Development of a novel laboratory photodynamic therapy device: automated multi-mode LED system for optimum well-plate irradiation.

Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.

Assessing cytotoxic activities, theoretical and in silico molecular docking calculations of phthalocyanines bearing cinnamyloxy-groups.

Cancer has been recognized as one of the deadliest diseases in the world in recent years. By chemically tailoring specific properties, anticancer agents can be prepared very effectively for the treatment of various cancer types. In this manner, as anticancer agents, a series of soluble metal-free and metallophthalocyanines carrying cinnamyloxy-groups at peripheral ß-positions have been prepared. All synthesized phthalocyanines were characterized by various spectroscopic approaches such as ultraviolet - visible (UV - Vis), Fourier transform infrared (FT-IR), and matrix-assisted laser deionization/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) techniques. These compounds are highly soluble in dimethyl sulfoxide (DMSO) and soluble in common organic solvents. The spectroscopic properties, cytotoxicity, and theoretical calculations of these complexes have been investigated. In cytotoxicity tests, compounds 1, 4, and 7 are the most active against HT-29 cell lines with IC50 values of 36.9 µM, 32.5 µM, and 51.1 µM, respectively. Also, the most and the least cytotoxic compounds against healthy CCD cell line is compounds 5 and 6 with the IC50 value of 13.4 µM and >250 µM, respectively. The PDB ID:4BQG target protein representing the HT-29 cancer cell line and the anti-cancer activities of phthalonitrile and its phthalocyanines were supported by molecular docking studies. Density Functional Theory (DFT) study supported the experimental results, including the spectral data, and implied that the compounds 5-7 are comparable by their characteristics, such as electronic properties, optical properties, electrostatic potentials, reactivity parameters, with the earlier studied compounds 2-4, which were successfully proved to be good candidates for cancer treatment.Communicated by Ramaswamy H. Sarma.

Complex bio rhythms.

Complex biorhythms are characteristic of ubiquitous phenomena appearing in many disciplines of human knowledge. This Special Issue collects articles devoted to different complex biorhythms phenomena such as cardiac dynamics, Covid-19 dynamics, dynamics of neural networks, cell dynamics, and a few articles devoted to general methods. It furnishes a rich overview of the field and can stimulate and inspire further researches.

Investigation of the therapeutic effect of 5-aminolevulinic acid based photodynamic therapy on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous type of cancer and current treatment options limit successful therapy outcomes. Photodynamic therapy (PDT) has attracted attention as an alternative approach in the treatment of different types of cancer. However, there is no study in the literature regarding the effect of PDT on HCC, in vitro. Therefore, the aim of this study was to determine the cytotoxic and apoptotic effects of 5-aminolevulinic acid (5-ALA)/PDT on two different HCC cell lines in terms of hepatitis B virus (HBV) infection. The therapeutic effects of 5-ALA-based PDT on HCC cell lines (Huh-7 and SNU-449) were evaluated by PpIX-fluorescence accumulation, WST-1 analysis, Annexin V analysis, and acridine orange/ethidium bromide staining after irradiation with different light doses through diode laser. The results showed that 1 mM 5-ALA displayed higher PpIX fluorescence in the SNU-449 cell line than the Huh-7 cell line after 4 h of incubation. After irradiation with different light doses (3, 6, 9, and 12 J/cm2), 5-ALA significantly reduced the proliferation of HCC cells and induced apoptotic cell death (p < 0.01). Furthermore, SNU-449 cells were more responsive to 5-ALA-based PDT than Huh-7 cells due to possibly its molecular features as well as viral HBV status. Our preliminary data obtained from this study may contribute to the development of 5-ALA/PDT-based treatment strategies in the treatment of HCC. However, this study could be improved by the elucidation of the molecular mechanisms of cell death induced by 5-ALA/PDT in HCC cells, the use of different photosensitizer, light sources, and in vivo experiments.

The effect of attentional focusing strategies on EMG-based classification.

Earlier studies showed that external focusing enhances motor performance and reduces muscular activity compare to internal one. However, low activity is not always desired especially in case of Human-Machine Interface applications. This study is based on investigating the effects of attentional focusing preferences on EMG based control systems. For the EMG measurements via biceps brachii muscles, 35 subjects were asked to perform weight-lifting under control, external and internal focus conditions. The difference between external and internal focusing was found to be significant and internal focus enabled higher EMG activity. Besides, six statistical features, namely, RMS, maximum, minimum, mean, standard deviation, and variance were extracted from both time and frequency domains to be used as inputs for Artificial Neural Network classifiers. The results found to be 87.54% for ANN1 and 82.69% for ANN2, respectively. These findings showed that one's focus of attention would be predicted during the performance and unlike the literature, internal focusing could be also useful when it is used as an input for HMI studies. Therefore, attentional focusing might be an important strategy not only for performance improvement to human movement but also for advancing the study of EMG-based control mechanisms.

