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1.
J Photochem Photobiol B ; 255: 112927, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701631

ABSTRACT

Since the mechanism underlying real-time acquisition of mechanical strength during laser-induced skin wound fusion remains unclear, and collagen is the primary constituent of skin tissue, this study investigates the structural and mechanical alterations in collagen at temperatures ranging from 40 °C to 60 °C using various spectroscopic techniques and molecular dynamics calculations. The COMSOL Multiphysics coupling is employed to simulate the three-dimensional temperature field, stress-strain relationship, and light intensity distribution in the laser thermal affected zone of skin wounds during dual-beam laser welding process. Raman spectroscopy, synchronous fluorescence spectroscopy and circular dichroism measurement results confirm that laser energy activates biological activity in residues, leading to a transformation in the originally fractured structure of collagen protein for enhanced mechanical strength. Molecular dynamics simulations reveal that stable hydrogen bonds form at amino acid residues within the central region of collagen protein when the overall temperature peak around the wound reaches 60 °C, thereby providing stability to previously fractured skin incisions and imparting instantaneous strength. However, under a 55 °C system, Type I collagen ensures macrostructural stability while activating biological properties at amino acid bases to promote wound healing function; this finding aligns with experimental analysis results. The COMSOL simulation outcomes also correspond well with macroscopic morphology after laser welding samples, confirming that by maintaining temperatures between 55 °C-60 °C during laser welding of skin incisions not only can certain instantaneous mechanical strength be achieved but irreversible thermal damage can also be effectively controlled. It is anticipated that these findings will provide valuable insights into understanding the healing mechanism for laser-welded skin wounds.


Subject(s)
Collagen , Lasers , Molecular Dynamics Simulation , Skin , Spectrum Analysis, Raman , Skin/chemistry , Skin/radiation effects , Collagen/chemistry , Collagen/metabolism , Wound Healing , Hydrogen Bonding , Finite Element Analysis , Animals , Circular Dichroism , Temperature , Spectrometry, Fluorescence
2.
GMS Hyg Infect Control ; 19: Doc21, 2024.
Article in English | MEDLINE | ID: mdl-38766639

ABSTRACT

Aim: Seasonal influenza poses a significant burden of disease, affecting not only older adults but also individuals under the age of 60. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may have reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by such antigen adaptation. This review aims to present real-world data (RWD) comparing the effectiveness of quadrivalent cell-based (QIVc) and egg-based (QIVe) influenza vaccines over three consecutive seasons. Methods: A comprehensive review was conducted, analyzing RWD from retrospective cohort and case-control studies on the relative vaccine effectiveness (rVE) of QIVc versus QIVe during the 2017/18-2019/20 seasons. Results: This study included six retrospective cohort studies and one case-control study, with a combined total of approximately 29 million participants. A cohort study involving people aged ≥4 years during the 2017/18 season showed a statistically significant rVE of QIVc compared to QIVe in preventing influenza-like illness, with a value of 36.2%. QIVc demonstrated statistically significant superiority over QIVe in preventing outpatient and inpatient medical encounters as observed in two cohort studies conducted during the 2018/19 and 2019/20 seasons. The rVE of QIVc compared to QIVe was found to be 7.6% in individuals aged ≥4 years and 9.5% in individuals aged ≥18 years. Three additional cohort studies conducted between 2017/18-2019/20 reported a statistically significant improvement in rVE (5.3-14.4%) of QIVc compared to QIVe in preventing influenza-related hospitalizations and emergency department visits due to influenza in individuals aged 4-64 years. In a case-control study across all three seasons, QIVc showed statistically significantly higher effectiveness compared to QIVe in preventing test-confirmed influenza, with rVEs of 10.0-14.8%. Conclusions: RWD from the 2017/18-2019/20 seasons demonstrated that QIVc is more effective than QIVe in preventing influenza-related outcomes in individuals aged 4-64 years. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population under 60 years of age.

3.
Lung Cancer ; 192: 107802, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692217

ABSTRACT

BACKGROUND: The role of cytoreductive surgery for epithelioid pleural mesothelioma within a multimodal treatment approach remains controversial. Carefully selected patients benefit from cytoreductive surgery and adjuvant chemotherapy, but there is no established biomarker to predict tumor recurrence or progression during the course of the disease. The aim of this study was to identify potential biomarkers to predict therapeutic response in terms of progression-free survival. METHODS: Between 03/2014 and 08/2022, preoperative blood samples were collected from 76 patients with epithelioid pleural mesothelioma who underwent cytoreductive surgery as part of a multimodal treatment approach. Identification of potential biomarkers was performed by determination of mesothelin and calretinin, as well as specific long non-coding RNAs and microRNAs. Receiver operating characteristic analysis, Kaplan-Meier survival analysis, and Cox regression were used to assess the association between biomarker concentrations and patient recurrence status and survival. RESULTS: MALAT1, GAS5, and calretinin showed statistically significant increased biomarker levels in patients with recurrence in contrast to recurrence-free patients after surgical treatment (p < 0.0001, p = 0.0190, and p = 0.0068, respectively). The combination of the three biomarkers resulted in a sensitivity of 68 % and a specificity of 89 %. CONCLUSION: MALAT1, GAS5, and calretinin could be potential biomarkers for the prediction of tumor recurrence, improving the benefit from multimodal treatment including cytoreductive surgery.


Subject(s)
Biomarkers, Tumor , Calbindin 2 , Disease Progression , Mesothelioma , RNA, Long Noncoding , Humans , Male , Female , RNA, Long Noncoding/genetics , RNA, Long Noncoding/blood , Aged , Middle Aged , Prognosis , Calbindin 2/metabolism , Mesothelioma/surgery , Mesothelioma/mortality , Mesothelioma/blood , Mesothelioma/pathology , Pleural Neoplasms/surgery , Pleural Neoplasms/pathology , Pleural Neoplasms/mortality , Pleural Neoplasms/blood , Neoplasm Recurrence, Local , Cytoreduction Surgical Procedures/methods , Adult , Aged, 80 and over , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Lung Neoplasms/mortality
4.
Wien Klin Wochenschr ; 136(Suppl 2): 35-42, 2024 Feb.
Article in German | MEDLINE | ID: mdl-38393348

ABSTRACT

The population < 60 years of age is also affected by a significant disease burden from seasonal influenza. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may experience reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by antigenic adaptations to the host system and showed better effectiveness in individuals 4-64 years old over several seasons compared to conventional egg-based influenza vaccines under real-world conditions. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population < 60 years of age.


Subject(s)
Influenza Vaccines , Influenza, Human , Humans , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Influenza, Human/prevention & control , Influenza, Human/epidemiology , Vaccination , Seasons , Cost of Illness
5.
Br J Hist Sci ; 56(4): 469-484, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37905553

ABSTRACT

This article interrogates the scientific conference as a means by which the organizers of the World League for Sexual Reform's 1929 conference attempted to marshal the 'scientific spirit' in order to present progressive sexual reform as a rational and scientifically informed undertaking. The conference was carefully curated to make the sex reform movement (and the assorted characters that gathered under its banner) look serious, legitimate and, most importantly, scientific. The conference was also an attempt by organizer Norman Haire to exert control over the strategy of sexology, an enterprise that put him at odds with other prominent sexologists of the time. Crucially, Haire understood sexology as inherently intellectually interdisciplinary, but was strategically convinced that the only sound rubric through which to promote and gain acceptance for the movement was through medical science. This central debate, about how best to define the contested concept of sexology, continues among historians today. By examining how the 1929 conference organizers wrestled to define their sex-reforming remit and how they curated the conference to that end, this paper will offer a window onto the mechanisms via which adherents of intellectual communities contend with heterogeneity, how we judge forms of knowledge and, ultimately, what constitutes science.


Subject(s)
Medicine , Sexology , Male , Humans
6.
Mol Syst Biol ; 16(5): e9370, 2020 05.
Article in English | MEDLINE | ID: mdl-32400114

ABSTRACT

Streptavidin-mediated enrichment is a powerful strategy to identify biotinylated biomolecules and their interaction partners; however, intense streptavidin-derived peptides impede protein identification by mass spectrometry. Here, we present an approach to chemically modify streptavidin, thus rendering it resistant to proteolysis by trypsin and LysC. This modification results in over 100-fold reduction of streptavidin contamination and in better coverage of proteins interacting with various biotinylated bait molecules (DNA, protein, and lipid) in an overall simplified workflow.


Subject(s)
Mass Spectrometry/methods , Metalloendopeptidases/chemistry , Proteins/analysis , Proteomics/methods , Streptavidin/chemistry , Trypsin/chemistry , Arginine/analogs & derivatives , Arginine/chemistry , Biotinylation/methods , Chromatin Immunoprecipitation/methods , HeLa Cells , Humans , Lysine/analogs & derivatives , Lysine/chemistry , Membrane Proteins/metabolism , Neoplasm Proteins/metabolism , Polycomb Repressive Complex 2/metabolism , Proteolysis , Transcription Factors/metabolism
7.
Bioorg Med Chem ; 18(2): 945-52, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-20005725

ABSTRACT

Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) and fatty acid amide hydrolase (FAAH) are enzymes, which have emerged as attractive targets for the development of analgetic and anti-inflammatory drugs. We recently reported that 1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (10) and related compounds are inhibitors of cPLA(2)alpha. Since cPLA(2)alpha and FAAH possess several common structural features, we now screened this substance series together with some new derivatives for FAAH inhibition. Some of the assayed compounds proved to be selective cPLA(2)alpha inhibitors, while others showed high FAAH and moderate cPLA(2)alpha inhibitory potency. Furthermore, several derivatives were favorably active against both enzymes and, therefore, could represent agents, which have improved analgetic and anti-inflammatory qualities in comparison with selective cPLA(2)alpha and FAAH inhibitors.


Subject(s)
Amidohydrolases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Group IV Phospholipases A2/antagonists & inhibitors , Heterocyclic Compounds/pharmacology , Indoles/pharmacology , Amidohydrolases/metabolism , Animals , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Group IV Phospholipases A2/isolation & purification , Group IV Phospholipases A2/metabolism , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Indoles/chemical synthesis , Indoles/chemistry , Molecular Conformation , Rats , Stereoisomerism , Structure-Activity Relationship
8.
Anal Bioanal Chem ; 394(6): 1679-85, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19484225

ABSTRACT

A fluorescent assay for the evaluation of inhibitors of fatty acid amide hydrolase (FAAH) is described. Microsomes from rat brain served as enzyme source. N-(2-Hydroxyethyl)-4-pyren-1-ylbutanamide was designed and synthesized as novel fluorogenic substrate. For substrate solubilization, Triton X-100 was employed. The FAAH activity was determined directly without further sample clean-up by measuring the amount of 4-pyren-1-ylbutanoic acid released by the enzyme with reversed-phase HPLC and fluorescence detection. The known FAAH inhibitors URB597, phenyl hexanoyl oxazolopyridine (PHOP) and [6-(2-methyl-4,5-diphenyl-1H-imidazol-1-yl)hexyl]carbamic acid phenyl ester were used to validate the test assay.


Subject(s)
Amidohydrolases/antagonists & inhibitors , Chromatography, High Pressure Liquid/methods , Enzyme Inhibitors/pharmacology , Fluorescent Dyes/analysis , Amidohydrolases/metabolism , Animals , Brain/drug effects , Brain/enzymology , Enzyme Inhibitors/chemistry , Female , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Molecular Structure , Rats , Rats, Sprague-Dawley , Substrate Specificity
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