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BackgroundIndocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery.PurposeThis study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery.MethodsColorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient’s age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM.ResultsIn the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5–1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859).ConclusionsPreoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.

Researchers have long focused on the accumulation of amyloid beta (Aβ) peptides in the brain as a primary pathological hallmark driving cognitive decline. This study investigated the neuroprotective effects of Rosa rugosa (RR) root extract and its key bioactive constituent, oleamide, against amyloid beta (Aβ)-induced neurotoxicity. Initially, an ethanolic extract of RR root was screened via in vitro assays to assess antioxidant and cytoprotective potential in rat pheochromocytoma cells. Subsequent fractionation, open-column chromatography, and preparatory thin-layer chromatography led to the isolation of oleamide, confirmed by gas chromatography–mass spectrometry and 1H/13C nuclear magnetic resonance analyses. In vivo experiments using intracerebroventricularly injected Aβ in male mice demonstrated that both RR root extract and oleamide significantly improved cognitive performance in the Y-maze and passive avoidance tests. Additionally, oleamide restored acetylcholine levels and reduced malondialdehyde concentrations in brain tissue, indicating mitigation of oxidative stress and support of cholinergic function. No significant toxicity was observed, as evidenced by stable serum transaminase levels and unaltered body or brain weights. These findings highlight oleamide’s potential to protect against Aβ-driven pathology through multiple mechanisms, including reduced lipid peroxidation and improved neurotransmission. Further investigations into oleamide’s molecular targets and synergy with existing therapies may advance its development as a novel candidate for Alzheimer’s disease prevention or adjunct treatment.

Patients with lung cancer harboring a KRAS oncogenic driver mutation have a very poor prognosis. Recently, we reported that SIRT1 is upregulated by the KRAS Mut –c-Myc axis, and that KRAS Mut -induced SIRT1 is stably deacetylated at lysine 104, which in turn increases KRAS Mut activity and enhances chemoresistance. Notably, SIRT1 activity as well as SIRT1 levels are more elevated in KRAS Mut cells compared with EGFR Mut , KRAS Mut - and EGFR Mut -negative cells, and nontumorigenic cells. This prompted us to investigate the mechanism by which SIRT1 activity was increased and the role of pSIRT1 in the chemoresistance of KRAS Mut lung cancer cells. The activated MEK–ERK pathway under KRAS Mut increased AP-1 transcription activity, which in turn enhanced TGF-β1 secretion. The secreted TGF-β1 activated the Smad2/3–JNK1 signaling pathway in an autocrine manner, increasing pSIRT1 S27 and pSIRT1 S47 , ultimately enhancing KRAS Mut activity through KRAS deacetylation and affecting chemoresistance. We identified a small molecule from the natural compound library—Kuwanon C (KWN-C), a SIRT1 activity inhibitor—which reduced pSIRT1 S27 and pSIRT1 S47 levels via a decrease in the activity of the TGF-β1–-Smad2/3–JNK1 signaling pathway. Treatment with the SIRT1 activity inhibitor triggered the anticancer effects of cisplatin and pemetrexed in human lung cancer cells, lung orthotopic tumors and a spontaneous in vivo model of KRAS Mut lung cancer. Our findings reveal a novel pathway critical for the regulation of SIRT1 activity in KRAS Mut lung cancer and provide important evidence for the potential application of SIRT1 activity inhibitors as an adjuvant chemotherapy, overcoming chemoresistance in patients with KRAS Mut lung cancer. SIRT1 inhibition enhances chemotherapy in KRAS lung cancer Mutations in the KRAS gene are common in several cancers, including lung cancer, and make treatment challenging. Researchers explore a new approach by focusing on a protein called SIRT1, which is found at higher levels in KRAS-mutated lung cancer cells. They used various laboratory techniques to study how SIRT1 interacts with KRAS mutations. They discovered that SIRT1 helps KRAS mutations become more active, which contributes to cancer growth and resistance to chemotherapy. By using natural compounds to inhibit SIRT1 activity, they found that they could make cancer cells more sensitive to existing chemotherapy drugs. The study suggests that targeting SIRT1 could be a promising strategy to improve treatment for patients with KRAS-mutated lung cancer. They propose that combining SIRT1 inhibitors with current chemotherapy could enhance treatment effectiveness and reduce drug resistance. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

We examined trends in the incidence and correlates of educational and skill mismatch in the United States. We focused on trends over time in the associations between various types of mismatch and a range of factors including contextual conditions. We explored whether contextual conditions at the transitional period from school to jobs increase or decrease the probability of mismatch and whether such relationships persist throughout the working career. Our central questions were how the incidence of and relationship between educational and skill mismatch in the U.S. changed between 1994, 2003, and 2012 and how this differed by age, gender, immigration status, educational attainment, and occupation. We used three cross-sectional surveys that had not previously been implemented for such an effort. These were the International Adult Literacy Survey (IALS) in 1994, the Adult Literacy and Life-skills (ALL) survey in 2003, and the Program for the International Assessment of Adult Competencies (PIAAC) in 2012. Repeated cross-sectional data provided us with substantial analytic leverage. Our findings point toward the key role of occupational or positional factors rather than individual worker characteristics as being most implicated in trends in mismatch. We describe the importance of our results for labor market theories.

Background: The aim of the present study was to compare the biological and mechanical properties of a novel dual-cure, resin-modified calcium silicate material, Theracal PT® (TP), with those of Theracal LC® (TL) and BiodentineTM (BD). Methods: The cell counting kit-8 was used on human dental pulp cells to test cell the viability of the three materials. Antibacterial activity of TP, TL, and BD against Enterococcus faecalis was investigated under anaerobic conditions. The ability of the materials to support odontogenic differentiation was studied by examining the relative gene expression of osteocalcin (OCN), osteopontin (OPN), and Collagen I (ColI) using real-time polymerase chain reaction. For mechanical property tests, microhardness was evaluated using the Vickers microhardness (VHN) test, and the bond strength to the resin was evaluated using a shear bond test machine. Results: There was no significant difference in cell viability between TL and TP after 48 h, and BD showed the highest cell viability, while TP showed the highest antibacterial effect. At the 12-h time point, there was no significant difference in ColI and OCN expression between BD and TP, but TP showed a higher expression of OPN than BD. However, at the 48-h time point, ColI and OCN showed higher levels of expression for BD than for TP and TL. At the same time point, only OPN had a higher diffusion for TP than for BD. TP demonstrated a VHN of approximately 30–35. This value was higher than that of TL and lower than that of BD. In contrast to VHN, the shear bond strength to resin was significantly higher for TL and TP than for BD. Conclusion: TP showed lower biocompatibility than BD but higher OPN expression and antibacterial effects than BD and TL. TP showed higher shear bond strength than BD and higher VHN than TL and BD at the 24-h time point.

Phellinus linteus is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, Phellinus linteus extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in Phellinus linteus. The intermediate-conductance calcium-activated potassium channel (IKCa) plays an important role in the regulation of the vascular smooth muscle cells’ (VSMCs) contraction and relaxation. The activation of the IKCa channel causes the hyperpolarization and relaxation of VSMCs. To examine whether Phellinus linteus extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 µM), Phellinus linteus extract was administered. The Phellinus linteus extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K+ channel blocker tetraethylammonium (TEA). TEA significantly abolished Phellinus linteus extract-induced vasodilation. Thus, we tested three different types of K+ channel blockers: iberiotoxin (BKca channel blocker), apamin (SKca channel blocker), and charybdotoxin (IKca channel blocker). Charybdotoxin significantly inhibited Phellinus linteus extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the Phellinus linteus extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC20).

Kirsten rat sarcoma viral oncogene homologue (KRAS) is a frequent oncogenic driver of solid tumors, including non-small cell lung cancer (NSCLC). The treatment and outcomes of KRAS-mutant cancers have not been dramatically revolutionized by direct KRAS-targeted therapies because of the lack of deep binding pockets for specific small molecule inhibitors. Here, we demonstrated that the mRNA and protein levels of the class III histone deacetylase SIRT1 were upregulated by the KRAS Mut -Raf-MEK-c-Myc axis in KRAS Mut lung cancer cells and in lung tumors of a mouse model with spontaneous Kras G12D expression. KRAS Mut -induced SIRT1 bound to KRAS Mut and stably deacetylated KRAS Mut at lysine 104, which increased KRAS Mut activity. SIRT1 knockdown (K/D) or the SIRT1 H363Y mutation increased KRAS Mut acetylation, which decreased KRAS Mut activity and sensitized tumors to the anticancer effects of cisplatin and erlotinib. Furthermore, in Kras G12D/+ ;Sirt1 co/co mice, treatment with cisplatin and erlotinib robustly reduced the tumor burden and increased survival rates compared with those in spontaneous LSL-Kras G12D/+ ;Sirt1 +/+ mice and mice in each single-drug treatment group. Then, we identified p300 as a KRAS Mut acetyltransferase that reinforced KRAS Mut lysine 104 acetylation and robustly decreased KRAS Mut activity. KRAS Mut lysine 104 acetylation by p300 and deacetylation by SIRT1 were confirmed by LC‒MS/MS. Consistent with this finding, the SIRT1 inhibitor EX527 suppressed KRAS Mut activity, which synergistically abolished cell proliferation and colony formation, as well as the tumor burden in KRAS Mut mice, when combined with cisplatin or erlotinib. Our data reveal a novel pathway critical for the regulation of KRAS Mut lung cancer progression and provide important evidence for the potential application of SIRT1 inhibitors and p300 activators for the combination treatment of KRAS Mut lung cancer patients. Lung cancer: Protein interaction as a target of chemotherapy The interaction between two key proteins in non-small cell lung cancers (NSCLCs) could be targeted to improve the success of chemotherapy. Mutations in the KRAS protein, a regulator of cell growth, are a common driver of NSCLCs, and are associated with poor prognosis. Treating NSCLCs harboring KRAS mutations has proven challenging, and further insights into the mechanisms driving KRAS activity are needed. Using cell cultures and mouse models, Dong Hoon Shin at the National Cancer Center in Goyang-si, South Korea, and co-workers demonstrated that KRAS mutations confer resistance to chemotherapy in NSCLC cells. KRAS mutations increase levels of a protein called SIRT1, and this interaction boosts cancer cell proliferation and tumour growth. Knocking out SIRT1 improved the success of chemotherapy in mouse models. Combined therapies involving SIRT1 inhibitors may therefore improve treatments for NSCLCs.

