRC and potential risk factors associated with post-procedural pleural complications.

Materials and methods: This was a retrospective cohort analysis of patients undergoing PRC at two tertiary hospital systems between 2016 and 2022. Patient characteristics, radiological and clinical data, and procedure techniques were collected in a database to identify potential risk factors.

Results: A total of 285 patients were identified who underwent 312 PRC procedures during the specified inclusion period. Among these, 10 procedures (3.2%) led to pleural complications, all manifesting as pleural effusions. Of these complications, 3 patients (1%) required pleural drainage. Factors associated with an increased risk of pleural complications included a larger mean tumor size (4.3 cm vs 2.7 cm, P = <0.001), cryoprobe applicator entry at the T10-T11 level as opposed to lower sites (P = 0.029), and a higher median number of cryoprobe applicators employed (3.5 vs 2.0, P = 0.001). Moreover, individuals who experienced pleural complications had a longer median hospital stay (4.0 vs 0, P≤0.001) and a higher rate of blood transfusions (40% vs 0.7%, P≤0.001).

Conclusion: Pleural complications from percutaneous renal cryoablation are rare. To further reduce the risk, higher insertion points (above T12) and utilizing more than two cryoprobe applicators should be avoided when feasible. Pleural complications in patients with new respiratory symptoms after PRC should be considered.

Background: Circular RNAs (circRNAs) belong to a family of covalently closed single-stranded RNAs that have been implicated in cancer progression. Previous studies have reported that hsa_circ_0087784 was abnormally expressed in breast cancer. However, the role of hsa_circ_0087784 in non-small cell lung cancer (NSCLC) is unknown.

Methods: Here, we used RT-qPCR and FISH to examine hsa_circ_0087784 expression in NSCLC cells and tissue samples. The dual-luciferase reporter assay was used to identify downstream targets of hsa_circ_0087784. Transwell migration, 5-ethynyl-2´-deoxyuridine, and CCK-8 assays were used to examine migration and proliferation. Tumorigenesis and metastasis assays were used to determine the role of hsa_circ_0087784 in NSCLC progression in a mouse tumor xenograft model in vivo.

Results: We found that hsa_circ_0087784 was expressed at significantly high levels in NSCLC tissue samples and cell lines. Downregulation of hsa_circ_0087784 suppressed NSCLC cellular proliferation, as well as migration. Our dual-luciferase reporter assay revealed that miR-576-5p and CDCA4 were downstream targets of hsa_circ_0087784. CDCA4 overexpression or miR-576-5p suppression reversed the effects of hsa_circ_0087784 silencing on NSCLC cell migration, and EMT-related protein expression levels.

Conclusion: Our findings suggested that downregulation of hsa_circ_0087784 inhibited NSCLC metastasis and progression through the regulation of CDCA4 expression and miR-576-5psponging.

Background: Although cystic fibrosis (CF) is widely considered a lung disease, the prevalence of CF-specific gastrointestinal symptoms and diseases has continued to rise. Peptic ulcer disease (PUD) has not been well-studied among people with CF (PwCF) and may be a common cause of abdominal symptoms. In PwCF, impaired bicarbonate secretion and unbuffered gastric acid production have been attributed to the development of ulcers, although ulcers remain uncommon. The objective of this study was to evaluate the prevalence of PUD in PwCF and assess for possible contributing factors.

Methods: This study utilized the National Inpatient Sample (NIS) database. All patients 18 years or older with CF were identified from 2014 to 2019. Relevant patient characteristics and procedures were identified using ICD-9 and ICD-10 codes. Linear trend, bivariate analyses, and multiple regression analysis were performed. The outcomes of interest were peptic ulcer disease, pancreatic insufficiency, and nonalcoholic steatohepatitis or NASH. All analyses accounted for complex sampling scheme of the NIS.

Results: The total prevalence of PwCF in the National Inpatient Sample (NIS) database was 0.08%, and the number was stable year to year from 2014 to 2019. Hispanic patients were more likely to be diagnosed with PUD than other white (aOR 1.802 [1.311,2.476]). Multiple regression analysis indicated that PUD in PwCF was strongly associated with a diagnosis of NASH (aOR 2.421[1.197, 4.898]). PUD patients were less likely to have pancreatic insufficiency compared to the non-PUD group (aOR 0.583 [0.455, 0.745]).

