Abstract: Background: The rate of coronary artery bypass grafting (CABG) procedures decreased generally over the past years while the relative number of off-pump coronary artery bypass grafting (OPCAB) procedures remained stable. OPCAB can be performed in different ways also using a minimally invasive direct approach (MIDCAB). This technique consists usually of the approach through the left anterior small thoracotomy (LAST) and is in principle limited for single LAD revascularization only. Lower mini-sternotomy (LOMS) is an optimization of the minimal-invasive approach permitting the harvest of both internal thoracic arteries (ITA) as well as excellent exposure and immobilization of the left and right coronary arteries.
Methods: Between January 2016 and June 2017 LOMS was performed in 31 patients to achieve access to the left and right internal thoracic arteries and to reach the left anterior descending coronary artery, diagonal branches, and right coronary artery for off-pump, all-arterial, aortic no-touch revascularization. Postoperative pain intensity was assessed on a daily basis for 7 days and patients were followed prospectively after operation at our outpatient clinic on a monthly basis in order to assess the incidence of complications.
Results: The mean operative time was 163 ± 49 minutes (range 119 to 260 minutes). The mean length of the skin incision was 7.4 ± 1.3 cm (range 6 to 11 cm). Neither hemodynamic changes nor transient S-T segment changes on the ECG occurred during the operation. In most patients, recovery was rapid and uneventful. No hospital death or morbidity was observed. No blood transfusion was required perioperatively. There were no perioperative neurological cognitive dysfunction events. Maximal pain levels were registered on postoperative day 2 or 3, and pain had abated in most patients on day 5. At follow-up, all patients were in New York Heart Association class I.
Conclusions: Despite more demanding surgical technique than with full-sternotomy OPCAB, our experience demonstrates that the LOMS for MIDCAB is a technically feasible procedure for myocardial revascularization. Not only the LAD and its branches but also the RCA and can be used safely with very good procedural outcomes.

Abstract: The therapeutic efficacy of combined chemotherapy and immunotherapy in solid tumors remains limited due to insufficient tumor targeting and accelerated T cell exhaustion driven by the immunosuppressive tumor microenvironment (TME). To address these challenges, we have identified novel antibodies targeting key immunotherapy markers, and applied computer-aided design to engineer these antibodies with optimized properties. Furthermore, we developed antibody-directed therapeutic strategies capable of modulating tumor metabolism, remodeling the immune landscape, and enhancing antitumor activity. Using yeast display in combination with computational design, these antibodies can be re-engineered into high-affinity variants that mediate tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) via natural killer (NK) cells. In addition, these antibodies can be converted into bispecific antibodies targeting both tumor cell antigens and NK cell markers, thereby recruiting NK cells to eliminate tumor cells. We also constructed chimeric antigen receptor (CAR)-modified T cells targeting non-small cell lung cancer (NSCLC). These findings support the further development of this class of therapeutic strategies in both preclinical and clinical studies.

Abstract: The clinical translation of highly efficacious natural compounds, such as celastrol, for obesity-associated metabolic syndromes is severely bottlenecked by their systemic toxicity. Overcoming this challenge requires innovative biotechnology to decouple pharmacological efficacy from adverse effects. In this study, we identify adipocyte-derived extracellular vesicles (exosomes) as natural nanocarriers of a novel therapeutic payload, microRNA-5099 (miR-5099), which mediates the potent anti-inflammatory benefits of celastrol without its associated toxicity.By integrating a systems biology approach, utilizing bulk and single-cell RNA sequencing, microRNA transcriptomics, and high-throughput multiplex cytokine arrays, we mapped the intercellular communication network between adipocytes and macrophages. We demonstrated that pharmacological stimulus effectively modulates exosomal sorting machinery, resulting in the significant enrichment of miR-5099 within adipocyte-derived exosomes. As a cell-free biotherapeutic, administration of these miR-5099-loaded exosomes or direct miR-5099 delivery robustly reprogrammed pro-inflammatory M1 macrophages into an anti-inflammatory state by directly targeting the Met/NF-κB signaling axis. In vivo evaluation in murine models revealed that this targeted biologic intervention significantly resolved adipose tissue inflammation, restored glucose homeostasis, and reversed hepatic steatosis. Collectively, our findings elucidate a novel exosome-mediated cross-talk mechanism and present miR-5099 as a highly promising, scalable biotherapeutic agent, offering a targeted and safe modality for treating obesity-driven metabolic dysfunctions.

Abstract: The invention of total-body PET is a significant milestone in the field of nuclear medicine. Due to their ultra-high sensitivity and extensive coverage, these systems make it possible to reveal dynamic physiological changes throughout the entire body for the first time. However, to promote this cutting-edge technology more widely, we must overcome the obstacles it faces in existing clinical applications. In this presentation, I will first introduce how to address the technical challenges of total-body PET faced by our clinical partners. Subsequently, I will share some of our ongoing efforts specifically focused on performing integrated analysis of whole-body PET/CT images and applying them in accurate cancer diagnosis and prognosis.

Abstract: Ischemic stroke causes local brain tissue damage, which not only leads to acute neurological deficits but also accelerates long-term cognitive decline. Preventing stroke is, therefore, a key strategy for preserving cognitive function in aging populations.

Atherosclerotic plaque rupture in carotid arteries remains a predominant cause of ischemic stroke. Beyond embolization, hemodynamically significant plaques also reduce cerebral perfusion pressure, leading to chronic hypoperfusion that further compromises brain health. Traditional risk stratification based solely on stenosis severity is insufficient, as many non-stenotic plaques are vulnerable while some severely stenotic lesions remain stable. Advanced high-resolution, multi-contrast MR vascular imaging enables detailed characterization of plaque components, fibrous cap, lipid-rich necrotic core, and intraplaque hemorrhage, which are directly linked to vulnerability. Complementing this, hemodynamic analysis quantifies wall shear stress and plaque structural stress: low shear stress promotes plaque initiation and progression, while elevated structural stress concentrates at the thin fibrous cap, increasing rupture risk. Integrating these biomechanical metrics with MR-derived anatomy significantly improves the accuracy of vulnerability assessment over stenosis-based evaluation.

Mechanosensitive ion channels, such as Piezo1 and TRP, play a critical role in transducing mechanical stimuli into cellular signals, mediating endothelial responses to shear stress and smooth muscle cell adaptation to structural stress. Elucidating these mechanobiological mechanisms is essential for understanding plaque destabilization. Future efforts should focus on large-scale prospective validation, development of mechanobiology-informed therapeutic strategies, and translation of integrated MR imaging, hemodynamic modeling, and molecular insights into clinical practice, ultimately enabling personalized prevention of both stroke and dementia.

Keywords: stroke; cognitive function; atherosclerosis; imaging; hemodynamics; mechanobiology

Abstract: Myocardial infarction (MI) is the leading cause of cardiovascular diseases. Reperfusion therapies are used to restore blood flow and oxygen in MI patients. However, myocardia ischemia reperfusion injury (MIRI) can further exacerbate myocardial damage. Sphingosine-1-phosphate receptor 2 (S1PR2) signalling has been implicated in cardiovascular pathology, particularly in MIRI. Positron emission tomography (PET) imaging with a novel S1PR2 radiotracer can advance our understanding of the role of S1PR2 in MIRI. However, no suitable S1PR2 radiotracer is currently available to study MIRI in vivo. Herein, we report our efforts on the design, synthesis, and evaluation of a series of novel S1PR2 compounds. Five potent and selective compounds 15a-e with IC50 values ranging from 10-120 nM were selected for F-18 radiolabelling to make radiotracers [18F]15a-e. Our PET imaging study in a mouse model of MIRI showed that all five radiotracers exhibited increased uptake in the infarct and peri-infarct regions of the heart in MIRI mice compared to control mice, consistent with the findings from autoradiography and immunostaining analysis of corresponding heart tissue sections. Our data showed that [18F]15b is a high potent (IC50 = 5.0 ± 4.24 nM) and selective S1PR2 radiotracer and had the highest uptake and the greatest signal-to-noise ratio in MIRI mice post-injury compared to other radiotracers. No radiometabolite was observed in mouse heart tissue at 60 min post injection of [18F]15b. Together, [18F]15b is a promising radiotracer with high sensitivity for imaging MIRI and it worths to further translational investigation of its implementation in MIRI patients.

Keywords: PET imaging, myocardial ischemia-reperfusion injury (MIRI), S1PR2, radiotracer

Abstract: Exosomes are cell-derived vesicles participating in cell-to-cell communications. Compared with conventional nanoparticles, exosomes are characterized by lipid bilayer membranes with abundant proteins and diverse types of cellular cargos. These unique features render exosomes a promising form of modality for therapeutic development. By utilizing genetic approaches, we engineered exosomes with cell-engaging antibodies on surfaces. These antibody-functionalized exosomes promote the formation of immunological synapses between cytotoxic T-lymphocytes and tumor cells and subsequent elimination of target cells. Furthermore, equipping exosomes with immunomodulatory domains resulted in potent anti-cancer immunity with high specificity in different preclinical animal models. These genetically reprogrammed exosomes provide a novel platform technology for the development of exosome-based immunotherapeutics.

Abstract: Functional differentiation of our body cell types depends on instruction transmitted via intercellular signaling. In prostate, the CD49a+CD90lo stromal smooth muscle cells (NPstrom) induce stem cells to differentiate by secreted hormones including proenkephalin (PENK). In cancer, PENK is absent in the CD90hi cancer-associated stromal cells (CPstrom). Without PENK, developing epithelial cells may differentiate into cells with overexpression of the adenocarcinoma antigen anterior gradient 2 (AGR2), a metastasis promoter. Cancer-secreted AGR2 also depletes NPstrom by inducing programmed cell death. Over the disease course, cancer cell differentiation is lost with emergence of more stem-like small cell carcinoma cells characterized by the expression of stem cell transcription factors (scTF) LIN28A, NANOG, POU5F1, SOX2, and decreased expression of β2-microglobulin (B2M) – phenotyped as scTF+B2Mlo. Experimentally, scTF transfection can convert scTF-B2Mhi adenocarcinoma cells into scTF+B2Mlo stem-like. PENK functions to inactivate scTF in stem cells as well as stem-like cancer cells to exit from the stem state and undergo differentiation with down-regulation of scTF and up-regulation of B2M. PENK, together with another hormone stanniocalcin 1 (STC1), can change cancer cells into ones that form gland-like structures containing a central lumen with apparent tight junctions between neighboring cells. Thus, the loss of cancer differentiation could be attributed to activation of scTF as in reprogramming, which could be reversed by PENK and STC1. Cancer cells, having multiple genomic alterations and being aneuploid, can still respond to these identified organ-specific signaling hormones. By gene expression, the PENK-negative CPstrom represents an underdeveloped PENK-positive NPstrom with lower expression of smooth muscle cell genes and genes associated with less differentiated cells. The bladder equivalent of NPstrom, CD13+ stromal cells in the lamina propria, also induce differentiation of stem cells from scTF+B2Mlo to scTF-B2Mhi but with expression of bladder instead of prostate genes demonstrating plasticity in stem cell response to different differentiation instructions.

