Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a critical medical condition during which sensorimotor function is lost. Current treatments are still unable to effectively improve these conditions, so it is important to pay attention to other effective approaches. Currently, we investigated the combined effects of human placenta mesenchymal stem cells (hPMSCs)-derived exosomes along with hyperbaric oxygen (HBO) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley (SD) rats were allocated into five equal groups, including; sham group, SCI group, Exo group (underwent SCI and received hPMSCs-derived exosomes), HBO group (underwent SCI and received HBO), and Exo+HBO group (underwent SCI and received hPMSCs-derived exosomes plus HBO). Tissue samples at the lesion site were obtained for the evaluation of stereological, immunohistochemical, biochemical, molecular, and behavioral characteristics. Findings showed a significant increase in stereological parameters, biochemical factors (GSH, SOD, and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in treatment groups, especially Exo+HBO group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells and gliosis, as well as expression of inflammatory genes (TNF-α and IL-1ß) were considerably reduced in treatment groups, especially Exo+HBO group, compared to SCI group. We conclude that co-administration of hPMSCs-derived exosomes and HBO has synergistic neuroprotective effects in animals undergoing SCI.

The Accuracy of Electrical Impedance Tomography for Breast Cancer Detection: A Systematic Review and Meta-Analysis.

Introduction: Incidence of breast cancer (BC) in 2020 is about 2.26 million new cases. It is the first common cancer accounting for 11.7% of all cancer worldwide. Disease complications and the mortality rate of breast cancer are highly dependent on the early diagnosis. Therefore, novel human breast-imaging techniques play an important role in minimizing the breast cancer morbidity and mortality rate. Electrical impedance tomography (EIT) is a noninvasive technique to image the breast using the electrical impedance behavior of the body tissues. Objectives: The aims of this manuscript are as follows: (1) a comprehensive investigation of the accuracy of EIT for breast cancer diagnosis through searching pieces of evidence in the valid databases and (2) meta-analyses of the results. Methods: The systematic search was performed in the electronic databases including PubMed, Web of Science, EMBASE, Science Direct, ProQuest, Scopus, and Google Scholar without time and language limitation until January 2021. Search terms were "EIT" and "Breast Cancer" with their synonyms. Relevant studies were included based on PRISMA and study objectives. Quality of studies and risk of bias were performed by QUADAS-2 tools. Then, relevant data were extracted in Excel form. The hierarchical/bivariate meta-analysis was performed with "metandi" package for the ROC plot of sensitivity and specificity. Forest plot of the Accuracy index and double arcsine transformations was applied to stabilize the variance. The heterogeneity of the studies was evaluated by the forest plots, χ2 test (assuming a significance at the a-level of 10%), and the I2 statistic for the Accuracy index. Results: A total of 4027 articles were found. Finally, 12 of which met our criteria. Overall, these articles included studies of 5487 breast cancer patients. EIT had an overall pooled sensitivity and specificity of 75.88% (95% CI, 61.92% to 85.89%) and 82.04% (95% CI, 69.72% to 90.06%), respectively. The pooled diagnostic odds ratio was 14.37 (95% CI, 6.22% to 33.20%), and the pooled effect of accuracy was 0.79 with 95% CI (0.73, 0.83). Conclusions: This study showed that EIT can be used as a useful method alongside mammography. EIT sensitivity could not be compared with the sensitivity of MRI, but in terms of specificity, it can be considered as a new method that probably can get more attention. Furthermore, large-scale studies will be needed to support the evidence.

Applications of Electrical Impedance Tomography in Neurology.

Introduction: Electrical impedance tomography (EIT) is a non-invasive technique utilized in various medical applications, including brain imaging and other neurological diseases. Recognizing the physiological and anatomical characteristics of organs based on their electrical properties is one of the main applications of EIT, as each variety of tissue structure has its own electrical characteristics. The high potential of brain EIT is established in real-time supervision and early recognition of cerebral brain infarction, hemorrhage, and other diseases. In this paper, we review the studies on the neurological applications of EIT. Methods: EIT calculates the internal electrical conductivity distribution of an organ by measuring its surface impedance. A series of electrodes are placed on the surface of the target tissue, and small alternating currents are injected. The related voltages are then observed and analyzed. The electrical permittivity and conductivity distributions inside the tissue are reconstructed by measuring the electrode voltages. Results: The electrical characteristic of biological tissues is remarkably dependent on their structures. Some tissues are better electrical conductors than the others since they have more ions that can carry the electrical charges. This difference is attributed to changes in cellular water content, membrane properties, and destruction of tight junctions within cell membranes. Conclusion: EIT is an extremely practical device for brain imaging, capturing fast electrical activities in the brain, imaging epileptic seizures, detecting intracranial bleeding, detecting cerebral edema, and diagnosing stroke.

The synergistic effect of topical insulin and clindamycin on acute dermal wound healing in rat model: a histological study.

Reducing the duration of wound healing is important to decrease the chance of infection. Insulin as a peptide hormone has a role in wound healing. Also, the use of clindamycin in the treatment of skin wounds has been studied very little. The aim of this study was to evaluate the synergistic effect of insulin and clindamycin on full-thickness wound healing. In this study, 24 Wistar rats (weight 180-200 g) were randomly divided into four equal groups: control (Eucerin), clindamycin, insulin, and insulin + clindamycin. Drugs were administered in the form of an ointment daily for twelve days. Wound healing rate and wound criteria such as epithelialization, neovascularization, collagen deposition, inflammation, and tissue granulation were investigated histologically on days 3, 7, and 14. The wound healing rate in the insulin + clindamycin group was significantly higher than the other groups on day 7 but there was no significant difference between groups on day 14. In addition, the combination of insulin and clindamycin had a beneficial effect on reducing inflammation and increasing collagen deposition, fibroblast maturation, neovascularization, and keratinization. The data showed that the topical application of insulin with clindamycin has an effective role in full-thickness wound healing by reducing inflammation and accelerating wound closure.

Sandblasting improves the performance of electrodes of miniature electrical impedance tomography via double layer capacitance.

Effect of sandblasting of the copper electrode structures before deposition of gold thin film for micro electrical impedance tomography (EIT) system has been studied experimentally. The comparison has been performed on the unmodified copper electrodes and the sandblasted electrodes before deposition of gold layer, using structural analysis while their performance in EIT system has been measured and analyzed. The results of scanning electron microscopy and atomic force microscopy show that the sandblasting of the electrodes results in the deposition of gold film with smaller grain size and uniformly, comparing to the unmodified structure. The measurement of impedance shows that the sandblasting will increase the double layer capacitance of electrode structure which improves the impedance measurement accordingly.

Protective effects of melatonin solid lipid nanoparticles on testis histology after testicular trauma in rats.

Testicular traumatic injuries occur frequently, which can result in an alteration in spermatogenesis. These injuries can also cause oxidative stress and male infertility. Antioxidant efficiency of melatonin (MLT), known as a potent antioxidant, will be improved if used in a form of solid lipid nanoparticles (MLT-SLN). The aim of the current study is to evaluate the effect of MLT-loaded SLN on traumatic testis in rats. In this study 32 adult male Wistar rats were divided into 4 groups. Group 1 (sham group), right testicle was drawn out from the scrotum and returned without manipulation. Group 2, right testicle was dropped by 25 g sinker for 4 times. Group 3, animals were received a single dose (25 mg/kg) of MLT intraperitoneally after trauma. Group 4, animals were received a single dose of MLT-SLN intraperitoneally after trauma. Under anaesthesia, rats were sacrificed, and their testicles were removed three days after the surgery. After tissue processing, the sample sections were H&E stained. MLT and MLT-SLN could partially repair spermatogenesis by Johnson's criteria but the repairs were significant only in MLT-SLN group (P = 0.02). Trauma decreased seminiferous tubule diameter and its epithelium height. MLT could restore epithelium height (P ≤ 0.05) but its NPs improved both epithelium diameter (P ≤ 0.05) and thickness (P ≤ 0.001). The Malondialdehyde increased significantly in trauma group (P = 0.002), but decreased in MLT and NPs groups compared to trauma group (P = 0.098 and P = 0.002 respectively). This decrease was significant only in NPs group. Testicular trauma disturbed spermatogenesis, morphometric, and oxidative parameters. MLT and specially MLT-SLN improved traumatic damages.

Protective effects of melatonin on testis histology following acute torsion-detorsion in rats.

BACKGROUND: Testicular damage due to spermatic cord torsion may lead to infertility. It is probably because of changes in oxidative stress factors such as malondialdehyde. OBJECTIVE: To investigate the protective effect of melatonin (MLT), as an antioxidant, on testicular damage induced by acute unilateral spermatic cord torsion and detorsion (T/D) in rats. MATERIALS AND METHODS: In this experimental study, 48 adult male Wistar rats were randomly divided into three groups (8 rats/group): sham group underwent right scrotal surgery only., the T/D group underwent right testicular torsion (for 1 hr) and detorsion, and the melatonin group underwent right testicular torsion, received 25 µg/kg melatonin intraperitoneally immediately after surgery of T/D. Then the histological parameters and malondialdehyde (MDA) changes were evaluated. RESULTS: Torsion and detorsion decreased the diameter of the tubules significantly compared to controls (p=0.003). Melatonin could increase the diameter, but it was not significant (p=0.26). The heights of the epithelium were constant in sham, T/D, and melatonin groups without any significant difference between groups (p=0.98). Based on Johnsen's score, spermatogenesis was normal in the sham group. The torsion significantly injured all lineage cells (p<0.001). There was no any spermatid or sperm in the seminiferous tubules. Melatonin improved the spermatogenesis significantly (p=0.02), but could not improve MDA level significantly (p=0.99). CONCLUSION: Severe degenerative changes of testis were induced by acute unilateral spermatic cord torsion and detorsion in rats, but it had no effect on MDA level.

The effect of the melatonin on cryopreserved mouse testicular cells.

BACKGROUND: After improvements in various cancer treatments, life expectancy has been raised, but success in treatment causes loss of fertility in many of the survived young men. Cryopreservation of immature testicular tissues or cells introduced as the only way to preserve fertility. However, freezing has some harmful effects. Melatonin, a pineal gland hormone, has receptors in reproductive systems of different species. It is assumed that melatonin has free radical scavenger properties. OBJECTIVE: The aim of this study was to evaluate the effects of melatonin on the cryopreserved testicular cells in mouse. MATERIALS AND METHODS: Cells from 7- 10 days old NMRI mice testes were isolated using two step enzymatic digestion. The testicular cells were divided into two groups randomly and cryopreserved in two different freezing media with and without the addition of 100 µm melatonin. Finally, apoptosis of the cells was assayed by flow cytometry. Also, lactate dehydrogenase activity test was performed to assess the cytotoxicity. RESULTS: The results of lactate dehydrogenase showed the nearly cytotoxic effect of melatonin. The results of flow cytometry showed increase in apoptosis in the cryopreserved cells in the media containing melatonin compared to the control group. CONCLUSION: The present study shows that melatonin has an apoptotic effect on cryopreserved mouse testicular cells.

Application of Allogeneic Fibroblast Cultured on Acellular Amniotic Membrane for Full-thickness Wound Healing in Rats.

OBJECTIVE: Utilization of the autologous and allogeneic skin substitutes seems to be a promising treatment option. In this study, the authors used amniotic membrane covered with cultured allogenic fibroblast as a skin substitute in the treatment of acute wounds. MATERIALS AND METHODS: Full-thickness wounds were created on rats' dorsum regions and treated with cultured allogenic fibroblast on an acellular amniotic membrane (AAM+F), an acellular amniotic membrane (AAM) alone, an allogenic fibroblast suspension (AFS), or normal saline as a control (C). Specimen biopsies were obtained 7 days after wounding. Quantitative wound healing parameters including the epidermal thickness, the mean number of keratinocytes, fibroblasts, and lymphocytes were assessed. RESULTS: All transplanted wounds exhibited significantly further contraction compared with the nontransplanted wounds. Wounds transplanted with AAM+F and AAM showed a significant increase in epidermal thickness compared to nontransplanted wounds. Wounds transplanted with AAM+F or AAM showed improved epidermal healing compared to nongrafted wounds. Furthermore, granulation of tissue formation in the AAM+F group was more organized when compared to AFS and the normal saline groups. CONCLUSION: Quantitative assessment of the full-thickness wounds showed transplantation of AAM+F and AAM better improve wound healing parameters when compared to treatment with AFS and the normal saline groups.

Melatonin and testicular damage in busulfan treated mice.

BACKGROUND: Advancement in the treatment of various types of cancer has led to greater patient survival. These treatments essentially have toxic effects on different kinds of cells, such as germ cells. Infertility as one of the side effects of cancer treatment has changed the quality of life of young cancer survivors dramatically. Melatonin is an antioxidant with receptors in the reproductive systems. OBJECTIVES: We supposed that melatonin, as an antioxidant, may protect testis against the toxic effects of the drugs. MATERIALS AND METHODS: In this experimental study, three groups with seven mice each, were allocated. The control group received normal saline for two months, and the busulfan group received a single dose of 40 mg/kg busulfan intra-peritoneally, and the melatonin group received 20 mg/kg melatonin daily for two months, 45 days after a single dose of busulfan. Next, after decapitation and removal of the testis, tissues were fixed in Bouin's solution and stained by H&E and TUNEL. The sections were evaluated, assessing morphology and spermatogenesis. RESULTS: In this research, a significant reduction in Johnson's criteria in the busulfan group (Mean rank = 15.50) was found versus the control group (Mean rank = 45.50), P < 0.001 and in the melatonin group (Mean rank = 45.50) compared to the busulfan group (Mean rank = 15.50), P < 0.001. There was a significant difference between the melatonin and control groups, P < 0.05. In addition, a significant decrease in seminiferous tubule diameter was observed in the busulfan group (763.2 ± 104.41) versus the control group (855.4 ± 52.35), P < 0.01 and melatonin group (834.2 ± 87.26), P < 0.05. Testicular epithelium height was significantly decreased in the busulfan group (Mean rank = 14.60) compared to the control group (Mean rank = 26.40), P < 0.01 and in the busulfan group (Mean rank = 14.95) in comparison with the melatonin group (Mean rank = 26.05), P < 0.01. Also melatonin group (Mean rank = 25.42) showed a significant reduction in epithelium height compared to the control group (Mean rank = 35.58), P < 0.05. Spermatogenesis was impaired in the busulfan group. Although melatonin reduced the rate of apoptosis in the busulfan group, yet it could not remove all apoptotic cells. CONCLUSIONS: This study indicated that melatonin ameliorates the cytotoxic effects of busulfan on germ cells.

Effect of curcumin on dexamethasone-induced testicular toxicity in mice.

CONTEXT: Curcumin is a yellow-orange polyphenol derived from turmeric [Curcuma longa L. (Zingiberaceaerhizomes)]. Turmeric is a main ingredient of Indian, Persian, and Thai dishes. Extensive studies within the last half a century have demonstrated the protective action of curcumin in many disorders of the body. OBJECTIVE: This study evaluated the protective effect of curcumin on dexamethasone-induced spermatogenesis defects in mice. MATERIALS AND METHODS: Thirty-two NMRI mice were randomly divided into 4 groups. The first (control) group received 1 mL/day of distilled water by intraperitoneal (i.p.) injection for 7 days. The second group received 200 mg/kg/day of curcumin (Cur) for 10 days. Third group received 7 mg/kg/day of dexamethasone (Dex) for 7 days. Forth group received 200 mg/kg of curcumin for 10 days after dexamethasone treatment. Testicular histopathology, morphometric analysis, head sperm counting, and immunohistochemistry assessments were performed for evaluation of the dexamethasone and curcumin effects. RESULTS: Expression of Bcl-2 was significantly increased in the curcumin + dexamethasone group compared with dexamethasone-treated animals (p < 0.05). Dexamethasone induced spermatogenesis defects including epithelial vacuolizations, sloughing of germ cells, reduction of seminiferous tubule diameter, reduction in the number of sperm heads and significant maturation arrest (p < 0.001). Curcumin + dexamethasone treatment significantly prevented these changes (p < 0.05). DISCUSSION AND CONCLUSION: The results of this study demonstrate that curcumin increases the expression of Bcl-2 protein, an important anti-apoptotic factor, and improves the spermatogenesis defects in dexamethasone treated mice. Curcumin has a potent protective effect against the testicular toxicity and might be clinically useful.

Toxic effects of Carthamus tinctorius L. (Safflower) extract on mouse spermatogenesis.

OBJECTIVE: To evaluate the effects of aqueous extract of Carthamus tinctorius L., also named safflower, on mouse spermatogenesis. METHODS: Sixteen adult male NMRI mice were used. Experimental group received Carthamus tinctorius L. extract at the dose of 200 mg/kg for 35 consecutive days and control group received only distilled water. Testicular histopathology, morphometric analysis and spermatogenesis assessments were performed for evaluation of the Carthamus tinctorius L. extract effects on testis. RESULTS: Histopathological criteria such as epithelial vacuolization, sloughing of germ and detachment were significantly decreased in Carthamus tinctorius L. treated mice (p < 0.001). Carthamus tinctorius L. extract induced formation of multinucleated giant cells in the germinal epithelium. Carthamus tinctorius L. extract also caused a significant decrease in seminiferous tubule diameter, seminiferous epithelium height and maturation arrest (p < 0.001). CONCLUSION: Carthamus tinctorius L. extract has toxic effects on mouse testicular tissue, and recommended to use it with caution if there is a reproductive problem.