"Enhancing polyamine enrichment from wheat germs: A study utilizing response surface methodology and liquid chromatography-mass spectrometry".

Wheat germ is one of the richest natural sources of polyamines, especially spermidine. Cell proliferation property of polyamines has given them inductive effects in the reduction of a variety of chronic diseases and fertility enhancement. Preparing a polyamine-rich extract powder from wheat germ for use in supplements is the aim of the present study. For the first time, the effects of three independent variables of clean-up replicate (A), extraction time (B), and solid-to-liquid ratio (C) on the response of total spermidine content (Y) were investigated using a central composite design optimizing polyamine enrichment. The optimal extraction conditions were 7 h, 3 clean-up replicates, and 1:4 solid to liquid ratio. This is the first production report of spermidine-enriched powder for encapsulation purposes. To obtain an acceptable rheological property, the polyamine-enriched extract was spray dried together with a selected group of excipients, among which glucose was evidenced as the best choice based on encapsulation properties.

Molecular identification of Shiitake (Lentinula edodes), analysis and production of beta-glucan using beech wood sawdust waste.

Lentinula edodes has the ability to grow and produce bioactive compounds on industrial by-products. This study aimed to produce B-glucan of cell wall Shiitake on Beechwood Sawdust (BWS) through a two-step procedure, which included fermentation and B-glucan extraction and purification. Shiitake mushrooms are cultivated by solid-state fermentation (SSF) using the Jamas method to increase the purity of B-glucan. The fermented substrate was first separated and then hydrolyzed by sodium hydroxide (NaOH) (10 M, 1 M), followed by acid hydrolysis extraction. The structure and purity of B-glucan were confirmed by FTIR, NMR, and AFM spectroscopy. The fungus used was molecularly identified by the 18 s rRNA method. Shiitake mushroom was produced by SSF using BWS and high purity ß-glucan was extracted from the produced polysaccharide in the amount of 67.33 mg/g. FTIR, NMR, and AFM analyses proved the production of beta-glucan, and based on molecular identification, it was determined that the mushroom used was Lentinula edodes. The results obtained show that SSF is a valuable technology for the production of biomass and polysaccharides by utilizing the strain of L. edodes. To the best of our knowledge, the yield reported is the highest by the strain of L. edodes using SSF.

Effects of Acute Exposure to Methylglyoxal or/and A Diet Rich in Advanced Glycation End Products on Sperm Parameters in Mice.

BACKGROUND: Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes, obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissue homeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models, considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs. MATERIALS AND METHODS: In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a control group (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8). After five weeks the level of fasting blood sugar (FBS), body weight, food intake, sperm parameters, and functional tests were evaluated. Furthermore, testicular superoxide dismutase (SOD) activity, malondialdehyde, and total antioxidant capacity (TAC) were assessed. RESULTS: After five weeks, AGE, AGE-MGO, and MGO groups showed the highest level of body weight and FBS in comparison to the control group. Mean sperm concentration, sperm malondialdehyde, testicular lipid peroxidation, and TAC did not differ significantly among the study groups. While, AGE, MGO, and AGE-MGO groups showed a significant reduction in sperm motility and progressive motility compared to the control group (P<0.05). The greatest increases in abnormal sperm morphology and intracytoplasmic reactive oxygen species (ROS) were observed in the MGO and AGE-MGO groups than in the control group (P<0.05). Sperm protamine deficiency and residual histone were significantly increased in the three treatment groups compared to the control group (P<0.05). Regarding the DNA damage, the AGE and AGE-MGO groups showed the most severe damage. The lowest amount of testicular superoxide dismutases (SOD, P<0.001) was observed in the AGE-MGO group. CONCLUSION: AGEs and MGO have a negative influence on sperm function and reproductive potential. These effects could be possibly attributed to both increased oxidative stress (OS) and inflammation.

Expanded inherited metabolic diseases screening by tandem mass spectrophotometry: The first report from Iran.

Inherited metabolic diseases (IMD) are a group of rare genetic disorders that can present with a variety of symptoms. Since these disorders are hard to treat once the symptoms occur, neonatal screening may be a logical strategy. Here we evaluate the first results of national expanded IMD screening in Iran. A total of 46 IMDs were screened in this national program. Between April 2018 and March 2022, all infants who underwent national IMD screening at Shahid Beheshti University of Medical Sciences were included in this study. History and Physical examinations of infants, screening results, recall rate, response rate, and prevalence of IMDs were evaluated. A total of 125,819 infants were screened during this period. The recall rate of the test was 0.81%. 124 cases were diagnosed with a definite IMD and the raw overall prevalence of IMDs was estimated to be 1:1015. Aminoacidopathies were the most commonly detected disorders and Hyperphenylalaninemia/PKU was the most prevalent disorder among all groups. Since IMDs vary from region even in a single country, screening for IMDs is crucial in societies with a high rate of consanguineous marriages. More studies are essential for figuring out the most efficient combination of diseases to be screened based on countries' facilities.

Development of a high-performance liquid chromatography using rhodamine B hydrazide as the derivatization reagent for determination of ß propiolactone residues in inactivated COVID-19 vaccines.

ß-propiolactone (BPL) is an alkylating agent used for inactivation of biological samples such as vaccines. Due to its known carcinogenic properties, complete hydrolysis of BPL is essential, and the detection of trace amounts is crucial. In this study a novel High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) method was developed. Rhodamine B hydrazide (RBH) was synthesized and utilized as a derivatizing reagent to react with BPL. The reaction was optimized in a weak acidic solution, resulting in a high yield. The separation of the RBH-derivatized BPL was achieved on a C8 column and detected by a UV detector at a wavelength of 560 nm. The method's validation demonstrated a high linearity (r2 > 0.99) over a concentration range of 0.5-50 µg/mL, with detection and quantification limits of 0.17 µg/mL and 0.5 µg/mL, respectively. The average recovery of samples was 85.20 % with a relative standard deviation (RSD) of 1.75 %. This method was successfully applied for BPL residue analysis in inactivated COVID-19 vaccines. This novel derivatization method offers a promising solution for monitoring BPL residues in the vaccine production process for quality control purposes and compliance with regulatory standards.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study.

BACKGROUND: The wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated. METHODS: In the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed. RESULTS: The HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure. CONCLUSIONS: This study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Effect of Advanced Glycation end Products (AGEs) on Sperm Parameters and Function in C57Bl/6 Mice.

This study investigated the deleterious impact of advanced glycation end products (AGEs), commonly present in metabolic disorders like diabetes, obesity, and infertility-related conditions, on sperm structure and function using a mouse model where AGE generation was heightened through dietary intervention. Five-week-old C57BL/6 mice were divided into two groups, one on a regular diet (control) and the other on an AGE-rich diet. After 13 weeks, various parameters were examined, including fasting blood glucose, body weight, food consumption, sperm parameters and function, testicular superoxide dismutase levels, malondialdehyde content, total antioxidant capacity, Johnson score, AGE receptor (RAGE) content, and carboxymethyl lysine (CML) content. The results showed that mice in the AGE group exhibited increased body weight and elevated fasting blood glucose levels. Furthermore, the AGE group displayed adverse effects on sperm, including reduced sperm counts, motility, increased morphological abnormalities, residual histone, protamine deficiency, sperm DNA fragmentation, reduced testicular antioxidant capacity, and higher levels of RAGE and CML proteins. These findings underscore the negative impact of AGEs on male reproductive health, particularly within the context of metabolic disorders, emphasizing the crucial role of the AGE/RAGE axis in male infertility, especially in the context of Western dietary patterns.

RGD-decorated nanoliposomes for combined delivery of arsenic trioxide and curcumin to prostate cancer cells.

Nanotechnology and drug co-delivery offer a novel avenue in drug delivery research liposome-based co-delivery of anticancer drugs targeting the apoptosis pathway as a promising new approach to treat cancer. In this study, a co-delivery system of liposomes (arsenic trioxide/curcumin) modified with RGD peptide was designed to aim for enhancing the treatment of prostate cancer cells (PC3 cell line). Liposomal co-loaded curcumin and arsenic trioxide modified by RGD peptide (NLPs-RGD-Cur-ATO) were prepared by thin-layer lipid hydration techniques for the treatment of prostate cancer. The stability of the NLPs-RGD-Cur-ATO was evaluated by particle size analysis through dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). The percentage of cytotoxicity and apoptotic effect in PC3 cells treated with NLPs-RGD-Cur-ATO were detected by MTT and Annexin V-FITC (fluorescein isothiocyanate)/PI affinity assay, respectively. The particle size of NLPs-RGD-Cur-ATO was approximately 100 nm, with an encapsulation efficiency of about 99.52% and 70.61%, for ATO and Cur, respectively. Besides, NLPs-RGD-Cur-ATO displayed an enhanced anti-proliferative effect, increased the percentage of apoptotic cells 98 ± 1.85% (p < 0.0001), and significantly reduced EGFR gene expression level (p < 0.001) in the cell line tested. These results indicated that our NLPs-RGD-Cur-ATO co-delivery system was a promising strategy for prostate cancer therapy.

Design, Synthesis, and Investigation of Cytotoxic Effects of 5-Hydroxyindole-3-Carboxylic Acid and Ester Derivatives as Potential Anti-breast Cancer Agents.

Breast cancer is a deadly disease with a high prevalence rate among females. Despite several treatments, scientists are still engaged in finding less invasive treatments for this disease. The cellular proliferation rate and cell viability survey are critical to assess the drug's effect on both normal and malignant cell populations. Indole derivatives are promising candidates for their cytotoxic effect causing on breast cancer cells; however, they are less toxic on normal cells. This study synthesized 23 novel 5-hydroxyindole-3-carboxylic acids and related esters featuring various linear, cyclic, and primary aromatic amines. The MTT assay indicated the cytotoxicity of all acid and ester derivatives against the MCF-7 cells with no significant cytotoxicity on normal human dermal fibroblasts cells. Compound 5d, an ester derivative possessing a 4-methoxy group, was the most potent compound, with a half-maximal effective concentration of 4.7 µM. Compounds 5a, 5d, and 5l bearing ester group in their structure demonstrated cytotoxicity values < 10 µM against the MCF-7 cell line and were safe for advanced screening.

Comparison of the Polyamine Content of Five Spring Flowers with Wheat Germ as a Rich Anti-aging Polyamine Source for Preparation of Nutraceutical Products.

Polyamines prolong longevity due to their role in cell proliferation and are regarded as an essential group of anti-aging substances that reduce the risk of cardiovascular, neurological, and chronic inflammatory illnesses, as well as cancer. Because of its importance in growth and tissue regeneration, discovering polyamine-rich sources has gotten a lot of interest. Given the role of polyamines in controlling plant growth and physiological changes in the spring after cold winter stress, high polyamine concentrations in quickly growing plant tissues such as flowers, blossoms, and germs are possible. Based on this premise, five different spring flowers were selected and isolated from relevant plants, dried, and then quantified for the first time using an accurate, simple, and repeatable quantification method, liquid chromatography-tandem mass spectrometry. According to the amount of spermidine found in the samples investigated in this study, dried flower powders of Wisteria sinensis (244.18 µg/g), Lonicera caprifolium (217.28 µg/g), and Jasminum officinale (200.33 µg/g) appear to be a good source of spermidine. With additional research, W. sinensis dried flower powder is a good source of polyamines, whereas L. caprifolium and J. officinale dried flower powders are recommended as a rich source of spermidine for the preparation of natural supplements for people over the age of 30 to improve cell proliferation and anti-aging.

Synthesis and functionalization of mucoadhesive mesoporous silica particles containing diphenhydramine for treatment of aphthous ulcers.

Introduction: Medications used to treat oral ulcers include corticosteroids, anesthetics, and antihistamines. These can be used as gels, mouthwashes, pastes, ointments, etc. Diphenhydramine hydrochloride (DPH) has local anesthetic properties that can help treat the aphthae. One of the drawbacks of the delivery to the transmucosal is the quick turnaround time of the gel, a mucous form that is located on the epithelial film surface. Methods: Therefore, it seems that the preparation of a carrier that has the characteristics of adhesive mucus can increase the duration of drug retention on the mucous surface. To solve this problem, mesoporous silica nanoparticles (MSNPs) were synthesized and functionalized with amino and thiol groups and suggested as a system of drug delivery. The properties and structure of MSNPs were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption isotherms (BET). Results: Our outcomes indicated that the average sizes of bare MSNPs (MSN), amino modified MSNPs (MSN-NH2), and thiol modified MSNPs (MSN-SH) were obtained to be 611, 655, and 655 nm respectively and the average pore size of MSN, MSN-NH2, and MSN-SH were about 2.42 nm, 2.42 nm, and 2.44 nm, respectively, according to the BJH (Barrett-Joyner-Halenda) pore size distribution. The release kinetics and release of DPH from mesoporous silica carriers were evaluated. Conclusion: Eventually, the mucoadhesive study and DPH-loaded particles were investigated. Also, the MSN-SH exhibited a high mucoadhesive capacity for buccal mucosa compared with MSN-NH2 and MSN.

Wheat germ, a byproduct of the wheat milling industry, as a beneficial source of anti-aging polyamines: A quantitative comparison of various forms.

Polyamines have received a lot of attention since the 1990s because of their anti-aging, anti-chronic disease, and proliferative effects. Wheat germ was reported as one of the natural sources of high polyamine, especially spermidine. The current study used three types of wheat germ: group A was industrially separated germ from whole grain, group B was the commercially available germinated wheat germ, and group C was manually separated wheat germ from germinated grain. The polyamine content of putrescine, spermidine, and spermine has been determined using a simplified isocratic LC-MS/MS method. An optimized extraction procedure was performed on all seven samples for obtaining a polyamine-enriched extract. The three dominant carbomylated polyamines were identified by analyzing the extracted samples in order to determine their relative abundance. Wheat germ powders contain the highest amount of polyamines (220-337 µg/g) of which spermidine is one of the most important. Germinated wheat grains, on the other hand, contain the least amount of this polyamine. The commercially available separated wheat germs are suggested as a good nutrition source of these polyamines.

In-vitro cytotoxic potential of aerial parts of Leutea avicennae Mozaff. in different Human cancer cell lines.

Medicinal plants such as Leutea avicennae Mozaff. (Apiaceae) have been shown some biological potential for preventing and treating diseases. Fractions and isolated compounds were tested on colon carcinoma (HT-29), cervical carcinoma (HeLa), breast carcinoma (MCF-7), and mouse embryonic fibroblast (NIH/3T3) cell lines. The BSLT method was used for the assessment of the general toxicity of the petroleum ether (PET), chloroform (CHCl3), ethyl acetate (EtOAc), and methanol (MeOH) fractions obtained from the aerial parts of L. avicennae. 1H-NMR and 13 C-NMR spectroscopy were used for structure elucidation. Five compounds, including two coumarins, osthole and umbelliferone, a diterpene phytol, ß-sitosterol, and lauric acid, were isolated for the first time from L. avicennae. Osthole showed potent cytotoxic activity against MCF-7 and HT-29 cell lines with IC50 values of 4.23 ± 0.26 and 12.11 ± 0.13 µg/mL, respectively. Phytol demonstrated potent cytotoxic activity towards MCF-7 and HeLa cell lines with IC50 values of 6.80 ± 0.08 and 12.27 ± 0.18 µg/mL, respectively.

Synthesis and Radiolabeling of Glu-Urea-Lys with 99mTc-Tricarbonyl-Imidazole-Bathophenanthroline Disulfonate Chelation System and Biological Evaluation as Prostate-Specific Membrane Antigen Inhibitor.

Background: The Glu-Urea-Lys (EUK) pharmacophore as prostate-specific membrane antigen (PSMA)-targeted ligand was synthesized, radiolabeled with 99mTc-tricarbonyl-imidazole-BPS chelation system, and biological activities were evaluated. The strategy [2 + 1] ligand is applied for tricarbonyl labeling. (5-imidazole-1-yl)pentanoic acid as a monodentate ligand and bathophenanthroline disulfonate (BPS) as a bidentate ligand formed a chelate system with 99mTc-tricarbonyl. EUK-pentanoic acid-imidazole and EUK were evaluated for PSMA active site using AutoDock 4 software. Materials and Methods: EUK-pentanoic acid-imidazole was synthesized in two steps. BPS was radiolabeled with 99mTc-tricarbonyl at 100°C for 30 min. The purified 99mTc(CO)3(H2O)BPS was used to radiolabel EUK-pentanoic acid-imidazole at 100°C, 30 min. Radiochemical purity, Log P, and stability studies were carried out within 24 h. Affinity of 99mTc(CO)3BPS-imidazole-EUK was performed in the saturation binding studies using LNCaP cells at 37°C for 1 h with a range of 0.001-1000 nM radiolabeled compound range. Internalization studies were performed in LNCaP cells with 1000 nM radiolabeled compound incubated for (0-2) h at 37°C. Biodistribution was studied in normal male Balb/c mice. The artificial intelligence predicts the uptake of radiolabeled compound in tumor. Results: The structures of synthesized compounds were confirmed by mass spectroscopy. Radiochemical purity, Log P, and protein binding were ≥95%, -0.2%, and 23%, respectively. The radiolabeled compound was stable in saline and human plasma within 24 h with radiochemical purity ≥90%. There was no release of 99mTc within 4 h in competition with histidine. The affinity was 82 ± 26.38 nM, and the activity increased inside the cells over time. Biodistribution studies showed radioactivity accumulation in kidneys less than 99mTc-HYNIC-PSMA. There was a moderate accumulation of radioactivity in the liver and intestine. Conclusion: Based on the results, 99mTc(CO)3BPS-imidazole-EUK can potentially be used as an imaging agent for studies at prostate bed and distal areas. The chelate system can be potentially labeled with rhenium for imaging studies (fluorescent or scintigraphy) and therapy.

Arsenic trioxide and Erlotinib loaded in RGD-modified nanoliposomes for targeted combination delivery to PC3 and PANC-1 cell lines.

During the past few years, advances in drag delivery have provided many opportunities in the treatment of various diseases and cancer. Arsenic trioxide (ATO) and Erlotinib (Erlo) are two drugs, approved by the United States Food and Drug Administration to treat cancer, but their use is limited in terms of the toxicity of ATO and the low solubility of Erlo. This study aimed to prepare arginine-glycine-aspartic acid (RGD)-decorated nanoliposomes (NLPs) containing Erlo and ATO (NLPs-ATO-Erlo-RGD) to increase the solubility and reduce the toxicity of Erlo and ATO for cancer treatment. The results of transmission electron microscopy and dynamic light scattering showed that NLPs were synthesized uniformly, with spherical shape morphology and particle sizes between 140 and 160 nm. High-performance liquid chromatography and ICP-MS results showed that about 90% of the drug was loaded in the NLPs. In comparison with NLPs-ATO-Erlo, NLPs-ATO-Erlo-RGD demonstrated considerable toxicity against the αvß3 overexpressing PC3 cell line in the MTT experiment. It had no effect on the PANC-1 cell line. In addition, apoptosis assays using Annexin V/PI demonstrated that NLPs-ATO-Erlo-RGD generated the highest apoptotic rates in PC3 cells when compared with NLPs-ATO-Erlo and the combination of free ATO and Erlo. Furthermore, treatment with NLPs-ATO-Erlo-RGD in (p < 0.05) PC3 cell line significantly reduced EGFR level. It is concluded NLPs-ATO-Erlo-RGD as a novel drug delivery system may be a promising platform for the treatment of cancer.

Synthesis and Biological Evaluation of Novel Thiadiazole Derivatives as Antiplatelet Agents.

A novel series of thiadiazole compounds was synthesized through the reaction of thiosemicarbazone intermediates with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The antiplatelet activity of the synthesized compounds was evaluated using an aggregation test with adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet aggregation inducers. Among the synthesized analogs, compound 3b exhibited the most potent inhibition of platelet aggregation induced by ADP (half maximal inhibitory concentration [IC50] = 39 ± 11 µM). Molecular docking studies of 3b revealed hydrogen bonds between the nitrogen of the thiadiazole ring and Lys280. The tolyl ring exhibited hydrophobic interactions with Tyr105, similar to the antagonist co-crystallized with P2Y12 (PDB ID: 4NTJ). These compounds have the potential to serve as lead molecules for designing P2Y12 inhibitors.

Health risk assessment of process-related contaminants in bread.

Bread constitutes a popular and even daily component of human diet world-wide, Iran included. However, there are concerns that various processing methods such as frying and baking could result in the production of potentially a source of known carcinogens such as acrylamide (AA) and benzo(a)pyrene (BaP). The present study tried to perform a risk assessment on seven categories of bread consumers, based on age and gender, calculating the Target Hazard Quotient (THQ), Incremental Lifetime Cancer Risk (ILCR), and Margin of Exposure (MOE) related to the dietary intake of AA and BaP. AA and BaP were analyzed in 87 bread samples using LC-MS/MS and GC-MS/MS, respectively. The results indicated that more than 94% (mean concentration: 25.9 ng/g) and about 20% (mean concentration: 1.98 ng/g) of the samples were contaminated with AA and BaP, respectively. The THQ of AA intake through bread consumption for seven categories was in the following decreasing order: semi-industrial Sangak bread of Shiraz (SIS-Sh)> traditional Sangak bread of Shiraz (TS-Sh)> traditional Sangak bread of Tehran (TS-Th)> commercial bread of Tehran (C-Th). The non-neoplastic and neoplastic MOE for AA (˂10,000) indicates a high risk of exposure for all people in Tehran and Shiraz through the consumption of all tested bread. Due to the consumption of TS, SIS, and C bread, the BaP MOE for all people in Tehran and Shiraz was >10 000, which shows a low health risk for consumers. Our findings showed that ILCR for AA in seven classes of people who had TS-Sh and TS-Th was remarkably higher than ILCR for all categories that consumed the C-Th. BaP ILCR for the people who ingested TS-Th, TS-Sh, SIS-Th, and SIS-Sh was about 2-4 times higher than people who had C-Th. This study indicates that bread is the main source of AA and BaP intake in Iran, which might elevate the cancer risk.

Design, synthesis, spectroscopic characterization, in vitro tyrosinase inhibition, antioxidant evaluation, in silico and kinetic studies of substituted indole-carbohydrazides.

In the current study, twenty-five indole-carbohydrazide derivatives linked to different aryl substitutions were rationally designed and synthesized. The structures of all derivatives were confirmed using different spectroscopic techniques including 1H NMR, 13C NMR, Mass spectrometry, and elemental analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC50 values in the range of 0.070 to > 100 µM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC50 = 0.070 µM), 8f (R = 4-OH, IC50 = 0.072 µM), and 19e (IC50 = 0.19 µM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited that compounds 4f, 8f, and 19e are mixed-type inhibitors. Furthermore, toxicity and cell-based anti-melanogenesis assessments were performed on the most potent derivatives and it was shown that 4f, 8f, and 19e had no toxicity at 8 µM and reduced the percent of melanin content to 68.43, 72.61, 73.47 at 8 µM, respectively. In silico analyses of absorption, distribution, metabolism, and excretion (ADME) profile of synthesized compounds showed that these molecules followed drug-likeness rules and acceptable predictive ADMET features. Results of the docking study were almost in line with biological results with ChemPLP values of 53.56 to 79.33. Also, the docking study showed the critical interactions of potent inhibitors with the active site of the enzyme which affects the potency of the synthesized hybrids. Based on molecular dynamic simulations, compound 4f exhibited pronounced interaction with the critical residues of the tyrosinase active site so that the indole ring participated in H-bond interaction with Gly281 and 4-hydroxy benzylidene recorded another H-bond interaction with Asp289 plus hydrophobic interactions with Phe292. Hydrazide linker also exhibited three H-bond interactions with His263 and Gly281.

A Neglected Challenge in the Analysis of Active Pharmaceutical Substances with Aldehyde Functional Group in Aqueous Matrices.

Aldehydes are compounds that are widely used and popular in organic synthesis due to their high reactivity. This advantage is a disadvantage in medicinal chemistry. Due to the ability of aldehydes to participate in nucleophilic reactions (especially in aqueous biological media) and access to nucleophiles such as amino acids and nucleic acids, drugs with aldehyde functional groups are always used with caution and carefully quantified in biological fluids. Our experience in working on biologically active aldehydes indicates the transformation of these groups of compounds in aqueous or alcoholic solution and thus the failure of analytical methods for their accurate monitoring in such media. Both mass spectrometry and Proton nuclear magnetic resonance spectroscopic findings indicate the reaction of spiramycin with water molecules in an aqueous solution, resulting in the conversion of spiramycin to a new molecule with 18 mass unit difference and thus, the residue amount which is measured and reported based on a mass spectrometries method does not show the correct amount of spiramycin in these samples.

Propolis: An update on its chemistry and pharmacological applications.

Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims.