Colchicine inhibits the proliferation and promotes the apoptosis of papillary thyroid carcinoma cells likely due to the inhibitory effect on HDAC1.

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target.

Higher serum ß2-microglobulin is a predictive biomarker for cognitive impairment in spinal cord injury.

Objective: Recent studies have suggested that high levels of ß2-microglobulin are linked to cognitive deterioration; however, it is unclear how this connects to spinal cord injury (SCI). This study sought to determine whether there was any association between cognitive decline and serum ß2-microglobulin levels in patients with SCI. Methods: A total of 96 patients with SCI and 56 healthy volunteers were enrolled as study participants. At the time of enrollment, specific baseline data including age, gender, triglycerides (TG), low-density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), smoking, and alcohol use were recorded. Each participant was assessed by a qualified physician using the Montreal cognitive assessment (MoCA) scale. Serum ß2-microglobulin levels were measured using an enzyme-linked immunosorbent assay (ELISA) reagent for ß2-microglobulin. Results: A total of 152 participants were enrolled, with 56 in the control group and 96 in the SCI group. There were no significant baseline data differences between the two groups (p > 0.05). The control group had a MoCA score of 27.4 ± 1.1 and the SCI group had a score of 24.3 ± 1.5, with the difference being significant (p < 0.05). The serum ELISA results revealed that the levels of ß2-microglobulin in the SCI group were considerably higher (p < 0.05) than those in the control group (2.08 ± 0.17 g/mL compared to 1.57 ± 0.11 g/mL). The serum ß2-microglobulin level was used to categorize the patients with SCI into four groups. As serum ß2-microglobulin levels increased, the MoCA score reduced (p < 0.05). After adjustment of baseline data, further regression analysis showed that serum ß2-microglobulin level remained an independent risk factor for post-SCI cognitive impairment. Conclusions: Patients with SCI had higher serum levels of ß2-microglobulin, which may be a biomarker for cognitive decline following SCI.

Serum neutrophil gelatinase-associated lipocalin as a potential biomarker for cognitive decline in spinal cord injury.

Objective: Neutrophil gelatinase-associated lipoprotein (NGAL), a protein encoded by the lipocalcin-2 (LCN2) gene, has been reported to be involved in multiple processes of innate immunity, but its relationship with spinal cord injury (SCI) remains unclear. This study set out to determine whether NGAL played a role in the development of cognitive impairment following SCI. Methods: At the Neck-Shoulder and Lumbocrural Pain Hospital, a total of 100 SCI patients and 72 controls were enrolled in the study through recruitment. Through questionnaires, baseline data on the participants' age, gender, education level, lifestyle choices (drinking and smoking) and underlying illnesses (hypertension, diabetes, coronary heart disease, and hyperlipidemia) were gathered. The individuals' cognitive performance was evaluated using the Montreal Cognitive Scale (MoCA), and their serum NGAL levels were discovered using ELISA. Results: The investigation included 72 controls and 100 SCI patients. The baseline data did not differ substantially between the two groups, however the SCI group's serum NGAL level was higher than the control group's (p < 0.05), and this elevated level was adversely connected with the MoCA score (p < 0.05). According to the results of the ROC analysis, NGAL had a sensitivity of 58.24% and a specificity of 86.72% for predicting cognitive impairment following SCI. Conclusions: The changes in serum NGAL level could serve as a biomarker for cognitive impairment in SCI patients, and this holds true even after taking in account several confounding variables.

Nutcracker syndrome: diagnosis and therapy.

Nutcracker syndrome (NCS) is an extrinsic compression of the left renal vein (LRV) by the superior mesenteric artery (SMA) anteriorly and aorta posteriorly resulting in renal vascular congestion manifesting as hematuria, proteinuria, orthostatic hypotension, pain, or even renal dysfunction. Long-standing venous compression can encourage collateral drainage pathways through gonadal and pelvic veins, which may explain reported symptom and syndrome overlap with pelvic congestion syndrome. Diagnosis can be challenging and variable, frequently involving a combination of ultrasound Doppler, cross-sectional, and invasive imaging. Often, intravascular pressure measurements are required to prove a renocaval pressure gradient to aid in a definitive diagnosis. Conservative management is appropriate, especially in children, who tend to outgrow the disorder. In the interim, medical management with angiotensin converting enzyme inhibitors (ACEIs) is a useful therapy to manage orthostatic hypotension in the pediatric population. In adults, invasive therapies are more frequently pursued. These are aimed at relieving the extrinsic compression on the LRV. The standard of care is renal vein transposition, with renal autotransplantation reserved for recalcitrant cases. Endovascular stenting is a less invasive option. Laparoscopic placement of an exovascular stent is a newer therapy intended to minimize trauma to the LRV. In this review, we will discuss the clinical manifestations, diagnostic criterion, imaging features, and conservative and surgical therapies for this condition.

Intravenous Antiplatelet Therapy Bridging in Patients Undergoing Cardiac or Non-Cardiac Surgery Following Percutaneous Coronary Intervention.

BACKGROUND: The effect of perioperative bridging therapy on risks of ischemic cardiac events and major bleeding complications in patients on dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains undefined. METHODS: We report on 60 consecutive patients between 2010 and 2017 who required cardiac (CS; n = 15) or non-cardiac (NCS; n = 45) surgeries following PCI at our institution. Short-acting intravenous (IV) antiplatelet (APT) bridging with eptifibatide, tirofiban and cangrelor were instituted after DAPT interruption. RESULTS: All patients were men with multiple atherosclerosis risk factors. An acute coronary syndrome indication (56.7%) was the most common PCI indication in the CS and NCS groups. Drug-eluting stents were used in 93.33% and 95.56% of the above groups, respectively. The median duration from PCI to CS and NCS were 11.17 and 18.25 months, respectively and 38.33% of all surgeries were performed within 6 months of the index PCI. Most patients were on background aspirin (83.33%) and clopidogrel (81.67%) and median duration of DAPT interruption was 7 days. Median duration of perioperative IV APT bridging was 3 days for CS and 5 days for NCS groups. In the CS group, two patients (13.33%) had non-fata myocardial infarction (MI), and four (26.67%) had clinically significant bleeding. No patients had perioperative stent thrombosis. In the NCS group, one patient (2.22%) had stent thrombosis; four (6.67%) had myocardial infarction, and five (11.11%) clinically significant bleeding. CONCLUSIONS: Despite using IV APT as bridging therapy during perioperative DAPT interruption in post-PCI patients, postoperative cardiac events and bleeding complications can still occur.

MicroRNA MultiTool: A Software for Identifying Modified and Unmodified Human microRNA Using Mass Spectrometry.

microRNA (miRNA) are short endogenous non-coding RNA that play a crucial role in post-transcriptional gene regulation and have been implicated in the initiation and progression of 160+ human diseases. Excellent analytical methods have been developed for the measurement of miRNA by mass spectrometry. However, interpretation of mass spectrometric data has been an incapacitating bottleneck in miRNA identification. This study details the development of MicroRNA MultiTool, a software for the identification of miRNA from mass spectrometric data. The software includes capabilities such as miRNA search and mass calculator, modified miRNA mass calculator, and miRNA fragment search. MicroRNA MultiTool bridges the gap between experimental data and identification of miRNA by providing a rapid means of mass spectrometric data interpretation.

Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells.

T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCRs). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. We introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8(+) T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen-inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high-affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high-affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications.