The future of diabetic wound healing: unveiling the potential of mesenchymal stem cell and exosomes therapy.

Diabetes mellitus (DM) is a significant public health problem and is one of the most challenging medical conditions worldwide. It is the severe complications that make this disease more intricate. A diabetic wound is one of these complications. Patients with diabetes are at higher risk of developing diabetic foot ulcers (DFU). Due to the ineffectiveness of Conventional treatments, growth in limb amputation, morbidity, and mortality have been recognized, which indicates the need for additional treatment. Mesenchymal stem cells (MSCs) can significantly improve wound healing. However, there are some risks related to stem cell therapy. Exosome therapy is a new treatment option for diabetic wounds that has shown promising results. However, an even more advanced form called cell-free therapy using exosomes has emerged. This upgraded version of stem cell therapy offers improved efficacy and eliminates the risk of cancer progression. Exosome therapy promotes wound healing from multiple angles, unlike traditional methods that primarily rely on the body's self-healing ability and only provide wound protection. Therefore, exosome therapy has the potential to replace conventional treatments effectively. However, further research is necessary to distinguish the optimal type of stem cells for therapy, ensure their safety, establish appropriate dosing, and identify the best management trail. The present study focused on the current literature on diabetic wound ulcers, their treatment, and mesenchymal stem cell and exosome therapy potential in DFU.

Applications of poly(lactic acid) in bone tissue engineering: A review article.

BACKGROUND: Bone tissue engineering is a promising approach to large-scale bone regeneration. This involves the use of an artificial extracellular matrix or scaffold and osteoblasts to promote osteogenesis and ossification at defect sites. Scaffolds are constructed using biomaterials that typically have properties similar to those of natural bone. METHOD: In this study, which is a review of the literature, various evidences have been discussed in the field of Poly Lactic acid (PLA) polymer application and modifications made on it in order to induce osteogenesis and repair bone lesions. RESULTS: PLA is a synthetic aliphatic polymer that has been extensively used for scaffold construction in bone tissue engineering owing to its good processability, biocompatibility, and flexibility in design. However, PLA has some drawbacks, including low osteoconductivity, low cellular adhesion, and the possibility of inflammatory reactions owing to acidic discharge in a living environment. To overcome these issues, a combination of PLA and other biomaterials has been introduced. CONCLUSIONS: This short review discusses PLA's characteristics of PLA, its applications in bone regeneration, and its combination with other biomaterials.

The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of Circulating Tumor Cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer.

The effects of pre-treatment with olibanum and its constituent, boswellic acid on synaptic plasticity impairments induced by lipopolysaccharide in rats.

OBJECTIVE: Olibanum (OLIB) and its component boswellic acid (BOSA) are suggested to have anti-inflammatory, anti-oxidant and neuroprotective effects. In the present work, we examined effect of OLIB, and BOSA on the synaptic plasticity impairment and oxidative stress indicators in a rat model of neuro-inflammation induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: Forty rats were divided into the following four groups: (1) Control, (2) LPS, (3) OLIB (200 mg/kg), and (4) BOSA (10 mg/kg). The animals were pre-treated with OLIB extract, BOSA or the vehicle 30 min before LPS (1 mg/kg) administration, for 6 days. On the 6th day, electrophysiological recording was done. Long-term potentiation (LTP) from CA1 area of hippocampus was assessed. The animals were then sacrificed and their brains were removed for evaluation of the levels of interleukin-6 (IL-6), nitric oxide (NO) metabolites, malondialdehyde (MDA), thiol, superoxide dismutase (SOD) and catalase (CAT) in the cortex. RESULTS: Administration of LPS decreased amplitude (p<0.001) and slope (p<0.01) of field excitatory postsynaptic potential (fEPSP). Pre-treatment enhanced these parameters (p<0.05 to p<0.001). LPS also increased cortical levels of IL-6 (P<0.01), NO, and MDA (p<0.001) while decreased thiol, SOD (p<0.001), and CAT (p<0.05). OLIB and BOSA diminished IL-6 (p<0.05-p<0.001), NO (p<0.01-p<0.001) and MDA level (p<0.01 and p<0.001, respectively) while improved SOD (p<0.05 and p<0.001, respectively), CAT (p<0.05 and p<0.001, respectively) and thiol content (p<0.001). CONCLUSION: The results showed that OLIB and BOSA could improve synaptic plasticity impairment induced by LPS as shown by a decrease in an inflammation indicator along with the anti-oxidant effects.

Neuronal Nitric Oxide Inhibitor 7-Nitroindazole Improved Brain-Derived Neurotrophic Factor and Attenuated Brain Tissues Oxidative Damage and Learning and Memory Impairments of Hypothyroid Juvenile Rats.

Hypothyroidism-associated learning and memory impairment is reported to be connected to oxidative stress and reduced levels of brain-derived neurotrophic factor (BDNF). The effects of neuronal nitric oxide inhibitor 7-nitroindazole (7NI) on brain tissues oxidative damage, nitric oxide (NO), BDNF and memory impairments in hypothyroid juvenile rats were investigated. Male Wistar juvenile rats (20 days old) were divided into five groups, including Martinez et al. (J Neurochem 78 (5):1054-1063, 2001). Control in which vehicle was injected instead of 7NI, (Jackson in Thyroid 8 (10):951-956, 1998) Propylthiouracil (PTU) where 0.05% PTU was added in drinking water and vehicle was injected instead of 7NI, (Gong et al. in BMC Neurosci 11 (1):50, 2010; Alva-Sánchez et al. in Brain Res 1271:27-35, 2009; Anaeigoudari et al. in Pharmacol Rep 68 (2): 243-249, 2016) PTU-7NI 5, PTU-7NI 10 and PTU-7NI 20 in which 5, 10, or 20 mg/kg7NI was injected intraperitoneally (i.p.). Following 6 weeks, Morris water maze (MMW) and passive avoidance learning (PAL) tests were used to evaluate the memory. Finally, the hippocampus and the cortex of the rats were removed after anesthesia by urethane to be used for future analysis. The escape latency and traveled path in MWM test was increased in PTU group (P < 0.001). PTU also reduced the latency to enter the dark box of PAL and the time spent and the distance in the target quadrant in MWM test (P < 0.001 and P < 0.01). Treatment with 7NI attenuated all adverse effects of PTU (P < 0.05 to P < 0.001). PTU lowered BDNF and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain but increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. In addition, 7NI improved thiol, SOD, CAT, thiol, and BDNF but attenuated MDA and NO metabolites. The results of the current study showed that 7NI improvement in the learning and memory of the hypothyroid juvenile rats, which was accompanied with improving of BDNF and attenuation of NO and brain tissues oxidative damage.

Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: Evidence from inflammation and oxidative stress.

OBJECTIVE: The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. MATERIALS AND METHODS: The animals were allocated to five groups (n = 10 in each) and treated by: (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. RESULTS: LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (SOD), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. CONCLUSION: It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.

The effects of acetyl-11-keto-ß-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats.

The therapeutic effects of the olibanum, the resin of Boswellia serrata on inflammatory diseases have been reported. There are more than 200 active ingredients in this resin including acetyl-11-keto-ß-boswellic acid (AKBA). We proposed that AKBA can improve memory impairment induced by cerebral inflammation following the administration of lipopolysaccharide (LPS). Forty male rats were grouped and received the following treatments: Control (diluted DMSO + saline), LPS (diluted DMSO + 1 mg/kg LPS), LPS- AKBA 5 and LPS- AKBA 10 (5 or 10 mg/ kg AKBA before LPS). Morris water maze (MWM), passive avoidance (PA) and biochemical tests were carried out. Pre-treatment with both doses of AKBA improved memory performance in MWM and PA tests (P < 0.05 to P < 0.001). Pre-treatment by AKBA improved the levels of hippocampal IL-10 (P < 0.001), BDNF (P < 0.001), CAT (P < 0.05 and P < 0.001), SOD P < 0.001 and thiols (P < 0.01 and P < 0.001) while reduced IL-6 (P < 0.001), TNF-α (P < 0.001), NO (P < 0.05 and P < 0.001), GFAP (P < 0.001) and MDA (P < 0.001) levels. AKBA effectively ameliorated LPS-induced learning and memory impairments and improved BDNF in a neuroinflammation animal model. The effects seem to be due to setting a positive balance between pro-inflammatory to inflammatory cytokines and reinvigorate the antioxidant system.

Hereditary thrombophilia genetic variants in recurrent pregnancy loss.

BACKGROUND: The relationship between thrombophilia genes and recurrent pregnancy loss has been discussed. The aim of this study was to investigate the association between of MTHFR C677T, A1298C, F2G20210A, and F5 G1691A genetic variants among Iranian women with recurrent miscarriage. METHODS: A total of 245 women with two or more recurrent pregnancy loss, with mean age years were enrolled in the study. To compare genotypes, we have selected 250 healthy women without history of miscarriage as control group. Genomic DNA of participants was evaluated using polymerase chain reaction followed by Sanger sequencing to determine the genotype frequency. RESULTS: The mean age were 32.16 ± (21-42) and 31.81 ± (19-40) for case and control groups respectively. MTHFR C677T and A1298C mutant alleles were found to be significantly more prevalent in patients than control. However, F2G20210A and F5 G1691A genetic variants showed no significance. CONCLUSION: The allele frequencies for the assessed genotypes in this study are consistent with the data obtained for other countries. We observed significant susceptible effects of MTHFR C677T, and A1298C among participants. According to the relatively high prevalence of these variants, we recommend genetic testing for women with RPL before therapeutic decisions.