High Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Associated With Sarcopenia Risk in Hospitalized Renal Cell Carcinoma Patients.

PURPOSE: This study aimed i) to identify the best cutoff points of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) that predict sarcopenia and ii) to illustrate the association between sarcopenia risk and NLR or PLR in renal cell carcinoma (RCC) patients undergoing laparoscopic partial or radical nephrectomy. METHODS: A total of 343 RCC patients who underwent laparoscopic partial or radical nephrectomy between 2014 and 2019 were enrolled in our study. Sarcopenia was assessed by lumbar skeletal muscle index (SMI). Receiver operating characteristic (ROC) curve was used to identify the best cutoff point of NLR or PLR to predict sarcopenia risk. Univariate and multivariate logistic regression and dose-response analysis curves of restricted cubic spline function were conducted to assess the relationship between sarcopenia and NLR or PLR. RESULTS: The best cutoff points of NLR >2.88 or PLR >135.63 were confirmed by the ROC curve to predict sarcopenia risk. Dose-response curves showed that the risk of sarcopenia increased with raising NLR and PLR. Patients with NLR >2.88 or PLR >135.63 had a higher sarcopenia risk than those in the NLR ≤2.8 or PLR ≤135.63 group, respectively. By adjusting for all variables, we found that patients with NLR >2.88 and PLR >135.63 had 149% and 85% higher risk to develop sarcopenia, respectively, than those with NLR ≤2.8 (aOR = 2.49; 95% CI = 1.56-3.98; p < 0.001) or PLR ≤135.63 (aOR = 1.85; 95% CI = 1.16-2.95; p = 0.010). CONCLUSION: In RCC patients receiving laparoscopic partial or radical nephrectomy, NLR and PLR, which were biomarkers of systemic inflammation, were associated with sarcopenia risk.

Checkpoint kinase­1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair.

Leukemia, a malignant hematological disease, has poor therapeutic outcomes due to chemotherapeutic resistance. Increasing evidence has confirmed that the elevated capacity for DNA damage repair in cancer cells is a major mechanism of acquired chemotherapeutic resistance. Thus, combining chemotherapy with inhibitors of DNA damage repair pathways is potentially an ideal strategy for treating leukemia. Checkpoint kinase 1 (CHK1) is an important component of the DNA damage response (DDR) and is involved in the G2/M DNA damage checkpoint. In the present study, we demonstrated that shRNA­mediated CHK1 silencing suppressed cell proliferation and enhanced the cytotoxic effects of etoposide (VP16) in the chronic myeloid leukemia (CML) cell line K562 through the results of CCK­8, and comet assay. The results demonstrated that shRNA­induced CHK1 silencing can override G2/M arrest and impair homologous recombination (HR) repair by reducing breast cancer susceptibility gene 1 (BRCA1) expression. Cells had no time, and thus limited ability, to repair the damage and were thus more sensitive to chemotherapy after CHK1 downregulation. Second, we tested the therapeutic effect of VP16 combined with CCT245737, an orally bioavailable CHK1 inhibitor, and observed strong synergistic anticancer effects in K562 cells. Moreover, we discovered that CCT245737 significantly prevented the G2/M arrest caused by acute exposure to VP16. Interestingly, CCT245737 inhibited both BRCA1 and Rad51, the most important component of the HR repair pathway. In conclusion, these results revealed that CHK1 is potentially an ideal therapeutic target for the treatment of CML and that CCT245737 should be considered a candidate drug.

Isolation and analysis of extracellular vesicles in a Morpho butterfly wing-integrated microvortex biochip.

With the function of mediating intercellular communication between cells, extracellular vesicles (EVs) have been intently studied for their physiopathology and clinical application values. However, efficient EV isolation from biological fluids remains a significant challenge. To address this, this work constructs a new microvortex chip that can isolate EVs efficiently by integrating the lipid nanoprobe modified Morpho Menelaus (M. Menelaus) butterfly wing into microfluidic chip. M. Menelaus wing is well known for its orderly arranged periodic nanostructures and can generate microvortex when liquid passes through it, leading to increased interaction between EVs and M. Menelaus wing. In addition, the nanoprobe containing lipid tails can be inserted into EVs through their lipid bilayer membrane structure. Based on the described properties, high-throughput enrichment of EVs with over 70% isolation efficiency was realized. Moreover, it was demonstrated that the nanoprobe system based on M. Menelaus wing enabled downstream biological analysis of nucleic acids and proteins in EVs. Microvortex chips showed potential application value in efficient EV isolation for biomedical research and cancer diagnosis.

P-Glycoprotein Antibody Decorated Porous Hydrogel Particles for Capture and Release of Drug-Resistant Tumor Cells.

Multidrug resistance is one of the leading causes of chemotherapy failure in cancer patients. Early detection and capture of drug-resistant tumor cells can facilitate the monitoring of the therapy process and improve the prognosis of patients. In this study, novel P-glycoprotein (P-gp) antibody modified porous hydrogel particles are proposed for drug-resistant tumor cells capture. The hydrogel particles employ a highly biocompatible hydrogel, methacrylate gelatin (GelMA), as the carrier and replicate from the silica colloidal crystal beads. By the modification of P-gp antibody probes on their surfaces, the hydrogel particles are endowed with the ability to capture drug-resistant tumor cells, which overexpress specific components of P-gp on their membranes. Additionally, the acquired ordered porous nanostructure of the particles can provide not only more surface area for antibody immobilization but also a nanopatterned platform for highly efficient target cell capture. The above advantages make the porous hydrogel particles ideal for efficient capture and detection of the drug-resistant tumor cells, which can be expected to facilitate the point-of-care pharmacotherapy and promisingly improve the patient outcomes.

Folic Acid-Functionalized Hybrid Photonic Barcodes for Capture and Release of Circulating Tumor Cells.

Recovery of circulating tumor cells (CTCs) from cancer patients by an efficient CTCs capture and release method can greatly increase their application in diagnostics and treatment of cancers. In this paper, we presented a folic acid (FA)-functionalized hybrid photonic barcode for capture and release of CTCs. The hybrid photonic barcodes were formed by two nano-ordered parts, poly(ethylene glycol) diacrylate (PEGDA) inverse opal structure for sustaining integrity and methacrylated gelatin (GelMA) gel filler for conjugating FA molecules to mediate cell capture. The nano-ordered structures of the hybrid photonic barcodes not only increased contact area, but also decreased steric hindrance among FA molecules. Thus, the topographic interaction between the barcodes and CTCs was greatly enhanced. In addition, GelMA gel was soft and extracellular matrix (ECM) alike, which was beneficial to decrease impairment to CTCs during the CTCs-barcode interaction as well as preserving their viability. Demonstrated by four CTCs types, Hela (epithelial tissue, folate receptor positive, FR+), A02 (bone marrow, FR+), Raji (lymphoid tissue, FR+), and A549 (epithelial tissue, folate receptor negative, FR-), FR+ CTCs could be captured efficiently with reliability and specificity. The captured cells could be controllably released with high viability just by quick trypsinization. The whole processes were simple and efficient. These features indicated that the FA-functionalized hybrid photonic barcodes were promising for full recovery of CTCs from cancer patients, which was important for diagnosis and treatment of cancer.

Responsive photonic barcodes for sensitive multiplex bioassay.

Barcodes have a demonstrated value for multiplex high-throughput bioassays. The tendency of this technology is to pursue high sensitivity target screening. Herein, we presented a new type of inverse opal-structured poly(N-isopropylacrylamide) (pNIPAM) hydrogel photonic crystal (PhC) barcodes with the function of fluorescent signal self-amplification for the detection. During the bio-reaction process at body temperature, the pNIPAM hydrogel barcodes kept swelling, and their inverse opal structure with interconnected pores provided unblocked channels for the targets to diffuse into the voids of the barcodes and react. During the detection process, the barcodes were kept at a volume phase transition temperature (VPTT) to shrink their volume; this resulted in an obvious increase in the density of fluorescent molecules and signal amplification. It was demonstrated that the responsive barcodes could achieve the limits of detection (LOD) of α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) at 0.623 ng mL-1 and 0.492 ng mL-1, respectively. In addition, the proposed barcodes showed good multiplex detection capacity with acceptable cross-reactivity, accuracy, and reproducibility, and the results were consistent with those of common clinical laboratory methods for the detection of clinical samples. These features of the inverse opal-structured responsive hydrogel barcodes indicate that they are ideal technology for high-sensitive multiplex bioassays.

Hybrid hydrogel photonic barcodes for multiplex detection of tumor markers.

Barcodes-based suspension array have for demonstrated values in multiplex assay of tumor markers. Photonic barcodes which are encoded by their characteristic reflection peaks are the important supports for suspension array due to their stable code, low fluorescent background and high surface-volume ratio. Attempts to develop this technology tend to improve the function of the photonic barcodes. Here, we present a new type of hybrid hydrogel photonic barcodes for efficient multiplex assays. This photonic barcodes are hybrid inverse opal hydrogel composed of poly(ethylene glycol) diacrylate (PEG-DA) and agarose. The polymerized PEG-DA hydrogel could guarantee the stabilities of the inverse opal structure and its resultant code, while the agarose could offer active chemical groups for the probe immobilization and homogeneous water surrounding for the bioassay. In addition, the interconnected pores inverse opal structure could provide channels for biomolecules diffusing and reaction into the voids of barcodes. These features imparted the hybrid hydrogel photonic barcodes with limits of detection (LOD) of 0.78ng/mL for carcinoembryonic antigen (CEA) and 0.21ng/mL for α-fetoprotein (AFP), respectively. It was also demonstrated that the proposed barcodes showed acceptable accuracy and detection reproducibility, and the results were in acceptable agreement with those from common clinic method for the detections of practical clinical samples. Thus, our technique provides a new platform for simultaneous multiplex immunoassay.

Applications of photonic crystals in medicine.

Photonic crystals are periodic optical nanostructures that affect the motion of photons in much the same way that ionic lattices affect electrons in solids. Even though porous silicon (pSi) was first obtained as early as 1956, it was long used only as electrical insulator. Unique optical and photophysical properties of this material have been studied in detail in the past decade and, in particular, the porosity has been found to affect the pSi refraction index. Until now, they have been used in many areas, but recent trends in the applications of pSi are related to biomedicine, such as drug delivery, biosensing, and photodynamic therapy. This paper concerns the medical applications in these fields and prospective analysis of photonic crystals.