The role of vertical ex vivo dermoscopy relevant to clinical diagnosis has not been investigated yet. Study objectives were defining, describing, and determining the importance of the structures visible using vertical ex vivo dermoscopy in the diagnosis of malignant skin lesions, as well as determining their accuracy in the assessment of tumor margins. A prospective, descriptive study was conducted in two University centers. Digital images of completely excised skin lesions, fixed in formalin, before histopathological diagnosis were used for analysis. BCCs had the most diverse dermoscopic presentation on the vertical section, while SCCs showed a similar presentation in most cases. Vertical dermoscopy of thin melanomas was almost identical, unlike nodular melanomas. Thickness accuracy assessed by dermatologist was 0.753 for BCC, 0.810 for SCC, and 0.800 for melanomas, whereas assessment by pathologist was 0.654, 0.752, and 0.833, respectively. The accuracy of tumor width assessment was 0.819 for BCCs, 0.867 for SCCs and 1.000 for melanoma as estimated by a Dermatologist. Interobserver agreement was 0.71 for BCC, 0.799 for SCC and 0.832 for melanomas. Vertical ex vivo dermoscopy may contribute to the distinction between BCCs, SCCs, and melanomas. Moreover, regardless of the doctor\'s specialty, it enables a good assessment of the tumor\'s margins.

BACKGROUND: This study evaluated electrical conductivity in human liver tissue in the 3-1000 kHz frequency range to compare normal versus tumor tissues under in vivo versus ex vivo conditions.
METHODS: Previous informed consent was obtained from twenty patients undergoing liver resection in whom liver electrical conductivity was measured during surgery and after resection.
RESULTS: We found higher electrical conductivity values in tumor tissues than in normal tissue in both in vivo (0.41 ± 0.10 vs. 0.13 ± 0.06 S/m) and ex vivo (0.27 ± 0.09 vs. 0.12 ± 0.07 S/m) conditions (at 3 kHz). The electric properties also showed a promising potential for distinguishing between different tissue types including metastasis, cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), hepatic cirrhosis, and normal liver (both in vivo and ex vivo). At 3 kHz, in vivo electrical conductivity for cholangiocarcinoma, HCC, and metastasis were 0.35, 0.42 ± 0.13, and 0.41 ± 0.08 S/m, respectively, which differed significantly from each other (p < 0.05).
CONCLUSIONS: These findings could potentially improve liver disease diagnostics through electrical conductivity measurements and treatment techniques involving electric fields. Future research should focus on expanding the sample size to refine the categorization and comparison processes across diverse human liver tissue types.

OBJECTIVE: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo.
METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings.
RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images.
CONCLUSIONS: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

The widespread use of bisphenol A (BPA) in polycarbonate plastics and epoxy resins has made it a prevalent environmental pollutant in aquatic ecosystems. BPA poses a significant threat to marine and freshwater wildlife due to its documented endocrine-disrupting effects on various species. Manufacturers are increasingly turning to other bisphenol compounds as supposedly safer alternatives. In this study, we employed in vitro reporter gene assays and ex vivo precision-cut liver slices from Atlantic cod (Gadus morhua) to investigate whether BPA and 11 BPA analogs exhibit estrogenic, antiestrogenic, androgenic, or antiandrogenic effects by influencing estrogen or androgen receptor signaling pathways. Most bisphenols, including BPA, displayed estrogenic properties by activating the Atlantic cod estrogen receptor alpha (gmEra). BPB, BPE, and BPF exhibited efficacy similar to or higher than that of BPA, with BPB and BPAF being more potent agonists. Additionally, some bisphenols, like BPG, induced estrogenic effects in ex vivo liver slices despite not activating gmEra in vitro, suggesting structural modifications by hepatic biotransformation enzymes. While only BPC2 and BPAF activated the Atlantic cod androgen receptor alpha (gmAra), several bisphenols exhibited antiandrogenic effects by inhibiting gmAra activity. This study underscores the endocrine-disrupting impact of bisphenols on aquatic organisms, emphasizing that substitutes for BPA may pose equal or greater risks to both the environment and human health.

Adipose tissue and skeletal muscle dysfunction play a central role in cardiometabolic morbidity. Ashwagandha and Andrographis are purported to have anti-inflammatory and antioxidant activity, but this is based on exposure of cells to the parent compounds ignoring phytochemical absorption and metabolism. We explored the anti-inflammatory/antioxidant effects of ashwagandha and Andrographis in ex vivo human models of skeletal muscle and adipose tissue. Healthy participants supplemented with 2000 mg/day Andrographis (n = 10) or 1100 mg/day ashwagandha (n = 10) for 28 days. Sera collected pre (D0) and post (D28) supplementation were pooled by timepoint and added to adipose explant (AT) and primary human myotube (SKMC) culture media (15% v/v) for treatment. A Taqman panel of 56 genes was used to quantify these. In AT, treatment with ashwagandha sera decreased the expression of genes involved in antioxidant defence and inflammatory response (CCL5, CD36, IL6, IL10, ADIPOQ, NFEL2, UCP2, GPX3, GPX4; geometric 95% CI for fold change > 1) and altered the expression of genes involved in fatty acid metabolism. In SKMC, ashwagandha sera altered FOXO1 and SREBF1 expression. Andrographis sera decreased IL18 and SERPINEA3 expression in AT. This physiologically relevant in vitro screening characterises the effects of ashwagandha in AT to guide future clinical trials.

