Natural polyphenols for the management of autism spectrum disorder: a review of efficacy and molecular mechanisms.

Natural polyphenols have been found to have some protective effects against neurodegenerative and neurodevelopmental disorders, which are attributed to a variety of biological properties, particularly antioxidant, immunomodulatory, and anti-inflammatory effects. Autism spectrum disorder is a complex neurological and neurodevelopmental disorder with no currently effective clinical treatment for its core symptoms. Regarding the management of autism spectrum disorder core symptoms, a number of experimental and clinical studies have been made using well-known dietary polyphenols with different effects and molecular mechanisms. The aim of this paper is to present the most effective natural polyphenols with the relevant molecular mechanisms in preclinical and clinical autism spectrum disorder studies.

Therapeutic potentials of the caffeine in polycystic ovary syndrome in a rat model: Via modulation of proinflammatory cytokines and antioxidant activity.

Recent studies have shown that polycystic ovary syndrome (PCOS) affects about 6% of women worldwide. It is associated with reproductive and metabolic dysfunction. Caffeine is naturally found in tea, cocoa, and coffee. It has been shown that caffeine can change hormonal profiles, stimulate ovulation, and enhance fertility. Therefore, in this study, the effects of caffeine on rats with PCOS were investigated. For this purpose, 40 female rats were divided into five groups: (1) control group (without any intervention), (2) sham group (administration of olive oil as a caffeine solvent), (3) PCOS group (injection of 2 mg of estradiol valerate for each rat), (4) caffeine group (administration of 37.5 mg/kg caffeine for each rat), and (5) PCOS + caffeine group. After 21 days of treatment, the ovaries of rats were removed and prepared for further evaluations, including hematoxylin and eosin staining, TUNEL assay, real-time PCR, and biochemical analysis. Administration of caffeine in PCOS mice considerably reduced both the volume of the ovary (P < 0.05) and follicular clusters (P < 0.01). However, superoxide dismutase and glutathione peroxidase were dramatically active in the PCOS + caffeine group compared to others (P < 0.05). Besides, caffeine treatment in PCOS mice led to Bax reduction and increased Bcl-2 expression. On the other hand, the expression of IL-6 and TNF-α in PCOS + caffeine group was high compared to other groups. We found that caffeine can reduce apoptosis and inflammation in PCOS ovaries and enhance the unpleasant symptoms of PCOS.

The effects of Feijoa sellowiana fruit extract on wound healing in rats: a stereological and molecular study.

OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and wound-healing potential of Feijoa sellowiana fruit extract using stereological and molecular methods in experimental rat models. MATERIALS: Male Wistar rats were divided into four equal groups: non-treated, vehicle, Feijoa sellowiana fruit extract ointment (5% weight/weight) and the reference drug (madecassol). All animals were treated topically once per day. At the end of the study, wound samples were harvested for histological, stereological, immunohistochemical and molecular assessments to determine the in vivo healing potential and anti-inflammatory activity. A high-performance liquid chromatography (HPLC) analysis was performed for the characterisation of the phenolic acids in the extract. RESULTS: The study included 64 rats in total. Our results showed that the wound closure, volume of new epidermis and dermis, density of fibroblasts and blood vessels, and the deposition of collagen were significantly higher in both extract and madecassol groups compared to the non-treated and vehicle groups, with superior healing in the extract group. The transcript for the transforming growth factor (TGF)-ß gene was significantly upregulated in both extract and madecassol groups compared to non-treated and vehicle groups and was highest for the extract group. The density of inflammatory cells and expression levels of the cyclooxygenase (COX)-2 protein and tumour necrosis factor (TNF)-α gene in the extract and madecassol groups, especially in the extract group, were significantly reduced compared to non-treated and vehicle groups. CONCLUSION: Our results confirm that the Feijoa sellowiana fruit extract is a valuable source of antioxidant and anti-inflammatory activities and can allow for damaged tissue in wounds to recover markedly.

Juglans Regia L. Leaf Extract Attenuates Diabetic Nephropathy Progression in Experimental Diabetes: An Immunohistochemical Study.

BACKGROUND: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against diabetic nephropathy (DN). METHODS: In total, 28 male adult Sprague-Dawley rats were used. The DN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats received intragastric administration of GRL leaf extract (200 mg/kg/day) starting 1 week (preventive group) and 4 weeks (curative group) after the onset of hyperglycemia up to the end of the 8th week, whereas other diabetic rats received only isotonic saline (diabetic group) as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic nephropathy, various parameters of apoptosis and inflammation were assessed. Statistical analysis was performed using the SPSS software, version 15.0. The data were compared between the groups using the Tukey's multiple comparison test and the analysis of the variance. P values ˂0.05 were considered statistically significant. RESULTS: Fasting blood sugar (FBS) levels (P=0.001) and histopathological changes in the kidney of diabetic rats attenuated after GRL leaf extract consumption. Greater caspase-3 (P=0.004), COX-2 (P=0.008), PARP (P=0.007), and iNOS (P=0.005) expression could be detected in the STZ-diabetic rats, which were significantly (P=0.009) attenuated after GRL leaf extract consumption. In addition, attenuation of lipid peroxidation in the diabetic rats was detected after GRL consumption (P=0.01). CONCLUSION: GRL leaf extract exerts preventive and curative effects against diabetic nephropathy.

Comparative virulence of Candida auris with Candida haemulonii, Candida glabrata and Candida albicans in a murine model.

The incidence of invasive fungal infections (IFIs) caused by uncommon Candida species with diverse virulence and susceptibility profiles has increased in recent years. Due to scarce clinical and experimental data on the pathogenicity of Candida auris, the aim of this study was to evaluate and compare the virulence of two rare clinically relevant species, C. auris and Candida haemulonii with Candida glabrata and Candida albicans in an immunocompetent murine model of disseminated infection. Immunocompetent ICR female mice were infected with three inoculum sizes (1 × 105 , 1 × 106 and 1 × 107 CFU/mouse) of two C. auris strains and one isolate of C. haemulonii, C. glabrata and C. albicans. Tissue burden on days 5 and 10 postchallenge and mortality rate were used as virulence markers. A high virulence was found for C. albicans, followed by C. auris, C. glabrata and C. haemulonii, respectively. Candida albicans showed high virulence with a medium survival time of 9.5 days for mice infected with 1 × 107 CFU/mouse. For inocula at 1 × 106 and 1 × 107 CFU/mouse, there were significant differences in fungal burden at day 10 between C. albicans, C. auris and C. glabrata isolates compared with C. haemulonii (P < .0001). Overall, no significant differences between C. albicans with C. auris and C. glabrata were observed in mice infected with three different inocula (P > .05). In general, the highest fungal load of all isolates was detected in kidney followed by spleen, liver and lung tested with three different inocula on the two different experimental days. Histopathological examination revealed the abundant presence of yeast cells with pseudohyphae for C. albicans and only yeast cells for C. auris, C. glabrata and C. haemulonii, in all the kidney tissue samples. In conclusion, C. albicans is a highly virulent opportunistic fungus, as the clinical and experimental data demonstrate, and also our results demonstrate a low virulence of C. haemulonii in immunocompetent animals. Altogether, this study highlights the pathogenic potential of C. auris.

Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.

Caffeine attenuates spermatogenic disorders in mice with induced chronic scrotal hyperthermia.

