Diagnostic accuracy of serum derived exosomes for hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Early and non-invasive detection of hepatocellular carcinoma (HCC), which is usually asymptomatic, can improve overall survival outcomes. The objective of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of serum-derived exosomes for diagnosing HCC. METHODS: PubMed, Web of Science, and Scopus databases were searched for relevant studies up to April 2023. The quality of included studies was assessed using the QUADAS-2 checklist, and data were extracted. Statistical analysis was performed on 18 studies from 3,993 records, and a diagnostic meta-analysis was conducted. Biomarkers were categorized into four groups based on their type (exosomal miRNAs, exosomal RNAs, alpha-fetoprotein (AFP), and exosomal RNAs+AFP panel), and a meta-analysis was conducted for each category separately. RESULTS: The highest pooled sensitivity was 0.86 for exosomal miRNAs, and exosomal RNAs+AFP had the highest pooled specificity; (0.89). Furthermore, exosomal RNAs+AFP had the highest pooled positive likelihood ratio; (7.55), the highest pooled diagnostic odds ratio (35.96) and the highest pooled area under the curve (0.93). Exosomal miRNAs had the lowest pooled negative likelihood ratio; (0.17). CONCLUSIONS: The diagnostic accuracy of exosomal biomarkers is superior to that of AFP, and combining the two in a panel yields the better results.

Chronic light deprivation induces different effects on spatial and fear memory and hippocampal BDNF/TRKB expression during light and dark phases of rat diurnal rhythm.

Disruptions in light/dark cycle have been associated with an altered ability to form and retrieve memory in human and animals. Animal studies have shown that chronic light deprivation disrupts the light/dark cycle and alters the neural connections that mediate hippocampal memory formation. In order to better understand how light deprivation affects the formation and retrieval of memory in adult rats, we examined the effect of total darkness on spatial and auditory fear learning and memory formation and BDNF/TRKB protein levels during the light and dark phases of the rat circadian cycle. Male Wistar rats (n = 60), were randomly divided into two main groups: normal rearing (NR, 12 h light/dark cycle for 3 weeks) and dark rearing (DR, kept in constant darkness for 3 weeks); and each of these groups had a "light (day)" and "dark (night)" sub-group. After 3 weeks, the Morris Water maze and auditory fear conditioning were used to assess spatial and fear memory acquisition and retrieval, respectively. BDNF and TRKB protein levels in the hippocampus of rats from the four sub-groups were measured by Western blot, at the completion of the 3 week constant darkness exposure and after the behavioral experiments. These studies revealed that DR for 3 weeks impaired spatial memory retrieval and enhanced extinction of auditory fear memory specifically during the light (day) phase. DR also eliminated the normal fluctuations in BDNF/TRKB levels observed in the hippocampus across the light/dark cycle.

Long-term administration of metformin ameliorates age-dependent oxidative stress and cognitive function in rats.

BACKGROUND: Aging is an inevitable physiological process, associated with a decline in cognitive function. Recently, metformin, as the first-line treatment for type II diabetes, has been shown to increase the life expectancy of diabetic patients. Therefore, researchers are paying increasing attention to its anti-aging properties. Oxygen free radicals are responsible for oxidative stress, which is a prominent factor in age-associated diseases. This study aimed to evaluate the effects of long-term administration of metformin on age-dependent oxidative stress and cognitive function. METHODS: In this experimental study, 32 normal (nondiabetic) male Wistar rats were randomly assigned into control and metformin groups (n = 16 per group). The metformin group received 100 mg/kg of metformin in drinking water daily for six months. The shuttle box test was used for the passive avoidance task in 24-month-old rats. For the biochemical assay, the total antioxidant capacity (TAC) and malondialdehyde (MDA) level were measured. Nissl and TUNEL staining were also used for histopathological assessments. Data were analyzed using independent t-test. RESULTS: The present findings revealed that metformin significantly reduced the MDA level and increased the TAC in the hippocampus of the metformin group (p < 0.05). The survival of hippocampal CA1 neurons was significantly higher in the metformin group as compared to the control group, while the number of TUNEL-positive neurons decreased significantly (p < 0.05). On the other hand, metformin markedly improved the passive avoidance memory in the metformin group as compared to the control group (p < 0.05). CONCLUSION: It can be concluded that long-term metformin intake, by modulating the oxidant/antioxidant mechanisms, prevents the loss of hippocampal neurons caused by age-dependent oxidative stress and improves memory.

Irisin protects the substantia nigra dopaminergic neurons in the rat model of Parkinson's disease.

OBJECTIVES: Exercise ameliorates the quality of life and reduces the risk of neurological derangements such as Alzheimer's (AD) and Parkinson's disease (PD). Irisin is a product of the physical activity and is a circulating hormone that regulates the energy metabolism in the body. In the nervous system, Irisin influences neurogenesis and neural differentiation in mice. We previously demonstrated that co-treatment of bone marrow stem cells (BMSCs) with a neurotrophic factor reduce Parkinson's symptoms. Our goal in this project was to evaluate whether Irisin with BMSCs can protect the dopaminergic (DA) neurons in PD. MATERIALS AND METHODS: 35 adult male Wistar rat weighing (200-250 g) were chosen. They were separated into five experimental groups (n=7). To create a Parkinson's model, intranasal (IN) administration of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used. The BMSCs (2×106) and Irisin (50 nm/ml) was used for 7 days for treatment after creation of the PD model. After completion of the tests (4 weeks), their brains were used for the TUNEL and immunohistochemical (IHC) assays. RESULTS: One of the important results of this study was that the Irisin induce BMSCs transport into the injured area of the brain. Co-treatment of the Irisin with BMSCs increased tyrosine hydroxylase-positive neurons (TH+) in substantia nigra (SN) and striatum of the PD mice brain. In this group, the number of TUNEL-positive cells significantly decreased. Behavioral symptoms were better in the combination group and Irisin simultaneously. CONCLUSION: Co- treatment of Irisin with BMSCs protects the DA neurons from degeneration and apoptotic process after MPTP injection.

Anti-Oxidative and Anti-Apoptotic Effects of Apigenin on Number of Viable and Apoptotic Blastomeres, Zona Pellucida Thickness and Hatching Rate of Mouse Embryos.

BACKGROUND: Apigenin is a plant-derived compound belonging to the flavonoids category and bears protective effects on different cells. The aim of this study was to evaluate the effect of apigenin on the number of viable and apoptotic blastomeres, the zona pellucida (ZP) thickness and hatching rate of pre-implantation mouse embryos exposed to H2O2 and actinomycin D. MATERIALS AND METHODS: In this experimental study, 420 two-cell embryos were randomly divided into six groups: i. Control, ii. Apigenin, iii. H2O2, iv. Apigenin+H2O2, v. Actinomycin D, and vi. Apigenin+Actinomycin D. The percentage of blastocysts and hatched blastocysts was calculated. Blastocyst ZP thickness was also measured. In addition, viable blastomeres quantity was counted by Hoechst and propidium iodide staining and the number of apoptotic blastomeres was counted by TUNEL assay. RESULTS: The results of viable and apoptotic blastomeres quantity, the ZP thickness, and the percentage of blastocysts and hatched blastocysts were significantly more favorable in the apigenin group, rather than the control group (P<0.05). The results of the apigenin+H2O2 group were significantly more favorable than the H2O2 group (P<0.05); and the results of apigenin+actinomycin D group were significantly more favorable than actinomycin D group (P<0.05). CONCLUSION: The results suggest that apigenin may protect mouse embryos against H2O2 and actinomycin D. So that it increases the number of viable blastomeres and decreases the number of apoptotic blastomeres, which may cause expanding the blastocysts, thinning of the ZP thickness and increasing the rate of hatching in mouse embryos.

Effect of quercetin on the number of blastomeres, zona pellucida thickness, and hatching rate of mouse embryos exposed to actinomycin D: An experimental study.

BACKGROUND: Quercetin is a flavonoid with the ability to improve the growth of embryos in vitro, and actinomycin D is an inducer of apoptosis in embryonic cells. OBJECTIVE: The aim was to evaluate the effect of quercetin on the number of viable and apoptotic cells, the zona pellucida (ZP) thickness and the hatching rate of preimplantation embryos exposed to actinomycin D in mice. MATERIALS AND METHODS: Two-cell embryos were randomly divided into four groups (Control, Quercetin, actinomycin D, and Quercetin + actinomycin D group). Blastocysts percentage, hatched blastocysts, and ZP thickness of blastocysts was measured. The number of blastomeres was counted by Hoechst and propidium iodide staining and the apoptotic cells number was counted by TUNEL assay. RESULTS: The results showed that the use of quercetin significantly improved the growth of embryos compared to the control group (p=0.037). Moreover, quercetin reduced the destructive effects of actinomycin D on the growth of embryos significantly (p=0.026). CONCLUSION: quercetin may protect the embryos against actinomycin D so that increases the number of viable cells and decreases the number of apoptotic cells, which can help the expansion of the blastocysts, thinning of the ZP thickness and increasing the hatching rate in mouse embryos.

Effect of Transplantation of Bone Marrow Stromal Cell- Conditioned Medium on Ovarian Function, Morphology and Cell Death in Cyclophosphamide-Treated Rats.

OBJECTIVES: Although stem cell transplantation has beneficial effects on tissue regeneration, but there are still problems such as high cost and safety issues. Since stem cell therapy is largely dependent on paracrine activity, in this study, utilization of transplantation of bone marrow stromal cells (BMSCs)-secretome instead of the cells, into damaged ovaries was evaluated to overcome the limitations of stem cell transplantation. MATERIALS AND METHODS: In this experimental study, BMSCs were cultured and 25-fold concentrated conditioned medium (CM) from BMSCs was prepared. Female rats were injected intraperitoneally with cyclophosphamide (CTX) for 14 days. Then, BMSCs and CM were individually transplanted into bilateral ovaries, and the ovaries were excised after four weeks of treatment. The follicle count was performed using hematoxylin and eosin (H and E) staining and the apoptotic cells were counted using TUNEL assay. Ovarian function was evaluated by monitoring the ability of ovulation and the levels of serum estradiol (E2) and follicle-stimulating hormone (FSH). RESULTS: Evaluation of the ovarian function and structure showed that results of secretome transplantation were almost similar to those of BMSCs transplantation and there was no significant differences between them. CONCLUSIONS: BMSCs-secretome is likely responsible for the therapeutic paracrine effect of BMSCs. Stem cellsecretome is expected to overcome the limitations of stem cell transplantation and become the basis of a novel therapy for ovarian damage.