Category Archives: RESEARCH ARTICLE

Dietary lithium stimulates female fecundity in Drosophila melanogaster

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Dietary lithium stimulates female fecundity in Drosophila melanogaster

Dietary lithium (0.1–5 mM LiCl) improved the lithium status of the female fruit fly Drosophila melanogaster and substantially increased egg production. These findings were accompanied by alterations in mRNA levels of genes encoding proteins involved with chorion formation and yolk protein biosynthesis, which are essential steps in Drosophila oogenesis. (Image created with BioRender.com).


Abstract

The trace element lithium exerts a versatile bioactivity in humans, to some extend overlapping with in vivo findings in the model organism Drosophila melanogaster. A potentially essential function of lithium in reproduction has been suggested since the 1980s and multiple studies have since been published postulating a regulatory role of lithium in female gametogenesis. However, the impact of lithium on fruit fly egg production has not been at the center of attention to date. In the present study, we report that dietary lithium (0.1–5.0 mM LiCl) substantially improved life time egg production in D. melanogaster w 1118 females, with a maximum increase of plus 45% when supplementing 1.0 mM LiCl. This phenomenon was not observed in the insulin receptor mutant InR E19 , indicating a potential involvement of insulin-like signaling in the lithium-mediated fecundity boost. Analysis of the whole-body and ovarian transcriptome revealed that dietary lithium affects the mRNA levels of genes encoding proteins related to processes of follicular maturation. To the best of our knowledge, this is the first report on dietary lithium acting as an in vivo fecundity stimulant in D. melanogaster, further supporting the suggested benefit of the trace element in female reproduction.

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA-containing immune complex (DNA-ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA-ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA-ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA-ICs on RelB, IL-10 and TNF-α in mDCs. Further analysis indicated that DNA-ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3-mediated effects. Co-culture of mDCs and CD4+ T cells showed that VitD3 inhibited multiple processes mediated by DNA-ICs, including proliferation, downregulation of IL-10, TGF-β and upregulation of TNF-α. Moreover, VitD3 could also reverse the effects of DNA-IC-induced imbalance of CD4+ CD127− Foxp3+ T cells and CD4+ IL17+ T cells. Taken together, our results indicated that autologous DNA-ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA-ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.

Using ultraviolet dermoscopy in diagnosing scabies

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Abstract

The latest generation ultraviolet (UV) dermatoscopes, which emit UV light at a wavelength of 365 nm and enlarge lesions, are practical devices that can facilitate the diagnosis and follow-up of some dermatological diseases with fluorescence that can be observed in skin lesions. In 305 patients, 468 tunnels were evaluated: first in polarized mode and later in UV mode. The recorded samples were compared one-to-one by the same dermatologist. Due to the study's design, images were examined in three stages: tunnel borders, tunnel content and mite appearance. In UV mode, the entire body of mites gives a bright reflex along with an oval-shaped diagnostic clue well beyond the delta sign. The borders of the tunnel reflect brightly in UV mode, with borders that are more sharply visible than in polarized mode. Although the tunnel content cannot be clearly distinguished in polarized mode, especially in people with hyperkeratotic palms, or ‘working hands’ (e.g. farmers, mechanics and construction workers), with the bright reflex, the tunnel borders in UV mode give a bright reflection and provide a clear view of tunnels. Tunnel content gives a bright reflection in UV mode. Our results show that UV dermatoscopes provide more effective and clearer images than polarized dermatoscopes in the diagnosis of scabies.

Breast cancer diagnosis and management guided by data augmentation, utilizing an integrated framework of SHAP and random augmentation

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Breast cancer diagnosis and management guided by data augmentation, utilizing an integrated framework of SHAP and random augmentation

The use of SHAP for feature engineering alongside random augmentation for data balancing for the diagnosis of breast cancer (BC) proposed some management strategies for BC before and after diagnosis Developed models that could help in the diagnosis of BC by prediction using various machine learning algorithms.


Abstract

Recent research indicates that early detection of breast cancer (BC) is critical in achieving favorable treatment outcomes and reducing the mortality rate associated with it. With the difficulty in obtaining a balanced dataset that is primarily sourced for the diagnosis of the disease, many researchers have relied on data augmentation techniques, thereby having varying datasets with varying quality and results. The dataset we focused on in this study is crafted from SHapley Additive exPlanations (SHAP)-augmentation and random augmentation (RA) approaches to dealing with imbalanced data. This was carried out on the Wisconsin BC dataset and the effectiveness of this approach to the diagnosis of BC was checked using six machine-learning algorithms. RA synthetically generated some parts of the dataset while SHAP helped in assessing the quality of the attributes, which were selected and used for the training of the models. The result from our analysis shows that the performance of the models used generally increased to more than 3% for most of the models using the dataset obtained by the integration of SHAP and RA. Additionally, after diagnosis, it is important to focus on providing quality care to ensure the best possible outcomes for patients. The need for proper management of the disease state is crucial so as to reduce the recurrence of the disease and other associated complications. Thus the interpretability provided by SHAP enlightens the management strategies in this study focusing on the quality of care given to the patient and how timely the care is.

Non‐invasive diagnosis of early cutaneous squamous cell carcinoma

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Abstract

Early cutaneous squamous cell carcinoma (cSCC) can be challenging to diagnose using clinical criteria as it could present similar to actinic keratosis (AK) or Bowen's disease (BD), precursors of cSCC. Currently, histopathological assessment of an invasive biopsy is the gold standard for diagnosis. A non-invasive diagnostic approach would reduce patient and health system burden. Therefore, this study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of histopathologically diagnosed AK, BD and cSCC, as well as matched normal samples. Proteomic data were analysed to identify proteins and biological functions that are significantly different between lesions. Additionally, a support vector machine (SVM) machine learning algorithm was used to assess the usefulness of proteomic data for the early diagnosis of cSCC. A total of 696 proteins were identified across the samples studied. A machine learning model constructed using the proteomic data classified premalignant (AK + BD) and malignant (cSCC) lesions at 77.5% accuracy. Differential abundance analysis identified 144 and 21 protein groups that were significantly changed in the cSCC, and BD samples compared to the normal skin, respectively (adj. p < 0.05). Changes in pivotal carcinogenic pathways such as LXR/RXR activation, production of reactive oxygen species, and Hippo signalling were observed that may explain the progression of cSCC from premalignant lesions. In summary, this study demonstrates that DIA-MS analysis of tape-stripped samples can identify non-invasive protein biomarkers with the potential to be developed into a complementary diagnostic tool for early cSCC.

Nuclear translocation of PKM2 mediates keratinocyte metabolic reprogramming in psoriasis

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Nuclear translocation of PKM2 mediates keratinocyte metabolic reprogramming in psoriasis

Metabolic abnormalities including perturbations in glucose metabolism are linked to psoriasis. In this study, we focus on the pyruvate kinase PKM2 and identify that its nuclear translocation underlies the metabolic reprogramming and aberrant activation of keratinocytes in psoriasis patients.


Abstract

PKM2 mediates the Warburg effects and is crucial for tumorigenesis, but its role in hyperplastic skin disorders remains elusive. In this study, we investigated the function of PKM2 in psoriatic keratinocytes. We found that PKM2 expression and its nuclear translocation were induced in the epidermis of psoriasis patients, contributing to aerobic glycolysis and cell growth. Moreover, mass spectrometry combined with immunoprecipitation analysis revealed that PKM2 could interact with TRIM33, an E3 ubiquitin ligase in the nucleus, and this interaction is critical for the nuclear retention of PKM2. As a result of TRIM33-mediated ubiquitination, PKM2 nuclear protein kinase function is promoted, thus leading to the phosphorylation of STAT3. In addition, blocking PKM2 nuclear translocation abrogated TRIM33-triggered glycolysis and cell proliferation in keratinocytes. Taken together, our experiments demonstrate that ubiquitination regulates the nuclear retention of PKM2 in keratinocytes. Moreover, our results highlight a novel mechanism accounting for the metabolic reprogramming of keratinocytes in psoriasis patients.

Gut microbiota contribution to selenium deficiency‐induced gut–liver inflammation

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Gut microbiota contribution to selenium deficiency-induced gut–liver inflammation

Se deficient imbalance the intestinal microbiota. Se deficient effects gut–liver axis via lipopolysaccharide. Lactobacillus reuteri could alleviate selenium deficiency-induced gut–liver axis injury.


Abstract

There is limited knowledge about the factors that drive gut–liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.

Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate

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Plant mycorrhizal associations mediate the zoogeochemical effects of calving subsidies by a forest ungulate

The authors demonstrate that white-tailed deer calving is a substantial zoogeochemical input in northeastern forests, which can ultimately contribute to fine-scale ecosystem heterogeneity. The impact of the subsidy, however, was strongly dependent on and modulated by the plant–fungal community, demonstrating the need for animal subsidies to be contextualized in plant–fungal frameworks.


Abstract

Animals interact with and impact ecosystem biogeochemical cycling—processes known as zoogeochemistry. While the deposition of various animal materials (e.g. carcasses and faeces) has been shown to create nutrient hotspots and alter nutrient cycling and storage, the inputs from parturition (i.e. calving) have yet to be explored. We examine the effects of ungulate parturition, which often occurs synchronously during spring green-up and therefore aligns with increased plant nitrogen demand in temperate biomes. Impacts of zoogeochemical inputs are likely context-dependent, where differences in material quality, quantity and the system of deposition modulate their impacts. Plant mycorrhizal associations, especially, create different nutrient-availability contexts, which can modify the effects of nutrient inputs. We, therefore, hypothesize that mycorrhizal associations modulate the consequences of parturition on soil nutrient dynamics and nitrogen pools. We established experimental plots that explore the potential of two kinds of zoogeochemical inputs deposited at ungulate parturition (placenta and natal fluid) in forest microsites dominated by either ericoid mycorrhizal (ErM) or ectomycorrhizal (EcM) plants. We assess how these inputs affect rates of nutrient cycling and nitrogen content in various ecosystem pools, using isotope tracers to track the fate of nitrogen inputs into plant and soil pools. Parturition treatments accelerate nutrient cycling processes and increase nitrogen contents in the plant leaf, stem and fine root pools. The ecosystem context strongly modulates these effects. Microsites dominated by ErM plants mute parturition treatment impacts on most nutrient cycling processes and plant pools. Both plant–fungal associations are, however, equally efficient at retaining nitrogen, although retention of nitrogen in the parturition treatment plots was more than two times lower than in control plots. Our results highlight the potential importance of previously unexamined nitrogen inputs from animal inputs, such as those from parturition, in contributing to fine-scale heterogeneity in nutrient cycling and availability. Animal inputs should therefore be considered, along with their interactions with plant mycorrhizal associations, in terms of how zoogeochemical dynamics collectively affect nutrient heterogeneity in ecosystems.

Microbial colonization dynamics of the postnatal digestive tract of Bos indicus calves

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Abstract

The rumen and the jejunum of calves have distinct functional roles; the former is in the storage and fermentation of feed, and the latter is in transporting digesta to the ileum. It is unknown how nutrition changes the evolution of the microbiome of these organs after birth. We sequenced and characterized the entire microbiome of the rumen and the jejunum from Bos indicus calves of the Mexican Tropics to study their dynamics at Days 0, 7, 28, and 42 after birth. Operational taxonomic units (OTUs) belonging to 185 and 222 genera from 15 phylum were observed in the organs, respectively. The most abundant OTUs were Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. We observed that proteobacterial species were outcompeted after the first week of life by Bacteroidetes and Firmicutes in the rumen and the jejunum, respectively. Moreover, Prevotella species were found to predominate in the rumen (36% of total OTUs), while the jejunum microbiome is composed of small proportions of several genera. Presumably, their high relative abundance assists in specialized functions and is more likely in fermentation since they are anaerobes. In summary, the rumen and the jejunum microbiomes were outcompeted by new microbiomes in a dynamic process that begins at birth.

Exploring the role of growth factors as potential regulators in psoriatic plaque formation

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Abstract

Psoriasis is a chronic inflammatory skin disease in which growth activity is more prominent than inflammatory activity at the centre of lesional skin (CE skin). This growth activity is partly influenced by growth factors (GFs) that play an important role in cell growth and inflammation during the plaque development. In this study, we identified potential GFs in CE skin and predicted their regulatory functions and biological activity in mediating transcripts in the plaques. Samples of uninvolved skin (UN skin) and CE skin were biopsied from patients with psoriasis vulgaris for RNA-sequencing analysis in order to identify differentially expressed genes (DEGs). Our finding revealed that epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) signalling were enriched by CE/UN skin-derived DEGs. Additionally, several EGFR ligands, namely EGF, heparin-binding EGF like growth factor (HB-EGF), amphiregulin (AREG) and transforming growth factor (TGF)-α, as well as TGF-β1, TGF-β2, vascular endothelial growth factor-A, FGFs, PDGF-B and HGF, were predicted to be GF regulators. The regulatory pattern and biological activity of these GF regulators on mediating the CE/UN skin-derived DEGs was demonstrated. This study provides a novel hypothesis regarding the overall regulatory function of GFs, which appear to modulate the expression of the transcripts involved in inflammation and growth in the CE skin. In addition, some GFs may exert anti-inflammatory effects. Further investigations on the mechanisms underlying this regulation may contribute to a deeper understanding of psoriasis and the identification of potential therapeutic targets for patients with psoriasis.