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Nisha Rani Agarwal,1,* Masoumeh Dowlatshahi Pour,2,* Maria Siekkeri Vandikas,3 Noora Neittaanmäki,4 Amra Osmancevic,3 Per Malmberg21Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 2Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden; 3Department of Dermatology, Sahlgrenska University Hospital at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Clinical Pathology, Institutes of Biomedicine and Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden*These authors contributed equally to this workBackground: Psoriasis is a systemic inflammatory disease characterized by epidermal proliferation in the skin. Altered lipid metabolism is considered to be a central factor in the psoriatic etiopathogenesis. Thus, it is necessary to visualize chemical specificity of the samples for better medical diagnosis and treatment. Here, we investigate its role in the development of psoriatic lesions, before and after ultraviolet phototherapy, in a case study.Methods: The distribution and morphology of different lipids and fibrous proteins in psoriatic (lesional) tissues were visualized by two complementary label-free imaging techniques: 1) non-linear microscopy (NLM), providing images of lipids/proteins throughout the skin layers at submicrometer resolution; and 2) mass spectrometry imaging (MSI), offering high chemical specificity and hence the detection of different lipid species in the epidermal and dermal regions. A conventional method of histological evaluation was performed on the tissues, with no direct comparison with NLM and MSI.Results: Psoriatic tissues had a higher lipid content, mainly in cholesterol, in both the epidermal and dermal regions, compared to healthy tissues. Moreover, the collagen and elastin fibers in the psoriatic tissues had a tendency to assemble as larger bundles, while healthy tissues showed smaller fibers more homogeneously spread. Although phototherapy significantly reduced the cholesterol content, it also increased the amounts of collagen in both lesional and non-lesional tissues.Conclusion: This study introduces NLM and MSI as two complementary techniques which are chemical specific and can be used to assess and visualize the distribution of lipids, collagen, and elastin in a non-invasive and label-free manner.Keywords: psoriasis skin tissue, non-linear microscopy, lipids, collagen, time-of-flight secondary ion mass spectrometry (ToF-SIMS)

Pregnancy is associated with numerous metabolic adaptations to meet the demands of the growing foetus. These adaptations could be perturbed during pregnancy due to preeclampsia (PE) and gestational diabetes (GDM). As these two obstetric aliments show some overlapping pathophysiology and similar biochemical dysregulation, the present study was undertaken to compare urine metabolome of PE and GDM with normal pregnancy (NT) in all trimesters of gestation using nuclear magnetic resonance spectroscopy-based metabolomics analysis to ascertain and compare metabolome in the study groups. We observed overlapping metabolic perturbations in PE and GDM. Though a study with a small sample size, this is the first report which confirms significantly differential metabolites in urine of both PE and GDM. Dimethylglycine and oxoglutaric acid were decreased while benzoic acid was increased in both the cases in all trimesters. Alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate and butanoate metabolism were the most perturbed pathways in both PE and GDM across pregnancy. These pathways have an association with energy metabolism, glucose homeostasis, insulin sensitivity and oxidative stress which play an important role in the development and progression of PE and GDM. In conclusion, our study showed that urine metabolome could reflect metabolic associations between PE and GDM and also in the identification of biomolecules that could be used as potential biomarker(s) for early detection of the metabolic diseases in pregnancy., Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01103-2., Competing Interests: Conflict of interestThe authors report there are no competing interests to declare., (© The Author(s), under exclusive licence to Association of Clinical Biochemists of India 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Plant-derived flavonoids have been the focus of research for many years mainly in the last decade owing to their therapeutic properties. So far, about 4000 flavonoids have been identified from plants and diosmin (a flavone glycoside) is one of them. Online databases, previous studies, and reviews have been used to gather information on anti-oxidant, immunomodulatory, anti-cancer, anti-parasitic, and anti-microbialproperties of diosmin. Effects of diosmin in combination with other flavonoids have been reviewed thoroughly and its administrative routes are also summarized. Additionally, we studied the effect of diosmin on critical protein networks. It exhibits therapeutic effects in diabetes and its associated complications such as neuropathy and dyslipidemia. Combination of diosmin with hesperidin is found to be very effective in the treatment of chronic venous insufficiency and haemorrhoids. Diosmin is an exquisite therapeutic agent alone as well as in combination with other flavonoids., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V.)

Colorimetric assays typically offer a rapid and convenient method to assess analytes that span healthcare monitoring to water quality testing. However, such tests can only provide qualitative results when employed in resource-limited settings or require bulky and expensive equipment such as lab spectrophotometers to allow quantitative measurements. In this paper, we report on the use of a handheld colorimeter to quantitatively determine the concentration of analytes in a manner that is independent of ambient lighting or initial sample color. The method combines the response of the sensor with first-principles modeling that better describes the nature of the assay compared to linear-in-parameters regression modeling that is typically performed in other studies. This method was successfully demonstrated using a number of colorimetric assays: (1) determination of solution pH using a universal indicator, (2) quantification of the DNase presence using a DNA-gold nanoparticle assay, and (3) quantification of the concentration of the antibiotic tetracycline using a cell-based assay., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

We present scanning near-field images of surface plasmon modes around a single elliptical nanohole in 88 nm thick Au film. We find that rotating surface plasmon vortex modes carrying extrinsic orbital angular momentum can be induced under linearly polarized illumination. The vortex modes are obtained only when the incident polarization direction differs from one of the ellipse axes. Such a direct observation of the vortex modes is possible thanks to the ability of the SNOM technique to obtain information on both the amplitude and the phase of the near-field. The presence of the vortex mode is determined by the rotational symmetry breaking of the system. Finite element method calculations show that such a vorticity originates from the presence of nodal points where the phase of the field is undefined, leading to a circulation of the energy flow. The configuration producing vortex modes corresponds to a nonzero total topological charge (+1).

Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth. Reduced growth rates and biomass yields were observed upon Aβ42 expression, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant mitochondrial structures. Genome-wide expression level analysis showed that Aβ42 expression triggered strong ER stress and unfolded protein responses. Equivalent expression of Aβ40, however, induced only mild ER stress, which resulted in hardly affected physiology. Using AD yeast models in well-controlled cultures strengthened our understanding on how cells translate different Aβ toxicity signals into particular cell fate programs, and further enhance their potential as a discovery platform to identify possible therapies.

Rectal cancer treatment still fails with local and distant relapses of the disease. It is hypothesized that radiotherapy could stimulate cancer cell dissemination and metastasis. In this study, we evaluated the effect of X-radiation on collagen type I strap formation potential, i.e. matrix remodeling associated with mesenchymal cell migration, and behaviors of SW480, SW620, HCT116 p53+/+ and HCT116 p53-/- colon cancer cells. We determined a radiation-induced increase in collagen type I strap formation and migration potentials of SW480 and HCT116 p53+/+. Further studies with HCT116 p53+/+, indicated that after X-radiation strap forming cells have an increased motility. More, we detected a decrease in adhesion potential and mature integrin β1 expression, but no change in non-muscle myosin II expression for HCT116 p53+/+ after X-radiation. Integrin β1 neutralization resulted in a decreased cell adhesion and collagen type I strap formation in both sham and X-radiated conditions. Our study indicates collagen type I strap formation as a potential mechanism of colon cancer cells with increased migration potential after X-radiation, and suggests that other molecules than integrin β1 and non-muscle myosin II are responsible for the radiation-induced collagen type I strap formation potential of colon cancer cells. This work encourages further molecular investigation of radiation-induced migration to improve rectal cancer treatment outcome.

Cancer cells exhibit various degrees of mitochondrial metabolic alterations. Owing to their multiple roles, mitochondria are attractive target for cancer therapy. Cancerous cells have high glucose (HG) requirements for their growth. Depriving them of glucose has been an approach used in many studies to restrict their perpetuation. However, such deprivation can negatively affect the surrounding normal cells in vivo. Keeping this in view, we treated HeLa cells with only physiological glucose (PG, 5.5 mM) and a combination of physiological glucose with a very low dose (1 nM) of rotenone (PGT), taking high glucose (HG, 25 mM)-treated HeLa cells as normal. We demonstrated that HeLa cells under PG condition mainly exhibited growth arrest. The PGT combination induced apoptosis in HeLa cells by generation of ROS, decrease in ATP production even with around 1.89-fold increase in glucose consumption, cell cycle arrest at S-phase and substantial increase in sub-diploid (Sub-D) population. The oxidative stress generated in both PG and PGT conditions stabilised p53 by localising it in the nuclei of HeLa cells, which would have otherwise undergone HPV-mediated inactivation. Pre-mature senescence induced due to limited glucose availability was found to be regulated by nuclear translocated p53 which, in turn, induced p21, pAkt and pERK. The cyto-toxic effect of rotenone on glucose deprived HeLa cells, synergistically activated NFκB, caspase-3 and Bax along with reduced expression of hyaluronan, a ROS scavenging molecule on their cell surface. Thus, our finding might be a valuable approach to specifically target cancerous cells in a more physiologically feasible condition and can serve as a relevant biochemical basis to gain new insights into cancer therapy., (© 2016 International Federation for Cell Biology.)

This study aimed to determine whether the prolonged exposure of the human trabecular meshwork (HTM) cell line to a low dose (1 nM) of rotenone could simulate a glaucomatous-like condition and serve as a cellular model for its etiological analysis. Under 1-nM rotenone exposure for 24-72 h, HTM cells showed a decrease in cell viability as assessed by an MTT assay and showed mitochondrial dysfunction as assessed by measuring H2 DCFDA fluorescence; a decrease in ATP level was also observed. Flow cytometric analysis showed an increase in cellular size and granularity. Elevated AF showed initial senescence. LF staining with SBB and its spectrofluorometric quantification confirmed growth arrest. An accumulation of cytoplasmic myocilin, IL-6, and MMP-9 at 72 h of exposure supported glaucomatous induction. TEM revealed morphological changes in mitochondria and nuclei of treated cells. Signaling cascades were assessed by immunoblotting and immunocytochemical analysis. This study showed a shift in status of the cells from initial senescence to induction of apoptosis in the HTM cell line due to continuous low-dose exposure to rotenone; however, at 72 h, both senescence and apoptotic features are apparent in these cells. This is the first report that reveals the potential of a prolonged low-dose exposure of rotenone to simulate senescence in the HTM cell line to cause a glaucomatous condition., (© 2015 International Federation for Cell Biology.)

The Raman optical activity (ROA) spectra of both enantiomers of 2-Br-hexahelicene in chloroform solution have been measured in the range 1700-300 cm(-1). Density functional theory (DFT) calculations accurately reproduce the observed features. The most intense ROA features are also the most intense Raman features, in the region 1350-1400 cm(-1), and correspond to the so-called D-modes, which play a major role in coronene and other PAHs (polycyclic aromatic hydrocarbons). Together with a detailed analysis of the normal mode structure, the polarizability tensors for the intense Raman features are investigated and related to the principal characteristics of helicene systems, namely, chirality and π-conjugation. Through electron-phonon coupling analysis, we propose a mechanism that justifies the intense ROA signals.

The automated metabolic profile provides the physician with a comprehensive review and graphic display of the patient's nutritional status, energy expenditure, substrate utilization, and nutritional requirements. A paramedical assistant performs all data acquisition, anthropometric and indirect calorimetric measurements. Data reduction is performed on a standard microcomputer system utilizing off-the-shelf peripherals. A standardized graphic sheet is used for the printout. The automated metabolic profile is utilized before initiation of nutritional therapy and subsequently to record the progress. Its use optimizes the clinical management of patients needing both ventilatory and nutritional support. By its use, total parenteral nutrition can be tailored to the requirements of the critically ill patient.