OBJECTIVE: Chronic scrotal hyperthermia (SHT) can lead to serious disorders of the male reproductive system, with oxidative stress playing a key role in the onset of these dysfunctions. Thus, we evaluated the impact of caffeine, a potent antioxidant, on cellular and tissue disorders in mice with chronic SHT. METHODS: In this experimental study, 56 adult male NMRI mice were allocated into seven equal groups. Apart from the non-treated control group, all were exposed to heat stress. Two groups, termed "preventive" and "curative," were orally administered caffeine. The preventive mice began receiving caffeine immediately prior to heat exposure, while for the curative group, a caffeine regimen was initiated 15 consecutive days following cessation of heat exposure. Each treated group was subdivided based on pairing with a positive control (Pre/curative [Cur]+PC) or a vehicle (Pre/Cur+vehicle). Upon conclusion of the study, we assessed sperm characteristics, testosterone levels, stereological parameters, apoptosis, antioxidant and oxidant levels, and molecular markers. RESULTS: Sperm parameters, testosterone levels, stereological parameters, biochemical factors (excluding malondialdehyde [MDA]), and c-kit gene expression were significantly elevated in the preventive and curative groups, especially the former, relative to the other groups. Conversely, expression levels of the heat shock protein 72 (HSP72) and nuclear factor kappa beta (NF-κß) genes, MDA levels, and apoptotic cell density were markedly lower in both caffeine-treated groups relative to the other groups, with more pronounced differences observed in the preventive group. CONCLUSION: Overall, caffeine attenuated cellular and molecular abnormalities induced by heat stress in the testis, particularly in the mice treated under the preventive condition.

Three-dimensional bioengineered dermal derived matrix scaffold in combination with adipose-derived stem cells accelerate diabetic wound healing.

Due to the multifactorial nature of diabetic wounds, the most effective treatments require combinatorial approach. Herein we investigated whether engraftment of a bioengineered three-dimensional dermal derived matrix scaffold (DDMS) in combination with adipose-derived stem cells (ADSs), could accelerate diabetic wound healing. Diabetic animals were randomly planned into the control group, DDMS group, ADS group, and DDMS+ADS group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. We found that the wound contraction rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts and blood vessels, collagen density, and tensiometrical parameters were meaningfully greater in the treated groups than in the control group, and these changes were more obvious in the DDMS+ADS ones (p < 0.05). Moreover, the expression of TGF-ß, bFGF, and VEGF genes were considerably upregulated in treated groups compared to the control group and were greater in the DDMS+ADS group (p < 0.05). This is while expression of TNF-α and IL-1ß, as well as the numerical densities of neutrophils and macrophages decreased more considerably in the DDMS+ADS group than in the other groups (p < 0.05). Overall, it was found that using both DDMS engraftment and ADS transplantation has more impact on diabetic wound healing.

Coenzyme Q10 attenuates neurodegeneration in the cerebellum induced by chronic exposure to tramadol.

BACKGROUND: Chronic use of tramadol can cause neurotoxic effects and subsequently cause neurodegeneration in the cerebellum. The main damage mechanisms identified are oxidative stress and inflammation. Currently, we investigated the effects of coenzyme Q10 (CoQ10) in attenuates of neurodegeneration in the cerebellum induced by chronic exposure to tramadol. MATERIAL AND METHODS: Seventy-two male mature albino rats were allocated into four equal groups, including; non-treated group, CoQ10 group (which received CoQ10 at 200 mg/kg/day orally for three weeks), tramadol group (which received tramadol hydrochloride at 50 mg/kg/day orally for three weeks), and tramadol+CoQ10 group (which received tramadol and CoQ10 at the same doses as the previous groups). Tissue samples were obtained for stereological, immunohistochemical, biochemical, and molecular evaluations. Also, functional tests were performed to evaluate behavioral properties. RESULTS: We found a significant increase in stereological parameters, antioxidant factors (catalase, glutathione, and superoxide dismutase), and behavioral function scores in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). In addition, malondialdehyde levels, the density of apoptotic cells, as well as the expression of pro-inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, and interleukin 6) and autophagy (lysosome-associated membrane protein 2, autophagy-related 5, beclin 1, and autophagy-related 12) genes were considerably reduced in the tramadol+CoQ10 group compared to the tramadol group (p < 0.05). CONCLUSION: We conclude that the administration of CoQ10 has neuroprotective effects in the cerebellum of rats that have chronic exposure to tramadol.

Transplantation of bioengineered dermal derived matrix-scaffold in combination with hyperbaric oxygen therapy improves wound healing in diabetic rats.

