An activity-guided isolation study on the EtOH extract prepared from the bulbs of Prospero autumnale yielded four new phenolic compounds, including a new stilbenoid (1), a new homoisoflavonoid derivative (8), a new homoisoflavonoid dimer (9), and an unprecedented homoisoflavone-stilbene heterodimer (10), together with six known (2-7) analogs. Their chemical structures were elucidated by spectroscopic analysis and theoretical NMR and ECD calculations. Compounds 9 and 10 are unique in their scaffolds. The in vitro cytotoxic activity of purified compounds was evaluated against eight tumor cell lines (HCT116, LoVo, DU145, PC3, HEP3B, HEPG2, MCF7, and MDA-MB-231) and one nontumor cell line (L929) by the MTS assay. Compounds 1, 2, 4, and 10 exhibited inhibition with IC50 values ranging from 8.2 to 37.6 μM. Cytotoxic cell death mechanisms were further investigated, indicating variability in apoptosis, necrosis, or cell cycle arrest.

• MeSH
• Apoptosis drug effects   MeSH
• Antineoplastic Agents, Phytogenic * pharmacology   chemistry   MeSH
• Isoflavones pharmacology   chemistry   isolation & purification   MeSH
• Plant Roots chemistry   MeSH
• Humans MeSH
• Molecular Structure MeSH
• Cell Line, Tumor MeSH
• Drug Screening Assays, Antitumor MeSH
• Stilbenes * pharmacology   chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Infections caused by antibiotic-drug-resistant microorganisms are a major global health concern, and they result in millions of deaths every year. Methicillin-resistant Staphylococcus aureus (MRSA) is one of such drug-resistant microbial strains, and new and effective antimicrobial agents are desperately needed to combat infections caused by MRSA. In the search for effective anti-MRSA agents, the leaves of Citrus grandis (Rutaceae), also known as C. maxima, were investigated. Implementing a bioassay-guided approach, sinensetin (2), which is a polymethoxyflavone, was isolated as a promising anti-MRSA compound, showing inhibitory activity against three (EMRSA-15, MRSA340802 and MRSA274819; MIC values 128-256 μg/mL) of five MRSA strains tested in the present study. Five other flavonoids 6,7,8,3',4'-pentamethoxyflavone (1), cirsilineol (3), nobiletin (4), 5-desmethylsinensetin (5) and hesperidin (6) were isolated from the dichloromethane extract of this plant. They displayed varied levels of antimicrobial activities against the tested microbial strains, Micrococcus luteus NCTC 7508, Escherichia coli NCTC 12241 and Pseudomonas aeruginosa NCTC 12903, and a fungal strain, Candida albicans ATCC 90028, but not against Staphylococcus aureus NCTC 12981. Sinensetin (2) also exhibited strong antimicrobial activity against the fungal strain C. albicans with an MIC value of 0.0625 mg/mL. The chemical structures of all isolated compounds were unequivocally elucidated by spectroscopic means (1D and 2D NMR and HR-ESIMS). The present study revealed sinensetin (2) as a potential structural template for generating structural analogues and developing anti-MRSA agents and provided scientific evidence supporting the traditional uses of C. grandis in the treatment of microbial infections.

• MeSH
• Anti-Bacterial Agents pharmacology   isolation & purification   chemistry   MeSH
• Candida albicans drug effects   MeSH
• Citrus * chemistry   MeSH
• Flavonoids * pharmacology   isolation & purification   MeSH
• Phytochemicals pharmacology   isolation & purification   MeSH
• Plant Leaves * chemistry   MeSH
• Methicillin-Resistant Staphylococcus aureus * drug effects   MeSH
• Microbial Sensitivity Tests * MeSH
• Molecular Structure MeSH
• Plant Extracts pharmacology   chemistry   MeSH
• Publication type
• Journal Article MeSH

STUDY QUESTION: Can oocyte functionality be assessed by observing changes in their intracytoplasmic lipid droplets (LDs) profiles? SUMMARY ANSWER: Lipid profile changes can reliably be detected in human oocytes; lipid changes are linked with maternal age and impaired developmental competence in a mouse model. WHAT IS KNOWN ALREADY: In all cellular components, lipid damage is the earliest manifestation of oxidative stress (OS), which leads to a cascade of negative consequences for organelles and DNA. Lipid damage is marked by the accumulation of LDs. We hypothesized that impaired oocyte functionality resulting from aging and associated OS could be assessed by changes in LDs profile, hereafter called lipid fingerprint (LF). STUDY DESIGN, SIZE, DURATION: To investigate if it is possible to detect differences in oocyte LF, we subjected human GV-stage oocytes to spectroscopic examinations. For this, a total of 48 oocytes derived from 26 young healthy women (under 33 years of age) with no history of infertility, enrolled in an oocyte donation program, were analyzed. Furthermore, 30 GV human oocytes from 12 women were analyzed by transmission electron microscopy (TEM). To evaluate the effect of oocytes' lipid profile changes on embryo development, a total of 52 C57BL/6 wild-type mice and 125 Gnpat+/- mice were also used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were assessed by label-free cell imaging via coherent anti-Stokes Raman spectroscopy (CARS). Further confirmation of LF changes was conducted using spontaneous Raman followed by Fourier transform infrared (FTIR) spectroscopies and TEM. Additionally, to evaluate whether LF changes are associated with developmental competence, mouse oocytes and blastocysts were evaluated using TEM and the lipid dyes BODIPY and Nile Red. Mouse embryonic exosomes were evaluated using flow cytometry, FTIR and FT-Raman spectroscopies. MAIN RESULTS AND THE ROLE OF CHANCE: Here we demonstrated progressive changes in the LF of oocytes associated with the woman's age consisting of increased LDs size, area, and number. LF variations in oocytes were detectable also within individual donors. This finding makes LF assessment a promising tool to grade oocytes of the same patient, based on their quality. We next demonstrated age-associated changes in oocytes reflected by lipid peroxidation and composition changes; the accumulation of carotenoids; and alterations of structural properties of lipid bilayers. Finally, using a mouse model, we showed that LF changes in oocytes are negatively associated with the secretion of embryonic exosomes prior to implantation. Deficient exosome secretion disrupts communication between the embryo and the uterus and thus may explain recurrent implantation failures in advanced-age patients. LIMITATIONS, REASONS FOR CAUTION: Due to differences in lipid content between different species' oocytes, the developmental impact of lipid oxidation and consequent LF changes may differ across mammalian oocytes. WIDER IMPLICATIONS OF THE FINDINGS: Our findings open the possibility to develop an innovative tool for oocyte assessment and highlight likely functional connections between oocyte LDs and embryonic exosome secretion. By recognizing the role of oocyte LF in shaping the embryo's ability to implant, our original work points to future directions of research relevant to developmental biology and reproductive medicine. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by National Science Centre of Poland, Grants: 2021/41/B/NZ3/03507 and 2019/35/B/NZ4/03547 (to G.E.P.); 2022/44/C/NZ4/00076 (to M.F.H.) and 2019/35/N/NZ3/03213 (to Ł.G.). M.F.H. is a National Agency for Academic Exchange (NAWA) fellow (GA ULM/2019/1/00097/U/00001). K.F. is a Diamond Grant fellow (Ministry of Education and Science GA 0175/DIA/2019/28). The open-access publication of this article was funded by the Priority Research Area BioS under the program "Excellence Initiative - Research University" at the Jagiellonian University in Krakow. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

• MeSH
• Adult MeSH
• Embryonic Development physiology   MeSH
• Humans MeSH
• Lipid Droplets metabolism   MeSH
• Lipid Metabolism MeSH
• Mice, Inbred C57BL * MeSH
• Mice MeSH
• Oocytes * metabolism   MeSH
• Oxidative Stress MeSH
• Spectrum Analysis, Raman MeSH
• Aging metabolism   MeSH
• Microscopy, Electron, Transmission MeSH
• Maternal Age MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

V léčbě mozkových metastáz (mMTS) je kladen čím dál větší důraz na kvalitu života. Stereotaktická radioterapie a radiochirurgie (SRT/SRS) mMTS je moderní technika, která kromě excelentní lokální kontroly nabízí méně nežádoucích účinků včetně zhoršení neurokognice. Náš unikátní výzkum využívající MR spektroskopii prokázal negativní vliv klasické celomozkové radioterapie na hipokampální koncentraci neuronálního markeru N-acetylaspartátu a současné snížení verbální paměti. Úbytek hipokampálních neuronálních kmenových buněk je nejčastěji uváděn jako patofyziologický podklad poradiační poruchy neurokognice. K plnému pochopení problematiky je nutné navázat studiem hipokampálních změn a poruch kognitivních funkcí po užití speciálních technik SRT/SRS s redukcí radiační zátěže hipokampů. V předkládaném projektu plánujeme měřit spektroskopický profil hippokampu po SRT/SRS mozkových metastáz. Projekt pomůže objasnit patofyziologii radiačního poškození kognice a snížení kvality života a přispěje tím k vývoji nových ozařovacích technik pro personalizovaný přístup k onkologickým pacientům.; Quality of life (QoL) is currently emphasized during the treatment of bran metastases (BM). Stereotactic radiotherapy and radiosurgery (SRT/SRS) is an advanced technique that – apart from excellent local control – also induces less adverse effects including cognitive impairment. Our unique research using MR spectroscopic imaging proved bad impact of conventional whole brain irradiation on hippocampal N-acetylaspartate concentrations and parallel decline in verbal memory. Decrease in hippocampal stem-cells is often asserted to be a pathophysiological basis for postradiation cognitive impairment. To fully understand the issue, a follow-up study is necessary focusing on hippocampal changes and neurocognitive impairment after SRT/SRS with reduced hippocampal radiation dose. In the present project, we are going to measure the spectroscopy profile of hippocampus after SRT/SRS of BM. We aim to add to clarify the pathophysiology of radiation-induced cognitive decline and QoL impairments, thus contributing to the development of new radiation techniques for more personal approach to patients.

• Keywords
• MR spektroskopie, MR spectroscopy, radioterapie, mozkové metastázy, hippokampus, neurokognice, radiotherapy, brain metastases, hippocampus, neurocognition,

• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.

• MeSH
• Early Detection of Cancer * methods   MeSH
• Adult MeSH
• Carcinoma, Hepatocellular * blood   diagnosis   diagnostic imaging   MeSH
• Body Mass Index MeSH
• Liver Cirrhosis blood   complications   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor blood   MeSH
• Liver Neoplasms * blood   diagnosis   diagnostic imaging   MeSH
• Obesity * complications   blood   MeSH
• Predictive Value of Tests MeSH
• Spectrum Analysis, Raman MeSH
• ROC Curve MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right-left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils.

• MeSH
• Phantoms, Imaging * MeSH
• Muscle, Skeletal * diagnostic imaging   chemistry   MeSH
• Lactic Acid chemistry   metabolism   MeSH
• Humans MeSH
• Magnetic Resonance Spectroscopy methods   MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Signal-To-Noise Ratio MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

In this study, we delve into the electronic structure, spectroscopic, and optical properties of five benzo derivatives of pyridine, namely, 5-(4-chlorophenyl)-2-fluoropyridine (1), 2-fluoro-5-(4-fluorophenyl)pyridine (2), 4-(2-fluoropyridin-5-yl)phenol (3), 5-(2,3-dichlorophenyl)-2-fluoropyridine (4), and 5-(5-bromo-2-methoxyphenyl)-2-fluoropyridine (5). Utilizing quantum chemical density functional theory calculations at the B3LYP and Perdew-Burke-Ernzerhof levels of theory combined with the 6-311G(d,p) and 6-311++G(d,p) basis sets, we investigated the electronic and optical characteristics of these compounds. Band structure calculations were conducted for their crystalline structures, revealing a direct band gap varying from 3.018 to 3.558 eV, with the valence band maximum and conduction band minimum located at the G point in the Brillouin zone. The optical properties were analyzed, including the dielectric functions, reflectivity, and refractive index. Notably, reflectivity was found to be minimal in the photon energy range of 0.0-3.0 eV, and the static refractive index, n(0), ranged from 1.55 to 1.70. The research also involved assessing the reactivity of the compounds through calculation of the frontier orbital energy gaps (ΔE), indicating a significant charge transfer and high reactivity. Additionally, we performed frequency analysis to unveil the Fourier-transform infrared spectra of compounds 1-5 at room temperature. Molecular electrostatic potential surfaces of the optimized structures were employed to map the electrophilic and nucleophilic regions of the compounds. This investigation provides a comprehensive understanding of the electronic and optical properties of these pyridine derivatives, shedding light on their potential applications in optoelectronics.

• Publication type
• Journal Article MeSH

PURPOSE: Water removal is one of the computational bottlenecks in the processing of high-resolution MRSI data. The purpose of this work is to propose an approach to reduce the computing time required for water removal in large MRS data. METHODS: In this work, we describe a singular value decomposition-based approach that uses the partial position-time separability and the time-domain linear predictability of MRSI data to reduce the computational time required for water removal. Our approach arranges MRS signals in a Casorati matrix form, applies low-rank approximations utilizing singular value decomposition, removes residual water from the most prominent left-singular vectors, and finally reconstructs the water-free matrix using the processed left-singular vectors. RESULTS: We have demonstrated the effectiveness of our proposed algorithm for water removal using both simulated and in vivo data. The proposed algorithm encompasses a pip-installable tool ( https://pypi.org/project/CSVD/), available on GitHub ( https://github.com/amirshamaei/CSVD), empowering researchers to use it in future studies. Additionally, to further promote transparency and reproducibility, we provide comprehensive code for result replication. CONCLUSIONS: The findings of this study suggest that the proposed method is a promising alternative to existing water removal methods due to its low processing time and good performance in removing water signals.

• MeSH
• Algorithms MeSH
• Magnetic Resonance Spectroscopy MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Reproducibility of Results MeSH
• Water * chemistry   MeSH
• Publication type
• Journal Article MeSH

Freezing and lyophilization have been utilized for decades to stabilize pharmaceutical and food products. Freezing a solution that contains dissolved salt and/or organic matter produces pure primary ice crystal grains separated by freeze-concentrated solutions (FCS). The microscopic size of the primary ice crystals depends on the cooling conditions and the concentration of the solutes. It is generally accepted that primary ice crystals size influences the rate of sublimation and also can impact physico-chemical behaviour of the species in the FCS. This article, however, presents a case where the secondary ice formed inside the FCS plays a critical role. We microscoped the structures of ice-cast FCS with an environmental scanning electron microscope and applied the aggregation-sensitive spectroscopic probe methylene blue to determine how the microstructure affects the molecular arrangement. We show that slow cooling at -50 °C produces large salt crystals with a small specific surface, resulting in a high degree of molecular aggregation within the FCS. In contrast, fast liquid nitrogen cooling yields an ultrafine structure of salt crystals having a large specific surface area and, therefore, inducing smaller aggregation. The study highlights a critical role of secondary ice in solute aggregation and introduces methylene blue as a molecular probe to investigate freezing behaviour of aqueous systems with crystalline solute.

• MeSH
• Ice * MeSH
• Freeze Drying MeSH
• Methylene Blue * MeSH
• Solutions MeSH
• Water chemistry   MeSH
• Freezing MeSH
• Publication type
• Journal Article MeSH

Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis.

• MeSH
• Carcinoma, Hepatocellular * MeSH
• Liver Cirrhosis diagnosis   MeSH
• Humans MeSH
• Liver Neoplasms * diagnosis   MeSH
• Proteomics methods   MeSH
• Spectrum Analysis MeSH
• Liquid Biopsy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH