ING2-WTAP is a potential therapeutic target in non-small cell lung cancer.

Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC.

The role of routine laboratory tests after unilateral total knee arthroplasty.

BACKGROUND: Recent studies suggest that routine laboratory tests are not required within 1 day after partial knee arthroplasty. In this study, we evaluated the utility of routine postoperative laboratory tests after initial unilateral total knee arthroplasty (TKA) in an Asian population. In addition, we explored risk factors associated with abnormal test results. METHODS: Clinical data of patients who underwent original unilateral TKA between 2015 and 2020 were retrospectively analyzed. Patient characteristics and laboratory test results were recorded. Multivariate binary logistic regression analysis was performed to identify risk factors associated with 3 abnormal laboratory results. RESULTS: A total of 713 patients, who underwent relevant laboratory tests within 3 days of TKA surgery, were enrolled. Among them, 8.1%, 9.9%, and 3.4% patients with anemia, hypoalbuminemia, and abnormal serum potassium levels required clinical intervention after surgery. Binary logistic regression analysis revealed that preoperative hemoglobin levels, estimated blood loss, and age were independent risk factors of postoperative blood transfusion in TKA patients. On the other hand, preoperative albumin levels, intraoperative blood loss, and operation time were risk factors associated with postoperative albumin supplementation. In addition, lower body mass index (BMI) and preoperative hypokalemia were potential risk factors of postoperative potassium supplementation. CONCLUSION: Considering that more than 90% of abnormal postoperative laboratory tests do not require clinical intervention, we believe that routine laboratory tests after surgery have little significance in patients with primary unilateral TKA. However, postoperative laboratory testing is necessary for patients with established risk factors.

Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one of the most common cancers worldwide with high rate of mortality and morbidity. At present, chemotherapy is one of the most effective treatments; however it often fails to meet the requirements in the clinical therapy. In the present study, we have successfully formulated ligand-decorated cancer-targeted CDDP-loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7 peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic effect in receptor-overexpressed OSCC cancer cells. RESULTS: Nanosized particles were formed and sustained release patterns were observed for PLGA/NR7 nanoparticles. Significantly higher cellular uptake was observed in HN6 OSCC cancer cells and superior anticancer effects are observed from the optimized targeted nanoparticles. Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP. The presence of the NR7-targeting moiety on the surface of PLGA carriers could allow the specific receptor-mediated internalization, enhanced cellular uptake, and higher cell killing potency. Especially, PLGA/NR7 NP exhibited a superior apoptosis effect in HN6 cancer cells with around ~45 % (early and late apoptotic stage) and ~59 % after 24 and 48 h incubation, respectively. It is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one. CONCLUSION: Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma. The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

A Bibliometric Analysis of Publications on Spinal Cord Injury Treatment With Glucocorticoids Using VOSviewer.

Background: Spinal cord injury (SCI) has devastating physical and social consequences for patients. Systemic administration of methylprednisolone (MP) at a higher dosage though can reduce neurological deficits following acute SCI. Still, this treatment regimen is controversial, owing to the apparent dose-related side effects and relatively minor improvement in neurological function. Therefore, this study aimed at the bibliometric analysis of published literature related to SCI treatment, which may lead to future research trends. Methods: The literature published relating to SCI and using glucocorticoids for its treatment between 1982 and 2022 was collected and scanned in the Web of Science collection database using the keywords glucocorticoid, dexamethasone, MP, corticosteroids, and SCI, followed by using VOSviewer for bibliometric analysis of these articles. Results: A total of 1,848 published articles and 7,448 authors on SCI and glucocorticoid usage were identified. The SCI total link strength accounts for 1,341, and MP for 762 has a strong link to neuroprotection and inflammation. The mean citation count for the top 20 most-cited articles was 682 (range: 358-1,828), where most of these were descriptive studies having focused on clinical features. The Journal of Neurotrauma was the highest-ranked journal with 6,010 citations. A total of 69 articles were published by Michael G Fehlings from the University of Toronto with 6,092 citations. The University of Toronto has published 90-related manuscripts with 7,632 citations. In contrast, 800 articles were published in the United States, with 39,633 citations and total link strength of 5,714. The second-ranked country was China, with 241 published articles and 3,403 citations. Conclusions: The research published on applying MP in treating SCI has increased with time. Although the United States has made a significant global contribution to this important field of research, it requires rigorous clinical trials designed to verify the therapeutic role of MP in SCI and its appropriate dosage to find solutions for neurological recovery.

Analysis of coupled microcircular resonators coupled to a bus waveguide with high output efficiency.

Coupled microcircular resonators tangentially coupled to a bus waveguide, which is between the resonators, are numerically investigated by the finite-difference time-domain technique. For symmetrically coupled microcircular resonators with refractive index of 3.2, radius of 2 microm, and width of the bus waveguide of 0.4 microm, a mode Q factor of the order of 10(5) is obtained for a mode at the frequency of 243 THz. An output coupling efficiency of as high as 0.99 is calculated for a mode with a Q factor ranging from 10(3) to 10(4). The mode Q factor is 2 orders larger than that of the modes confined in a single circular resonator tangentially coupled to the same bus waveguide. Furthermore, the high Q traveling modes in the coupled microcircular resonators are suitable for optical single processing.

Investigation of mode coupling in a microdisk resonator for realizing directional emission.

Mode coupling between the whispering-gallery modes (WGMs) is numerically investigated for a two-dimensional microdisk resonator with an output waveguide. The equilateral-polygonal shaped mode patterns can be constructed by mode coupling in the microdisk, and the coupled modes can still keep high quality factors (Q factors). For a microdisk with a diameter of 4.5 microm and a refractive index of 3.2 connected to a 0.6-microm-wide output waveguide, the coupled mode at the wavelength of 1490 nm has a Q factor in the order of 10(4), which is ten times larger than those of the uncoupled WGMs, and the output efficiency defined as the ratio of the energy flux confined in the output waveguide to the total radiation energy flux is about 0.65. The mode coupling can be used to realize high efficiency directional-emission microdisk lasers.

Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy.

Optical bistability in InP/GaInAsP equilateral-triangle-resonator microlasers.

Optical bistability is reported in InP/GaInAsP equilateral-triangle-resonator (ETR) microlasers, which are fabricated by planar technology. For a 30 mum side ETR microlaser with a 2-mum-wide output waveguide connected to one of the vertices of the ETR, hysteresis loops are observed for the output power versus the injection current from 215 to 235 K. The laser output spectra are measured in the upper and lower states of the hysteresis loop, which show strong mode competition among transverse modes. The hysteresis loops are demonstrated by two-mode rate equations with asymmetric cross gain saturation and different output efficiencies.

Directional emission InP/GaInAsP square-resonator microlasers.

InP/GaInAsP square-resonator microlasers with an output waveguide connected to the midpoint of one side of the square are fabricated by standard photolithography and inductively-coupled-plasma etching technique. For a 20-mum-side square microlaser with a 2-mum-wide output waveguide, cw threshold current is 11 mA at room temperature, and the highest mode Q factor is 1.0x10(4) measured from the mode linewidth at the injection current of 10 mA. Multimode oscillation is observed with the lasing mode wavelength 1546 nm and the side-mode suppression ratio of 20 dB at the injection current of 15 mA.