Prognosis prediction of procalcitonin within 24 h for acute diquat poisoning.

BACKGROUND: To explore the predictive value of procalcitonin (PCT) within 24 h after poisoning for prognosis of acute diquat poisoning. METHODS: This retrospective study included acute diquat poisoning patients in the Nanyang City Hospital between May 2017 and July 2021. RESULTS: Among the 45 patients included, 27 survived. The maximum PCT value within 24 h after poisoning was significantly higher in the non-survival patients [9.65 (2.63, 22.77) vs. 0.15 (0.10, 0.50) µg/mL, P < 0.001] compared to the survival patients. The area under the ROC curve (AUC) indicated that the maximum PCT value within 24 h had a good predictive value (AUC = 0.905, 95% CI: 0.808-1.000) compared to ingested quantity (AUC = 0.879, 95% CI: 0.776-0.981), serum creatinine (AUC = 0.776, 95% CI: 0.640-0.912), or APACHE II score (AUC = 0.778, 95% CI: 0.631-0.925). The predictive value of maximum PCT value within 24 h was comparable with blood lactate (AUC = 0.904, 95%CI: 0.807-1.000). CONCLUSIONS: The maximum PCT value within 24 h after poisoning might be a good predictor for the prognosis of patients with acute diquat poisoning.

Physapubescin B enhances the sensitivity of gastric cancer cells to trametinib by inhibiting the STAT3 signaling pathway.

Given the poor prognosis of unresectable advanced gastric cancer (GC), novel therapeutic strategies are needed. The mitogen-activated protein kinase (MAPK) signaling cascade, the most frequently activated pathway in GC, plays an important role in tumorigenesis and metastasis. The MAPK/extracellular signal-regulated kinase (ERK) pathway is an attractive therapeutic target for GC. In this study, trametinib, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, reduced the p-ERK level and significantly increased signal transducer and activator of transcription 3 (STAT3) phosphorylation in GC cells, resulting in reduced sensitivity to trametinib. Physapubescin B (PB), a steroidal compound extracted from the plant Physalis pubescens L., inhibited the proliferation and induced the apoptosis of GC cells by suppressing STAT3 phosphorylation. The combination of PB and trametinib suppressed the STAT3 phosphorylation induced by trametinib, and synergistically suppressed gastric tumor growth in vitro and in vivo. Together, these results indicate that inhibition of both MEK and STAT3 may be effective for patients with MAPK/ERK pathway-addicted GC.

Microchips for detection of exfoliated tumor cells in urine for identification of bladder cancer.

Bladder cancer (BC) is a common malignancy, and it accounts for one of the highest management costs among urogenital cancers. As a non-invasive method, urine cytology plays an important role in the detection of exfoliated tumor cells (ETCs) for early diagnosis of BC. However, urine cytology suffers from its low sensitivity and reliance on microscopic examination. To address this issue, an integrated filtration device was developed with a pore size of 5 µm that isolated and enriched ETCs from discarded urine samples, and then quantified ETCs using a microchip ELISA method. The results revealed that the number of urinary ETCs from BC patients (n = 35) was obviously higher than the number of ETCs from healthy donors (n = 20). The ROC curve showed that the integrated filtration microfluidic device had a sensitivity of 77.1% when the specificity was set at 90% in identifying BC patients. Thus, the integrated filtration device holds great potential for the screening of BC or the follow-up analysis of treatment efficacy in point-of-care (POC) settings.

Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing.

Cancer poses a great health threat to both developed and developing countries, and anti-cancer drugs are of important interest for improved clinical outcomes. Although tumor-on-a-chip technologies offer a feasible approach to screening drug toxicity, their capability to mimic the native tumor microenvironment (TME) is still limited. For better mimicry of the TME, we developed a biomimetic three-dimensional (3D) liver tumor-on-a-chip with the integration of essential components derived from decellularized liver matrix (DLM) with gelatin methacryloyl (GelMA) in a microfluidics-based 3D dynamic cell culture system. The biomimetic liver tumor-on-a-chip based on the integration of DLM components with GelMA, as opposed to GelMA only, had an increased capability to maintain cell viability and to enhance hepatocyte functions under flow conditions. The improved performance of the DLM-GelMA-based tumor-on-a-chip may be attributed to the provision of biochemical factors (e.g., growth factors), the preservation of scaffold proteins, and the reestablishment of biophysical cues (e.g., stiffness and shear stress) for better recapitulation of the 3D liver TME. Furthermore, this DLM-GelMA-based tumor-on-a-chip exhibited linear dose-dependent drug responses to the toxicity of acetaminophen and sorafenib. Taken together, our study demonstrates that the DLM-GelMA-based biomimetic liver tumor-on-a-chip better mimics the in vivo TME and holds great promise for a breadth of pathological and pharmacological studies.

Tumor-on-a-chip platforms for assessing nanoparticle-based cancer therapy.

Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.

A decade of progress in liver regenerative medicine.

Liver diseases can be caused by viral infection, metabolic disorder, alcohol consumption, carcinoma or injury, chronically progressing to end-stage liver disease or rapidly resulting in acute liver failure. In either situation, liver transplantation is most often sought for life saving, which is, however, significantly limited by severe shortage of organ donors. Until now, tremendous multi-disciplinary efforts have been dedicated to liver regenerative medicine, aiming at providing transplantable cells, microtissues, or bioengineered whole liver via tissue engineering, or maintaining partial liver functions via extracorporeal support. In both directions, new compatible biomaterials, stem cell sources, and bioengineering approaches have fast-forwarded liver regenerative medicine towards potential clinical applications. Another important progress in this field is the development of liver-on-a-chip technologies, which enable tissue engineering, disease modeling, and drug testing under biomimetic extracellular conditions. In this review, we aim to highlight the last decade's progress in liver regenerative medicine from liver tissue engineering, bioartificial liver devices (BAL), to liver-on-a-chip platforms, and then to present challenges ahead for further advancement.

An Integrated Double-Filtration Microfluidic Device for Detection of Extracellular Vesicles from Urine for Bladder Cancer Diagnosis.

Extracellular vesicles (EVs) are present in a variety of bodily fluids and they play an important role in cellular communications and signal transduction mechanisms. Studies have shown that the number of EVs and EV-associated biomarkers (i.e., proteins, nucleic acids and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for EV isolation, it is not practical for clinical settings. Here, we developed an integrated double-filtration device that isolated and enriched EVs from urine, and subsequently detected/quantified EVs from urine via microchip ELISA. Results showed that the concentration of EVs was significantly elevated compared to healthy controls. Receiver operating characteristic analysis demonstrated that this integrated EV quantification device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and eight healthy controls). Thus, this integrated device shows great potential to supplement urine cytology for diagnosis of bladder cancer in point-of-care (POC) settings.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer.

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30-200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings.