Effect of silymarin on liver size and nonalcoholic fatty liver disease in morbidly obese patients: A randomized double-blind clinical trial.

Background: A large liver size is a factor that may increase the difficulty of bariatric surgery (BS) and unwanted complications. Some agents have been used to decrease the liver size before BS. Silymarin has been used as an antioxidant agent to improve liver function tests. This study was designed to evaluate the effects of silymarin on liver dimensions, function, and lipid profile. Materials and Methods: A double-blind randomized clinical trial was performed on 56 patients. The patients were divided into silymarin and placebo groups. Blood samples and sonographic examinations were taken from the patients before and 4 weeks after the administration of the silymarin or placebo. In the first group, 140 mg silymarin was prescribed every 8 h for 4 weeks, and the other group received placebo in the same way with the same tablet shape. After the completion of the 4-week treatment, laboratory tests and ultrasonography were carried out again. Results: Thirty-nine (69.6%) patients were female with a mean body mass index (BMI) of 46.2 kg/m2 and a mean age of 36.8 years. Most of the patients had a compliance of 80% and higher. The analysis did not show any significant difference in aspartate transaminase, alkaline transaminase, liver size, cholesterol, and triglyceride changes among the silymarin and placebo groups. BMI loss was slightly higher in the silymarin group although the difference was not statistically significant. Conclusion: The present findings show that silymarin administration for 4 weeks does not affect liver size and function, but further evaluations should be carried out on the subject.

The anticancer properties of metal-organic frameworks and their heterogeneous nanocomposites.

Herein, silver-based metal-organic framework (AgMOF) and its graphene oxide (GO)-decorated nanocomposite (GO-AgMOF) are proposed for use in emerging biomedical applications. The nanocomposites are characterized, and hence, in vitro apoptotic and antibacterial features of AgMOF and GO-AgMOF nanomaterials were investigated. An MTT cytocompatibility assay indicates that these nanomaterials have dose-dependent toxicity in contact with SW480, colon adenocarcinoma cells. In addition, the cell death mechanism was explored by analyzing flow cytometry and caspase activity. Furthermore, the expressions of pro-apoptotic and anti-apoptotic genes were investigated using quantitative polymerase chain reaction (qPCR). Comparing the control group with the groups treated by the nanomaterials indicates up-regulation of the BAX/BCl2 ratio. We also measured the minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) of these nanomaterials acting on S. mutans and S. aureus, which indicates excellent antibacterial properties. Showing inhibition effect on the viability of cancerous cells through apoptosis and antibacterial effects simultaneously, AgMOF and GO-AgMOF can be regarded as potential therapeutics for cancer.

Collagen type XIX regulates cardiac extracellular matrix structure and ventricular function.

The cardiac extracellular matrix plays essential roles in homeostasis and injury responses. Although the role of fibrillar collagens have been thoroughly documented, the functions of non-fibrillar collagen members remain underexplored. These include a distinct group of non-fibrillar collagens, termed, fibril-associated collagens with interrupted triple helices (FACITs). Recent reports of collagen type XIX (encoded by Col19a1) expression in adult heart and evidence of its enhanced expression in cardiac ischemia suggest important functions for this FACIT in cardiac ECM structure and function. Here, we examined the cellular source of collagen XIX in the adult murine heart and evaluated its involvement in ECM structure and ventricular function. Immunodetection of collagen XIX in fractionated cardiovascular cell lineages revealed fibroblasts and smooth muscle cells as the primary sources of collagen XIX in the heart. Based on echocardiographic and histologic analyses, Col19a1 null (Col19a1N/N) mice exhibited reduced systolic function, thinning of left ventricular walls, and increased cardiomyocyte cross-sectional areas-without gross changes in myocardial collagen content or basement membrane morphology. Col19a1N/N cardiac fibroblasts had augmented expression of several enzymes involved in the synthesis and stability of fibrillar collagens, including PLOD1 and LOX. Furthermore, second harmonic generation-imaged ECM derived from Col19a1N/N cardiac fibroblasts, and transmission electron micrographs of decellularized hearts from Col19a1N/N null animals, showed marked reductions in fibrillar collagen structural organization. Col19a1N/N mice also displayed enhanced phosphorylation of focal adhesion kinase (FAK), signifying de-repression of the FAK pathway-a critical mediator of cardiomyocyte hypertrophy. Collectively, we show that collagen XIX, which had a heretofore unknown role in the mammalian heart, participates in the regulation of cardiac structure and function-potentially through modulation of ECM fibrillar collagen structural organization. Further, these data suggest that this FACIT may modify ECM superstructure via acting at the level of the fibroblast to regulate their expression of collagen synthetic and stabilization enzymes.

Relationship between the severity of endometriosis symptoms (dyspareunia, dysmenorrhea and chronic pelvic pain) and the spread of the disease on ultrasound.

OBJECTIVES: About 10-15% of women of childbearing age have endometriosis. The present study aimed to investigate the relationship between the severity of symptoms of endometriosis and the spread as well as the stage of the disease on ultrasonography. The present cross-sectional study evaluates the relationship between the severity of endometriosis symptoms and the spread of disease on ultrasonography in patients with endometriosis. RESULTS: Considering different analyses, the cumulative size of posterior deep infiltrative endometriosis (DIE) (less than 1 cm) is significantly correlated with minimal severity of dyspareunia and chronic pelvic pain. The incidence of dyspareunia was more prevalent in patients with complete stenosis of Douglas pouch than those with incomplete stenosis. Furthermore, the incidence of severe and very severe pain in patients with Douglas pouch stenosis is relatively higher than that in patients without stenosis. Only dyspareunia is related to the stage of endometriosis, and patients with dyspareunia are five times more at risk of a higher stage of the disease. The severity of dyspareunia is related to the stage of endometriosis and the severity of Douglas pouch stenosis. The results showed a correlation between chronic pelvic pain and r-ASRM score (revised American Society for Reproductive Medicine score).

The Effect of Propofol on the Success Rate of Transurethral Lithotripsy by Holmium Laser: A Randomized Clinical Trial.

Introduction: Urinary stone disease is the third most common affliction of the urinary tract that has been associated with an increasing incidence. Over decades, great advances have been made in the minimally invasive treatment of urinary stones. Recently, transurethral lithotripsy (TUL) by holmium laser was introduced as a possible therapeutic option. This study evaluated the effect of propofol on the success rate of TUL by holmium laser. Methods: A double-blind randomized controlled trial was conducted on 180 patients to investigate the effect of propofol on the success and complication rate of TUL by holmium laser. The enrolled patients were divided into two groups: the first group received sodium thiopental (n=89) while the second group received propofol (n=91). The two groups were compared in terms of the fluctuations of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), operation time, future stone-free rate (SFR), stone migration, post-operative fever, and ureteral complications such as perforation and mucosal damage. Other developed complications were also recorded. After data gathering, statistical analysis was performed with SPSS version 21. Results: the patients' data such as age, sex, stone diameter, stone laterality, duration of stone impaction, primary SBP, DBP and HR were not significantly different between the two groups (P>0.05). TUL and anesthesia duration, first-minute and fifth-minute SBP and DBP, and also changes of HR were significantly lower in the propofol group compared with the sodium thiopental group (P <0.001). Moreover, SFR of TUL was more evident in the propofol group. Ureteral mucosal damage was significantly less in the propofol group. Conclusion: Propofol was associated with a higher reduction in SBP and DBP, decreased duration of TUL, fewer fluctuations in HR, and an increased success rate of stone removal by TUL with holmium laser.

The Discrepancy between Needle Biopsy and Radical Prostatectomy Gleason Score in Patients with Prostate Cancer.

PURPOSE: Gleason score (GS), as well as other prognostic and diagnostic modalities, can predict the possibility of tumor growth and metastasis during the life of patients with prostate cancer. Based on the prostate biopsy GS, clinicians choose the most appropriate therapy for managing patients. The objective of this cross-sectional study was to determine the discrepancy between needle biopsy and radical prostatectomy GS and to identify its predictive factors among the Iranian population. MATERIALS AND METHODS: A total of 1147 patients who underwent radical prostatectomy from 2009 to 2019 were initially enrolled in this study. After consideration of the inclusion and exclusion criteria, 439 patients were finally included. The demographic variables and clinical data including age, PSA level, prostate volume, PSA density, GS derived from ultrasonography-guided core needle biopsy specimen, and GS derived from radical prostatectomy specimen were collected from the medical records of patients with prostate adenocarcinoma and were reviewed by a urology resident. Statistical analysis was done by using the Social Sciences Software version 21. RESULTS: The average age of patients was 64.5 years (range 48-84 years), and the average preoperative PSA level was 14.8 ng/mL. On histopathological examination, no changes in GS were observed in 237 (53.9%) patients, whereas GS was upgraded in 144 (32.8%) patients and downgraded in 58 (13.2%) patients at radical prostatectomy. The number of patients who had extracapsular extension, seminal vesicle invasion and positive lymph nodes was significantly higher in the upgraded group compared with the non-upgraded group.  Conclusion: In this study, there was a steady decrease in GS upgrading with the prostate size extending up to 49.7 g. There was also an association between downgrading and extending prostate size. Due to the greater risk of high-grade disease in men with small prostates, smaller prostate bulks are most probably upgraded after radical prostatectomy. A higher maximum percentage of involvement per core was an independent predictive factor of upgrading from biopsy grade 1 to grade ≥ 2. Our study showed that patients' age was not predictive of upgrading, which is consistent with other studies. Also, we demonstrated a non-significant relationship between PSA level and upgraded GS. Findings in this study did not demonstrate a significant relationship between PSA level and upgrading.

The Effect of Cardiogenic Factors on Cardiac Mesenchymal Cell Anti-Fibrogenic Paracrine Signaling and Therapeutic Performance.

Intrinsic cardiogenic factor expression, a proxy for cardiomyogenic lineage commitment, may be an important determinant of donor cell cardiac reparative capacity in cell therapy applications; however, whether and how this contributes to their salutary effects remain largely ambiguous. Methods: The current study examined the consequences of enhanced cardiogenic factor expression, via lentiviral delivery of GMT (GATA4, MEF2C, and TBX5), on cardiac mesenchymal cell (CMC) anti-fibrogenic paracrine signaling dynamics, in vitro, and cardiac reparative capacity, in vivo. Proteome cytokine array analyses and in vitro cardiac fibroblast activation assays were performed using conditioned medium derived from either GMT- or GFP control-transduced CMCs, to respectively assess cardiotrophic factor secretion and anti-fibrogenic paracrine signaling aptitude. Results: Relative to GFP controls, GMT CMCs exhibited enhanced secretion of cytokines implicated to function in pathways associated with matrix remodeling and collagen catabolism, and more ably impeded activated cardiac fibroblast Col1A1 synthesis in vitro. Following their delivery in a rat model of chronic ischemic cardiomyopathy, conventional echocardiography was unable to detect a therapeutic advantage with either CMC population; however, hemodynamic analyses identified a modest, yet calculable supplemental benefit in surrogate measures of global left ventricular contractility with GMT CMCs relative to GFP controls. This phenomenon was neither associated with a decrease in infarct size nor an increase in viable myocardium, but with only a marginal decrease in regional myocardial collagen deposition. Conclusion: Overall, these results suggest that CMC cardiomyogenic lineage commitment biases cardiac repair and, further, that enhanced anti-fibrogenic paracrine signaling potency may underlie, in part, their improved therapeutic utility.

Is active surveillance an appropriate approach to manage prostate cancer patients with Gleason Score 3+3 who met the criteria for active surveillance?

OBJECTIVE: Prostate cancer is one of the common malignant tumors in men worldwide. Nowadays it seems that Gleason Score 3+3 may not need definite treatment and some of the experts even ignore it as a cancer but we should be aware that in some patients with Gleason Score 3+3 there is a higher risk for harboring higher-grade cancer. We had done this study to evaluate patients with prostate cancer with Gleason Score 3+3 to determine the value of tumor volume in these cases. MATERIAL AND METHODS: From September 2010 to October 2017, radical prostatectomy was done for 123 sequential patients with localized prostate cancer in two referral centers of Shahid Beheshti Medical University, Tehran, Iran, and 42 cases with Gleason Scores 3+3 which who were candidates for active surveillance were included in the study. RESULTS: Thirty of 42 (71.4%) patients had significant tumor volumes (≥0/5 cm3). When tumor volume was less than 0.5 cm3, none of the patients had extra prostatic tumor extension. In patients with tumor volume greater than 0.5 cm3, two cases (6.6%) had extra prostatic extension, 4 cases (13.3%) had positive margins, four cases (13.3%) reactive lymph nodes and 16 cases (53.3%) perineural invasion. CONCLUSION: We suggest that some patients with Gleason Score 3+3 have tumor volume >0.5 cm3 who are considered having significant cancer pathology and active surveillance may not be appropriate approach to manage all cases with Gleason Score 3+3.

The clinical significance of complete class switching defect in Ataxia telangiectasia patients.

BACKGROUND: Ataxia telangiectasia (AT) is a primary immunodeficiency associated with recurrent infections. We aimed to investigate clinical and immunological classification in AT patients who suffer from a different spectrum of humoral immune defects. METHODS: AT patients were categorized according to the ability of class switching and patients with hyper IgM (HIgM) profile were defined as class switching defect (CSD). RESULTS: Serum immunoglobulin profile in 66 AT patients showed normal immunoglobulin level (22.8%), IgA deficiency (37.9%) and hypogammaglobulinemia (18.1%) in the majority of patients, while 21.2% had HIgM profile revealing CSD. CSD does not affect the frequency of infections, however, the frequency of lymphoproliferation (p < 0.001), and autoimmunity (p = 0.004) were significantly higher in this group. Neurologic symptoms in CSD patients are mild or appear after recurrent infections, therefore these patients were usually misdiagnosed as HIgM syndrome. CONCLUSIONS: Although most of AT patients have reduced IgA levels or normal immunoglobulin levels, but a fraction of these patients may show CSD ensuing HIgM-profile. CSD poses affected individuals at higher risk of non-infectious complications.

Hydroxycitric acid ameliorates inflammation and oxidative stress in mouse models of multiple sclerosis.

Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-inflammatory effects. Multiple sclerosis can cause an inflammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis, i.e., experimental autoimmune encephalomyelitis, using Complete Freund's Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35-55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reductase activities. These findings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inflammation and oxidative stress.

Monogenic Auto-inflammatory Syndromes: A Review of the Literature.

Auto-inflammatory syndromes are a new group of distinct hereditable disorders characterized by episodes of seemingly unprovoked inflammation (most commonly in skin, joints, gut, and eye), the absence of a high titer of auto-antibodies or auto-reactive T cells, and an inborn error of innate immunity. A narrative literature review was carried out of studies related to auto-inflammatory syndromes to discuss the pathogenesis and clinical manifestation of these syndromes. This review showed that the main monogenic auto-inflammatory syndromes are familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). The data suggest that correct diagnosis and treatment of monogenic auto-inflammatory diseases relies on the physicians' awareness. Therefore, understanding of the underlying pathogenic mechanisms of auto-inflammatory syndromes, and especially the fact that these disorders are mediated by IL-1 secretion stimulated by monocytes and macrophages, facilitated significant progress in patient management.