Successful treatment of diabetic wounds requires multifactorial approaches. Herein we investigated the effects of a bioengineered three-dimensional dermal derived matrix-scaffold (DMS) in combination with hyperbaric oxygen (HBO) in repairing of wound model in diabetic rats. Thirty days after induction of diabetes, a circular wound was created and treatments were performed for 21 days. Animals were randomly allocated into the untreated group, DMS group, HBO group, and DMS+HBO group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. Our results showed that the wound closure rate, volume of new dermis and epidermis, numerical density fibroblasts and blood vessels, collagen density, and biomechanical characterize were significantly higher in the treatment groups than in the untreated group, and these changes were more obvious in the DMS+HBO ones. Moreover, the expression of TGF-ß, bFGF, miRNA-21, miRNA-146a, and VEGF genes were meaningfully upregulated in treatment groups compared to the untreated group and were greater in the DMS+HBO group. This is while expression of TNF-α and IL-1ß, as well as the numerical density of neutrophil and macrophage decreased more considerably in the DMS+HBO group than in the other groups. Overall, using both DMS engraftment and HBO treatment has more effects on diabetic wound healing.

Stem cell-derived extracellular vesicle-based therapy for nerve injury: A review of the molecular mechanisms.

Recent evidence suggests that stem cell therapy has beneficial effects on nerve damage. These beneficial effects were subsequently found to be exerted in part in a paracrine manner by the release of extracellular vesicles. Stem cell-secreted extracellular vesicles have shown great potential to reduce inflammation and apoptosis, optimize the function of Schwann cells, regulate genes related to regeneration, and improve behavioral performance after nerve damage. This review summarizes the current knowledge on the effect of stem cell-derived extracellular vesicles on neuroprotection and regeneration along with their molecular mechanisms after nerve damage.

Accelerated wound healing using three-dimensional amniotic membrane scaffold in combination with adipose-derived stem cells in a diabetic rat model.

The most important factors in the non-optimal healing of diabetic wounds are the lack of a suitable scaffold in the wound site for the migration and replacement of cells, as well as the lack of blood supply and effective growth factors in the wound site. Herein we investigated whether a bioengineered micro-porous three-dimensional decellularized amniotic membrane-scaffold (DAMS) in combination with adipose-derived stem cells (ASCs) could promote healing in ischemic wounds in diabetic type 1 rat. The diabetic animals were randomly divided into non-treated (untreated group), engraftment by DAMS (DAMS group), transplanted by ASCs (ASC group), and DAMS in combination with ASCs (DAMS+ASC group). Stereological, immunohistochemical, molecular, and tensiometrical assessments were performed on post-surgical days 7, 14, and 21. We found that the rate of wound closure, the volumes of new epidermis and dermis, the numerical density of fibroblasts and blood vessels, the numbers of proliferating cells and collagen deposition as well as biomechanical properties of the healed wounds were significantly higher in the treatment groups in comparison to the untreated group, and were the highest in DAMS+ASC ones. The transcripts for TGF-ß and VEGF genes were significantly upregulated in all treatment regimens compared to the untreated group and were the highest for DAMS+ASC group. This is while expression of TNF-α and IL-1ß as well as cell density of neutrophils decreased more significantly in DAMS+ASC group as compared with other groups. Overall, it was found that using both DAMS engraftment and ASC transplantation has more impact on diabetic wound healing.

Protective effects of epigallocatechin gallate in the mice induced by chronic scrotal hyperthermia.

One of the most common complications of chronic scrotal hyperthermia (SHT) is a serious disorder in the male reproductive system. The most important factor in the occurrence of these disorders is oxidative stress. Currently, we investigated the effects of epigallocatechin gallate (EGCG), as a highly potent antioxidant, against cells and tissue disorders in mice affected by chronic SHT. Fifty-six male adult NMRI mice were allocated into seven equal groups. Except the non-treated (Control) group, six other groups were exposed to heat stress. Two treated groups including Preventive and Curative received oral administration of EGCG (50 mg/kg/day) starting immediately before heat exposure and fifteen consecutive days after the end of the heat exposure, respectively. For each treated group, two subgroups including positive control (Pre/Cur + PC groups) and vehicle (Pre/Cur + vehicle groups) were considered. At the end of the study, sperm characteristics, testosterone levels, stereological parameters, apoptosis, oxidant state, and molecular assessments were performed. We found that the sperm parameters, testosterone levels, the numerical density of spermatogonia, primary spermatocytes, spermatids, sertoli, leydig cells, and seminiferous tubules, biochemical factors (except MDA), and expression of c-kit gene were significantly higher in the Preventive and Curative groups, especially in Preventive ones, compared to other groups (P < 0.05). This is while expression of HSP72 and NF-κß genes, MDA levels, as well as density of apoptotic cells considerably decreased in both EGCG-treated groups compared to other groups and it was more pronounced in Preventive ones (P < 0.05). Generally, EGCG attenuated cellular and molecular disorders induced by heat stress in the testis and it was more pronounced in Preventive status.

Exosomes derived from human adipose mesenchymal stem cells loaded bioengineered three-dimensional amniotic membrane-scaffold-accelerated diabetic wound healing.

The occurrence of wounds and defects in the healing process is one of the main challenges in diabetic patients. Herein, we investigated whether adipose-derived stem cells (ADSCs)-derived exosomes loaded bioengineered micro-porous three-dimensional amniotic membrane-scaffold (AMS) could promote healing in diabetic rats. Sixty diabetic rats were randomly allocated into the control group, exosome group, AMS group, and AMS + Exo group. On days 7, 14, and 21, five rats from each group were sampled for stereological, immunohistochemical, molecular, and tensiometrical assessments. Our results indicated that the wound closure rate, the total volumes of newly formed epidermis and dermis, the numerical densities of fibroblasts and proliferating cells, the length density blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably greater in the treated groups than in the control group, and these changes were more obvious in the AMS + Exo ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes was meaningfully upregulated in all treated groups compared to the control group and were greater in the AMS + Exo group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils, M1 macrophages, and mast cells decreased more considerably in the AMS + Exo group in comparison with the other groups. Generally, it was found that using both AMS transplantation and ADSCs-derived exosomes has more effect on diabetic wound healing.

Exosomes derived from human placental mesenchymal stem cells in combination with hyperbaric oxygen synergically alleviates spinal cord ischemia-reperfusion injury.

Spinal cord ischemia-reperfusion injury (IR) is a terrible non-traumatic injury that occurs after abdominal aortic occlusion and causes serious damage to neurological function. Several treatment strategies have been suggested for IR, but they were not unable to effectively improve these conditions. Herein we investigated whether exosomes derived from human placental mesenchymal stem cells (hpMSCs-Exos) in combination with hyperbaric oxygen (HBO) could alleviate injury and promote recovery in IR rats. Eighty male Sprague-Dawley rats were randomly allocated into five equal groups. In addition to the control group that only underwent laparotomy, IR animals were planned into four groups as follows: IR group; IR-Exos group; IR-HBO group; and IR-Exos + HBO group. Neurological function evaluated before, 6 h, 12 h, 24 h, and 48 h after injury. After the last neurological evaluation, tissue samples were obtained for stereological, biochemical, and molecular assessments. Our results indicated that the neurological function scores (MDI), the numerical density of neurons, the levels of antioxidative factors (GSH, SOD, and CAT), and anti-inflammatory cytokine (IL-10) were considerably greater in treatment groups than in the IR group, and these changes were more obvious in the IR-Exos + HBO ones. This is while the numerical density of glial cells, the levels of an oxidative factor (MDA) and inflammatory cytokines (IL-1ß, TNF-α, and IL-18), as well as the expression of an apoptotic protein (caspase-3) were meaningfully decreased in treatment groups, especially IR-Exos + HBO group, compared to the IR group. Generally, it was found that co-administration of hpMSCs-Exos and HBO has synergistic neuroprotective effects in the rats undergoing IR.

Hyperbaric oxygen therapy and coenzyme Q10 synergistically attenuates damage progression in spinal cord injury in a rat model.

