Protective effect of dental pulp stem cells' conditioned medium against cisplatin-induced testicular damage in rats.

Cisplatin is a highly effective chemotherapy drug used to treat most solid tumors. However, one of its side effects is testicular toxicity, which can lead to fertility abnormalities. This study investigated the effectiveness of dental pulp mesenchymal stem cells conditioned medium (DPSC-CM) on cisplatin-induced testicular toxicity. In this study, 36 eight-week-old male Wistar rats were randomly divided into three groups equally (n = 12). Group 1 control "CTR", which received normal saline (0.5 ml) intraperitoneally (i.p), group 2 "Cis" which received an intraperitoneal dose of cisplatin (7 mg/kg), and group 3 "Cis+CM" which received an i.p injection of DPSC-CM (0.5 mg/kg) after cisplatin injection. Biochemical, histomorphometric, and histopathological studies were performed on the testis. Our results exhibited that cis administration led to a decline in total body weight, testis weight, diameter, and volume. A decrease in testosterone and IL-6 serum levels, as well as a decrease in IL-6 and TNFα levels, the activity of catalase and SOD enzymes, and an increase in MDA in testicular tissue were detected. Testicular tissue damage was associated with a significant decrease in tube diameter, germinal epithelium height, number of spermatogonia and Sertoli cells, along with a noticeable increase in basement membrane thickness, and perivascular fibrosis. DMSC-CM improved all the mentioned parameters. Taken together, our results demonstrated that DMSC-CM due to its antioxidant and anti-inflammatory properties, could be effective in reversing cisplatin-induced testicular toxicity.

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence.

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.

Nanowarming improves survival of vitrified ovarian tissue and follicular development in a sheep model.

Tissue cryopreservation has allowed long term banking of biomaterials in medicine. Ovarian tissue cryopreservation in particular helps patients by extending their fertility window. However, protection against tissue injury during the thawing process has proven to be challenging. This is mainly due to the heterogenous and slow distribution of the thermal energy across the vitrified tissue during a conventional warming process. Nanowarming is a technique that utilizes hyperthermia of magnetic nanoparticles to accelerate this process. Herein, hyperthermia of synthesized PEGylated silica-coated iron oxide nanoparticles was used to deter the injury of cryopreserved ovarian tissue in a sheep model. When compared to the conventional technique, our findings suggest that follicular development and gene expression in tissues warmed by the proposed technique have been improved. In addition, Nanowarming prevented cellular apoptosis and oxidative stress. We therefore conclude that Nanowarming is a potential complementary candidate to increase efficiency in the ovarian cryopreservation field.

Effect of melatonin on male offspring testis and sperm parameters in BALB/c mice after exposing their mother to METHamphetamine during pregnancy and lactation.

Objectives: Methamphetamine (METH) is a psychostimulant that has harmful effects on all organs, the nervous system, cardiovascular system, and reproductive system. Since many METH consumers are young people of reproductive age, it poses a risk to the next generation of METH consumers. METH can pass through the placenta and is also secreted into breast milk. Melatonin (MLT) is the primary hormone of the pineal gland that regulates the circadian cycle, and it is also an antioxidant that can mitigate the effects of toxic substances. This study aims to investigate the protective effect of melatonin against the detrimental effects that METH has on the reproductive system of male newborns, whose mothers consumed METH during pregnancy and lactation. Materials and Methods: In the current study, 30 female adult balb/c mice were divided into three groups: control group, vehicle group that received normal saline, and the experimental group that received 5 mg/kg METH intraperitoneally during gestation and lactation. After lactation, the male offspring of each group were randomly divided into two subgroups, one of which received 10 mg/kg melatonin intragastrically for 21 days (corresponding to the lactation period of the mice) (METH-MLT) and the other did not (METH -D.W). After treatment, the mice were sacrificed and testicular tissue and epididymis were obtained for the following tests. Results: The diameter of seminiferous tubules, SOD activity, total Thiol groups concentration, catalase activity, sperm count, and PCNA and CCND gene expression were significantly increased in the METH-MLT group compared with the METH-DW. Apoptotic cells and MDA level ameliorated in the METH-MLT group compared with METH-D.W, and testicular weight had no notable change. Conclusion: The current study represents that consumption of METH during pregnancy and lactation can have adverse effects on the histological and biochemical factors of testis and sperm parameters of male newborns, which can be mitigated by taking melatonin after the end of the breastfeeding period.

Ameliorative effects of crocin against electromagnetic field-induced oxidative stress and liver and kidney injuries in mice.

Objective: The current study's goal was to examine how crocin affects organ damage such as damage to the kidney and liver in mice treated by 2100 MHz Electro Magnetic Field. Materials and Methods: The liver and kidneys of mice exposed to EMFs were used in this study to examine how crocin affected them. 24 male NMARI mice were randomly divided into 4 groups: EMF group (2100 MHZ); Crocin (Cr) group (50 mg/kg); EMF+Crocin group (2100 MHZ+50 mg/kg), and control group. The antioxidant enzymes and some serum biochemical parameters were assessed in blood samples collected after the experiment. After the animals were put to sleep, liver and kidney samples were taken for histopathological and liver samples were taken for ultrastructural analyses. Results: The serum levels of urea and creatinine, and serum activities of alanine transaminase, aspartate transaminase, and alkaline phosphatase were higher in the EMF group than the control group, and this difference was significant. When compared to the control group, the EMF group's antioxidants, (catalase and superoxide dismutase) activity were decreased. These metrics significantly improved in the EMF + Cr group when compared to the EMF group. Different pathological damages were present in the liver and kidney of the EMF group, and the liver's ultrastructure had changed. Crocin administration decrease these changes. Conclusion: Crocin, an antioxidant agent, may provide defense against tissue damage brought on by EMF by reducing oxidative stress.

The therapeutic effect of melatonin on female offspring ovarian reserve and quality in BALB/c mice after exposing their mother to methamphetamine during pregnancy and lactation.

Objectives: Nowadays, methamphetamine (METH) abuse as a psychotropic drug is increasing. There is insufficient information about its adverse effects on the ovarian reserve of the next generation. Herein, we tried to investigate the effect of METH abuse during pregnancy and lactation and, subsequently, the therapeutic effect of melatonin on ovarian reserve in offspring. Materials and Methods: In the present study, BALB/c pregnant female mice were divided into 3 groups: Control, Saline, and METH (5mg/Kg). METH was injected during pregnancy and lactation, and the female offspring of each group was divided into 2 subgroups: A) treated with 10 mg/kg Melatonin daily until puberty (6 weeks old) and B) received distilled water. The animals were sacrificed at 6 weeks of age, and blood samples were collected for hormonal assessments; the right ovaries were removed and fixed for TUNEL and Hematoxylin & Eosin staining, and the left ovaries were removed and stored for gene expression and oxidative stress evaluation. Results: In the MTEH group, two indicators of ovarian reserve (including anti-Müllerian hormone (AMH) and primordial follicle, and Cyclin D1 (CCND-1) and proliferating cell nuclear antigen (PCNA) genes expression significantly decreased, and the oxidative stress and apoptosis significantly increased in comparison with other groups. After lactation in the MTEH group, melatonin treatment significantly improved the ovarian reserve and gene expression and declined apoptosis and oxidative stress. Conclusion: METH abuse during pregnancy and lactation decreased ovarian reserve in offspring. The administration of melatonin as an anti-oxidant agent after lactation can counteract the adverse effects of METH on offspring ovaries.

Exosomes and Nano-SDF Scaffold as a Cell-Free-Based Treatment Strategy Improve Traumatic Brain Injury Mechanisms by Decreasing Oxidative Stress, Neuroinflammation, and Increasing Neurogenesis.

Traumatic brain injury (TBI) causes a variety of complex pathological changes in brain parenchymal tissue by increasing neuroinflammatory and apoptosis responses. Currently, there is no treatment to resolve the consequences related to TBI. Recently, an extensive literature has grown up around the theme of bystander effects of stem cells, a mechanism of stem cells without the need for cell transplantation, which is called cell-free therapy. The purpose of this investigation was to determine the efficacy of a cell-free-based therapy strategy using exosomes derived from human neural stem cells (hNSCs) and a novel nano-scaffold in rats subjected to TBI. In this study, a series of in vitro and in vivo experiments from behavior tests to gene expression was performed to define the effect of exosomes in combination with a three-dimensional (3D) nano-scaffold containing a bio-motif of SDF1α (Nano-SDF). Application of exosomes with Nano-SDF significantly decreased oxidative stress in serum and brain samples. Moreover, treatment with exosomes and Nano-SDF significantly reduced the expression of Toll-like receptor 4 and its downstream signaling pathway, including NF-kß and interleukin-1ß. We also found that the cell-free-based therapy strategy could decrease reactive gliosis at the injury site. Interestingly, we showed that exosomes with Nano-SDF increased neurogenesis in the sub-ventricular zone of the lateral ventricle, indicating a bio-bridge mechanism. To sum up, the most obvious finding to emerge from this study is that a cell-free-based therapy strategy can be an effective option for future practice in the course of TBI.

Zinc- and Copper-Doped Mesoporous Borate Bioactive Glasses: Promising Additives for Potential Use in Skin Wound Healing Applications.

In this study, zinc (Zn)- and copper (Cu)-doped 13-93B3 borate mesoporous bioactive glasses (MBGs) were successfully synthesized using nitrate precursors in the presence of Pluronic P123. We benefited from computational approaches for predicting and confirming the experimental findings. The changes in the dynamic surface tension (SFT) of simulated body fluid (SBF) were investigated using the Du Noüy ring method to shed light on the mineralization process of hydroxyapatite (HAp) on the glass surface. The obtained MBGs were in a glassy state before incubation in SBF. The formation of an apatite-like layer on the SBF-incubated borate glasses was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The incorporation of Zn and Cu into the basic composition of 13-93B3 glass led to changes in the glass transition temperature (Tg) (773 to 556 °C), particle size (373 to 64 nm), zeta potential (−12 to −26 mV), and specific surface area (SBET) (54 to 123 m2/g). Based on the K-means algorithm and chi-square automatic interaction detection (CHAID) tree, we found that the SFT of SBF is an important factor for the prediction and confirmation of the HAp mineralization process on the glasses. Furthermore, we proposed a simple calculation, based on SFT variation, to quantify the bioactivity of MBGs. The doped and dopant-free borate MBGs could enhance the proliferation of mouse fibroblast L929 cells at a concentration of 0.5 mg/mL. These glasses also induced very low hemolysis (<5%), confirming good compatibility with red blood cells. The results of the antibacterial test revealed that all the samples could significantly decrease the viability of Pseudomonas aeruginosa. In summary, we showed that Cu-/Zn-doped borate MBGs can be fabricated using a cost-effective method and also show promise for wound healing/skin tissue engineering applications, as especially supported by the cell test with fibroblasts, good compatibility with blood, and antibacterial properties.

Co-transplantation of novel Nano-SDF scaffold with human neural stem cells attenuates inflammatory responses and apoptosis in traumatic brain injury.

Traumatic brain injury (TBI) causes long-term disability and mortality worldwide. The prime pathological players in TBI are neuroinflammation and apoptosis. These pathological changes lead to a limited capacity of regeneration after TBI. To alleviate inflammatory responses and apoptosis triggered by TBI, developing bioactive scaffolds conjoined with stem cells is a decisive approach in neural tissue engineering. The aim of this study was to fabricate a novel nano-scaffold made of RADA-16 with a bioactive motif of stromal cell-derived factor-1 α (SDF-1α) and evaluate its effects with stem cell transplantation on inflammatory pathways, reactive gliosis, and apoptosis after TBI. Co-transplantation of Nano-SDF and human neural stem cells (hNSCs) derived from fetus brain in adult rats subjected to TBI led to the improvement of motor activitycompared with the control group. The treated animals with hNSCs + Nano-SDF had a significantly lower expression of toll-like receptor 4 and nuclear factor-kappa B at the injury site than the control animals. A significant reduction in the number of reactive astrocytes was also observed in rats that received hNSCs + Nano-SDF compared with the vehicle and Nano-SDF groups. Furthermore, the TUNEL assay indicated a significant reduction in TUNEL positive cells in the hNSCs + Nano-SDF group compared with the TBI, vehicle, and Nano-SDF groups. These data demonstrated co-transplantation of hNSCs with Nano-SDF can reduce inflammatory responses and cell death after TBI via creating a more supportive microenvironment. Further research is required to establish the therapeutic efficacy of Nano-SDF with stem cells for TBI.

Anti-apoptotic and neurogenic properties in the hippocampus as possible mechanisms for learning and memory improving impacts of vitamin D in hypothyroid rats during the growth period.

The current study was designed to investigate the protective effects of Vitamin D (VD) on hippocampal neurogenesis, apoptosis, and subsequent hippocampal-dependent learning and memory performance in hypothyroid juvenile rats. Twenty eight male Wistar rats were randomly divided into four groups as; control, Hypothyroid (Hypo), Hypo-VD100 and Hypo-VD500. Hypothyroidism was induced by giving 0.05 % propylthiouracil (PTU), and VD (100 or 500 IU/kg) treatment was performed daily by gavage. At the end of treatment, Morris water maze (MWM) was carried out and evaluated hippocampal neurogenesis, apoptosis, and dark neurons (DNs). Our results revealed that the escape latency and the traveled distance to find the platform in the Hypo group were significantly longer but the time spent and distance traveled in the target area in probe trial was lower than the control group. Hypothyroidism was accompanied by a marked decrease in hippocampal neurogenesis, and a significant increase in the number of apoptotic neurons and DNs compared to the control group. VD decreased escape latency and the traveled distance to find the platform but increased the time spent and distance traveled in the target area in probe trial than the Hypo group. VD also increased neurogenesis, reduced apoptosis and DNs production compared to the Hypo group. In conclusion, these results support a role for VD in the restoring hippocampal neurogenesis impairment, reducing neuronal apoptosis, and DNs in hypothyroid rats as well as raise the possibility that VD may contribute as a therapeutic approach to improve the learning and memory deficits associated with hypothyroidism.

Roles of the miR-155 in Neuroinflammation and Neurological Disorders: A Potent Biological and Therapeutic Target.

Neuroinflammation plays a crucial role in the development and progression of neurological disorders. MicroRNA-155 (miR-155), a miR is known to play in inflammatory responses, is associated with susceptibility to inflammatory neurological disorders and neurodegeneration, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis as well as epilepsy, stroke, and brain malignancies. MiR-155 damages the central nervous system (CNS) by enhancing the expression of pro-inflammatory cytokines, like IL-1ß, IL-6, TNF-α, and IRF3. It also disturbs the blood-brain barrier by decreasing junctional complex molecules such as claudin-1, annexin-2, syntenin-1, and dedicator of cytokinesis 1 (DOCK-1), a hallmark of many neurological disorders. This review discusses the molecular pathways which involve miR-155 as a critical component in the progression of neurological disorders, representing miR-155 as a viable therapeutic target.

The benefits of grape seed extract in neurological disorders and brain aging.

Common neurological disorders, including neurodegenerative diseases, stroke, epilepsy, autism and psychiatric disorders, affect many people worldwide and threaten their lives and health by inducing movement disorders, behavioral disorders, or a combination of both. Oxidative stress and neuroinflammation play a central role in neuronal damage and neurological diseases induction and progression. In addition, protein homeostasis (proteostasis) impairment occurs in many neurodegenerative diseases, which plays a critical role in the progression of the pathology. Grape seed contains several flavonoids and non-flavonoids and exerts potent antioxidant and anti-inflammatory effects. In addition, polyphenols and flavanols can maintain cellular proteostasis. Since impaired proteostasis is closely involved in all amyloid diseases, particularly neurodegenerative diseases, grape seeds extract can be a valuable therapeutic agent. Therefore, this review discusses the protective and therapeutic mechanisms of grape seed against neurological disorders and, in the end, links GSE to microRNAs as future therapeutic developments.

Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes.

OBJECTIVES: Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI. METHODS: AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups. RESULTS: A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals. CONCLUSIONS: The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

Targeting miR-21 in spinal cord injuries: a game-changer?

Spinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI.

Protective Effect of Portulaca oleracea on Streptozotocin-Induced Type I Diabetes-Associated Reproductive System Dysfunction and Inflammation.

BACKGROUND: Type-one diabetes (T1D), a chronic autoimmune disease with marked inflammatory responses, is associated with infertility complications and implications. Based on the anti-diabetic, antioxidant, and anti-hyperlipidemic potential of Portulaca oleracea (PO), this study aimed to evaluate the protective effect of this plant extract on streptozotocin-induced type-I-diabetes-associated reproductive system dysfunction and inflammation. METHODS: Male rats were randomly divided into four experimental groups: control, diabetic, and treatment/s (PO extract at 100 or 300 mg/kg/daily). Then food and water consumption, body, testis and epididymis weights, histopathological evaluation, seminiferous tubules diameter, sperm count and motility, glucose levels, sex hormones, and inflammatory and oxidative stress markers were evaluated. RESULTS: Our results showed that streptozotocin-induced diabetes significantly increased food and water consumption; increased glucose, MDA, TGF-ß1, and TNF-α levels; and decreased the seminiferous tubules diameter, sperm count and motility, levels of LH, testosterone, total thiol, VEGF, and SOD activity. Interestingly, PO extract (phytochemically characterized by using liquid chromatography-mass spectrometry to detect bioactive molecules) significantly ameliorated these parameters and histopathological indexes' damage in rats. CONCLUSION: Even if more preclinical assessments are needed to better characterize the mechanism/s of action, the results of this study will pave the way for the rational use of PO on diabetic-associated clinical complications and implications.

Decellularization of human amniotic membrane using detergent-free methods: Possibilities in tissue engineering.

The human amniotic membrane (HAM) is widely used as a natural scaffold in tissue engineering due to its excellent biological characteristics, including anti-microbial, anti-inflammatory, low immunogenicity, and pro-angiogenic properties. This study aimed to develop simple and cost-effective protocols for the decellularization of HAM (d-HAM) using detergent-free methods, i.e., mechanical force (brushing) and physical treatment (heating 45-55 °C). The effectiveness of the methods of interest was compared with a chemical-based approach (EDTA + NaOH + NH4Cl). The prepared d-HAMs were characterized using a series of physico-chemical, mechanical, and biological evaluations. The results from DAPI staining revealed that the chemical method could completely remove epithelial cells from HAM, while the two other approaches only reduced the number of epithelial cells. All three decellularization methods led to a sharp reduction (P < 0.001) in the DNA content of the tissue samples (< 50 ng/mg). Histological evaluations showed the preservation of the d-HAMs' integrity along with the conservation of collagen and glycosaminoglycans (GAGs). Although the chemical method caused the lowest mechanical deterioration (3.55 MPa in ultimate tensile stress), the mechanical method preserved the highest hydroxyproline levels (3.13 mg/mL). On the other hand, the physical method (heating to 45 and 50 °C) encouraged cell proliferation more than the chemical and mechanical approaches. All of the samples proved to be suitable for cell attachment and could induce cell migration. In conclusion, the present study showed that the use of detergent-free protocols is applicable for the decellularization of HAM, and the obtained tissues may be considered as inexpensive dressings for numerous tissue engineering applications.

A Comparative Analysis of Photobiomodulation-Mediated Biological Effects of Single Versus Double Irradiation on Dental Pulp Stem Cells: An In Vitro Study.

Objective: In recent years, fractionated irradiation protocols, rather than a simple plan of exposure, have been proposed as a more effective method in the field of tissue regeneration. Thus, this study aimed at a comparative analysis of single versus double irradiation of an 808-nm diode laser, in terms of dental pulp stem cells' (DPSCs) viability and proliferation in vitro. Methods: Subcultured DPSCs were either irradiated, or not (control group), with energy densities of 3, 7, and 12 J·cm-2 in a single- or double-session manner (24 h apart). On 0, 12, 24, 48, and 72 h postirradiation, cell viability and proliferation were evaluated through Trypan Blue and alamarBlue assays, respectively. Results: During the first 48 h postirradiation, the highest rates of DPSC proliferation were assigned to double irradiation at 3 or single exposure to 7 J⋅cm-2, with no cytotoxic effects on cell viability. Inversely, single irradiation at 12, or a double session of exposure to 7 or 12 J⋅cm-2, led to a significant descent in the rates of proliferation and cell viability. Conclusions: Within the limitations of this study, evidence suggests a positive impact on the biological responses of DPSCs following double session of exposure to lower energy densities as well as a single irradiation at a higher energy dosage.

Preparation and Characterization of Platelet Lysate (Pl)-Loaded Electrospun Nanofibers for Epidermal Wound Healing.

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing.

The protective effect of co-administration of platelet-rich plasma (PRP) and pentoxifylline (PTX) on cyclophosphamide-induced premature ovarian failure in mature and immature rats.

Cyclophosphamide (CP), as an antineoplastic agent, causes premature ovarian failure (POF) due to ovarian toxicity and subsequent infertility in women. Platelet-rich plasma (PRP) has accumulated significant attention in regenerative medicine. Pentoxifylline (PTX) as a methylxanthine derivative has been shown to have antioxidant and antiapoptotic properties. The aim of this study was to evaluate the protective effect of PRP and PTX on CP-induced POF. Fifty mature and immature female rats were assigned into five groups: control, CP (75 mg/kg, intraperitoneal [ip] on days 1 and 10 to induce POF), CP + PRP (200 µl, ip, half an hour after CP injection on day 1 and 10), CP + PTX (50 mg/kg, orally, half an hour after CP injection daily for 21 day), and CP + PRP + PTX. At the end of experiments on day 21, measurement of body weight, ovarian parameters (ovarian volume, follicular granulosa cell layers diameter, oocyte diameter, and the number of granulosa cells), measurement of ovarian hormone in sera for estradiol (E2), and anti-Mullerian hormone (AMH), as well as biochemical assessment were performed.The results showed that CP significantly reduced the ovarian parameters, E2, AMH, superoxide dismutase (SOD) activity and increased Malondialdehyde (MDA) levels compared to the control group (p < 0.001). Our results also indicated that all histomorphometric parameters and biochemical markers in CP-induced POF, were preserved close to normal by PRP and PTX treatments in both mature and immature rats (p < 0.001). Therefore, it is concluded that the co-administration of PRP and PTX can protect the ovary from CP-induced POF.

Neural stem cell therapy in conjunction with curcumin loaded in niosomal nanoparticles enhanced recovery from traumatic brain injury.

Despite a great amount of effort, there is still a need for reliable treatments of traumatic brain injury (TBI). Recently, stem cell therapy has emerged as a new avenue to address neuronal regeneration after TBI. However, the environment of TBI lesions exerts negative effects on the stem cells efficacy. Therefore, to maximize the beneficial effects of stem cells in the course of TBI, we evaluated the effect of human neural stem/progenitor cells (hNS/PCs) and curcumin-loaded niosome nanoparticles (CM-NPs) on behavioral changes, brain edema, gliosis, and inflammatory responses in a rat model of TBI. After TBI, hNS/PCs were transplanted within the injury site and CM-NPs were orally administered for 10 days. Finally, the effect of combination therapy was compared to several control groups. Our results indicated a significant improvement of general locomotor activity in the hNS/PCs + CM-NPs treatment group compared to the control groups. We also observed a significant improvement in brain edema in the hNS/PCs + CM-NPs treatment group compared to the other groups. Furthermore, a significant decrease in astrogliosis was seen in the combined treatment group. Moreover, TLR4-, NF-κB-, and TNF-α- positive cells were significantly decreased in hNS/PCs + CM-NPs group compared to the control groups. Taken together, this study indicated that combination therapy of stem cells with CM-NPs can be an effective therapy for TBI.