Optical coherence elastography measures the biomechanical properties of the ex vivo porcine cornea after LASIK.

Significance: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact. Aim: To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas. Approach: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the fellow eye underwent LASIK. Changes in stiffness as a function of intraocular pressure (IOP) before and after LASIK were measured using each technique. Results: ACUS-OCE showed that corneal stiffness changed as a function of IOP for both the untreated and the treated groups. The elastic wave speed after LASIK was lower than before LASIK. Hb-OCE and compression OCE showed regional changes in corneal strain after LASIK, where the absolute strain difference between the cornea anterior and posterior increased after LASIK. Conclusions: The results of this study suggest that LASIK may soften the cornea and that these changes are largely localized to the region where the surgery was performed.

TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer.

Natural killer (NK) cells are commonly reduced in human tumors, enabling many to evade surveillance. Here, we sought to identify cues that alter NK cell activity in tumors. We found that, in human lung cancer, the presence of NK cells inversely correlated with that of monocyte-derived macrophages (mo-macs). In a murine model of lung adenocarcinoma, we show that engulfment of tumor debris by mo-macs triggers a pro-tumorigenic program governed by triggering receptor expressed on myeloid cells 2 (TREM2). Genetic deletion of Trem2 rescued NK cell accumulation and enabled an NK cell-mediated regression of lung tumors. TREM2+ mo-macs reduced NK cell activity by modulating interleukin (IL)-18/IL-18BP decoy interactions and IL-15 production. Notably, TREM2 blockade synergized with an NK cell-activating agent to further inhibit tumor growth. Altogether, our findings identify a new axis, in which TREM2+ mo-macs suppress NK cell accumulation and cytolytic activity. Dual targeting of macrophages and NK cells represents a new strategy to boost antitumor immunity.

A new approach used in docking study for predicting the combination drug efficacy in EML4-ALK target of NSCLC.

Combination drug treatments are usually used in many diseases, including cancers and AIDS. This treatment strategy is known as one of the cornerstone in therapies, which potentially reduces drug toxicity and drug resistance and also enhances therapeutic efficacy. Before using a drug in treatment, several experimental studies are done in vivo and in vitro to ensure the drug's efficacy. In such experimental studies, the drug's efficacy is evaluated with the help of drug dose ratio. In the combination drug experimental studies, the efficacy of the drugs is quantified with the Combination Index (CI) value and then interpreted by various terminologies like synergy, additive, and antagonism. Several computational models have now been invented for the speedy identification of combination drug efficacy. Unfortunately, none of these models have predicted the atomic level interaction of the combination drug with the target protein. This type of intermolecular interaction can be identified with the help of docking software. In the proposed work, we try to identify the intermolecular interaction and efficacy of the combination drug Crzizotinib and Temozolomide in the target of EML4-ALK in NSCLC by in silico study. The result of the study was evaluated with drug properties and Complex Energy (CE) of the docked complex rather than using docking score and binding energy. From this study, we could understand that first, Crizotinib and then after the Temozolomide drug binded on the EML4-ALK protein complex, showed very least CE and also identified that the combination of Crizotinib and Temozolomide drug are more effective in NSCLC.Communicated by Ramaswamy H. Sarma.

Assessing colitis ex vivo using optical coherence elastography in a murine model.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. In addition to traditional colonoscopy, ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed to detect UC with higher resolution. However, UC can potentially alter tissue biomechanical properties, providing additional contrast for earlier and potentially more accurate detection. Although clinically available elastography techniques have been immensely useful, they do not have the resolution for imaging small tissues, such as in small mammalian disease models. However, OCT-based elastography, optical coherence elastography (OCE), is well-suited for imaging the biomechanical properties of small mammal colon tissue. METHODS: In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source OCE system, and the wave velocity was translated into stiffness. Measurements were taken at six positions for each sample to assess regional sample elasticity. Additional contrast between the control and diseased tissue was detected by analyzing the dispersion of the elastic wave and tissue optical properties obtained from the OCT structural image. RESULTS: The results show distinct differences (P<0.05) in the stiffness between control and colitis disease samples, with a Young's modulus of 11.8±8.0 and 5.1±1.5 kPa, respectively. The OCT signal standard deviations for control and diseased samples were 5.8±0.3 and 5.5±0.2 dB, respectively. The slope of the OCT signal spatial frequency decay in the control samples was 92.7±10.0 and 87.3±4.7 dB∙µm in the colitis samples. The slope of the linearly fitted dispersion curve in the control samples was 1.5 mm, and 0.8 mm in the colitis samples. CONCLUSIONS: Our results show that OCE can be utilized to distinguish tissue based on stiffness and optical properties. Our estimates of tissue stiffness suggest that the healthy colon tissue was stiffer than diseased tissue. Furthermore, structural analysis of the tissue indicates a distinct difference in tissue optical properties between the healthy and UC-like diseased tissue.

Detecting murine Inflammatory Bowel Disease using Optical Coherence Elastography.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes regions of ulceration within the interior of the colon. UC is estimated to afflict hundreds of thousands of people in the United States alone. Ultrasonic techniques can detect colitis, but have limited spatial resolution, which frequently results in underdiagnoses. Nevertheless, clinical diagnosis of colitis is still generally performed via colonoscopy. Optical techniques such as confocal microscopy and optical coherence tomography (OCT) have been proposed as higher resolution alternative imaging modalities to detect colitis. Additionally, IBD can potentially alter tissue biomechanical properties, which cannot be quantified from structural imaging alone. Elastography is a potential method to assess colon biomechanical properties to provide additional contrast for distinguishing healthy and diseased colon tissue. In this work, we induced elastic waves in ex vivo mouse colon tissue using a focused air-pulse. The elastic waves were detected using a phase-stabilized swept source optical coherence elastography system, and the wave velocity was translated into stiffness. Measurements were taken at six random positions for each sample in order to assess regional sample elasticity. The results show distinct differences ($p \lt 0.05$) in the stiffness between healthy and IBD-diseased samples, with a Young's Modulus of $10.2 \pm 3.7$ kPa and $4.9 \pm 0.3$ kPa, respectively. Dispersion analysis presents another parameter to distinguish tissue health. The high frequency components of the phase velocity dispersion curve indicate a variation between healthy and IBD colonic tissue. Our results show that OCE may be useful for detecting IBD noninvasively.