BACKGROUND: Identifying effective spinal cord injury (SCI) treatments remains a major challenge, and current approaches are still unable to effectively improve its. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with coenzyme Q10 (CoQ10) in the recovery of SCI in rats. MATERIAL AND METHODS: Ninety female mature Sprague-Dawley rats were allocated into five equal groups, including; sham group, SCI group, HBO group (underwent SCI and received HBO), CoQ10 group (underwent SCI and received CoQ10), and HBO+CoQ10 group (underwent SCI and received HBO plus CoQ10). Tissue samples at the lesion site were obtained for evaluation of stereological, immunohistochemical, biochemical, molecular. Also, functional tests were performed to evaluate of behavioral properties. RESULTS: We found that a significant increase in stereological parameters, biochemical factors (GSH, SOD and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells, as well as expression of inflammatory genes (TNF-α and IL-1ß) were considerably reduced in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. CONCLUSION: We conclude that co-administration of HBO and HBO+CoQ10 has a synergistic neuroprotective effects in animals undergoing SCI.

In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model.

BACKGROUND: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. MATERIALS & METHODS: The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. RESULTS: ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. CONCLUSION: Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.

Promotion of cutaneous diabetic wound healing by subcutaneous administration of Wharton's jelly mesenchymal stem cells derived from umbilical cord.

Wound healing is a major problem in diabetic patients, and current treatments have been confronted with limited success. The present study examined the benefit of Wharton's jelly mesenchymal stem cells (WJ-MSCs) derived from the human umbilical cord (UC) in wound healing in diabetic rats. Thirty days after inducing diabetes, a circular excision was created in the skin of rats, and the treatments were performed for 21 days. Two groups were studied, which included the Control group and WJ-MSCs group. The studied groups were sampled on the 7th, 14th, and 21st days after wounding. Histological ultrasound imaging of dermis and epidermis in the wound area for thickness and density measurement and skin elasticity were evaluated. Our results on post-wounding days 7, 14, and 21 showed that the wound closure, thickness, and density of new epidermis and dermis, as well as skin elasticity in the healed wound, were significantly higher in the WJ-MSCs group compared to the Control group. Subcutaneous administration of WJ-MSCs in diabetic wounds can effectively accelerate healing. Based on this, these cells can be used along with other treatment methods in the healing of different types of chronic wounds.

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.

Synergistic neuroprotective effects of hyperbaric oxygen and methylprednisolone following contusive spinal cord injury in rat.

OBJECTIVE: Recent studies revealed the neuroprotective effects of hyperbaric oxygen (HBO) on spinal cord injury (SCI). Meanwhile, the use of methylprednisolone (MP) is one of the current protocols with limited effects in SCI patients. Accordingly, the aim of the present study was to investigate the effect of combined HBO and MP treatment on SCI. DESIGN: The present study was conducted on five groups of rats each as follows: Sham group (underwent laminectomy alone at T9 level vertebra); SCI group (underwent moderate contusive SCI); MP group (underwent SCI and received MP); HBO group (underwent SCI and received HBO); HBO + MP group (underwent SCI and simultaneously received MP and HBO). Blood serum and Spinal cord tissue samples were taken 48 h after SCI for analysis of serum ferric reducing antioxidant power (FRAP) and tissue malodialdehyde (MDA) levels as well as immunohistochemistry of caspase-3 and tumor necrosis factor-alpha (TNF-α). Neurological function was evaluated by the Basso-Beattie-Bresnehan (BBB) locomotion scores until the end of experiments. Additionally, histopathology was assessed at the end of the study. SETTING: Mazandaran University of Medical Sciences, Sari, Iran. RESULTS: Combination therapy with HBO and MP in the HBO + MP group significantly decreased MDA as well as increased FRAP levels compared to other treatment groups. Meanwhile, attenuated TNF-α and Caspase-3 expression could be significantly detected in the HBO + MP group. At the end of treatment, the neurological outcome was significantly improved and the extent of injured spinal tissue was also significantly reduced in the HBO + MP compared to other treatment groups. CONCLUSION: The results suggest that combined therapy with MP and HBO has synergistic effects on SCI treatment.