Lung diseases such as cancer substantially alter the mechanical properties of the organ with direct impact on the development, progression, diagnosis, and treatment response of diseases. Despite significant interest in the lung\'s material properties, measuring the stiffness of intact lungs at sub-alveolar resolution has not been possible. Recently, we developed the crystal ribcage to image functioning lungs at optical resolution while controlling physiological parameters such as air pressure. Here, we introduce a data-driven, multiscale network model that takes images of the lung at different distending pressures, acquired via the crystal ribcage, and produces corresponding absolute stiffness maps. Following validation, we report absolute stiffness maps of the functioning lung at microscale resolution in health and disease. For representative images of a healthy lung and a lung with primary cancer, we find that while the lung exhibits significant stiffness heterogeneity at the microscale, primary tumors introduce even greater heterogeneity into the lung\'s microenvironment. Additionally, we observe that while the healthy alveoli exhibit strain-stiffening of ∼1.75 times, the tumor\'s stiffness increases by a factor of six across the range of measured transpulmonary pressures. While the tumor stiffness is 1.4 times the lung stiffness at a transpulmonary pressure of three cmH2O, the tumor\'s mean stiffness is nearly five times greater than that of the surrounding tissue at a transpulmonary pressure of 18 cmH2O. Finally, we report that the variance in both strain and stiffness increases with transpulmonary pressure in both the healthy and cancerous lungs. Our new method allows quantitative assessment of disease-induced stiffness changes in the alveoli with implications for mechanotransduction.

In this study, scalp tissues from Korean adults between 20 and 80 without skin disease were used. Scalp tissues were processed, and hair follicles were isolated and cultured with different treatments (including Bioscalp, Ultra Exo Booster, and Ultra S Line Plus) from Ultra V company. Over 12 days, observations and measurements of hair follicle characteristics were recorded at intervals (Days 0, 3, 6, 9, and 12). The study assessed the impact of these substances on hair follicle growth and morphology. Bioscalp, combined with Ultra Exo Booster and Ultra S Line Plus, showed significant hair elongation in ex vivo. Preservation of hair bulb diameter was observed, indicating potential for sustained hair growth by exosome-based products. The hair growth cycle analysis suggested a lower transition to the catagen stage in test products from Ultra V compared to non-treated groups. The research findings indicated that the tested formulations, especially the combination of Bioscalp, Ultra Exo Booster, and Ultra S Line Plus, demonstrated significant effectiveness in promoting hair growth, maintaining the integrity of the hair bulb, and reducing the transition to the catagen stage. The study suggests promising alternative treatments for hair loss, illustrating results that were as good as those of the conventional testing product groups.

A scientific interrogation-driven approach to the clinical management of cancer patients is based on molecular profiling of the tumor. Empowered by the knowledge of oncogenic drivers and biomarkers, oncologists chart an optimal treatment path toward increasing the mathematical probability of a positive outcome. In this entire chain of events, an experimental proof of logical interrogation has never been incorporated before. Here, we provide the first evidence that the result of ex vivo testing of a drug matched to the genomic profiling of an N-of-1 tumor can deliver meaningful insight connecting scientific interrogation and a clinical event. Using resected tissues from endometrial (EC) and ovarian (OC) cancer patients, we designed a personalized ex vivo platform to test combinations of drugs in the default histological architecture of the individual tumors. Following the CART-T cells\' principle, we co-cultured with autologous T-cells to test targeted drugs and immune checkpoint inhibitors. The study was designed with a limited clinical information window from patient registration/consent to obtaining the tumor tissues, and adjuvant treatment/post-surgery event (PSE) data were accessed retrospectively. Using a checkerboard analysis, we found that PSE-free survival time was longer in patients whose therapy \"matched\" the effective drug combination in ex vivo culture/co-cultures compared to those with no effect. Specifically, out of 32 EC patients in the \"test & treatment-matched\" category whose tumor cells failed to respond to ex vivo drug testing, none achieved > 4 and > 3 years of PSE-free survival. In contrast, out of 38 EC patients in the \"test & treatment-matched\" category, 4 and 6 patients, whose tumor cells responded to drugs in ex vivo culture, achieved > 4 and > 3 years of PSE-free survival, respectively. Cases with genomically-guided ex vivo testing showed that a \"match\" between an effective ex vivo drug combination and therapy resulted in late PSE, whereas a \"match\" between prescribed treatment and an ineffective drug combination in ex vivo testing led to early PSE. Our study demonstrates that integrating genomic data with personalized drug testing on an ex vivo culture/co-culture platform is an effective tool for modeling functional precision medicine in gynecological cancers. This approach bridges the gap between next-generation drug testing in translational research and patient care, providing insight for improved treatment outcomes.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

暂无摘要。