Untargeted metabolomics study and identification of potential biomarkers in the six sections of the genus Stachys L. (Lamiaceae) using HPLC-MQ-API-MS/MS.

INTRODUCTION: The genus Stachys L., belonging to the family Lamiaceae, is one of the largest genera with remarkable medicinal properties. Plants of this genus produce a broad range of secondary metabolites. OBJECTIVES: Due to the incomplete comprehensive assessment of chemical profiles in Stachys species, we conducted an untargeted metabolomics study and identified potential biomarkers in the six sections of Stachys with chemotaxonomic importance. MATERIAL AND METHODS: Dried leaves of 17 taxa were utilized for analysis of all the constituents using HPLC-MQ-API-MS. The obtained data were processed and analyzed using multivariate statistical methods, including heatmaps, PLS-DA score plots, functional analysis of metabolic pathways, metabolite set enrichment analysis, and biomarker and network analysis. RESULTS: Among the 129 metabolites, 111 flavonoids and 18 non-flavonoids were recognized. The most represented flavonoids, including 41 flavones and 20 flavonols, displayed remarkable abundance. In non-flavonoid compounds, a total of six coumarins and six phenolic acids were present at high levels. In terms of approved markers in six sections, 76 chemical compounds, mainly flavonoids, coumarins, quinic acids, and cinnamic acids, were identified as potential biomarkers or chemotaxonomic indicators. Accordingly, the taxonomic complexities of some Stachys species in sections Fragilicaulis, Aucheriana, and Setifolia were properly resolved. CONCLUSION: An HPLC-MS/MS-based metabolomics approach integrated with multivariate statistical methods was employed to identify (1) valuable markers and analyze metabolic diversity and (2) predict the pharmaceutical properties of Stachys species. The obtained chemical profiles provide a new perspective for investigation of the Stachys genus.

Evaluation of gametogenic potential of vitrified human umbilical cord Wharton's jelly-derived mesenchymal cells.

BACKGROUND AIMS: Vitrification as an advanced cryopreservation method is recommended for cell storage toward future applications. The purpose of this report was to appraise whether gametogenic potential of these cells is altered by vitrification. METHODS: A two steps method was applied for hUCM cells vitrification. An n-hUCM group of hUCM cells served as control. In order to differentiation of hUCM cells into male germ cells, the cells were induced by retinoic acid, testosterone and testicular-cell-conditioned medium. To evaluate induced hUCM cells toward germ cells, we used immunocytochemistry and karyotyping methods. RESULTS: v-hUCM cells similar to n-hUCM cells formed flat cells after gametogenic induction, and showed protein expression of germ-cell-specific markers DAZL, VASA (DDX4) and SCP3. Karyotyping pattern remained unchanged in the either groups. CONCLUSIONS: The analysis of these results demonstrates that vitrification does not alter differentiation potential of hUCMs to male germ like cells. These results may set an in vitro pattern to study germ-cell formation from hUCM cells and also as a potential source of sperms for male infertility.

Economical Evaluation of Cancer Types Using Intensity-Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy: A Systematic Review.

Background: Cancer is the second most common cause of death worldwide. Economic evaluation of cancer treatment to reduce costs can save the health care system millions of dollars while optimizing care. Therefore, this systematic review aimed to study the economic evaluation of cancer treatment using intermediate intensity radiation therapy (IMRT) compared to conventional 3D conformal radiation therapy (3D-CRT). Methods: Literatures from PubMed, Embase, Cochran Library, Google scholar, Scopus and Iranian databases were retrieved since Jan 2000 to Apr 2020 for eligible English studies. The quality of the studies was evaluated using Cheers' checklist and then the textual data were analyzed manually by content analysis method. Results: Overall, 1790 articles were retrieved, of which 12 studies were reviewed. The article quality score ranged from 14.5 to 23 out of a maximum of 24 points. Eleven studies referred to cost-effectiveness analysis and one study referred to cost-utility analysis. Studies have been conducted in the United States, Canada, Australia, Brazil, the Netherlands, the United Kingdom, and Hungary. IMRT appears to be a cost-effective treatment strategy for rectal cancer, soft tissue sarcoma, and localized carcinoma of the pharynx, and for prostate cancer in terms of prolonging survival, but it is a cost-effective treatment strategy for head cancer. In addition, the neck was not in India's cancer control program. Conclusion: The results can help to decide whether to use radiation therapy and radiotherapy in the standard treatment path. Furthermore, they underline that IMRT treatment technique was cost effective for a long-time care service.

The role of synbiotics as adjunctive agents in the treatment of allergic rhinitis: A randomized controlled trial.

Introduction: Allergic rhinitis (AR) is a prevalent chronic disease affecting a significant portion of the global population. The substantial economic burden associated with treating AR necessitates the exploration of alternative therapies. Probiotics have gained attention due to their availability, minimal adverse effects, and cost-effectiveness. The present study aims to investigate the role of synbiotics as adjunctive agents in the treatment of AR when added to standard treatment. Method: Thirty patients with persistent allergic rhinitis (PAR) were randomly assigned to receive routine diet therapy plus synbiotics or routine diet therapy plus placebo per day for 4 months. The data analysis was conducted using SPSS Version 20. Result: This study revealed a notable difference in immunoglobulin (Ig)E levels between the placebo and synbiotics groups (p = 0.035) following the intervention. Although a statistically significant difference (p = 0.039) was observed in the changes before and after the intervention (synbiotics and placebo) in the SNOT22 questionnaire, this finding was not observed for the MiniRQLQ questionnaire. For the MiniRQLQ questionnaire, the within-group analysis showed significant changes in activity variables (p = 0.023), ocular symptoms (p = 0.036), and practical problems (p = 0.043) exclusively in the synbiotics group. Additionally, changes in nasal symptoms were observed in both synbiotics (p = 0.006) and placebo (p = 0.007) groups. Conclusion: This study suggests that synbiotics supplementation for 4 months can impact IgE levels compared with placebo in individuals with PAR, while also exhibiting positive effects on symptomology.

Comparative studies on the interaction of spermidine with carboxypeptidase A using multispectroscopic and docking methods.

Carboxypeptidase A (CPA) (EC 3.4.17.1) is one of the main members of the M14 family that release one amino acid from the C-terminal region of the polypeptides at each time. The purpose of the present study was to study the effect of spermidine (NH2(CH2)3NH(CH2)4NH2) on the conformation, thermal stability, and activity of native CPA from bovine pancreas, by employing ultraviolet-visible (UV-Vis) spectroscopy, intrinsic fluorescence, thermal stability, circular dichroism (CD), kinetic techniques and molecular docking. It was found that the decrease in the CPA, UV-Vis absorption could be due to the formation of the CPA-spermidine complexes. The results of fluorescence spectroscopic measurements at the temperatures of 308 and 318 K also revealed that spermidine had the capability to quench the intrinsic fluorescence of CPA with the static mode. Further, the thermodynamic parameters, (Gibbs free-energy, enthalpy and entropy changes) showed that the binding process of spermidine to CPA was spontaneous and the main force in stabilizing the complex was the van der Waals and hydrogen interactions, along with the molecular docking results. In addition, CD spectra and fluorescence results revealed that spermidine had a partial effect on the CPA structure, leading to some changes in its secondary structure. The Tm studies of the CPA-spermidine complex also indicated that the Tm values were enhanced with increasing the spermidine concentration. Kinetic studies further showed that by spermidine binding, the Vmax value and activity of the enzyme were increased.

Spermine as a possible endogenous allosteric activator of carboxypeptidase A: multispectroscopic and molecular simulation studies.

Carboxypeptidase A (EC.3.4.17.1) is a zinc-containing proteolytic enzyme that removes the C-terminal amino acid from a peptide chain with the free carboxylate-terminal. In this study, the effect of spermine interaction on the structure and thermal stability of Carboxypeptidase A was investigated by ultraviolet - visible spectroscopy, fluorescence spectroscopy, circular dichroism, Kinetic measurement, molecular docking and simulation studies have also been followed at the pH of 7.5. The transition temperature of Carboxypeptidase A, as a criterion of protein thermal stability, in the presence of spermine was enhanced by increasing the concentration of spermine. The results of fluorescence intensity changes, at two temperatures of 308 and 318 K, also suggested that spermine had a great ability to quench the fluorescence of Carboxypeptidase A through the static quenching procedure. The thermodynamic parameters changes, including standard Gibbs free-energy, entropy and enthalpy, showed that the binding of spermine to Carboxypeptidase A was spontaneous and the hydrogen bonding and van der Waals interactions played a major role in stabilizing the Carboxypeptidase A-spermine complex. The changes in the content of the α-helix and the ß-sheet of the Carboxypeptidase A with binding to spermine were shown by the CD spectra method. Further, kinetic studies revealed that by increasing concentration of spermine, the activity of Carboxypeptidase A was enhanced. Also, the docking study revealed that the hydrogen bonding and van der Waals interactions played a major role in stabilizing the Carboxypeptidase A-spermine complex. As a result, spermine could be considered as an activator and a stabilizer for Carboxypeptidase A.Communicated by Ramaswamy H. Sarma.