Measuring the Effects of Berberine on Serum Prooxidant-Antioxidant Balance in Metabolic Syndrome.

Disturbances in the prooxidant-antioxidant balance can occur in metabolic syndrome. Here, we present a protocol for the setup of a clinical trial of metabolic syndrome patients treated with berberine, a dietary phytochemical of the Berberis vulgaris plant, or placebo. The main aim is to obtain a quick and real-time assessment on the overall redox state based on measurement of the prooxidant-antioxidant balance.

Testing the Anti-inflammatory Effects of Curcuminoids in Patients with Colorectal Cancer.

Colorectal cancer is the third most common cancer and accounts for the second highest number of cancer-related deaths worldwide. Natural products such as the turmeric-derived curcuminoids are known to have protective effects against several kinds of cancers by acting as antioxidant and anti-inflammatory agents. Here, we present a protocol for assessing the effects of curcuminoids on serum cytokine profiles in a double-blind placebo-controlled trial of patients with stage 3 colorectal cancer undergoing chemotherapy. The protocol could also be applied to other cancer types.

Targeting interleukin-ß by plant-derived natural products: Implications for the treatment of atherosclerotic cardiovascular disease.

Inflammation is the main contributing factor to atheroma formation in atherosclerosis. Interleukin-1 beta (IL-1ß) is an inflammatory mediator found in endothelial cells and resident leukocytes. Canakinumab is a selective monoclonal antibody against IL-1ß which attenuates inflammation and concurrently precipitates fatal infections and sepsis. Natural products derived from medicinal plants, herbal remedy and functional foods are widely used nowadays. Experimental and clinical trial evidence supports that some natural products such as curcumin, resveratrol, and quercetin have potential effects on IL-1ß suppression. In this review, we tried to document findings that used medicinal plants and plant-based natural products for treating atherosclerosis and its related diseases through the suppression of IL-1ß.

Carbon-based Nanomaterials and Curcumin: A Review of Biosensing Applications.

Curcumin, the main active constituent of turmeric (Curcuma longa L.), is a naturally occurring phenolic compound with a wide variety of pharmacological activities. Although it has multiple pharmaceutical properties, its bioavailability and industrial usage are hindered due to rapid hydrolysis and low water solubility. Due to the growing market of curcumin, exact determination of curcumin in trade and human biological samples is important for monitoring therapeutic actions. Different nanomaterials have been suggested for sensing curcumin; and in this case, carbon-based nanomaterials (CNMs) are one of the most outstanding developments in nanomedicine, biosensing, and regenerative medicine. There are a considerable number of reports which have shown interesting potential of CNMs-based biosensors in the sensitive and selective detection of curcumin. Therefore, this review aims to increase understanding the interaction of curcumin with CNMs in the context of biosensing.

Design, synthesis and biological evaluation of novel 5-(imidazolyl-methyl) thiazolidinediones as antidiabetic agents.

A newly designed series of imidazolyl-methyl- l-2,4-thiazolidinediones 9 (a-m) were synthesized and In Silico studies were carried out to rationalize their anti-diabetic activity. Generally, all newly synthesized thiazolidinediones had anti-hyperglycemic activity compared with a diabetic-control group, without toxicity in 3T3 cells (viability ≥ 90%). These studies revealed that the compounds 9e and 9b (11∗10-6mol/kg) lowered blood glucose more effectively when compared to pioglitazone at the same dose. Following the administration of compound 9e, no weight gains or any serious side effects on liver and pancreas were observed. Moreover, the glucose consumption assay results showed a significant glucose-lowering effect (p < 0.001) in HepG2 cells, which were exposed to 11 mM of glucose at concentrations of 1.25-10 mM of compound 9e. Also, the PPAR-γ gene expression study revealed that pioglitazone and 9e showed similar behavior relative to the control group.

Resveratrol and endothelial function: A literature review.

Endothelial dysfunction is a major contributing factor to diseases such as atherosclerosis, diabetes mellitus, obesity, hypertension, acute lung injury, preeclampsia, among others. Resveratrol (RSV) is a naturally occurring bioactive polyphenol found in grapes and red wine. According to experimental studies, RSV modulates several events involved in endothelial dysfunction such as impaired vasorelaxation, eNOS uncoupling, leukocyte adhesion, endothelial senescence, and endothelial mesenchymal transition. The endothelial protective effects of RSV are found to be mediated by numerous molecular targets (e.g. Silent Information Regulator 1 (SIRT1), 5' AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), nuclear factor-erythroid-derived 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor (PPAR), Krüppel-like factor-2 (KLF2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)). Herein, we present an updated review addressing pharmacological effects and molecular targets of RSV in maintaining endothelial function, and the potential of this phytochemical for endothelial dysfunction-associated disorders.

The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine.

BACKGROUND: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. RESULTS: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.

Associations between Pre-Bariatric High-Sensitivity C-Reactive Protein and Post-Surgery Outcomes.

BACKGROUND: Obesity is a chronic inflammatory condition associated with increased circulating levels of C-reactive protein (CRP). Bariatric surgery has been reported to be effective in improving both inflammatory and liver status. Our aims were to elucidate the relationships between pre-surgery high sensitivity-CRP (hs-CRP) values and post-surgery weight loss and liver steatosis and fibrosis in patients with severe obesity undergoing Roux-en-Y gastric bypass. METHODS: We conducted an observational prospective study on 90 individuals with morbid obesity, who underwent gastric bypass. Anthropometric indices, laboratory assessment (lipid panel, glycemic status, liver enzymes, and hs-CRP), liver stiffness and steatosis were evaluated at baseline and 6-months after surgery. RESULTS: There was a significant post-surgery reduction in all the anthropometric variables, with an average weight loss of 33.93 ± 11.79 kg; the mean percentage of total weight loss (TWL) was 27.96 ± 6.43%. Liver elasticity was significantly reduced (from 6.1 ± 1.25 to 5.42 ± 1.52 kPa; p = 0.002), as well as liver aminotransferases, nonalcoholic fatty liver disease fibrosis score (NFS) and the grade of steatosis. Serum hs-CRP levels significantly reduced (from 9.26 ± 8.45 to 3.29 ± 4.41 mg/L; p < 0.001). The correlations between hs-CRP levels and liver fibrosis (elastography), steatosis (ultrasonography), fibrosis-4 index, NFS, and surgery success rate were not significant. Regression analyses showed that serum hs-CRP levels were not predictive of liver status and success rate after surgery in both unadjusted and adjusted models. CONCLUSIONS: In patients with morbid obesity, bariatric surgery caused a significant decrease in hs-CRP levels, liver stiffness and steatosis. Baseline hs-CRP values did not predict the weight-loss success rate and post-surgery liver status.

Regulation of microRNA-21 expression by natural products in cancer.

Natural products have been of much interest in research studies owing to their wide pharmacological applications, chemical diversity, low side effects, and multitarget activities. Examples of these compounds include matrine, sulforaphane, silibinin, curcumin, berberin, resveratrol, and quercetin. Some of the present anticancer drugs, such as taxol, vincristine, vinblastine, and doxorubicin are also derived from natural products. The anti-carcinogenic effects of these products are partly mediated through modulation of microRNA-21 (miR-21) expression. To date, numerous downstream targets of miR-21 have been recognized, which include phosphatase and tensin homolog (PTEN), ras homolog gene family member B (RHOB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), programmed cell death 4 (PDCD4), signal transducer and activator of transcription (STAT)-3, and nuclear factor kappa B (NF-κB) pathways. These signaling pathways, their regulation by oncomiR-21 in cancer, and the modulating impact of natural products are the main focus of this review.

Antifungal Activity of Curcuminoids and Difluorinated Curcumin Against Clinical Isolates of Candida Species.

BACKGROUND: Acquired resistance to antifungals is rising particularly among Candida species. Herbal ingredients have biological and pharmacological activities, which make them potential fungicidal agents. The present study investigated the effects of curcumin (CUR) and difluorinated curcumin (CDF) on Candida species. MATERIAL AND METHOD: CUR and CDF were examined against Candida isolates obtained from patients candidemia due to C. albicans (n = 13), C. dubliniensis (n = 2), C. parapsilosis (n = 2), and C. tropicalis (n = 1); and laboratory strains of C. albicans (TIMML 1292 and TIMML 183), C. krusei (TIMML 1321), C. parapsilosis (TIMML 2201), and C. tropicalis (TIMML 731) based on the M27-A3 guideline. RESULTS: At the concentrations of 1-512µg/mL, none of the CDF and CUR showed a significant minimum inhibitory concentration (MIC) range against Candida isolates. There was no significant difference between the effects of CUR and CDF against Candida species. CONCLUSION: The CUR and CDF did not exert any inhibitory effect on the growth of Candida strains. Any possible effect on other yeast and filamentous fungi needs to be further investigated.

Resolution of Inflammation in Neurodegenerative Diseases: The Role of Resolvins.

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

Hepatic Function and Fibrosis Assessment Via 2D-Shear Wave Elastography and Related Biochemical Markers Pre- and Post-Gastric Bypass Surgery.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) exhibits a worldwide distribution and encompasses a wider range of hepatic abnormalities that can culminate in serious clinical outcomes. The growing incidence of NAFLD necessitates more efficient management strategies particularly in clinically severe obese patients. Weight reduction is the cornerstone of NAFLD treatment; therefore, bariatric surgery could be a therapeutic approach in selected obese patients afflicted with NAFLD and other cardiometabolic comorbidities. OBJECTIVE: The present study focused on the potential role of bariatric surgery on hepatic function and NAFLD-related histopathological features measured through a noninvasive method. METHOD: Ninety patients entered to this study and underwent initial preoperative assessments including demographic profile, anthropometric measurements, standard laboratory tests, and hepatic biopsy. Liver stiffness was also evaluated via two-dimensional shear wave elastography (2D-SWE). All assessments were repeated over the subsequent 6 months following surgery except for liver biopsy. RESULTS: Postoperative hepatic elasticity was lessened after 6 months (p = 0/002).The levels of alanine aminotransferase, gamma-glutamyl transferase, total protein, lipid indices, glucose, and platelet count were also improved following surgery (p < 0/001). Further progression of fibrosis was observed in 25% of patients after surgery. CONCLUSION: Bariatric surgery was associated with a favorable impact on anthropometric and hepatic elasticity indices as well as metabolic parameters. The ideal target population for bariatric surgery should be thoroughly addressed, and the underlying risk factors for fibrosis progression need to be controlled before surgery. However, expanded research designed as comprehensive randomized controlled trials are recommended to confirm these findings.

Evaluation of Cyclooxygenase-2 Expression in Association with Clinical-Pathological Factors in Malignant Melanoma.

BACKGROUND AND OBJECTIVE: The primary goal of this study is to develop a rigorous understanding of the correlation between COX-2 expression and malignant melanoma prognostic factors. MATERIAL AND METHODS: In this cross-sectional study, we analyzed 60 cases of cutaneous malignant melanoma. The related stained slides were reviewed by two pathologists. The results were interpreted according to the COX2 staining index (SI), tumor thickness (Breslow, Clark), number of mitoses per 10 hpf, and melanoma types. Gender, lymph node involvement, metastasis, and survival were considered as evaluation factors as well. RESULTS: The expression of the COX-2 protein was evident in 98.4% of cases. A strong Staining Index(SI) was reported in 60% of all melanomas, moderate staining was detected in 20.8% and weak staining in 10%; 1.6% of studied cases showed no staining. Benign nevus specimens showed no staining for the COX-2 enzyme. CONCLUSION: We have demonstrated that COX-2 is strongly expressed in the majority of malignant melanomas and that the SI score of COX-2 is related to the number of mitoses, tumor thickness (based on Clark level and Breslow), melanoma sub-type, lymph node involvement, and metastases; No association was noted between the anatomic site, gender, and survival. COX-2 can be applied as a prognostic factor in malignant melanoma and a promising candidate for future target therapies.

Evaluation of CD30/CD4/CD8 in triple-negative invasive ductal carcinoma of breast in association with clinicopathological prognostic factors.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks the benefits of receptor-targeted therapeutic strategies. The limitations in treatment options along with poor patients' outcome heighten the need for novel approaches. Due to recent concentration on the role of biomarkers in prognosis, treatment, and survival of various cancer subtypes, this study involves an investigation of CD4, CD8, and CD30 markers detected by immunohistochemistry in TNBCs and their association with clinicopathological and prognostic factors. MATERIALS AND METHODS: Tissue samples of 85 hormone receptor- and human epidermal growth factor receptor-2-negative ductal breast carcinomas extracted from the archive of pathology department. Regarding CD4/CD8 ratio, the infiltrated T-lymphocytes were investigated. The tumoral tissue regions were also identified to be immunohistochemically assessed for the CD30 expression levels. RESULTS: With an elevated CD4/CD8 ratio, a significant increase in lymph node involvement was observed (P < 0.05); in contrast, increased expression levels of CD8 were related to significant reduction of lymph node involvement. CD30 overexpression was found to be significantly associated with shortened overall survival (OS) and highly involvement of lymph nodes. CONCLUSION: Following the progression in stage and grade of tumor, CD4/CD8 ratio and CD30 expression levels are increased and are accompanied by adverse prognosis and poor OS, while CD8-enhanced expression carries a favorable prognostic impact as it improves OS status. Therefore, all these findings could be of interest in the field of target therapy.

Evaluation of photoshop based image analysis in cytologic diagnosis of pleural fluid in comparison with conventional modalities.

BACKGROUND: The aim of this study is to investigate and compare the results of digital image analysis in pleural effusion cytology samples with conventional modalities. MATERIALS AND METHODS: In this cross-sectional study, 53 pleural fluid cytology smears from Qaem hospital pathology department, located in Mashhad, Iran were investigated. Prior to digital analysis, all specimens were evaluated by two pathologists and categorized into three groups as: benign, suspicious, and malignant. Using an Olympus microscope and Olympus DP3 digital camera, digital images from cytology slides were captured. Appropriate images (n = 130) were separately imported to Adobe Photoshop CS5 and parameters including area and perimeter, circularity, Gray Value mean, integrated density, and nucleus to cytoplasm area ratio were analyzed. RESULTS: Gray Value mean, nucleus to cytoplasm area ratio, and circularity showed the best sensitivity and specificity rates as well as significant differences between all groups. Also, nucleus area and perimeter showed a significant relation between suspicious and malignant groups with benign group. Whereas, there was no such difference between suspicious and malignant groups. CONCLUSION: We concluded that digital image analysis is welcomed in the field of research on pleural fluid smears as it can provide quantitative data to apply various comparisons and reduce interobserver variation which could assist pathologists to achieve a more accurate diagnosis.