Controlled Sr(ii) ion release from in situ crosslinking electroactive hydrogels with potential for the treatment of infections.

The development of electrochemical stimuli-responsive drug delivery systems is of both academic and industrial interest due to the ease with which it is possible to trigger payload release, providing drug delivery in a controllable manner. Herein, the preparation of in situ forming hydrogels including electroactive polypyrrole nanoparticles (PPy-NPs) where Sr2+ ions are electrochemically loaded for electrically triggered release of Sr2+ ions is reported. The hydrogels were characterized by a variety of techniques including Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), X-ray diffraction (XRD), cyclic voltammetry (CV), etc. The cytocompatibility towards human mesenchymal stem cells (MSCs) and fibroblasts were also studied. The Sr2+ ion loaded PEC-ALD/CS/PPy-NPs hydrogel showed no significant cytotoxicity towards human mesenchymal stem cells (MSCs) and fibroblasts. Sr2+ ions were electrochemically loaded and released from the electroactive hydrogels, and the application of an electrical stimulus enhanced the release of Sr2+ ions from gels by ca. 2-4 fold relative to the passive release control experiment. The antibacterial activity of Sr2+ ions against E. coli and S. aureus was demonstrated in vitro. Although these prototypical examples of Sr2+ loaded electroactive gels don't release sufficient Sr2+ ions to show antibacterial activity against E. coli and S. aureus, we believe future iterations with optimised physical properties of the gels will be capable of doing so.

Preparation and Characterization of Graphene-Based 3D Biohybrid Hydrogel Bioink for Peripheral Neuroengineering.

Peripheral neuropathies can occur as a result of axonal damage, and occasionally due to demyelinating diseases. Peripheral nerve damage is a global problem that occurs in 1.5%-5% of emergency patients and may lead to significant job losses. Today, tissue engineering-based approaches, consisting of scaffolds, appropriate cell lines, and biosignals, have become more applicable with the development of three-dimensional (3D) bioprinting technologies. The combination of various hydrogel biomaterials with stem cells, exosomes, or bio-signaling molecules is frequently studied to overcome the existing problems in peripheral nerve regeneration. Accordingly, the production of injectable systems, such as hydrogels, or implantable conduit structures formed by various bioprinting methods has gained importance in peripheral neuro-engineering. Under normal conditions, stem cells are the regenerative cells of the body, and their number and functions do not decrease with time to protect their populations; these are not specialized cells but can differentiate upon appropriate stimulation in response to injury. The stem cell system is under the influence of its microenvironment, called the stem cell niche. In peripheral nerve injuries, especially in neurotmesis, this microenvironment cannot be fully rescued even after surgically binding severed nerve endings together. The composite biomaterials and combined cellular therapies approach increases the functionality and applicability of materials in terms of various properties such as biodegradability, biocompatibility, and processability. Accordingly, this study aims to demonstrate the preparation and use of graphene-based biohybrid hydrogel patterning and to examine the differentiation efficiency of stem cells into nerve cells, which can be an effective solution in nerve regeneration.

Formulating and Characterizing an Exosome-based Dopamine Carrier System.

Exosomes between 40 and 200 nm in size constitute the smallest subgroup of extracellular vesicles. These bioactive vesicles secreted by cells play an active role in intercellular cargo and communication. Exosomes are mostly found in body fluids such as plasma, cerebrospinal fluid, urine, saliva, amniotic fluid, colostrum, breast milk, joint fluid, semen, and pleural acid. Considering the size of exosomes, it is thought that they may play an important role in central nervous system diseases because they can pass through the blood-brain barrier (BBB). Hence, this study aimed to develop an exosome-based nanocarrier system by encapsulating dopamine into exosomes isolated from Wharton's jelly mesenchymal stem cells (WJ-MSCs). Exosomes that passed the characterization process were incubated with dopamine. The dopamine-loaded exosomes were recharacterized at the end of incubation. Dopamine-loaded exosomes were investigated in drug release and cytotoxicity assays. The results showed that dopamine could be successfully encapsulated within the exosomes and that the dopamine-loaded exosomes did not affect fibroblast viability.