Chemotherapy is a common treatment technique that uses chemical drugs to kill cancer cells. This technique affects normal healthy tissues being unspecific and has toxic adverse effects. Nowadays, nanotechnology applications in cancer chemotherapy have helped to solve the uncontrolled problems involving distribution of medicine particles and other side effects. Nanoparticles (NPs) can offer significant advantages over conventional drug delivery to have magnificent properties such as controlled mode of action, various methods of administration, and the ability to transport both organic/inorganic drug particles. Special ligands containing polymeric NPs preferentially hit the tumour site because of their chemical affinity to malignant tissues. This article, reviews the fabrication, characterization, and applications of NPs being used in chemotherapy. Furthermore, different forms of polymeric and especially polymeric chemotherapy were also explored and discussed to understand better the effects of NPs on cancer chemotherapy.

Background/Objectives: This study evaluated the impact of fluorescence lymph node mapping (FLNM) using indocyanine green (ICG) on the diagnostic accuracy of preoperative computed tomography (CT) in right-sided colon cancer. Methods: A total of 218 patients who underwent laparoscopic right hemicolectomy with D3 lymph node dissection (LND) were analyzed: 86 patients in the FLNM group and 132 in the conventional surgery group. The FLNM technique allowed for enhanced intraoperative visualization of lymph node (LN) and more precise dissection, improving the identification of metastatic LNs. The diagnostic value of preoperative CT staging was assessed in both the FLNM and control groups by calculating the apparent prevalence, true prevalence, sensitivity, specificity, positive predictive value (PPV), negative predictive value, positive likelihood ratio (PLR), negative likelihood ratio, false positive and false negative proportions, and accuracy. Results: FLNM increased the accuracy of CT staging for detecting D3 LN metastasis in advanced cancer cases, with a higher PPV, PLR, and accuracy. In the FLNM group, the false-positive rate was significantly reduced, and the specificity was higher compared to the control group. Multivariate analysis identified FLNM as an independent factor associated with improved D3 LN metastasis detection. These findings suggest that incorporating FLNM into surgical procedures enhances the diagnostic value of preoperative CT by improving the precision of LND, particularly in patients with advanced colon cancer. Conclusions: The use of FLNM for D3 LND enhances the diagnostic accuracy of cN staging in right-sided colon cancer by improving surgical precision.

The aim of this case report is to describe comprehensive imaging such as CT scanning, endoscopy, histopathology, and clinical outcomes following medical and endoscopic treatment. A 5-year-old spayed female Chihuahua presented with chronic unilateral nasal discharge, congestion, and intermittent stertor, unresponsive to initial antibiotics and steroids. Further diagnostics, including endoscopy, revealed a cystic lesion with osseous fragments in the left nasal cavity, while CT imaging identified a soft tissue mass with associated bone resorption. Histopathology confirmed chondro-osseous respiratory epithelial adenomatoid hamartoma (COREAH), a rare benign lesion characterized by respiratory epithelium, fibrovascular proliferation, and osseous components, along with lymphoplasmacytic and eosinophilic inflammation. Clinical signs improved following endoscopic aspiration and drainage, which restored nasal cavity space. This case highlights the importance of combining endoscopy, advanced imaging, and histopathology for accurate diagnosis and effective management of COREAH, a condition with potential for recurrence. The use of endoscopy enabled real-time visualization and precise tissue sampling, distinguishing this case from others relying solely on imaging. This report contributes to the limited veterinary literature on COREAH and underscores the need for long-term monitoring due to its uncertain pathogenesis and variable presentation.