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Background: Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies and growing challenges of global health. In this study, for the first time in Iran, we investigated the 5-year survival rate and prognostic factors in patients with HCC. Materials and Methods: In this historical cohort study, we examined the medical records of 227 HCC patients who were registered in the central tumor registry of our institution from September 2007 to September 2017. Demographic data, clinical parameters, received treatments, and survival curves from time of diagnosis were evaluated. Kaplan-Meier was used for univariate analysis, and multivariable analysis was performed by Cox regression. Results: A total of 208 (91.63%) patients were dead. The 5-year survival rate was estimated 19 (8.37%). The average follow-up in this study was 14.3 months. Overall median survival rate was 12.1 months. Univariate analysis showed that tumor size, metastasis, number of involved lymph node, hepatitis type, and treatment were significantly related to the survival rate, and Cox regression analysis revealed that the tumor size >3 cm (hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.68-4.97; P = 0.027), involved lymph nodes >2 (HR = 4.12, 95% CI = 2.66-6.38; P = 0.001), metastasis (HR = 3.87, 95% CI = 3.13-6.54; P = 0.011), combination therapy with surgery and chemotherapy (HR = 0.4, 95% CI = 0.15-0.79; P = 0.023), and coinfection with hepatitis B virus and hepatitis C virus (HR = 2.11, 95% CI = 1.81-4.6; P = 0.036) are the most relevant prognostic factors with 5-year survival rate in patients with HCC. Conclusion: Results of this study will help estimate survival rates for patients with HCC according to their clinical status.

Background One of the most serious nervous system diseases is spinal cord injury(SCI), which is increasing for various reasons. Although no definitive treatment has yet been identified for SCI, one possible treatment is adipose-derived stem cells(ADSCs). However, a key issue in transplantation is improving cells’ survival and function in the target tissue. Melatonin(MT) hormone with antioxidant properties can prolong cell survival and improve cell function. This study investigates the pre-conditioning of ADSCs with melatonin for enhancing the engraftment and neurological function of rats undergoing SCI. Methods 42 male Sprague–Dawley rats were divided into six groups, including Control, Sham, Model, Vehicle, and Lesion treatments A and B. After acquiring white adipose tissue, stem cells were evaluated by flow cytometry. SCI was then applied in Model, Vehicle, A, and B groups. Group A and B received ADSCs and ADSCs + melatonin, respectively, 1 week after SCI, but the vehicle received only an intravenous injection for simulation; The other groups were recruited for the behavioral test. Immunohistochemistry(IHC) was used to assess the engraftment and differentiation of ADSCs in the SCI site. Basso, Beattie, and Bresnahan's score was used to evaluate motor function between the six groups. Results Histological studies and cell count confirmed ADSCs implantation at the injury site, which was higher in the MT-ADSCs (P < 0.001). IHC revealed the differentiation of ADSCs and MT-ADSCs into neurons, astrocytes, and oligodendrocyte lineage cells, which were higher in MT-ADSCs. Functional improvement was observed in SCI + ADSCs and SCI + MT-ADSCs groups. Conclusion The pre-conditioning of ADSCs with melatonin positively affects engraftment and neuronal differentiation in SCI but does not impact performance improvement compared to the ADSCs.

Dental pulp stem cells (DPSCs) show potential for treating neurodegenerative and traumatic diseases due to their neural crest origin. Melatonin (MT), an endogenous neurohormone with well-documented anti-inflammatory and antioxidant properties, has shown promising results with MSCs in terms of engraftment, proliferation, and neuronal differentiation in animal SCI models. However, the effects of melatonin preconditioning on human dental pulp stem cells (hDPSCs) for SCI treatment remain unclear. This study investigates the impact of melatonin preconditioning on hDPSCs engraftment, neural differentiation, and neurological function in rats with SCI. Forty-two male Sprague–Dawley rats were divided into six groups: Control, Sham, Model, Vehicle, Lesion Treatment A (SCI + hDPSCs), and Lesion Treatment B (SCI + MT-hDPSCs). After obtaining hDPSCs, stem cells were evaluated using flow cytometry. Cell viability was assessed using the MTT assay. SCI was induced in the Model, Vehicle, Lesion Treatment A, and Lesion Treatment B groups. The Lesion Treatment A and B groups received hDPSCs and hDPSCs pretreated with melatonin, respectively, 1 week after SCI, while the Vehicle group received only an intravenous injection of DMEM to simulate treatment. The other groups were used for behavioral testing. Immunohistochemistry (IHC) was employed to assess hDPSCs engraftment and differentiation at the SCI site. Motor function across the six groups was evaluated using the Basso, Beattie, and Bresnahan (BBB) score. Histological studies and cell counts confirmed hDPSCs implantation at the injury site, with a significantly higher presence in the MT-hDPSCs compared to hDPSCs ( p  < 0.01). IHC revealed that hDPSCs and MT-hDPSCs differentiated into neurons and astrocytes, with greater differentiation observed in the MT-hDPSCs compared to the hDPSCs ( p  < 0.01 and p  < 0.05, respectively). Functional improvement was noted in both SCI + hDPSCs and SCI + MT-hDPSCs groups compared to SCI and Vehicle groups from Week 4 onward ( p  < 0.001). Significant differences were also observed between the SCI + hDPSCs and SCI + MT-hDPSCs groups starting from Week 7 ( p  < 0.01). Preconditioning hDPSCs with melatonin enhances engraftment, neuronal differentiation, and greater performance improvement compared to hDPSCs alone in the SCI animal model.

Introduction: The present systematic review and meta-analysis aims to investigate the role of Posterior Tibial Nerve Stimulation (PTNS) in the control of fecal incontinence (FI).Methods: Two independent reviewers extensively searched in the electronic databases of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, CINAHL, and Scopus for the studies published until the end of 2016. Only randomized clinical trials were included. The studied outcomes included FI episodes, FI score, resting pressure, squeezing pressure, and maximum tolerable pressure. The data were reported as Standardized Mean Differences (SMD) with 95% confidence interval.Results: Five articles were included in the present study (249 patients under treatment with PTNS and 239 in the sham group). Analyses showed that PTNS led to a significant decrease in the number of FI episodes (SMD=-0.38; 95% CI: -0.67-0.10; P=0.009). Yet, it did not have an effect on FI score (SMD=0.13; 95% CI: -0.49-0.75; P=0.68), resting pressure (SMD=0.12; 95% CI: -0.14-0.37; P=0.67), squeezing pressure (SMD=-0.27; 95% CI: -1.03-0.50; P=0.50), and maximum tolerable pressure (SMD=-0.10; 95% CI: -0.40-0.24; P=0.52).Conclusion: Based on the results, it seems that the prescription of PTNS alone cannot significantly improve FI.

Natural compounds extracted from marine organisms consisting of biological active materials like collagen provide a major source of compound with medical applications including wound dressing particularly in co-treatment with other natural or synthetic materials to quick the wound healing process. The current study investigates the potential of Rutilus kutum skin-extracted collagen in combination with chitosan [collagen-chitosan (Col-CH) gel] for in vivo second-degree burn wound healing in rats following finding of the most effective collagen-chitosan ratio. Collagen and chitosan were extracted from R. Kutum skin and shell waste of shrimp, respectively, using acid–base method. SDS-PAGE was performed to determine subunit composition of collagen. After amino acid analysis using HPLC, different ratios of collagen and chitosan mixture (Col-CH, 1:3, 1:1 and 3:1) were prepared to fine the most effective of Col-CH gel on burn wound healing and compare to animals treated with silver sulfadiazine ointment. Wound surface area was analyzed using ImageJ software on days 15 and 30. H&E staining was performed to show the epithelialization, collagen deposition, fibroblast cell accumulation and vessel formation on days 15 and 30. The results from H&E were scored and quantified by pathologist. SDS-PAGE technique revealed that extracted-collagen was type 1 composed of two α (α1 and α2) chains. HPLC showed that Glycine was the most abundant amino acid which included one-third of total amino acid in the skin. The wound surface measurement showed a significant reduction in wound size in animals treated with Col-CH (1:1) compared to silver sulfadiazine treated group at day 25. Histopathological findings represented high score in epithelialization, vessel formation and a decrease in inflammatory cells infiltration in Col-CH (1:1) treated group on days 15 and 30. These data suggest collagen in combination with chitosan with 1:1 ratio can significantly restore burn wound compared to silver sulfadiazine ointment.

Background Coronary Heart Disease (CHD) is the leading cause of death in industrialized countries. There is currently no direct relation between CHD and type 2 diabetes mellitus (T2D), one of the major modifiable risk factors for CHD. This study was carried out for genes expression profiling of T2D associated genes to identify related biological processes/es and modulated signaling pathway/s of male subjects with CHD. Method the subjects were divided into four groups based on their disease, including control, type 2 diabetes mellitus (T2D), CHD, and CHD + T2D groups. The RNA was extracted from their blood, and RT 2 Profiler™ PCR Array was utilized to determine gene profiling between groups. Finally, the PCR Array results were validated by using Q-RT-PCR in a more extensive and independent population. Result PCR Array results revealed that the T2D and T2D + CHD groups shared 11 genes significantly up-regulated in both groups. Further analysis showed that the mRNA levels of AKT2, IL12B, IL6, IRS1, IRS2, MAPK14, and NFKB1 increased. Consequently, the mRNA levels of AQP2, FOXP3, G6PD, and PIK3R1 declined in the T2D + CHD group compared to the T2D group. Furthermore, in silico analysis indicated 36 Gene Ontology terms and 59 signaling pathways were significantly enriched in both groups, which may be a culprit in susceptibility of diabetic patients to CHD development. Conclusion Finally, the results revealed six genes as a hub gene in altering various biological processes and signaling pathways. The expression trend of these identified genes might be used as potential markers and diagnostic tools for the early identification of the vulnerability of T2D patients to develop premature CHD. Graphical Abstract

Autologous fibroblast transplantation has been proven to be a promising method in wound healing with no side effects. This is the first study aimed to determine the efficacy and safety of autologous fibroblast cell injection to the atrophic scar caused by cutaneous leishmaniasis as an endemic disease in many middle-eastern countries. It causes chronic skin lesions and permanently disfiguring scars. Autologous fibroblasts were obtained from the patient’s ear skin and were injected intradermally twice at 2-month intervals. Outcomes were measured using ultrasonography, VisioFace, and Cutometer. No adverse reaction was observed. The results showed improvements in epidermal thickness and density, melanin level, and skin lightening. Moreover, the skin elasticity in the scar area increased after the second transplantation. No improvement was observed in dermal thickness and density. A longer follow-up with more patients is recommended to investigate the effectiveness of fibroblast transplantation better.

Introduction: Cholinergic-associated diseases currently constitute a significant cause of neurological and neurodegenerative disabilities. As the drugs are not efficient in improving the suffered tissues, stem cell treatment is considered an effective strategy for substituting the lost cells.Methods: In the current study, we set out to investigate the differentiation properties of human Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) into cholinergic-like cells by two morphogens of Retinoic Acid (RA) and Sonic Hedgehog (Shh) using a three-step in vitro procedure. The results were evaluated using real-time PCR, flow cytometry, and immunocytochemistry for two weeks.Results: Our data showed that the cells could express cholinergic specific markers, including Islet-1, Acetylcholinesterase (AChE), SMI-32, and Nestin, at mRNA and protein levels. We could also quantitatively evaluate the expression of Islet-1, AChE, and Nestin at 14 days post-induction using flow cytometry.Conclusion: Human AD-MSCs are potent cells to differentiate into cholinergic-like cells in the presence of RA and Shh through a three-step protocol. Thus, they could be a suitable cell candidate for the regeneration of cholinergic-associated diseases. However, more functional and electrophysiological analyses are needed in this regard.

Introduction: The mechanism of putative cytotoxicity of 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidone (rolipram), a specific phosphodiesterase-4 (PDE4) inhibitor, on glioblastoma multiforme (GBM) is almost unknown. This study aimed to investigate the role of protein kinase B (Akt) pathway in the cytotoxic effect of rolipram on human GBM U87 MG cell line and tumor-initiating cells (TICs) isolated from patient's GBM specimen. Methods: TICs were characterized by using flow cytometry and quantitative real-time PCR. The cells were treated with rolipram at inhibitory concentration of 50% (IC50) in the presence or absence of SC79 (4µg/mL), a specific AKT activator, for 48 hours. The cell viability and apoptosis were measured by MTT assay and TUNEL staining, respectively. The relative expression of Phospho-Akt (Ser473), matrix metalloproteinase 2 (MMP2), and vascular endothelial growth factor A (VEGFA) were detected using Western blotting. Results: The findings showed that rolipram could suppress cell viability in both U87MG and TICs, dose-dependently. Interestingly, the rolipram-induced cytotoxicity was significantly reduced in the presence of SC79. Nevertheless, in rolipram-treated cells, the pretreatment with SC79 significantly led to increase in U87 MG cells and TICs apoptosis and decrease in viability of U87 MG cells but not TICs relative to corresponding control. In U87 MG and TICs, rolipram-induced reduction of Phospho-Akt (Ser473) and MMP2 levels were significantly suppressed by SC79. Conclusion: There is a cell type-specific mechanism of anti-proliferative action of rolipram on GBM cells. The reduction of intracellular level of MMP2 but not VEGFA by rolipram is conducted through the inhibition of Akt signal. Rolipram-induced apoptosis is mediated via Akt dependent/independent mechanisms.

Introduction: Tinnitus is one of the complex symptoms of hearing described as a phantom auditory sensation without any external stimulation. Due to the subjective nature of tinnitus, perception and discomfort of tinnitus vary among the patients. The main aim of this study is to investigate the effects of gender, age and the degree of hearing loss on discomfort due to tinnitus. Methods: Eighteen patients with tinnitus, aged 21-72 years, (9 males and 9 females) were recruited. Tinnitus discomfort was investigated by Tinnitus Handicap Inventory (THI) questionnaire. Psychoacoustic assessments of tinnitus and auditory threshold assessments were evaluated using a 2-channel clinical audiometer. Results: The results showed no significant correlation between THI scores with loudness matching (P=0.187), mean of auditory threshold (P=0.304), gender (P=0.93) and age (P=0.200). Also, no significant correlation was found between maximal level of hearing loss and pitch matching (P=0.208). Conclusion: The study findings suggests that tinnitus is not correlated with age, gender and hearing loss. Overall, tinnitus is a complicated clinical condition which its real impact and degree of discomfort are unclear. More investigation is needed to clarify the factors involving in tinnitus annoyance.