Olfactory ensheathing cells: Unique glial cells promising for treatments of spinal cord injury.

Spinal cord injury (SCI) is generally the consequence of physical damage, which may result in devastating consequences such as paraplegia or paralysis. Some certain candidates for SCI repair are olfactory ensheathing cells (OECs), which are unique glial cells located in the transition region of the peripheral nervous system and central nervous system and perform neuron regeneration in the olfactory system throughout life. Culture studies have clarified many properties of OECs, but their mechanisms of actions are not fully understood. Successful results achieved in animal models showcased that SCI treatment with OEC transplants is suitable for clinical trials. However, clinical trials are limited by difficulties like cell acquisition for autograft transplantation. Despite the improvements in both animal and clinical studies so far, there is still insufficient information about the mechanism of actions, adverse effects, proper application methods, effective subtypes, and sources of cells. This review summarizes pre-clinical and clinical literature focused on the cellular characterization of both OECs in vitro and post-transplantation. We highlight the roles and effects of OECs on (a) the injury-induced glial milieu, (b) neuronal growth/regeneration, and (c) functional recovery after injury. Due to the shown benefits of OECs with in vitro and animal studies and a limited number of clinical trials, where safety and effectivity were shown, it is necessary to conduct more studies on OECs to obtain effective and feasible treatment methods.

Stem Cell Based Therapy Option in COVID-19: Is It Really Promising?

The COVID-19 patients were first detected in China, in December 2019, then the novel virus with associated pneumonia and other diseases spread quickly to worldwide becoming a serious public health intimidation. Despite all the efforts, the pharmacological agents used for controlling or treating the disease, especially respiratory problems, have not been accomplished so far. Among various treatment options, mesenchymal stem cell-based cellular therapies are being investigated, because of their regeneration ability and multipotency along with other features like immunomodulation, antifibrosis and anti-inflammatory effects. This paper intends to analyze the current clinical trials on stem cell treatment of novel virus, searching and reviewing the available information and the International Clinical Trials Registry Platform (ICTRP) of World Health Organization (WHO). We concluded that the stem cell treatment of COVID-19 is found promising with pilot studies' results, but still in the early development phase. There is an urgent need for large-scale investigations to confirm and validate the safety and efficacy profile of these therapies with reliable scientific evidence.

Synthesis, FT-IR and NMR characterization, antimicrobial activity, cytotoxicity and DNA docking analysis of a new anthraquinone derivate compound.

A new anthraquinone [1-(2-Aminoethyl)piperazinyl-9,10-dioxo-anthraquinone] derivative was synthesized and characterized by density functional theory (DFT) calculations, experimental and theoretical vibrational spectroscopy and NMR techniques. The most stable molecular structure of the title molecule was determined by DFT B3LYP method with 6-31++G(d,p) and 6-311++G(d,p) basis sets. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the investigated molecule were calculated and compared with the experimental vibrational spectra. The vibrational assignment of the molecule was done using the potential energy distribution analysis. The molecular electrostatic potential (MEP), highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) were also calculated. The antibacterial activities of the new anthraquinone derivative against Gram-positive and Gram-negative bacteria were determined, and it was shown that the highest effectiveness was against Staphylococcus aureus and S. epidermidis while no activity was against Gram-negative bacteria. Moreover, the antimycotic activity of the title compound was examined and the cytotoxicity of anthraquinone derivate was determined. In order to find the possible inhibitory activity of the title compound, molecular docking of the molecule was carried out against DNA. The results indicated that the mentioned compound has a good binding affinity to interact with the DC3, DG4, DA5, DC21 and DC23 residues of DNA via the intermolecular hydrogen bonds. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Histomorphometric and Histopathologic Evaluation of the Effects of Systemic Fluoride Intake on Orthodontic Tooth Movement.

OBJECTIVES: The aim of this study was to determine the effects of systemic fluoride intake on orthodontic tooth movement with histomorphometric and histopathologic methods. MATERIALS AND METHODS: Forty-eight Wistar albino rats were randomly divided into four groups of 12 rats each. Group I received fluoridated water and underwent orthodontic tooth movement. Group II received fluoridated water and did not undergo orthodontic tooth movement. Group III received nonfluoridated water and underwent orthodontic tooth movement. Group IV received nonfluoridated water and did not undergo orthodontic tooth movement. At the beginning of the experiment (T1), impressions were taken from the maxilla of the rats in groups I and III under general anesthesia, and a NiTi closed coil spring appliance was ligated between the left maxillary central incisors and maxillary first molar. The orthodontic force applied was approximately 75 g, and the duration of the experimental period was 18 days. During the experimental period, appliances were controlled daily. At the end of the experimental period (T2), the rats were sacrificed with an overdose of a ketamine/xylasine combination, and their impressions were obtained. The upper first molars were subsequently dissected for histological examination. Incisor-molar distance, number of osteoblasts, number of osteoclasts and periodontal ligament (PDL) space widths on the compression and tension sides were measured. STATISTICAL ANALYSIS: All measurements were statistically analyzed with SPSS for Windows version 18.0 (SPSS Inc., Chicago, IL, USA). Repeated measures ANOVA and posthoc Tukey tests were used to compare the groups. RESULTS: No statistically significant difference was found with respect to the amount of tooth movement between the fluoridated and nonfluoridated groups (p > 0.05). Orthodontic force application increased the number of osteoblasts at the tension sides and reduced it at the compression sides (p < 0.001). An increased number of osteoclasts was observed in the nonfluoridated group relative to the fluoridated group (p < 0.01). CONCLUSIONS: No difference was observed with respect to the amount of tooth movement between the fluoridated and nonfluoridated groups. Fluoride significantly reduced the number of osteoclasts in the experimental groups.

Lysozyme gene treatment in testosterone induced benign prostate hyperplasia rat model and comparasion of its' effectiveness with botulinum toxin injection

ABSTRACT Objectives: To compare the effects and histopathological changes of botulinum neurotoxin type A and lysozyme gene injections into prostate tissue within a testosterone induced benign prostate hyperplasia rat model. Materials and Methods: 40 male Wistar rats were randomized into four Groups. Group-1: Control, Group-2: Testosterone replacement, Group-3: Testosterone+botulinum neurotoxin type A, Group-4: Testosterone+plazmid DNA/liposome complex. Results: Estimated prostate volume of the testosterone injected Groups were higher than the control (p <0.05). Actual prostate weight of the testosterone injected Groups was higher than the control Group (p <0.05). Testosterone undecanoate increased the prostate weight by 39%. Botulinum neurotoxin type A treatment led to an estimated prostate volume and actual prostate weights decreased up to 32.5% in rats leading to prostate apoptosis. Lysozyme gene treatment led to an estimated prostate volume and actual prostate weights decrease up to 38.7%. Conclusion: Lysozyme gene and botulinum neurotoxin type A treatments for prostate volume decreasing effect have been verified in the present study that could be anew modality of treatment in prostatic benign hyperplasia that needs to be verified in large randomized human experimental studies.

Lysozyme gene treatment in testosterone induced benign prostate hyperplasia rat model and comparasion of its' effectiveness with botulinum toxin injection.

