As jobs disappear and wages flatline, paid work is an increasingly fragile basis for dignified life. This predicament, deepened by the COVID-19 pandemic, is sparking urgent debates about alternatives ...such as a universal basic income (UBI). In this incisive new book, Hein Marais casts the debate about a UBI in the wider context of the dispossessing pressures of capitalism and the turmoil of global warming, pandemics and social upheaval. Marais surveys the meaning, history and appeal of a UBI before even-handedly weighing the case for and against it. The book explores the vexing questions a UBI raises about the relationship of paid work to social rights, about prevailing notions of entitlement and dependency, and about the role of the state in contemporary capitalism. Along with cost estimates for different versions of a basic income in South Africa, it discusses financing options and lays out the social, economic and political implications. Highly topical and distinctive in its approach, In the Balance: The Case for a Universal Basic Income in South Africa and Beyond is the most rounded and up-to-date examination yet of the need and prospects for a UBI in a global South setting such as South Africa.
This insightful book provides a comprehensive analysis of the nationwide randomised Finnish basic income experiment 2017 to 2018, from planning and implementation through to the end results. It ...presents the background of the social policy system in which the experiment was implemented and details the narratives of the planning process alongside its constraints, as well as a final evaluation of the results.Empirical chapters analyse the outcomes of the experiment in relation to the employment, health and well-being, in various forms, of the recipients of unconditional income transfer. Phenomenological aspects of living on basic income, based on face-to-face interviews, are also reported, as well as media discourse on the experiment and its results. This thought-provoking book concludes with an examination of the political feasibility of basic income in Finland.Offering important lessons on the planning and implementation of such experiments in a developed welfare state, this unique book will be a vital resource for scholars and students of social policy, welfare economics, basic security and basic income.
•HPLC-MS/MS method was developed and validated for analysis of 52 multiclass illegal dyes.•ESI polarity switching for analysis of acidic, neutral and basic analytes in one run.•Dispersive SPE ...eliminated interfering compounds.•All illegal dyes were observed with acceptable matrix effects at 100-fold dilutions.
Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic–basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2–111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods.
TGF-β1 expression closely associates with activation and conversion of fibroblasts to a myofibroblast phenotype and synthesis of an alternatively spliced cellular fibronectin variant, Fn-ED-A. ...Reactive oxygen species (ROS), such as superoxide, which is a product of NAD(P)H oxidase, also promote the transition of fibroblasts to myofibroblasts, but whether these two pathways are interrelated is unknown. Here, we examined a role for NAD(P)H oxidase–derived ROS in TGF-β1–induced activation of rat kidney fibroblasts and expression of α-smooth muscle actin (α-SMA) and Fn-ED-A.
In vitro
, TGF-β1 stimulated formation of abundant stress fibers and increased expression of both α-SMA and Fn-ED-A. In addition, TGF-β1 increased both the activity of NADPH oxidase and expression of Nox2 and Nox4, homologs of the NAD(P)H oxidase family, indicating that this growth factor induces production of ROS. Small interfering RNA targeted against Nox4 markedly inhibited TGF-β1–induced stimulation of NADPH oxidase activity and reduced α-SMA and Fn-ED-A expression. Inhibition of TGF-β1 receptor 1 blocked Smad3 phosphorylation; reduced TGF-β1–enhanced NADPH oxidase activity; and decreased expression of Nox4, α-SMA, and Fn-ED-A. Diphenyleneiodonium, an inhibitor of flavin-containing enzymes such as the Nox oxidases, had no effect on TGF-β1–induced Smad3 but reduced both α-SMA and Fn-ED-A protein expression. The Smad3 inhibitor SIS3 reduced NADPH oxidase activity, Nox4 expression, and blocked α-SMA and Fn-ED-A, indicating that stimulation of myofibroblast activation by ROS is downstream of Smad3. In addition, TGF-β1 stimulated phosphorylation of extracellular signal–regulated kinase (ERK1/2), and this was inhibited by blocking TGF-β1 receptor 1, Smad3, or the Nox oxidases; ERK1/2 activation increased α-SMA and Fn-ED-A. Taken together, these results suggest that TGF-β1–induced conversion of fibroblasts to a myofibroblast phenotype involves a signaling cascade through Smad3, NAD(P)H oxidase, and ERK1/2.
BACKGROUND Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver ...fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown. AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model. METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays. RESULTS The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation. CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.
BACKGROUND Colorectal polyps that develop via the conventional adenoma-carcinoma sequence e.g. , tubular adenoma (TA) often progress to malignancy and are closely associated with changes in the ...composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps control group (CT), n = 40, patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus ), Bacteroides fragilis , and Clostridium symbiosum , were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g. , mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.
Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.BACKGROUNDMonopolar spindle-binding ...protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.To investigate the role of MOB3B in colorectal cancer (CRC).AIMTo investigate the role of MOB3B in colorectal cancer (CRC).This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results.METHODSThis study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results.MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.RESULTSMOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.CONCLUSIONLoss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.
Significance Statement
Macrophages and autoantibodies play a central role in the pathology of lupus nephritis in patients with lupus and in the MRL-
Faslpr
mouse model. The authors demonstrate that ...IL-34 and its two receptors, cFMS and PTPRZ, are upregulated in the kidney with advancing nephritis in MRL-
Faslpr
mice. Genetically deleting IL-34 in these mice suppresses nephritis and the systemic illness
via
macrophage- and autoantibody-mediated mechanisms within and outside of the kidney. The authors also found that patients with lupus nephritis have elevated IL-34 in serum and urine; intrarenal and systemic expression of IL-34, cFMS, and PTPRZ similar to that displayed in MRL-
Faslpr
mice; and IL-34 expression that correlates with histopathologic index of disease activity. These findings suggest that IL-34 is a promising novel therapeutic target for patients with lupus nephritis.
Background
In people with SLE and in the MRL-
Faslpr
lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ.
Methods
To investigate whether IL-34–dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL-
Faslpr
mice expressing IL-34 and IL-34 knockout (KO) MRL-
Faslpr
mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis.
Results
Intrarenal IL-34 and its two receptors increase during lupus nephritis in MRL-
Faslpr
mice. In knockout mice lacking IL-34, nephritis and systemic illness are suppressed. IL-34 fosters intrarenal macrophage accumulation
via
monocyte proliferation in bone marrow (which increases circulating monocytes that are recruited by chemokines into the kidney) and
via
intrarenal macrophage proliferation. This accumulation leads to macrophage-mediated TEC apoptosis. We also found suppression of circulating autoantibodies and glomerular antibody deposits in the knockout mice. This is consistent with fewer activated and proliferating intrarenal and splenic B cells in mice lacking IL-34, and with our novel discovery that PTPRZ is expressed by macrophages, B and T cells. These findings appear translatable to human patients with lupus nephritis, whose expression of IL-34, cFMS, and PTPRZ is similar to that seen in the MRL-
Faslpr
lupus mouse model. Moreover, expression of IL-34 in TECs correlates with disease activity.
Conclusions
IL-34 is a promising novel therapeutic target for patients with lupus nephritis.
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