Comparison of the efficacy of royal jelly and melatonin combinations in experimentally induced wounds in geriatric and young mice.

BACKGROUND: Wound healing involves the repair of skin and other soft tissues after an injury. Royal jelly, a product of bees, possesses antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Melatonin, a circadian indoleamine, is produced in the pineal gland and other organs. This study explores the effects of melatonin and royal jelly, both individually and combined, on wound healing in geriatric and young mice. METHODS: The study includes 90 Balb/C mice divided into ten groups to assess the effects of royal jelly and melatonin on wound healing. Royal jelly was applied topically at a concentration of 300 mg/kg. Melatonin was formulated in a vaseline-based pomade at a concentration of 5 mg/kg. The substances were applied either separately or in combination to wounds created on the mice. RESULTS: Both substances significantly enhanced wound healing at a macroscopic level in both age groups. Melatonin was found to be more effective during the initial wound formation process, whereas royal jelly was more beneficial during the granulation phase. However, significant results at a histopathological level were observed only in geriatric animals. CONCLUSION: The findings suggest a potential new therapeutic approach to enhance wound healing, particularly in elderly individuals. However, these findings need to be supported through further research and clinical trials.

Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.

BACKGROUND: Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. OBJECTIVE: This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. METHODS: MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. RESULTS: Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. CONCLUSION: Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.

CNT incorporation improves the resolution and stability of porous 3D printed PLGA/HA/CNT scaffolds for bone regeneration.

In this study, 3D printed porous poly(lactide-co-glycolide) (PLGA) and its nanocomposites with 5 wt. % hydroxyapatite (HA) and 0.5, 1 and 2 wt. % carboxyl-functionalized multi-walled carbon nanotube (CNT) scaffolds were fabricated by using extrusion-based printing. The printing parameters were optimized by rheological studies. The rheological studies demonstrated shear thinning properties for all compositions and an increase in storage modulus was observed after the addition of CNT. Porous PLGA/HA/CNT scaffolds were printed by applying a pressure of 4.76 bar at 125 °C. The addition of 0.5 wt. % of CNT reduced the strut size and increased the porosity from 42% to 60%. The increase in storage modulus and decrease in strut size were related to hydrogen bonding between CNT, HA and PLGA which ultimately improved shape fidelity. The scaffolds were characterized by analysis of their chemical structure, water contact angle measurement,in vitrobioactivity test, biodegradation test, mechanical analysis, andin vitrocell studies. The scaffolds were found to be more hydrophilic by the incorporation of CNTs. Also, degradation studies showed that the microstructure of the scaffold became more stable with the addition of HA and CNT. The compressive modulus of PLGA/HA/CNT2 scaffold was found to be 548.5 MPa, which is found suitable to replace cancellous bone. The scaffolds were found to be highly biocompatible which is possibly due to alignment of CNT and PLGA during 3D printing process. Alizarin red staining indicated improvement of mineralization of MC3T3-E1 cells on the CNT incorporated porous 3D scaffolds. The results suggest that the produced porous 3D printed PLGA/HA/CNT scaffolds are promising for bone regeneration applications.

Profitability and Cost Analysis for Contract Broiler Production in Turkey.

This study uses the data obtained from 63 broiler farms engaged in contract farming in Akhisar, Turkey. The average feed conversion ratio in the broiler farms is 1.75, the average live weight 2.25 kg, and the mean market age 38.9 days. The feed conversion rate and the income generated are highly correlated (r = -0.76). The production index is 313.4. According to this production index value, 47.6% of the enterprises are below the average production index. It is highest when the marketing age is greater than 38 days, less than and equal to 40. In other words, it is the optimum market age range where carcass yield is at maximum. The average mortality rate is 4.68%. In 52.4% of the enterprises, the mortality rate is above 5%. There is a low level of correlation between the mortality rate and income (r = -0.26). In broiler farming, mortality rate, and feed conversion ratio are factors that directly affect the success and income of the breeder. In broiler farming, the heating cost has the largest share of the total cost, followed by the litter cost. They are followed by labor, electricity, and pesticide costs. Variable costs account for three-quarters of the total operating costs. The farms have a mean gross value of production of $23.797 per m2 and $1.400 per broiler in a breeding period. The profit margin is 0.572 $/kg per broiler. The mean enterprise net income in the breeding period is $9.197 per m2 and $0.541 per broiler. These findings suggest that broiler farming is a profitable venture.

Measuring the Effects of Detomidine and Medetomidine Alone and in Combination with Ketamine on Tear Production and Intraocular Pressure in Common Buzzards (Buteo buteo).

The purpose of this study was to measure the effects of detomidine and medetomidine alone or in combination with ketamine on Schirmer tear test I (STT I) results and intraocular pressures (IOPs) in the common buzzard (Buteo buteo). Fourteen ophthalmologically healthy common buzzards were randomly assigned to 1 of 2 α-2 adrenoreceptor agonist groups: a detomidine group (group 1) and a medetomidine group (group 2). The detomidine group had 2 subgroups, detomidine alone or in combination with ketamine. Similarly, the medetomidine group had 2 subgroups, medetomidine alone or in combination with ketamine. Five minutes after α-2 adrenoreceptor agonist administration, the first measurements of STT I and IOP were collected. Ketamine was injected intramuscularly immediately after the first measurements were recorded. Schirmer tear test I and IOP measurements were repeated 5 minutes after ketamine administration. Measurements were obtained for 3 subgroups per agonist grouping: baseline 1, detomidine alone and detomidine with ketamine for group 1, and baseline 2, medetomidine alone and medetomidine with ketamine for group 2. Both IOP and STT I decreased significantly after sedation, anesthesia, or both. Intraocular pressure was significantly lower in the detomidine-ketamine group compared with the detomidine alone group. The IOP and STT I significantly decreased in both the medetomidine alone and medetomidine-ketamine groups when compared with those for all 14 unanesthetized animals before administering the α-2 adrenoreceptor agonist and ketamine. When α-2 adrenoreceptor agonists were considered as a single group (groups 1 and 2 combined), IOP also showed a significant decrease in the α-2 adrenoreceptor agonist-ketamine groups compared with the α-2 adrenoreceptor agonists alone, but STT I did not. According to the results obtained from these common buzzards, no statistical differences were found between the detomidine and medetomidine (alone) groups or detomidine-ketamine and medetomidine-ketamine groups in terms of STT I and IOP.

Dental follicle mesenchymal stem cells ameliorated glandular dysfunction in Sjögren's syndrome murine model.

OBJECTIVE: Dental mesenchymal stem cells (MSCs) are potential for use in tissue regeneration in inflammatory diseases due to their rapid proliferating, multilineage differentiation, and strong anti-inflammatory features. In the present study, immunoregulatory and glandular tissue regeneration effects of the dental follicle (DF)MSCs in Sjögren's Syndrome (SS) were investigated. METHODS: Dental follicle (DF) tissues were obtained from healthy individuals during tooth extraction, tissues were digested enzymatically and DFMSCs were cultured until the third passage. DFMSCs were labeled with Quantum dot 655 for cell tracking analysis. The induction of the SS mouse model was performed by the injection of Ro60-273-289 peptide intraperitoneally. DFMSCs were injected intraperitoneally, or into submandibular, or lacrimal glands. Splenocytes were analyzed for intracellular cytokine (IFN-γ, IL-17, IL-10) secretion in T helper cells, lymphocyte proliferation, and B lymphocyte subsets. Histologic analysis was done for submandibular and lacrimal glands with hematoxylin-eosin staining for morphologic examination. RESULTS: The systemic injection of DFMSCs significantly reduced intracellular IFN-γ and IL-17 secreting CD4+ T cells in splenocytes (p<0.05), and decreased inflammatory cell deposits and fibrosis in the glandular tissues. DFMSCs differentiated to glandular epithelial cells in submandibular and lacrimal injections with a significant reduction in lymphocytic foci. The results showed that few amounts of DFMSCs were deposited in glandular tissues when applied intraperitoneally, while high amounts of DFMSCs were located in glandular tissues and differentiated to glandular epithelial cells when applied locally in SS murine model. CONCLUSION: DFMSCs have the potential for the regulation of Th1, Th17, and Treg balance in SS, and ameliorate glandular dysfunction. DFMSCs can be a beneficial therapeutic application for SS.

Discovering Potential Taxonomic Biomarkers of Type 2 Diabetes From Human Gut Microbiota via Different Feature Selection Methods.