Abstract: Heart failure (HF) is diagnosed using echocardiographic indices of filling pressure and systolic function, yet echocardiography is unavailable in most first-contact settings where patients with dyspnea first present. This paper describes a dual-signal smart stethoscope that simultaneously records chest phonocardiography and finger photoplethysmography. The stethoscope system is driven by a multimodal deep-learning model that estimates HF-relevant echocardiographic indices—pulmonary artery systolic pressure (PASP), E/e′, left atrial volume index (LAVI), and left ventricular ejection fraction (EF)—from a single 20-second recording. The model was trained on 1,828 recordings from 1,635 patients paired with same-day echocardiography at a tertiary hospital and evaluated on an independent held-out cohort of 118 recordings from 96 patients. The estimated indices discriminated guideline cut-offs with areas under the ROC curve of 0.81 for PASP ≥ 40 mmHg, 0.79 for LAVI > 34 mL/m², 0.77 for EF ≤ 40%, 0.78 for EF < 50%, and 0.66 for E/e′ > 14. Two pre-registered screening axes—a filling-pressure axis combining PASP, E/e′, and LAVI, and an EF axis—showed a double dissociation: the pressure axis identified HF with preserved EF physiology (AUROC 0.75 vs 0.37 for the EF axis), whereas the EF axis identified reduced EF (0.77 vs 0.62). A lightweight model deployed on the smartphone reproduced these results (correlation 0.98–0.99 with the research ensemble), and the two axes are presented in the clinical application as a staged display (normal, pre-HF, HF suspected). A 20-second bedside recording can therefore flag HF physiology before echocardiography, supporting point-of-care triage and earlier referral.
Keywords: heart failure; phonocardiography; photoplethysmography; echocardiography; multimodal deep learning; smart stethoscope

Abstract: When we started extracting tea catechins in grams-Kgs for the first time in the world since around 1985, many researchers wanted to have those samples for their study to prove the health benefits of tea. I supplied those samples to them, such as Epigallocatechin gallate(EGCg) and other minor catechins for free, for nearly 10 years before selling them to Sigma. Potent health promoting effects of tea catechins induced explosive expansion in two ways: one is a booming green tea bottled drinks and the other is the strong enthusiasm for the study of cancer prevention and on other diseases. I supplied kgs of Polyphenon®E(EGCg70%) and pure EGCg to the Clinical Trials Program of NCI(US National Cancer Institute) starting from 1996. Separately, I got involved in the pharmaceutical project of treating Genital Warts(caused by papilloma virus) by Polyphenon®E ointment from 1999 in the States. In 2006, US FDA approved the marketing of Veregen® in the States as a Genital Warts Healing Ointment with 10% Polyphenon®E as an API(Active Pharmaceutical Intredient). It was the first ever “Botanical Drug” approved by FDA.
In recent years, several projects, EGCg as an API, are seeking pharmaeutical sponsors
*A project to treat CIN(Cervical Intraepithelial Neoplasia) by EGCg suppossitory is now under Phase 2 trial.
*A project to treat sexual pain(vulvodynia) and enhance sexual arousal by EGCg ointment.
*A project to treat IBD(Inflammatory Bowel Diseases) by EGCg capsule intake.
*And others.

Abstract: Corneal transplantation is an important surgical intervention for restoring vision in patients with severe corneal diseases. However, postoperative complications, particularly immune-mediated graft rejection and microbial infections, remain significant challenges that may compromise graft survival. Cyclosporine A (CsA), an immunomodulatory agent, has been investigated for its potential to reduce immune-mediated graft rejection, whereas posaconazole (POS), a broad-spectrum antifungal agent, may offer an alternative approach for the management of ocular fungal infections. Based on these considerations, the present study aims to develop and characterize dual drug loaded nanofibrous formulations containing CsA and POS for potential topical ocular administration following corneal transplantation. Chitosan and Eudragit® RS 100 were investigated separately as polymeric carriers to evaluate their influence on nanofiber formation, physicochemical properties, drug loading, and release characteristics. The formulations were prepared using the electrospinning technique and characterized in terms of fiber morphology, diameter distribution, thermal properties, drug–polymer interactions, and in vitro drug release profiles. Furthermore, cytotoxicity and antifungal activity studies were conducted to investigate the biological performance of the developed formulations. This study is expected to provide preliminary insights into the feasibility of a dual drug delivery platform designed to combine immunomodulatory and antifungal activities, with potential applications in postoperative ocular drug delivery.
Keywords: Cyclosporine A, posaconazole, polymeric nanofiber, ocular drug delivery
Acknowledgements: The authors would like to thank to Anadolu University-BİBAM for SEM and 1H-NMR analyses, to Anadolu University-MERLAB for FT-IR analyses.