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.

Post-transplant diabetes mellitus (PTDM) is a well-known solid organ transplant complication, which can be related to immunosuppressants, particularly tacrolimus. We report an unusual presentation of PTDM with diabetic ketoacidosis (DKA). This is unique as PTDM typically resembles Type 2 DM, whereas DKA is associated with Type 1 DM and has rarely been reported as a complication of tacrolimus. A 38-year-old African American male on LCP-tacrolimus presented four months post kidney transplant with vomiting, weakness, poor appetite, and polyuria. Labs demonstrated hyperglycemia, ketonuria, and high anion gap metabolic acidosis. He was nonobese and had no personal or family history of Type 2 DM. DKA was suspected to be secondary to tacrolimus-induced pancreatic beta cell damage worsened by supratherapeutic tacrolimus levels. Latent autoimmune diabetes in adults (LADA) was diagnosed when further testing showed insulinopenia, low C-peptide, and anti-glutamic acid decarboxylase (GAD) autoantibodies. He required 120-units of subcutaneous insulin daily. Our literature review revealed only 16 other tacrolimus-induced DKA cases. No cases reported anti-GAD positivity and most showed beta cell toxicity reversibility with tacrolimus tapering or substitution. Our patient was early post-transplant with leukocytopenia, so tacrolimus was not exchanged. This unusual PTDM case may have resulted from both autoimmune and tacrolimus-induced beta cell destruction. Physicians should be aware of new onset LADA post-transplantation and tacrolimus toxicity leading to DKA, even in patients without traditional risk factors. Anti-GAD antibody screening in patients on tacrolimus who develop PTDM may identify patients less likely to recover beta cell function with immunosuppression augmentation which requires careful monitoring.

Background: Circular RNAs (circRNAs) are involved in tumorigenesis and the progression of cancer through various pathways. However, the detailed regulatory mechanisms of circRNAs in cervical cancer are not fully understood. The present study was designed to explore the biological functions and potential mechanisms of circCLIP2 (has_circ_0001717) in cervical cancer.

Methods: The expression profiles of circRNAs in cancerous and adjacent normal tissues of cervical cancer patients were examined using RNA sequencing. Gain- and loss-of-function experiments were carried out to determine the biological functions of circCLIP2 in the proliferation, invasion, migration and apoptosis of cervical cancer cells. qRT-PCR was also used to evaluate the expression of circCLIP2, miR-361-3p and STAT2 in cervical cancer cells. The protein levels of STAT2 were determined by western blotting.

Results: CircCLIP2 was identified as the most down-regulated molecule in the cancerous tissues of cervical cancer patients compared to the adjacent normal tissues. Moreover, the levels of circCLIP2 was decreased in cervical cancer patients with metastasis and advanced tumour stage, and patients with high-circCLIP2-expression exhibited poorer survival rate. In addition, over-expression of circCLIP2 suppressed the proliferation, invasion and migration of cervical cancer cells, whereas cell apoptosis was enhanced. Moreover, down-regulated circCLIP2 functioned as the sponge of miR-361-3p, which reduced the expression of STAT2. Furthermore, knockdown of STAT2 inhibited the expression of circCLIP2 at the transcriptional level.

Conclusion: The circCLIP2/miR-361-3p/STAT2 signalling could mediate the progression of cervical cancer. CircCLIP2 may become a novel target for the diagnosis and treatment of cervical cancer.