Human gut microbiota is a complex community of organisms including trillions of bacteria. While these microorganisms are considered as essential regulators of our immune system, some of them can cause several diseases. In recent years, next-generation sequencing technologies accelerated the discovery of human gut microbiota. In this respect, the use of machine learning techniques became popular to analyze disease-associated metagenomics datasets. Type 2 diabetes (T2D) is a chronic disease and affects millions of people around the world. Since the early diagnosis in T2D is important for effective treatment, there is an utmost need to develop a classification technique that can accelerate T2D diagnosis. In this study, using T2D-associated metagenomics data, we aim to develop a classification model to facilitate T2D diagnosis and to discover T2D-associated biomarkers. The sequencing data of T2D patients and healthy individuals were taken from a metagenome-wide association study and categorized into disease states. The sequencing reads were assigned to taxa, and the identified species are used to train and test our model. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization, Maximum Relevance and Minimum Redundancy, Correlation Based Feature Selection, and select K best approach. To test the performance of the classification based on the features that are selected by different methods, we used random forest classifier with 100-fold Monte Carlo cross-validation. In our experiments, we observed that 15 commonly selected features have a considerable effect in terms of minimizing the microbiota used for the diagnosis of T2D and thus reducing the time and cost. When we perform biological validation of these identified species, we found that some of them are known as related to T2D development mechanisms and we identified additional species as potential biomarkers. Additionally, we attempted to find the subgroups of T2D patients using k-means clustering. In summary, this study utilizes several supervised and unsupervised machine learning algorithms to increase the diagnostic accuracy of T2D, investigates potential biomarkers of T2D, and finds out which subset of microbiota is more informative than other taxa by applying state-of-the art feature selection methods.

Bioinspired hydrogel surfaces to augment corneal endothelial cell monolayer formation.

Corneal endothelial cells (CECs) have limited proliferation ability leading to corneal endothelium (CE) dysfunction and eventually vision loss when cell number decreases below a critical level. Although transplantation is the main treatment method, donor shortage problem is a major bottleneck. The transplantation of in vitro developed endothelial cells with desirable density is a promising idea. Designing cell substrates that mimic the native CE microenvironment is a substantial step to achieve this goal. In the presented study, we prepared polyacrylamide (PA) cell substrates that have a microfabricated topography inspired by the dimensions of CECs. Hydrogel surfaces were prepared via two different designs with small and large patterns. Small patterned hydrogels have physiologically relevant hexagon densities (∼2000 hexagons/mm2 ), whereas large patterned hydrogels have sparsely populated hexagons (∼400 hexagons/mm2 ). These substrates have similar elastic modulus of native Descemet's membrane (DM; ∼50 kPa) and were modified with Collagen IV (Col IV) to have biochemical content similar to native DM. The behavior of bovine corneal endothelial cells on these substrates was investigated and results show that cell proliferation on small patterned substrates was significantly (p = 0.0004) higher than the large patterned substrates. Small patterned substrates enabled a more densely populated cell monolayer compared to other groups (p = 0.001 vs. flat and p < 0.0001 vs. large patterned substrates). These results suggest that generating bioinspired surface topographies augments the formation of CE monolayers with the desired cell density, addressing the in vitro development of CE layers.

Substrate stiffness effects on SH-SY5Y: The dichotomy of morphology and neuronal behavior.

Like many other cell types, neuroblastoma cells are also known to respond to mechanical cues in their microenvironment in vitro. They were shown to have mechanotransduction pathways, which result in enhanced neuronal morphology on stiff substrates. However, in previous studies, the differentiation process was monitored only by morphological parameters. Motivated by the lack of comprehensive studies that investigate the effects of mechanical cues on neuroblastoma differentiation, we used SH-SY5Y cells differentiated on polyacrylamide (PA) gels as a model. Cells differentiated on the surface of PA hydrogels with three different elastic moduli (0.1, 1, and 50 kPa) were morphologically evaluated and their electrophysiological responsiveness was probed using calcium imaging. Immunodetection of neural marker TUJ1 and p-FAK was used for biochemical characterization. Groups with defined stiffness that are matching and nonmatching to neural tissue extracellular matrix were used to distinguish biomimetic results from other effects. Results show that while cells display morphologies that do not resemble neurons on soft substrates, they are in fact electrophysiologically more responsive and abundant in neuronal marker TUJ1. Our findings suggest that while neuronal differentiation occurs more efficiently in microenvironments mechanically mimicking neural tissue, the SH-SY5Y model demonstrates morphologies that conflict with neuronal behavior under these conditions. These results are expected to contribute considerable input to researchers that use SH-SY5Y as a neuron model.