OBJECTIVES: To compare the effects and histopathological changes of botulinum neurotoxin type A and lysozyme gene injections into prostate tissue within a testosterone induced benign prostate hyperplasia rat model. MATERIALS AND METHODS: 40 male Wistar rats were randomized into four Groups. Group-1: Control, Group-2: Testosterone replacement, Group-3: Testosterone+botulinum neurotoxin type A, Group-4: Testosterone+plazmid DNA/liposome complex. RESULTS: Estimated prostate volume of the testosterone injected Groups were higher than the control (p <0.05). Actual prostate weight of the testosterone injected Groups was higher than the control Group (p <0.05). Testosterone undecanoate increased the prostate weight by 39%. Botulinum neurotoxin type A treatment led to an estimated prostate volume and actual prostate weights decreased up to 32.5% in rats leading to prostate apoptosis. Lysozyme gene treatment led to an estimated prostate volume and actual prostate weights decrease up to 38.7%. CONCLUSION: Lysozyme gene and botulinum neurotoxin type A treatments for prostate volume decreasing effect have been verified in the present study that could be anew modality of treatment in prostatic benign hyperplasia that needs to be verified in large randomized human experimental studies.

The efficiency of Poly(ADP-Ribose) Polymerase (PARP) cleavage on detection of apoptosis in an experimental model of testicular torsion.

The aim of this study was to evaluate the histopathological and apoptotic changes occurring in the rat ipsilateral and contralateral testes, after experimental spermatic cord torsion, and to explore and the role of poly(ADP-ribose) polymerase (PARP) cleavage in testicular torsion-detorsion injury. A total of 37 Wistar albino rats were subjected to 720° unilateral spermatic cord torsion for 1, 2 and 4 h, followed by 4-h reperfusion, or else to a sham operation (control group). Histology of the testicle was evaluated using haematoxylin-eosin (H&E) staining and Johnsen's scoring system. Germ cell apoptosis was evaluated via active caspase-3 immunostaining, and PARP expression levels were evaluated via Western blotting. The mean Johnsen's tubular biopsy scores (JTBS) of the ipsilateral testicles were lower for all torsion groups than for the controls (P < 0.05), but the JTBS of the contralateral testicles were only lower in the 4-h torsion group (P < 0.05). The mean apoptosis score (AS) of the ipsilateral and contralateral testicles was significantly higher in the torsion groups than in the sham group. AS increased correlatively with torsion time, in both testicles. The effect of testicular torsion on PARP cleavage was time dependent, with the highest effect observed after 4 h of testicular torsion (P < 0.05). Testicular torsion caused time-dependent histological changes, apoptosis and increases in PARP cleavage. Our results suggest that testicular torsion-detorsion injury caused cell damage and germ cell apoptosis that apparently involved cleavage of PARP. Increased PARP cleavage could, in turn, lead to enhanced apoptosis.

The effects of long-term exposure to a 2450 MHz electromagnetic field on growth and pubertal development in female Wistar rats.

The aim of this study was to investigate the effects of a 2450 MHz electromagnetic field (EMF) (wireless internet frequency) on the growth and development of female Wistar rats. The study was conducted on three groups of rats. The prenatal and postnatal groups were exposed to EMF 1 h/day beginning from intrauterine and postnatal periods, respectively. The third group was the sham-exposed group. Growth, nutrition and vaginal opening (VO) were regularly monitored. Serum and tissue specimens were collected at puberty. Histological examinations, total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) measurements in ovary and brain tissues and also immunohistochemical staining of the hypothalamus were performed besides the determination of serum FSH, LH, E2 and IGF-1 values. Birth masses of the groups were similar (p > 0.05). Mass gain per day was significantly lower and the puberty was significantly later in the prenatal group. Brain and ovary TOS and OSI values in the prenatal group were significantly increased (p < 0.05) compared to the control group. Serum LH levels of the prenatal and postnatal groups were increased, although serum FSH, and E2 values did not differ among the groups (p > 0.05). Histological examinations of the specimens revealed no statistically significant difference between the groups (p > 0.05). Exposure to 2450 MHz EMF, particularly in the prenatal period, resulted in postnatal growth restriction and delayed puberty in female Wistar rats. Increased TOS and OSI values in the brain and ovary tissues can be interpreted as a sign of chronic stress induced by EMF. This is the first longitudinal study which investigates the effects of EMF induced by wireless internet on pubertal development beside growth.

The effect of micronized purified flavonoid fraction on the prevention of testicular pathologies in adolescent rats with experimentally induced varicocele.

PURPOSE: We investigated the effect of micronized purified flavonoid fraction on the prevention of testicular pathologies following varicocele induction. MATERIALS AND METHODS: A total of 66 adolescent (6-week-old) male Wistar rats were included in study. Rats were divided into 7 groups, including group 1--control, group 2--sham operation, group 3--left varicocele induced, group 4--varicocele induced, varicocelectomy done 4 weeks later and micronized purified flavonoid fraction administered for 4 weeks, group 5--varicocele induced and micronized purified flavonoid fraction administered for 8 weeks, group 6--varicocele induced and beginning 4 weeks later micronized purified flavonoid fraction administered for 4 weeks, and group 7--varicocele induced and varicocelectomy done 4 weeks later. Before sacrifice bilateral real-time testicular microvascular perfusion of all rats was measured using the PeriFlux System 5000 PF 5010 LDPM Unit (Perimed, Järfälla, Sweden). All testes were graded according to the Johnsen scoring system. To assess apoptosis caspase-3 levels were measured. RESULTS: Testicular weight in group 3 was markedly decreased and the extent of seminiferous tubular damage was significantly increased compared with the other groups. Bilateral testicular blood flow and the number of apoptotic germ cells were greater in group 3. Significantly higher Johnsen scores and a meaningful decrease in the apoptotic index were detected in groups 4 to 7 compared with group 3. CONCLUSIONS: We observed favorable effects of micronized purified flavonoid fraction on the regression of testicular damage secondary to varicocele.

The efficacy of single-dose 5-fluorouracil therapy in experimental caustic esophageal burn.

INTRODUCTION: Accidental ingestion of caustic substances may cause serious problems in children. Approximately 20% of caustic ingestions result in esophageal stricture formation, resulting from excessive collagen synthesis to the extracellular matrix by fibroblasts. Recent studies showed that a single application of 5-fluorouracil (5-FU) is a very effective inhibitor of fibroblast proliferation and differentiation for prolonged periods. Using an experimental model, we investigated the efficacy of single-dose 5-FU on stricture formation after caustic esophageal burn. MATERIALS AND METHODS: Forty Wistar-Albino rats were divided randomly into 4 equal groups: group 1 (sham-operated group), the esophagus was uninjured and untreated; group 2 (control group), the esophagus was injured and left untreated; group 3 (intraperitoneal treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraperitoneal dose (20 mg/kg) of 5-FU; group 4 (local treatment group), the esophagus was injured and treated immediately after the burn injury with a single intraesophageal application of 5-FU at a concentration of 25 mg/mL. Caustic esophageal burn was produced by instilling 10% NaOH in the distal esophagus. The distal esophagi were harvested at 28 days postoperatively. Histologic sections were assessed by measuring the stenosis index (SI) and histopathologic damage score. Hydroxyproline (HP) levels in the tissues were determined biochemically. RESULTS: There were significant reductions in the SI (P < .05), histopathologic damage score (P < .05), and HP level (P < .05) in the intraperitoneal treatment group when compared with the control group. No significant differences in the SI and histopathologic damage score were detected between the control and local treatment groups (P > .05), whereas significant reduction in the HP level was determined between these groups (P < .05). CONCLUSION: A single intraperitoneal dose of 5-FU had a preventive effect on stricture formation after caustic esophageal burn. This observation suggests that 5-FU may prevent this undesirable complication in the clinical setting. Clinical studies are now required to verify this form of treatment. Local intraesophageal application of 5-FU immediately after the burn injury was not effective. Further investigations are required to determine the appropriate timing of application of 5-FU at the local site of injury.

Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats.

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation.