Journal of applied biomedicine最新文献

Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-β1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-β1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-β1 expression.

Skin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

Background: Femoral posterior hip dislocation with associated femoral head fractures (Pipkin fractures) are rare high-energy injuries. Published treatment modalities involve conservative treatment, head fragment resection, open reduction and internal fixation, and total hip replacement. The experience with mini-invasive screw osteosynthesis of these fractures is the main focus of our study.

Methods: Seven Pipkin fractures (five Pipkin II and two Pipkin I) in six patients were treated by closed reduction of hip dislocation, followed by minimal invasive lag screw osteosynthesis. Cancellous screw(s) were inserted from the incision on the lateral hip through the femoral neck to the reduced fracture fragment. In all patients, postoperative CT was performed to check the quality of surgery. Active physiotherapy with immediate toe-touch weight bearing was the routine postoperative protocol. In all patients, radiological and clinical results were evaluated with the Thompson Epstein, Merle d'Aubigne and Postel score, and Harris hip score.

Results: All fractures united, and all femoral heads survived. Infectious complications were not observed, and no secondary surgery was needed. After an average follow-up of 18.4 months, the average Merle d'Aubigne and Postel score was 17.7 points, while the mean Harris hip score reached 98.1 points. The majority of patients achieved an excellent Thompson-Epstein clinical and radiological outcome. All patients returned to their original occupation.

Conclusions: Mini-invasive screw osteosynthesis can be used for the treatment of Pipkin type I-II femoral head fractures. Successful reduction of hip dislocation and head fracture is necessary for using this technique. Long-term follow-up is necessary to confirm this technique.

Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.

Periodontal regenerative techniques are performed to accomplish the restitution of soft and hard teeth-supporting tissues that have been lost due to trauma or inflammatory disease. Periodontal membranes are used for these techniques to provide support and a framework for cell growth and tissue regeneration. They act as a temporary and selective barrier to cell proliferation. Easy clinical handling, biomechanical specifications, high biocompatibility, cell-occlusivity, and satisfactory bioresorption rate are essential properties a membrane needs to be effective. The creation and maintenance of a secluded space is also a fundamental rule in periodontal regenerative techniques. The use of barrier membranes in the field of restorative dentistry has progressed toward the use of minimally invasive approaches optimizing wound closure and limiting patient morbidity. This review intends to provide an overview of the major cellular events in the surgical wound and membrane surface. It was also performed to assess, from literature data, the pertinence of using non-resorbable and resorbable membranes for this regenerative purpose. Special attention will be given to collagen membranes.

This study constitutes a cross sectional analysis of the association between cognitive impairment defined by neuropsychological tests and carotid stenosis. The main objective was to compare the results of the Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination-Revised (ACE-R) with regard to the degree of carotid stenosis. The sample comprised 744 patients who underwent a carotid duplex ultrasound and cognitive function testing (by ACE-R and MMSE). A multivariable analysis of potential confounding factors was completed. The significance of the different number of positive (MMSE ≤ 27, ACE-R ≤ 88) and negative (MMSE ≥ 28, ACE-R ≥ 89) results of the neuropsychological tests was analysed with regard to the degree of carotid stenosis (50-99%). Neuropsychological test results were also compared between carotid stenosis of 50-69%, 70-89%, and 90-99%. For both the MMSE and ACE-R, a difference was observed between positive and negative test results when higher degrees of stenosis were present. However, for the ACE-R only, more severe stenosis (80-89%, 90-99%) was predominantly associated with positive test results (p-value < 0.017). The same dependence for ACE-R (although not statistically significant) was observed in the group of patients without an ischemic stroke (confounding factor). In the case of the MMSE and more severe stenosis, negative results predominated, regardless of the confounding factor. There were no statistically significant differences in test results between carotid stenosis of 50-69%, 70-89%, and 90-99%. The results suggest that for assessing the early risk of cognitive impairment in patients with carotid atherosclerosis, the ACE-R appears more suitable than the MMSE.

Background: The ADIPOQ gene encodes a fat-derived protein hormone with a preponderant role in the homeostasis of glucose and fatty acids. However, previous association studies between ADIPOQ genetic variants and metabolic disorders have shown controversial results. In this study, we evaluated the effect of the ADIPOQ-rs2241766 polymorphism on diverse biochemical parameters (i.e., insulin resistance, atherogenic index, overweight and obesity) in an adolescent population from Mexico.

Methods: A cross-sectional study with convenience sampling was carried out in 356 adolescents from Northern Mexico. They were classified by sex and BMI-z score. The biochemical parameters were measured from blood samples using conventional methods. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: In low and normal weight groups, GG carriers had a significantly higher cholesterol level (P ≤ 0.05) than TG and TT carriers. However, there was no association between ADIPOQ-rs2241766 polymorphism and atherogenic index, overweight, or obesity.

Conclusions: Our findings suggest that the cholesterol levels are under the influence of the ADIPOQ-rs2241766 polymorphism in Mexican adolescents and may explain how ADIPOQ variants increase the risk of developing metabolic disorders. Nevertheless, further studies are required to rule out the influence of other genetic and non-genetic factors.

Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.

Objectives: This study aims to evaluate the pharmacological role of indigo extract in accelerating the wound healing in a rat model.

Methods: Female Sprague-Dawley rats were anesthetized with ketamine (30 mg/kg, i.p.) and the full thickness of the marked skin was then cut carefully and wounds were left undressed. Indigo extract (5%) in PBS was applied topically twice daily until healing was complete. A control group of rats was treated with povidone-iodide (Betadine®). Rats treated with phosphate buffer saline were used as a negative control group. The rate of wound healing was assessed daily. Histopathological examination of skin sections were qualitatively assessed by independent evaluators. The inflammatory and apoptotic markers were assessed in skin tissue homogenates using ELISA.

Results: Histopathology data showed that applying indigo to skin wounds enhanced the healing process, resulting in a significant decrease in dermal inflammation in comparison to untreated rats. Topical application of indigo significantly increased antioxidant enzyme activities with reduced malondialdehyde (MDA) levels in wound tissues. The levels of matrix metalloproteases-2 and -9 were significantly lower with an accompanied increase in the level of TGF-β1 in skin tissues from rats treated with indigo compared to the control group treated with PBS.

Conclusions: The antioxidant and anti-inflammatory properties of indigo leaf extract accelerate the healing of skin injuries.