Phenotypic and functional maturation of murine dendritic cells induced by 18 alpha- and beta-glycyrrhetinic acid

Various studies have described glycyrrhizin (GL), an active triterpenoic saponin extract of licorice roots, as an anti-inflammatory, antiviral, antimicrobial, anti-tumor and immunomodulating agent. The activity of GL has been mainly attributed to its metabolites, 18-alpha (GA) and 18-beta-glycyrrhetinic acid (GB), which their mechanism of action on the immune system cells is not clearly known. In this study, we have investigated the effects of GA and GB on the immune system by targeting dendritic cells and analyzing phenotypic and functional maturity of murine dendritic cells (DCs) after treatment with these components. Stimulation of DCs with GA and GB resulted in up-regulation of CD40, CD86 and MHC-II molecules indicating their effects on the maturation of DCs. These components induced the allogenic immunostimulatory capacity of DCs by stimulating the proliferation of T cells and production of the T helper (h)1-promoting cytokine, IL-12. They also increased the production of IFN-γ by T cells in mixed-lymphocyte reaction. In conclusion, these results indicate that GA and GB may insert their immunomodulatory effects by enhancing DC maturation and modulating Th1/Th2 response through an increase in Th1 responses, implying their beneficial in host defense against infectious diseases.     

Tolerogenic dendritic cells produced by lentiviral‐mediated CD40‐ and interleukin‐23p19‐specific shRNA can ameliorate experimental autoimmune encephalomyelitis by suppressing T helper type 17 cells

Down‐regulation of soluble or membrane‐bound co‐stimulatory molecules by RNAi in dendritic cells can prevent the activation of immune responses. Therefore, this study was designed to evaluate the therapeutic efficacy of bone marrow‐derived DCs (BMDCs) transduced with lentiviral vectors to permanently expressed shRNA specific for CD40 (CD40LV‐DCs) and/or p19 subunit of interleukin (IL)‐23 (p19LV‐DCs) mRNAs in experimental autoimmune encephalomyelitis (EAE). In‐vitro studies showed that double‐transduced BMDCs (CD40⁺p19LV‐DCs) resemble tolerogenic DCs due to profound down‐regulation of CD40, lower expression of proinflammatory cytokines (IL‐6 and IL‐12), increased IL‐10 production and stronger stimulation of myelin oligodendrocyte glycoprotein (MOG)_35–55‐specific T cells for production of IL‐10 compared with CD40LV‐DCs, p19LV‐DCs and BMDCs transduced with control lentiviral vector (CoLV‐DCs). Moreover, injection of transduced CD40⁺p19LV‐ BMDCs in EAE mice resulted in more reduction in clinical score, significant reduction in IL‐17 or increased production of IL‐10 by mononuclear cells derived from the lymph nodes or spinal cord compared with CoLV‐DCs‐treated EAE mice. In conclusion, simultaneous knock‐down of CD40 and IL‐23 production by BMDCs may represent a promising therapeutic tool for the treatment of IL‐17‐dependent autoimmune diseases, including multiple sclerosis.     

A humanized tissue-engineered in vivo model to dissect interactions between human prostate cancer cells and human bone

Currently used xenograft models for prostate cancer bone metastasis lack the adequate tissue composition necessary to study the interactions between human prostate cancer cells and the human bone microenvironment. We introduce a tissue engineering approach to explore the interactions between human tumor cells and a humanized bone microenvironment. Scaffolds, seeded with human primary osteoblasts in conjunction with BMP7, were implanted into immunodeficient mice to form humanized tissue engineered bone constructs (hTEBCs) which consequently resulted in the generation of highly vascularized and viable humanized bone. At 12 weeks, PC3 and LNCaP cells were injected into the hTEBCs. Seven weeks later the mice were euthanized. Micro-CT, histology, TRAP, PTHrP and osteocalcin staining results reflected the different characteristics of the two cell lines regarding their phenotypic growth pattern within bone. Microvessel density, as assessed by vWF staining, showed that tumor vessel density was significantly higher in LNCaP injected hTEBC implants than in those injected with PC3 cells (p < 0.001). Interestingly, PC3 cells showed morphological features of epithelial and mesenchymal phenotypes suggesting a cellular plasticity within this microenvironment. Taken together, a highly reproducible humanized model was established which is successful in generating LNCaP and PC3 tumors within a complex humanized bone microenvironment. This model simulates the conditions seen clinically more closely than any other model described in the literature to date and hence represents a powerful experimental platform that can be used in future work to investigate specific biological questions relevant to bone metastasis.     

Detection of human cytomegalovirus in glioma tumor tissues

A brain tumor that develops from glial cells is called a glioma. About half of all primary brain tumors form from glial cells. Gliomas are divided into subgroups, depending on the origin of the glial cells. Detection of human cytomegalovirus in tumor tissues of glioma patient was performed for the first time in Iran. These data show an association between human cytomegalovirus (HCMV) and malignant gliomas and suggest that HCMV may play an active role in glioma pathogenesis. Cytomegalovirus surgical biopsy specimens of glioma tissues (n?=?28) and non-tumor brain tissues (n?=?8) were obtained. Total DNA of specimens was extracted, and then, extracted DNA was evaluated by polymerase chain reaction for evidence of HCMV nucleic acids. Here, we show that a high percentage of malignant gliomas are infected by HCMV. Seventy-five percent of grade 4 glioma, 57 % of grade 3 glioma, and 33 % of grade 2 glioma were HCMV positive. All specimens of grade 1 glioma and control tissues were HCMV negative. The relationship between the grade of glioma and the presence of HCMV is significant (P value?=?0.035). Fisher exact test was used for statistical analysis.     

A Computer-Aided Type-II Fuzzy Image Processing for Diagnosis of Meniscus Tear

Meniscal tear is one of the prevalent knee disorders among young athletes and the aging population, and requires correct diagnosis and surgical intervention, if necessary. Not only the errors followed by human intervention but also the obstacles of manual meniscal tear detection highlight the need for automatic detection techniques. This paper presents a type-2 fuzzy expert system for meniscal tear diagnosis using PD magnetic resonance images (MRI). The scheme of the proposed type-2 fuzzy image processing model is composed of three distinct modules: Pre-processing, Segmentation, and Classification. λ-nhancement algorithm is used to perform the pre-processing step. For the segmentation step, first, Interval Type-2 Fuzzy C-Means (IT2FCM) is applied to the images, outputs of which are then employed by Interval Type-2 Possibilistic C-Means (IT2PCM) to perform post-processes. Second stage concludes with re-estimation of “η” value to enhance IT2PCM. Finally, a Perceptron neural network with two hidden layers is used for Classification stage. The results of the proposed type-2 expert system have been compared with a well-known segmentation algorithm, approving the superiority of the proposed system in meniscal tear recognition.     

Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

Early Echocardiographic Findings in ��-Thalassemia Intermedia Patients Using Standard and Tissue Doppler Methods

Heart complications are among the serious problems of patients with β-thalassemia intermedia. This study aimed to evaluate myocardial function in these patients. Clinical parameters and both standard Doppler and pulsed Doppler tissue imaging parameters were compared in 51 β-thalassemia intermedia patients (mean age, 17.05 ± 5.8 years) and 20 normal subjects (mean age, 17.81 ± 7.35 years, p = 0.98). In 11 patients (21.5%), pulmonary artery hypertension was detected. M-mode echocardiographic findings such as ejection fraction and fractional shortening did not show statistically significant changes (p > 0.005). Pulsed Doppler showed a significant difference in the early (E) to late diastolic (A) velocity ratio of the tricuspid and mitral valve between the patients and the control subjects (p < 0.05). In the pulsed tissue Doppler study, the peak systolic velocity of the septum (Ss), the peak atrial velocity of the septum (Aas), the peak systolic velocity of the tricuspid annulus (St), the peak early diastolic velocity of the tricuspid annulus (Eat), and the peak late diastolic velocity of the tricuspid annulus (Aat) were increased significantly (p < 0.05). The pulse tissue Doppler of the lateral mitral annulus did not change significantly (p > 0.005). The peak systolic velocity of the posterior wall and the peak late diastolic velocity of the anterior wall changed significantly (p < 0.05). This study showed that β-thalassemia intermedia patients with normal M-mode and two-dimensional echocardiography had statistically significant changes in pulsed Doppler and pulsed tissue Doppler imaging.     

Evaluating the efficacy of extracted squalene from seed oil in the form of microemulsion for the treatment of COVID-19: A clinical study

This study investigates the effect of the nanostructure of squalene in the form of microemulsion on COVID-19 patients. In this blinded clinical trial, a comparison was made between the efficacy of squalene treatment and controls. A total of 30 COVID-19 patients admitted to the emergency department, and the infection ward was equally allocated to case (n = 15) and control (n = 15) groups according to their age and underlying diseases. The baseline characteristics of subjects, including age, gender, time of treatment onset, underlying condition, white blood cells count, and lymphocyte count were similar (p < 0.05). Baseline laboratory tests and computed tomography (CT) scans were performed for the study groups. The treatment group received 5 mg of intravenous squalene twice a day and standard treatment for 6 days, while controls received only standard treatment. After 6 days of treatment, clinical and CT scan changes were evaluated and compared in intervention and control groups. The need for oxygen therapy (p = 0.020), 2 days of no fever (p = 0.025), cough alleviation (p = 0.010), and lung high-resolution computed tomography improvement (p = 0.033) were significantly different between cases and controls within 7 days of admission. No adverse effects were observed in the treatment group. Our data suggest that squalene could be considered as a potential treatment for COVID-19, and further studies are required to confirm the results.