Changes in older people’s quality of life in the COVID-19 era: a population-based study in Finland

Quality of Life Research - We investigated how quality of life (QoL) changed between 2018 and 2020, and how its related factors, i.e., communication with friends and family, loneliness, and...     

Contribution of bacterial cells as nucleation centers in microbiologically induced CaCO3 precipitation—A mathematical modeling approach

The microbiologically induced calcite precipitation (MICP) has been extensively studied for geotechnical engineering through simultaneous action of natural phenomena and engineering processes. The focus of bacterial contribution to the MICP has been directed to calcium carbonate productivity, while the additional bacterial role as a crystal nucleation center was not explained especially from a mathematical prediction modeling point of view. Therefore, this study provides explanations and a mathematical modeling approach of bacterial influence on the MICP induced by newly-isolated ureolytic Bacillus strains and Sporosarcina pasteurii DSM 33. Using the obtained results of low-cost, rapid, and simple assays, artificial neural network modeling was applied for cell surface predispositions, pH changes as well as calcium-involved function in biofilm formation during the MICP, for the first time. Based on the obtained contribution of the alkalophilic/alkaloresistant bacteria, calcite precipitation can be significantly directed by the presence, of ureolytic bacterial cells as nucleation centers during CaCO₃ precipitation as well as their morphology, surface characteristics, potential to form a biofilm, and/or generate pH changes.     

UHPLC–MS/MS quantitation of porphyroxine in opium and application of porphyroxine‐acetylated products as signature markers for heroin

Porphyroxine, a trace alkaloid in opium, was identified in the early 1800s and isolated/characterized in the 1960s. Recently, two significant porphyroxine‐related byproducts found in the acidic and neutral extracts of illicit heroin were characterized by this laboratory as the N‐acetyl‐O¹⁴‐desmethyl‐epi‐porphyroxine ( B ) and N,O⁸‐diacetyl‐O¹⁴‐desmethyl‐epi‐porphyroxine ( C ). The prevalence of the B and C compounds has been consistent in the following order of abundance for the thousands of authentic heroin samples analyzed: Southwest Asia (SWA) > South America (SA) > Southeast Asia (SEA) > Mexico (MEX). In this research, a rapid and efficient ultra‐high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was developed to determine the content of porphyroxine and five primary alkaloids (morphine, codeine, thebaine, noscapine, and papaverine) in opium after extraction with methanol/water (50/50). The method was validated in terms of linearity, accuracy, recovery, and precision for porphyroxine. The limit of quantitation (LOQ) for porphyroxine was 2.5 ng/mL. The developed method was successfully applied to a total of 114 authentic opium samples from the major poppy‐growing regions. The amount of porphyroxine was determined at the level of part per thousand (‰) and the relative concentrations to morphine were in the range of 1x10^?4 and 1x10^?2 with an order of SWA > SEA, SA > MEX for its average abundance, which is consistent with the order of the average abundance of its acetylated products ( B , C ) in illicit heroin. This study reveals the significance of porphyroxine and its acylated compounds in classifying heroin and opium samples to major geographical regions of production.     

White adipose tissue mitochondrial metabolism in health and in obesity

White adipose tissue is one of the largest organs of the body. It plays a key role in whole‐body energy status and metabolism; it not only stores excess energy but also secretes various hormones and metabolites to regulate body energy balance. Healthy adipose tissue capable of expanding is needed for metabolic well‐being and to prevent accumulation of triglycerides to other organs. Mitochondria govern several important functions in the adipose tissue. We review the derangements of mitochondrial function in white adipose tissue in the obese state. Downregulation of mitochondrial function or biogenesis in the white adipose tissue is a central driver for obesity‐associated metabolic diseases. Mitochondrial functions compromised in obesity include oxidative functions and renewal and enlargement of the adipose tissue through recruitment and differentiation of adipocyte progenitor cells. These changes adversely affect whole‐body metabolic health. Dysfunction of the white adipose tissue mitochondria in obesity has long‐term consequences for the metabolism of adipose tissue and the whole body. Understanding the pathways behind mitochondrial dysfunction may help reveal targets for pharmacological or nutritional interventions that enhance mitochondrial biogenesis or function in adipose tissue.     

Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation

Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. Conclusion: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy.     

Does Senna Extract Promote Growth of Aberrant Crypt Foci and Malignant Tumors in Rat Colon?

Current evidence suggests that aberrant cryptfoci (ACF) can be used to evaluate agents for theirpotential colon carcinogenic activity. The aim of thepresent study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the ratcolon or increases the development of ACF and tumorsinduced by azoxymethane (AOM). A daily administration ofSE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself causethe appearance of ACF or tumors. The numbers of ACF andtumors induced by AOM were, however, increased by a doseof SE (100 mg/kg) able to induce chronic diarrhea over three months. These resultssuggest that SE does not cause the appearance of ACF ortumors in the rat colon nor does it have a promotingeffect when given to rats at a dose that produceslaxation (10 mg/kg), whereas a diarrhogenic dose (100mg/kg) increases the appearance of tumors induced byAOM.     

Evidence for an exclusive association of matrix metalloproteinase-9 with dysfunctional high-density lipoprotein: A novel finding

Objective

High-density lipoprotein is a heterogeneous class of lipoprotein with diverse antiatherogenic functions. However, these antiatherogenic properties of HDL can be compromised in atherosclerotic conditions. We have recently identified dysfunctionality in HDL even among healthy subjects, during systemic inflammation. This study was carried out with the objective of examining whether dysfunctional HDL is associated with pro-inflammatory proteins other than the acute phase proteins as reported earlier.

Methods

Serum HDL was isolated by three different methods-density gradient ultracentrifugation, PEG precipitation and electroelution. The antioxidant property of HDL was assessed as change in oxidation of LDL based on Dichloro-dihydro-fluorescein diacetate assay. HDL was subjected to gelatin zymography and western blot for assessment of MMP 9 activity.

Results

Dysfunctional HDL did not prevent the auto-oxidation of LDL. On the contrary the oxidation was enhanced. The zymogram data indicated enhanced MMP-9 activity selectively in dysfunctional HDL, irrespective of HDL isolation methods. This was confirmed by western blot of HDL probed with antibody specific to MMP 9. We also observed that dysfunctional HDL induced inflammatory response in monocyte/macrophages as evidenced by enhanced TNF-α and decreased IL-10 production. Further, invitro incubation of functional HDL with MMP-9 provided direct evidence for the association of MMP-9 with HDL and the role of MMP-9 in HDL dysfunction.

Conclusion

A remarkable finding in the present study is the previously unrecognized association of MMP-9 with dysfunctional HDL and its proinflammatory property, indicating a novel molecular connection that can enhance the risk of cardiovascular disease in subjects with dysfunctional HDL.     

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.