Sandwich-type electrochemical immunosensing of CA125 by using nanoribbon-like Ti3C2Tx MXenes and toluidine blue/UIO-66-NH2.

CA125 (carbohydrate antigen 125) is an important biomarker of ovarian cancer, so developing effective method for its detection is of great significance. In the present work, a novel sandwich-like electrochemical immunosensor (STEM) of CA125 was constructed by preparing nanoribbon-like Ti3C2Tx MXenes (Ti3C2TxNR) to immobilize primary antibody (PAb) of CA125 and UIO-66-NH2 MOFs structure to immobilize second antibody (SAb) and electroactive toluidine blue (Tb) probe. In this designed STEM assay, the as-prepared Ti3C2TxNR nanohybrid offers the advantages in large surface area and conductivity as carrier, and UIO-66-NH2 provided an ideal platform to accommodate SAb and a large number of Tb molecules as signal amplifier. In the presence of CA125, the peak currents of Tb from the formed STEM structure increase with the increase of CA125 level. After optimizing the related control conditions, a wide linear range (0.2-150.0 U mL-1) and a very low detection limit (0.05 U mL-1) of CA125 were achieved. It's thus expected the developed STEM strategy has important applications for the detection of CA125.

USP36 plays an oncogenic role in colorectal cancer cells.

Cancer stem cells (CSCs) have emerged as crucial contributors to tumor relapse and chemoresistance, making them promising targets for treating cancers like colorectal cancer (CRC). However, the mechanisms governing CSC maintenance in CRC remain poorly characterized. In this study, we investigated the potential role of ubiquitin-specific protease 36 (USP36) in CRC. Our bioinformatic analysis revealed a significant upregulation of USP36 expression in CRC, and high USP36 levels were associated with poor prognosis in CRC patients. Furthermore, we observed an increase in USP36 expression in CRC cell lines. Knockdown of USP36 resulted in reduced viability, cell cycle arrest, increased apoptosis, and impaired migration and invasion in CRC cells. Additionally, the colony formation and sphere formation ability, as well as the expression of stem cell markers and pluripotent transcription factors, were substantially reduced in USP36-deficient CRC cells. These findings emphasize the role of USP36 as an oncogene in CRC, highlighting its potential as a therapeutic target for the treatment of CRC.

High expression of DARS2 indicates poor prognosis in lung adenocarcinoma.

BACKGROUND: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated. METHODS: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro. RESULTS: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result. CONCLUSION: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.

In vitro and in vivo Effect of Antimicrobial Agent Combinations Against Carbapenem-Resistant Klebsiella pneumoniae with Different Resistance Mechanisms in China.

OBJECTIVE: This study aimed to evaluate the in vitro and in vivo effects of different combinations of antimicrobial agents against carbapenemase-producing and non-producing Klebsiella pneumoniae from China. METHODS: A checkerboard assay of meropenem (MEM), amikacin (AK), tigecycline (TGC), colistin (COL) and their combinations was carried out against 58 clinical carbapenem-resistant K. pneumoniae (CRKp) isolates, including 11 carbapenemase-non-producing K. pneumoniae isolates and 21 isolates producing KPC-2 enzyme, 11 NDM-1, 13 IMP, one VIM-1 and one OXA-48. The checkerboard assay was analyzed by the fractional inhibitory concentration index (FICI). A time-kill assay and Galleria mellonella infection model were conducted to evaluate the in vitro and in vivo effects of the four drugs alone and in combination. RESULTS: In the checkerboard assay, TGC+AK and MEM+AK combinations showed the highest synergistic effect against KPC-2 and NDM-1 carbapenemase-producing isolates, with synergy+partial synergy (defined as FICI <1) rates of 76.2% and 71.4% against KPC-2 producers, and 54.5% and 81.8% against NDM-1 producers. TGC+AK and MEM+COL combinations showed the highest rate of synergistic effect against IMP-producing isolates. Against carbapenemase-non-producing isolates, TGC+COL and TGC+AK combinations showed the highest rate of synergy effect (63.6% and 54.5%). MEM+AK showed a synergistic effect against one VIM-1 producer (FICI=0.31) and an additivite effect (FICI=1) against one OXA-48 producer. In the time-kill assay, COL+AK, COL+TGC, COL+MEM and AK+TGC showed good synergistic effects against the KPC-2-producing isolate D16. COL+MEM and COL+TGC combinations showed good effects against the NDM-1-producing isolate L13 and IMP-4-producing isolate L34. Against the carbapenemase-non-producing isolate Y105, MEM+TGC and COL+AK showed high synergistic effects, with log10CFU/mL decreases of 6.2 and 5.5 compared to the most active single drug. In the G. mellonella survival assay, MEM-based combinations had relatively high survival rates, especially when combined with colistin, against KPC-2 producers (90% survival rate) and with amikacin against metallo-beta-lactamase producers (95-100% survival rate). CONCLUSION: Our study suggests that different antimicrobial agent combinations should be considered against CRKp infections with different resistance mechanisms.

Dynamic analysis of pulmonary computed tomography (CT) characteristics in cured coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: To retrospectively analyze the pulmonary computed tomography (CT) characteristics and dynamic changes in the lungs of cured coronavirus disease 2019 (COVID-19) patients at discharge and reexamination. METHODS: A total of 155 cured COVID-19 patients admitted to designated hospitals in Yunnan Province, China, from February 1, 2020, to March 20, 2020, were included. All patients underwent pulmonary CT at discharge and at 2 weeks after discharge (during reexamination at hospital). A retrospective analysis was performed using these two pulmonary CT scans of the cured patients to observe changes in the number, distribution, morphology, and density of lesions. RESULTS: At discharge, the lung CT images of 15 cured patients showed no obvious lesions, while those of the remaining 140 patients showed different degrees of residual lesions. Patients with moderate disease mostly had multiple pulmonary lesions, mainly in the lower lobes of both lungs. At reexamination, the lung lesions in the patients with moderate disease had significantly improved (P<0.05), and the lung lesions in the patients with severe disease had partially improved, especially in patients with multi-lobe involvement (χ 2 =3.956, P<0.05). At reexamination, the lung lesions of patients with severe disease did not show significant changes (P>0.05). CONCLUSIONS: The pulmonary CT manifestations of cured COVID-19 patients had certain characteristics and variation patterns, providing a reference for the clinical evaluation of treatment efficacy and prognosis of patients.

Endogenous SARI exerts oncogenic functions in human K562 leukemia cells by targeting the PI3K/Akt/mTOR and NF-κB signaling pathways.

Suppressor of activator protein-1, regulated by interferon (SARI), is a novel basic leucine zipper containing type I IFN-inducible early response protein that plays an important regulatory role in a wide variety of tumors, including leukemia. However, the functional role of SARI in myeloid leukemia is not thoroughly understood. In this study, we discovered that knock-down of SARI expression suppressed cell growth and colony formation, inhibited invasion, enhanced imatinib (STI571)-mediated apoptosis, and induced G0/G1 and G2/M arrest in human K562 myeloid leukemia cells. Moreover, using immunoblotting, we provide evidence that silencing of SARI resulted in declined expression of cyclinD1 and cyclinA2, as well as down-regulation of mTOR, c-myc p-mTOR, p-PI3K (p85), p-Akt, p70-S6K, p-p70-S6K and NF-κB (p65) that involved in the PI3K/Akt/mTOR and NF-κB signaling pathways. Taken together, our results demonstrate that SARI functions as an oncogenic role in K562 myeloid leukemia cells through regulating the PI3K/Akt/mTOR and NF-κB signaling pathways.

MicroRNAs as a Novel Class of Diagnostic Biomarkers in Detection of Oral Carcinoma: a Meta-Analysis Study.

BACKGROUND: Recent studies have highlighted the potential diagnostic values of microRNAs (miRNA) in various cancers involving oral cancer. This meta-analysis sought to summarize the global diagnostic accuracy of miRNAs for patients with oral cancer (OC). METHODS: A systematic review of multiple databases was performed to obtain original studies fulfilling search criteria and the quality of studies was assessed by the QUADAS tool. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve. Influence analysis, meta-regression, and publication bias assay were all conducted using Stata 12.0 software. The trim-fill adjustment method was used to further assess the possible effect of publication bias. RESULTS: A total of 8 studies were included. The SROC analysis showed that miRNA profiling allowed for the discrimination between patients with high-risk oral lesions (OC or pre-cancer) and healthy donors, with a sensitivity of 0.84 (95% CI: 0.78-0.88) and specificity of 0.83 (95% CI: 0.78-0.87), corresponding to an area under curve (AUC) of 0.90. Our subgroup analyses suggested that miRNA signature harbored higher accuracy in diagnosing oral squamous cell carcinoma (OSCC) than pre-cancer lesions (AUC, sensitivity, and specificity of 0.90, 0.83, or 0.82, respectively). Moreover, stratified analyses revealed that parallel miRNA profiling, plasma- and Caucasian-based analyses all conferred promising accuracies for OC detection. The funnel plot assay manifested evidence of a publication bias. After the adjustment by the trim and fill method, the pooled adjusted efforts were slightly attenuated. CONCLUSIONS: MiRNA profiles hallmark a potential diagnostic value for detection of OC and potentially malignant disorders. Further studies should be performed to rigorously evaluate the diagnostic accuracy of miRNA profiling for OC.