Investigation of LED-based photodynamic therapy efficiency on breast cancer cells.

Photodynamic therapy (PDT) is based on special light source, photosensitizer (PS), and in the presence of oxygen. Different light sources have been used for PDT applications. Recent studies have focused on LED light sources for PDT applications due to reducing the cost of laser-based PDT and providing easy access for research laboratory or clinic facilities. LED-mediated PDT applications have shown promising results for the treatment of different types of disease. However, few studies have determined the effects of LED-based PDT on cancer cells. For the first time, the aim of this study was to explore the therapeutic effects of 5-aminolevulinic acid (5-ALA)-mediated PDT after LED irradiation on two sub-types (a poorly aggressive MCF-7 and a highly aggressive MDA-MB-231) of breast cancer cell lines. The effectiveness of 5-ALA PDT treatment was evaluated by WST-1, annexin V, and acridine orange staining with different energy levels. The LED system was specially developed with optical power and wavelength stability techniques. The system consists of user interface and embedded LED controller with real-time optic power output calibration by photodiode feedback. Our results demonstrated that the cell viability of breast cancer cells was considerably decreased a LED dose-dependent manner (P < 0.05). Additionally, a significant increase in the percentage of apoptotic cells was detected in breast cancer cells after irradiation with LED at a density of 18 and 30 J/cm2 energy. Consequently, the LED system could be effectively used for irradiation of 5-ALA in the treatment of breast cancer cells.

Development of new descriptor for melanoma detection on dermoscopic images.

Early detection of melanoma has critical importance for the success of the treatment. However, a successful early diagnosis is only possible with the existence of discriminative features. In this study, a new descriptor based on the number of colors was developed in order to successfully diagnose lesions of melanoma. The number of colors is the main feature in the identification of melanoma-type skin lesions. The user must select a threshold value when calculating the number of colors of the lesion. The incorrect threshold value selection of non-expert users disrupts the aforementioned feature and also leads to significant diagnostic errors. In this study, it was revealed that color counting threshold values have a significant effect on the distinctiveness of the number of colors. In the three dermoscopic databases, color counting threshold values that provide the maximum distinctiveness on melanoma and benign lesions were determined as 0 and 0.123 respectively. By using these color counting threshold values, the number of colors for each sample in the data sets was calculated separately. Following that, a novel attribute called the number of color difference was defined as a function of color counting threshold values. Experiments using only the proposed new descriptor yielded 52.7% higher f-measure and 84.5% higher true-positive performance than the number of colors used in the literature. The results obtained in this study revealed the importance of accurately determining the number of colors the lesions had and states that the applied color counting threshold significantly influences the classification results. Thereby, a new method is proposed for determining the critical color counting threshold. We claim that the classical ABCD rule should be improved by our new descriptor. Graphical abstract Fig. 1 Selection of threshold has vital effect on skin lesion classification. A new method to select the correct threshold value and a new attribute for correct classification were developed.

Optimization of 5-aminolevulinic acid-based photodynamic therapy protocol for breast cancer cells.

BACKGROUND: Photodynamic therapy (PDT) is a therapeutic strategy for the treatment of cancer. 5-aminolevulinic acid (5-ALA) as a precursor of the protoporphyrin IX (PpIX) has a great potential for PDT application. Although 5-ALA-based PDT has been studied in many pre-clinical and clinical studies for breast cancer, there are different PDT application protocols in the literature. Therefore, the aim of this study was to determine the optimal in vitro protocol for 5-ALA-based PDT in breast cancer treatment. METHODS: The therapeutic effects of 5-ALA (1 and 2.5 mM) on two different subtypes of breast cancer cell line (MCF-7 and MDA-MB-231) were evaluated by PpIX-fluorescence accumulation and WST-1 analysis. Then, the cells were irradiated with diode laser at different doses (1.5, 3, 6, 9 and 12 J/cm2). After irradiation, the anticancer effects of 5-ALA were analyzed through cell viability and cell death analysis. RESULTS: Our results showed that 5-ALA exhibited a higher PpIX fluorescence in both breast cancer cells for 4 h incubation. After irradiation, 1 mM 5-ALA significantly reduced the proliferation of breast cancer cells in a laser dose-dependent manner and induced apoptotic cell death upon 24 h incubation (p < 0.05). However, MDA-MB-231 cells were more sensitive to 5-ALA-based PDT than MCF-7 cells in a dose of 9 J/cm2 and 12 J/cm2. CONCLUSION: Our preliminary findings proposed an optimal in vitro protocol of 5-ALA-based PDT by using a laser diode for breast cancer. However, there is a need to investigate the underlying molecular mechanisms of 5-ALA/PDT sensitivity among the subtypes of breast cancer.

A New handheld singlet oxygen detection system (SODS) and NIR light source based phantom environment for photodynamic therapy applications.

Photodynamic therapy (PDT) is an emerging treatment modality in various areas such as cancer treatment and disinfection. The photosensitizer and oxygen have crucial roles for effective PDT treatment. The quantitative evaluation of singlet oxygen, which is a gold standard for monitoring effective treatment, remains as an important problem for PDT. However, low quantum yield and low life span of the singlet oxygen make the system expensive, unnecessarily large and unadaptable for clinical usage. In our study, a new mobile singlet oxygen detection system (SODS) was designed to detect singlet oxygen illumination during PDT and a new singlet oxygen phantom environment was constituted to test the designed SODS system. The singlet oxygen phantom environment composed of fast switching led driver & microcontroller and led light source (1200-1300 nm radiation). The elements of the singlet oxygen detection system are optic filter and collimation, avalanche photodiode transimpedance amplifier, differential amplifier and a signal processing block. According to the performance evaluation of the system on the phantom environment, the presented SODS can measure the illuminations at 1270 nm wavelength between 10 ns and 15 µs timespans. The results showed that the proposed system might be a good candidate for clinical PDT applications.

Relationship between vibrotactile detection threshold in the Pacinian channel and complex mechanical modulus of the human glabrous skin.

The goal of this study was to investigate the relationship between the psychophysical vibrotactile thresholds of the Pacinian (P) channel and the mechanical properties of the skin at the fingertip. Seven healthy adult subjects (age: 23-30) participated in the study. The mechanical stimuli were 250-Hz sinusoidal bursts and applied with cylindrical contactor probes of radii 1, 2, and 3.5 mm on three locations at the fingertip. The duration of each burst was 0.5 s (rise and fall time: 50 ms). The subjects performed a two-interval forced-choice task while the stimulus levels changed for tracking the threshold at 75% probability of detection. There were significant main effects of contactor radius and location (two-way ANOVA, values of p < 0.001). The thresholds decreased as the contactor radius increased (i.e., spatial summation effect) at all locations. The thresholds were lowest near the whorl at the fingertip. Additionally, we measured the mechanical impedance (specifically, the storage and loss moduli) at the contact locations. The storage moduli did not change with the contactor location, but the loss moduli were lowest near the whorl. While the loss moduli decreased, the storage moduli increased (e.g., more springiness) as the contactor radius increased. There was moderate and barely significant correlation between the absolute thresholds and the storage moduli (r = 0.650, p = 0.058). However, the correlation between the absolute thresholds and the loss moduli was high and very significant (r = 0.951, p < 0.001). The results suggest that skin mechanics may be important for locally shaping psychophysical detection thresholds, which would otherwise be expected to be constant due to uniform Pacinian innervention density at the fingertip.

An optoelectromechanical tactile sensor for detection of breast lumps.

We developed a compact tactile imaging (TI) system to guide the clinician or the self-user for noninvasive detection of breast tumors. Our system measures the force distribution based on the difference in stiffness between a palpated object and an abnormality within. The average force resolution, force range, and the spatial resolution of the device are 0.02 N, 0-4 N, and 2.8 mm, respectively. To evaluate the performance of the proposed TI system, compression experiments were performed to measure the sensitivity and specificity of the system in detecting tumor-like inclusions embedded in tissue-like cylindrical silicon samples. Based on the experiments performed with 11 inclusions, having two different sizes and two different stiffnesses located at three different depths, our TI system showed an average sensitivity of 90.8 ± 8.1 percent and an average specificity of 89.8 ± 12.7 percent. Finally, manual palpation experiments were performed with 12 human subjects on the same silicon samples and the results were compared to that of the TI system. The performance of the TI system was significantly better than that of the human subjects in detecting deep inclusions while the human subjects performed slightly better in detecting shallow inclusions close to the contact surface.