The Sources of Essential Fatty Acids for Allergic and Cancer Patients; a Connection with Insight into Mammalian Target of Rapamycin: A Narrative Review

Background: Disturbance in essential fatty acids (EFA) metabolism plays a key role in autoimmune diseases, butEFA supplementation with sources of borage, evening primrose, hemp seed and fish oils was not effective in atopicand cancer diseases, as that seen in the case of multiple sclerosis. It seems that two complexes of the mammalian targetof rapamycin (mTOR) signaling, mTORC1 and mTORC2, are congruent with the two bases of the Traditional IranianMedicine (TIM) therapy, Cold and Hot nature, which are essential for the efficacy of functional oils for controllingimmune responses in autoimmune diseases. Methods: We searched PubMed database, Web of Science (WOS), GoogleScholar, Scopus and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data.Results: The oils controlled by Cold or Hot nature may be helpful in maintaining homeostasis and preventing autoimmunediseases. In summary, studies of randomized controlled trials for allergy and cancer patients found no improvementin the signs or response to tests, despite a remarkable change in EFA fractions in the blood by supplementation withsources of borage, evening primrose, hemp seed and fish oils. In contrast, portulaca oleracea oil exhibited protectiveeffects by anti-inflammatory properties via the PI3K/Akt/mTORC2 pathway with a deviation immune response to Th1to treat atopic diseases and cancer. Conclusions: According to the concept of Traditional Iranian Medicine therapy, incontrast to Cold-nature oils, EFA supplementation with the sources of Hot-nature oilsis not suitable for the treatmentof atopic and cancerous diseases.     

Anin vitro model for studying mechanisms underlying synoviocyte-mediated cartilage invasion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of joints involving the pathological development of an invasive and destructive pannus tissue which contributes to the loss of cartilage and bone. To further analyze the process of cartilage degradation and invasion, we have developed an in vitro model composed of cartilage matrix and synoviocytes (isolated from RA pannus tissue, as well as normal synovial membrane). The matrix is derived from pig articular cartilage and contains collagen type II and proteoglycans and is similar in composition to human cartilage. Data generated from this model reveal that synoviocytes isolated from RA pannus tissue invaded cartilage matrix in a manner which directly correlated with the severity of the disease. Analysis of mechanisms associated with the invasive process demonstrate that highly invasive RA synoviocytes maintain a round morphology during attachment and spreading on cartilage matrix, compared with their normal counterparts. Furthermore, the level of secretion of matrix metalloproteinase (MMP) activity was shown to correlate with the RA phenotype, which could be modulated with a novel MMP inhibitor. Normal synoviocytes could be "converted" to an RA phenotype by specific inflammatory cytokines, such that invasion of cartilage matrix was augmented by culturing these cells in the presence of 5 U/ml IL-1b or 18 U/ml TGFb. Invasion was inhibited by 150 U/ml TNFa, and unaffected by 100 ng/ml PDGF. In addition, synovial fluid from RA patients induced invasion of normal synoviocytes, in a concentration dependent manner, from 150% to 460%; however, synovial fluid from another inflammatory arthritidy (Crohn's) did not augment invasion to the same degree. Moreover, this "conversion effect" appears to be specific for synoviocytes, since similar effects could not be achieved with human skin fibroblasts. This in vitro model of synoviocyte-mediated cartilage invasion allows for further molecular characterization of the invasive properties of the synoviocyte which contribute to RA.     

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double‐blinded, placebo‐controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250‐mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12‐week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino‐terminal propeptide (P1NP) levels and a significant decrease in C‐terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.     

Effects of intracellular poly(3-hydroxybutyrate) reserves on physiological–biochemical properties and growth of Ralstonia eutropha

Microbial polyhydroxyalkanoates (PHAs), because of their well studied complex physiology and commercial potential, are vehicles for carbon and potential storage reduction for many microbial species. Even with the wealth of studies about microbial PHAs in the scientific literature, polymer accumulation and degradation are still not comprehensively understood. Poly(3-hydroxybutyrate) (P3HB) granule formation and polymer mobility were studied here in the bacterium Ralstonia eutropha strain B5786 in autotrophic cultures. Electron microscopy studies revealed decreasing cell size concomitant with enlargement of size and number of intracellular granules, and inhibition of cell division during intracellular polymer production. Activities of key P3HB biosynthetic enzymes demonstrated correlations with each other during polymer accumulation, suggesting an intricately regulated P3HB cycle in autotrophically grown R. eutropha cells.     

Single Tc99m Sestamibi injection,double acquisition gated SPECT after stress and during low-dose dobutamine infusion: a new suggested protocol for evaluation of myocardial perfusion

Background The ability of low dose dobutamine (LDD) has been established in exploiting the reserved contractility of ischemic myocardium. This study was designed to assess the value of a new protocol, with an additional stress imaging during LDD infusion instead of the rest images, for evaluation of coronary artery disease (CAD) and perfusion reversibility. Methods A total of 51 patients (42 men, 9 women; 57.2 ± 11.3 years) were included in the study and underwent three sequential steps of imaging; the first step-stress gated SPECT with Tc-99m sestamibi, immediately followed by the second step-gated SPECT during constant infusion of 7.5 μg/kg/min dobutamine and finally the third step-rest phase scan following trinitroglycerine administration in the next day. The findings were interpreted using the images in three sets of display; first vs. second step-single injection-double acquisition gated SPECT before and during LDD (SIDAGS-LDD), first vs. third step-standard stress/rest protocol, and only first step-gated stress-only SPECT. In all cases, the Visual perfusion index of each protocols were calculated by summating the premeditated 5-point scale (5: normal, 4: completely reversible, 3: partially reversible, 2: nontransmural fixed and 1: transmural fixed defects) of 17 standard myocardial segments. The accuracy as well as the correlation and agreement of protocols for detecting perfusion abnormality and corresponding reversibility were statistically analyzed. Results Calculated sensitivity, specificity, positive predictive value, negative predictive value and accuracy regarding the presence of CAD in both SIDAGS-LDD and standard protocols were 90.9% (40/44), 71.4% (5/7), 95.2% (40/42), 55.6% (5/9) and 88.2% (45/51), respectively. The extent and localization of perfusion abnormality with the new protocol were correlated well with standard method. The estimation of reversibility, however, was considerably improved by SIDAGS-LDD, especially in those with history of previous myocardial infarction (MI). Conclusion Our proposed protocol demonstrates good correlation and agreement with standard method and even is superior in some cases especially for estimation of viability after MI. Regarding no need for the rest phase radiotracer injection and imaging, this protocol can be more convenient (except the need for close monitoring of the patient during LDD infusion), less time-consuming, less expensive and moreover with less radiation burden to the patients and personnel.     

Maspin: molecular mechanisms and therapeutic implications

Maspin, a non-inhibitory member of the serine protease inhibitor superfamily, has been characterized as a tumor suppressor gene in multiple cancer types. Among the established anti-tumor effects of Maspin are the inhibition of cancer cell invasion, attachment to extracellular matrices, increased sensitivity to apoptosis, and inhibition of angiogenesis. However, while significant experimental data support the role of Maspin as a tumor suppressor, clinical data regarding the prognostic implications of Maspin expression have led to conflicting results. This highlights the need for a better understanding of the context dependencies of Maspin in normal biology and how these are perturbed in the context of cancer. In this review, we outline the regulation and roles of Maspin in normal and developmental biology while discussing novel evidence and emerging theories related to its functions in cancer. We provide insight into the immense therapeutic potential of Maspin and the challenges related to its successful clinical translation.     

Regulating the tumor suppressor gene maspin in breast cancer cells: a potential mechanism for the anticancer properties of tamoxifen.

PURPOSE: Mammary epithelial cells and the majority of breast cancer tumors require estrogen for continued growth. Antiestrogen therapy alone, or in combination with other drugs, has long been a common procedure for breast cancer treatment and prophylaxis. Thus, there is a critical need to elucidate the mechanism(s) of action of antiestrogen treatment, especially for patients who are at risk of breast cancer development or who are currently receiving hormone therapy. In this study, we examined the ability of hormones to regulate the expression of a tumor suppressor gene, maspin, which is a serine protease inhibitor (serpin) that plays an important role in mammary gland development and is silenced during breast cancer progression. Specifically, our hypothesis tested the clinical efficacy of tamoxifen to regulate maspin expression. EXPERIMENTAL DESIGN: We used maspin promoter luciferase reporter plasmids that were transfected into normal human mammary epithelial (HMEC1331) and MCF-7 breast cancer cells, followed by determination of the effect of hormones and their antagonists on maspin promoter activity. At the protein level, cytosolic fractions from both cell types before and after hormone treatment were subjected to Western blot analysis to determine maspin level. RESULTS AND CONCLUSIONS: Our studies revealed that the antiestrogen tamoxifen induces maspin promoter activity. Interestingly, antiandrogen flutamide could also induce maspin in both cell lines tested. These observations were further confirmed in patient tissues. These novel findings provide a new mechanism of action for tamoxifen under normal and pathological conditions. More significantly, these findings could have a potential impact on future therapeutic intervention strategies for breast cancer.     

The impact of self‐transcendence on physical health status promotion in multiple sclerosis patients attending peer support groups

This study aimed to investigate the effect of self‐transcendence on the physical health of multiple sclerosis (MS) patients attending peer support groups. This study was a quasi‐experimental before‐and‐after design including 33 MS patients in three groups: 10 men in the men‐only group, 11 women in the women‐only group, and 12 men and women in the mixed group. Participants were required to attend eight weekly sessions of 2 h each. Instruments included the physical health section of the Multiple Sclerosis Quality of Life Inventory and Reed's Self‐Transcendence Scale. Peer support group attendance was found to have a significant positive effect on the physical health and self‐transcendence of MS patients when comparing average scores before and after attendance. Regression analysis showed that improvement in self‐transcendence predicted improvement in physical health. Results show the positive effects of peer support groups on self‐transcendence and physical health in MS patients, and suggest that improvement in well‐being can be gained by promoting self‐transcendence and physical health.     

Tension-free vaginal tape versus transobturator tape for treatment of stress urinary incontinence: A comparative randomized clinical trial study

ObjectiveThe objective of this study is to evaluate short- and mid-term results of tension-free vaginal tape (TVT) and transobturator tape (TOT) for the treatment of female stress urinary incontinence (SUI) in Imam Reza Academic Hospital.MethodsA total of 100 women with SUI treated using TVT (n = 50) or TOT (n = 50) between March 2008 and October 2010 were included in this prospective randomized clinical trial study. Preoperative workups, including case history, clinical examination, cough test, urodynamic study with abdominal leak point pressure and postvoiding residue measurements, pad test, transvaginal scan, and evaluation with International Consultation on Incontinence Modular Questionnaire–Urinary Incontinence (ICIQ-UI) and International Consultation on Incontinence Modular Questionnaire–Quality of Life (ICIQ-QOL), were performed. During hospitalization, the type of anesthesia, operative time, hospital stay, and catheter indwelling time were recorded. Postoperatively, continence status and subjective patient satisfaction were evaluated using a cough test and in some patients by a pad test also; transvaginal scan and ICIQ-UI and ICIQ-QOL evaluations at 1, 3, 6, 12, and 18 months of follow-up were performed for all patients.ResultsThe mean age was 52.02 ± 7.37 years in the TVT group and 52.27 ± 7.34 years in the TOT group. The rate of complications was similar in both groups. The operative time was 14.50 ± 7.40 and 15.00 ± 7.48 minutes (p = 0.86), hospital stay time 1.56 ± 0.51 and 1.52 ± 0.47 days (p = 0.76), and catheter indwelling time 1.58 ± 0.41 and 1.55 ± 0.47 days (p = 0.651) in the TVT and TOT groups, respectively. At 1, 3, 6, 12, and 18 months after intervention, ICIQ-UI and ICIQ-QOL were completed for all the patients and no significant difference was found between them.ConclusionOur study results showed that TVT and TOT methods have similar efficacy and safety for SUI, although the catheter indwelling time was significantly longer in the TVT group.