Morphactin influences guggulsterone production in callus cultures of <Emphasis Type="Italic">Commiphora wightii</Emphasis>

Guggulsterone, a hypolipidemic natural agent, is produced in resin canals of the plant Commiphora wightii. In this study, the efficacy of different plant growth regulators was evaluated for optimizing its production. Morphactin was found to be effective in enhancing the accumulation of guggulsterones in callus cultures. Maximum callus growth was recorded on medium containing morphactin (0.1 mg l⁻¹) and 2iP (2.5 mg l⁻¹), whereas maximum guggulsterone production occurred when the calluses were cultured on medium containing 0.1 mg l⁻¹ morphactin and 1.0 mg l⁻¹ 2iP. Morphactin and 2iP interacted significantly to enhance the callus growth and guggulsterone production by about 8-folds in one-year-old cultures. However, the effect of morphactin on callus growth and guggulsterone production was not uniform over the levels of 2iP tested. Such an effect of morphactin has never been reported on the production of secondary metabolites.     

Green synthesis-assisted copper nanoparticles using Aegle marmelos leaves extract: physical,optical, and antimicrobial properties

In the present report, Aegle marmelos leaf powder was used to synthesize copper nanoparticles (CuNPs) using a simple and cost-effective method. A. marmelos leaves have various medicinal uses including for the treatment of diarrhoea, constipation, diabetes, cholera, skin diseases, earache, blood purification, heart problems, and so on. The plant biomolecules induce the reduction of Cu²⁺ ions to CuNPs and also act as a capping and stabilizing agent. The formation of CuNPs was confirmed using photoluminescence (PL) excitation and emission spectra on a Shimadzu RF-5301 PC spectrofluorophotometer and the absorbance spectra of a UV–visible spectrophotometer at different stages during the synthesis process. In addition, other properties of synthesized CuNPs were also investigated using X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy techniques. The average size of the synthesized CuNPs was in the range 20–40 nm. Furthermore, the synthesized NPs were also considered for an antimicrobial study against Gram-positive Staphylococcus aureus and Proteus, and Gram-negative Escherichia coli and Salmonella spp. using the agar well diffusion method. The zone of inhibition against the Gram-positive bacteria was greater than the zone of inhibition against the Gram-negative bacteria. These investigation results suggest that synthesized NPs are promising nanomaterials for use as antimicrobial agents.     

Mammalian target of rapamycin is a therapeutic target for murine ovarian endometrioid adenocarcinomas with dysregulated Wnt/β-catenin and PTEN

Despite the fact that epithelial ovarian cancers are the leading cause of death from gynecological cancer, very little is known about the pathophysiology of the disease. Mutations in the WNT and PI3K pathways are frequently observed in the human ovarian endometrioid adenocarcinomas (OEAs). However, the role of WNT/β-catenin and PTEN/AKT signaling in the etiology and/or progression of this disease is currently unclear. In this report we show that mice with a gain-of-function mutation in β-catenin that leads to dysregulated nuclear accumulation of β-catenin expression in the ovarian surface epithelium (OSE) cells develop indolent, undifferentiated tumors with both mesenchymal and epithelial characteristics. Combining dysregulated β-catenin with homozygous deletion of PTEN in the OSE resulted in development of significantly more aggressive tumors, which was correlated with inhibition of p53 expression and cellular senescence. Induced expression of both mTOR kinase, a master regulator of proliferation, and phosphorylation of its downstream target, S6Kinase was also observed in both the indolent and aggressive mouse tumors, as well as in human OEA with nuclear β-catenin accumulation. Ectopic allotransplants of the mouse ovarian tumor cells with a gain-of-function mutation in β-catenin and PTEN deletion developed into tumors with OEA histology, the growth of which were significantly inhibited by oral rapamycin treatment. These studies demonstrate that rapamycin might be an effective therapeutic for human ovarian endometrioid patients with dysregulated Wnt/β-catenin and Pten/PI3K signaling.     

A double blind,randomized, placebo controlled study of the efficacy and safety of 5-Loxin<Superscript>®</Superscript>for treatment of osteoarthritis of the knee

Introduction

5-Loxin^® is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin^® in the treatment of osteoarthritis (OA) of the knee.

Methods

Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin^® daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne''s Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin^® in OA patients.

Results

Seventy patients completed the study. At the end of the study, both doses of 5-Loxin^® conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin^® as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.

Conclusion

5-Loxin^® reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin^® may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.

Trail Registration

(Clinical trial registration number: ISRCTN05212803.)     

Proteomic Analysis of Stromal and Epithelial Cell Communications in Human Endometrial Cancer Using a Unique 3D Co‐Culture Model

Epithelial and stromal communications are essential for normal uterine functions and their dysregulation contributes to the pathogenesis of many diseases including infertility, endometriosis, and cancer. Although many studies have highlighted the advantages of culturing cells in 3D compared to the conventional 2D culture system, one of the major limitations of these systems is the lack of incorporation of cells from non‐epithelial lineages. In an effort to develop a culture system incorporating both stromal and epithelial cells, 3D endometrial cancer spheroids are developed by co‐culturing endometrial stromal cells with cancerous epithelial cells. The spheroids developed by this method are phenotypically comparable to in vivo endometrial cancer tissue. Proteomic analysis of the co‐culture spheroids comparable to human endometrial tissue revealed 591 common proteins and canonical pathways that are closely related to endometrium biology. To determine the feasibility of using this model for drug screening, the efficacy of tamoxifen and everolimus is tested. In summary, a unique 3D model system of human endometrial cancer is developed that will serve as the foundation for the further development of 3D culture systems incorporating different cell types of the human uterus for deciphering the contributions of non‐epithelial cells present in cancer microenvironment.     

Bladder Leiomyoma Presenting With LUTS and Coexisting Bladder and Uterine Leiomyomata: A Review of Two Cases

Mesenchymal tumors of the urinary bladder are a rare occurrence, the most common among them being leiomyoma of the bladder. These tumors commonly present with irritative urinary symptoms progressing gradually to obstructive symptoms as the size increases. We report on two patients who presented with lower urinary tract symptoms (LUTS). One of the patients also had concomitant bladder and uterine leiomyomata, which is the first such case to be reported in the literature. It is essential to differentiate leiomyoma from other common causes of LUTS. Cold cup biopsy has a significant false-negative rate and, in such cases, a wide local excision provides an optimal cure with excellent results.Key words: Bladder leiomyoma, Uterine fibroid, Lower urinary tract symptomsBenign tumors of the urinary bladder are rare and can present with a wide spectrum of complaints ranging from irritative to obstructive urinary symptoms.¹ Here we report on two patients who presented with lower urinary tract symptoms (LUTS), one of whom also had concomitant multiple uterine fibroids. To our knowledge, this is the first case to be reported in the literature.     

In vivo assessment of antidiabetic and antioxidative activity of natural phytochemical isolated from fruit-pulp of Eugenia jambolana in streptozotocin-induced diabetic rats

Objectives: Eugenia jambolana (E. jambolana) is well known for its antidiabetic potential. The aim of the present study was to investigate the antidiabetic and antioxidative effect of an active compound (FIIc) isolated from fruit-pulp of E. jambolana in streptozotocin (45?mg/kg body weight)-induced diabetic rats.

Methods: FIIc was isolated from the crude aqueous extract of fruit-pulp by ion-exchange column chromatography and high-performance column chromatography. Detailed UV, NMR, and IR spectra suggested that FIIc is α-hydroxy succinamic acid. FIIc was orally administered to diabetic rats at a dose of 10, 15, and 20?mg/kg body weight (mg/kg bwt.) to determine its effective dose. Thereafter, effective dose was administered to 8 weeks to determine its antidiabetic and antioxidative activity by estimation of glycemic index, lipid profile, key enzymes of carbohydrate metabolism, and oxidative stress parameters.

Results: Administration of 15?mg/kg dose daily for 8 weeks led to significant (P?P?Discussion: The results demonstrate that FIIc possesses significant antidiabetic and antioxidative activity.     

SUPFAM: A database of sequence superfamilies of protein domains

Background  

SUPFAM database is a compilation of superfamily relationships between protein domain families of either known or unknown 3-D structure. In SUPFAM, sequence families from Pfam and structural families from SCOP are associated, using profile matching, to result in sequence superfamilies of known structure. Subsequently all-against-all family profile matches are made to deduce a list of new potential superfamilies of yet unknown structure.     

An improved protein structure evaluation using a semi-empirically derived structure property

Background

In the backdrop of challenge to obtain a protein structure under the known limitations of both experimental and theoretical techniques, the need of a fast as well as accurate protein structure evaluation method still exists to substantially reduce a huge gap between number of known sequences and structures. Among currently practiced theoretical techniques, homology modelling backed by molecular dynamics based optimization appears to be the most popular one. However it suffers from contradictory indications of different validation parameters generated from a set of protein models which are predicted against a particular target protein. For example, in one model Ramachandran Score may be quite high making it acceptable, whereas, its potential energy may not be very low making it unacceptable and vice versa. Towards resolving this problem, the main objective of this study was fixed as to utilize a simple experimentally derived output, Surface Roughness Index of concerned protein of unknown structure as an intervening agent that could be obtained using ordinary microscopic images of heat denatured aggregates of the same protein.

Result

It was intriguing to observe that direct experimental knowledge of the concerned protein, however simple it may be, might give insight on acceptability of its particular structural model out of a confusion set of models generated from database driven comparative technique for structure prediction. The result obtained from a widely varying structural class of proteins indicated that speed of protein structure evaluation can be further enhanced without compromising with accuracy by recruiting simple experimental output.

Conclusion

In this work, a semi-empirical methodological approach was provided for improving protein structure evaluation. It showed that, once structure models of a protein were obtained through homology technique, the problem of selection of a best model out of a confusion set of Pareto-optimal structures could be resolved by employing a structure agent directly obtainable through experiment with the same protein as experimental ingredient. Overall, in the backdrop of getting a reasonably accurate protein structure of pathogens causing epidemics or biological warfare, such approach could be of use as a plausible solution for fast drug design.