Conclusion: Although cystic fibrosis has been historically known as a disease of childhood, advancements in therapy have led to prolonged life expectancy and higher prevalence for cystic fibrosis-related digestive diseases. This study revealed a low prevalence of PUD in PwCF. Hispanics and those with NASH are more likely to develop peptic ulcers.

Background: Current guidelines lack clarity about the optimal duration of octreotide therapy for patients with esophageal variceal hemorrhage (EVH). To address this lack of evidence, we conducted a randomized clinical trial (RCT) of 24-hours versus 72-hours continuous infusion of octreotide for patients with EVH.

Methods: This multi-center, prospective RCT (NCT03624517), randomized patients with EVH to 24-hour versus 72-hour infusion of octreotide. Patients were required to undergo esophageal variceal band ligation prior to enrollment. The primary endpoint was rebleeding rate at 72 hours. The study was terminated early due to an inability to recruit during and after the COVID-19 epidemic.

Results: For patients randomized to 72-hours (n = 19) of octreotide vs 24-hours (n = 15), there were no differences in the need for transfusion, average pRBC units transfused per patient (3 units vs 2 units), infection (5% vs 0%), mechanical ventilation (11% vs 7%), or the need for vasopressors (5% vs 3%), respectively (none of these differences were statistically significantly different). There were 2 re-bleeding events in the 72-hour group (11%), and no re-bleeding events in the 24-hour group (p = 0.49). 8/15 of patients receiving 24 hours of octreotide were discharged at or before hospital day 3 while none in the 72-hour group was discharged before day 3 (p < 0.001). There was one death (in the 72-hour group) within 30 days.

Conclusions: A 24-hour infusion is non-inferior to a 72-hour infusion of octreotide for prevention of re-bleeding in patients with EVH. We propose that shortened octreotide duration may help reduce hospital stay and related costs in these patients.

Background: Cisplatin-based chemoresistance is major obstacle for breast cancer (BC) including Triple-negative breast cancer (TNBC). SIRT7 is reportedly involved in the progression of BC, the underlining mechanism in Cisplatin-based chemoresistance in BC remains unclear. This work is to elucidate effects of SIRT7 on cisplatin resistance in breast cancer regulated by miR-152-3p.

Methods: The RNA expression of SIRT7 and miRNAs in breast cancer were available from TCGA database. SIRT7-targeted miRNAs were predicted by TargetScan, miRanda, miRDB databases. The association of SIRT7 expression with predicted miRNA was validated by Luciferase assay. Cell apoptosis was determined by Flow cytometry. Cell viability was detected by CCK8 assay. The mRNA expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Protein expression was determined by Western blotting assay.

Results: SIRT7 mRNA levels were dramatically enhanced in BC tissues compared to para-carcinoma tissues, also increased in BC patients with Cisplatin-based chemotherapy containing TNBC compared with those without. The increase of SIRT7 expression was obviously relevant to shorter survive time of them. Importantly, SIRT7 inhibition facilitated Cisplatin-induced cell apoptosis of TNBC (MDA-MB-231 and MDA-MB-468) and non- TNBC (MCF-7). Notably, miR-152-3p was predicted as a negative regulator of SIRT7 by overlapping downregulated miRNAs in BC patients treated with Cisplatin-based chemotherapy and miRNAs to target SIRT7. Mechanically, miR-152-3p blocked SIRT7 to stimulate an activation of FOXO3a, cleaved PARP1 and Caspase-3, sensitizing Cisplatin-induced apoptosis of BC cells.

Conclusions: Inhibition of SIRT7 by miR-152-3p may be a promising strategy against the resistance to cisplatin-based chemotherapy in BC containing TNBC.

Interstitial lung disease (ILD) represents a heterogeneous group of disorders characterized by inflammation and fibrosis of the pulmonary interstitium. Risk factors for ILD include various environmental exposures and identifying specific exposures offers a point of intervention for preventing disease. Here, we present several cases of patients who worked in the dry-cleaning business and have ILD or abnormalities consistent with early ILD on chest CT imaging. While this report does not attempt to establish causality, we hypothesize that exposure to the industrial solvent tetrachloroethylene may serve as a contributing factor given its links to epithelial injury, inflammation, redox imbalance and apoptosis. We hope that this report serves to not only inform readers of this possible connection between dry cleaning and ILD but also lay the foundation for additional studies examining the effects of tetrachloroethylene on the lung.