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Plant Biotechnology Journal Jun 2024In photosynthetic cells, plants convert carbon dioxide to sugars that can be moved between cellular compartments by transporters before being subsequently metabolized to... (Review)
Review
In photosynthetic cells, plants convert carbon dioxide to sugars that can be moved between cellular compartments by transporters before being subsequently metabolized to support plant growth and development. Most pathogens cannot synthesize sugars directly but have evolved mechanisms to obtain plant-derived sugars as C resource for successful infection and colonization. The availability of sugars to pathogens can determine resistance or susceptibility. Here, we summarize current progress on the roles of sugar transporters in plant-pathogen interactions. We highlight how transporters are manipulated antagonistically by both host and pathogens in competing for sugars. We examine the potential application of this target in resistance breeding and discuss opportunities and challenges for the future.
PubMed: 38879813
DOI: 10.1111/pbi.14408 -
The Journal of International Medical... Jun 2024Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy.... (Review)
Review
Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.
Topics: Humans; Pregabalin; Rhabdomyolysis; Female; Male; Aged, 80 and over; Analgesics; Creatine Kinase
PubMed: 38879799
DOI: 10.1177/03000605241257776 -
Health Expectations : An International... Jun 2024People with severe mental illness (SMI) experience higher rates and poorer outcomes of physical long-term conditions (LTCs). The management of SMI and LTCs is highly...
BACKGROUND
People with severe mental illness (SMI) experience higher rates and poorer outcomes of physical long-term conditions (LTCs). The management of SMI and LTCs is highly complex and many people with SMI rely on informal carers for support, which may lead to high levels of caregiver burden, and caregiver burnout. Caregiver burnout can result in poor health outcomes for informal carers and a reduction in the quality of care they are able to provide. Therefore, it is important to understand the caring experience to identify and address factors that contribute to burden and burnout.
METHODS
This paper reports a secondary qualitative analysis of semistructured interviews and focus groups conducted with informal carers of people who have coexisting SMI and LTCs. We recruited 12 informal carers in England between December 2018 and April 2019. The transcripts were coded and analysed thematically.
RESULTS
We identified two overarching themes and five subthemes. The themes included 'Fighting on all fronts: Mounting strain between demands and resources', which described the challenge of providing care in the context of coexisting SMI and LTCs, and 'Safekeeping: The necessity of chronic hypervigilance', which captured how informal carers' roles were defined by managing high-risk situations, leading to hypervigilance and paternalistic approaches to care.
CONCLUSION
The experience of informal carers for people with SMI and coexisting LTCs is marked by limited access to support and the management of significant risk, which could contribute to high caregiver burden. Further primary research is needed to understand how the experiences of the caregiver role for people with SMI and LTCs influence caregiver burden.
PATIENT OR PUBLIC CONTRIBUTION
Our PPI panel DIAMONDS Voice provided guidance on this study from conception, design and development of interview guides and recruitment materials to final write-up. DIAMONDS Voice consists of service users and carers who have experience of SMI and LTCs. Three carer members reviewed the final manuscript, and two are credited as authors.
Topics: Humans; Caregivers; Female; Qualitative Research; Male; Middle Aged; Mental Disorders; Chronic Disease; Adult; Focus Groups; England; Interviews as Topic; Aged
PubMed: 38879785
DOI: 10.1111/hex.14119 -
Scientific Reports Jun 2024Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the...
Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.
Topics: Humans; Pancreatic Neoplasms; Biomarkers, Tumor; Prognosis; Gene Expression Regulation, Neoplastic; Female; Male; Kaplan-Meier Estimate; ROC Curve; Lymphocytes, Tumor-Infiltrating; Protein Interaction Maps; Middle Aged
PubMed: 38879709
DOI: 10.1038/s41598-024-64720-2 -
Scientific Reports Jun 2024Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut...
Dapagliflozin (DAPA) demonstrates promise in the management of diabetic mellitus (DM) and cardiomyopathy. Trimethylamine N-oxide (TMAO) is synthesized by the gut microbiota through the metabolic conversion of choline and phosphatidylcholine. Ferroptosis may offer novel therapeutic avenues for the management of diabetes and myocardial ischemia-reperfusion injury (IRI). However, the precise mechanism underlying ferroptosis in cardiomyocytes and the specific role of TMAO generated by gut microbiota in the therapeutic approach for DM and myocardial IRI utilizing DAPA need to be further explored. Nine male SD rats with specific pathogen-free (SPF) status were randomly divided equally into the normal group, the DM + IRI (DIR) group, and the DAPA group. The diversity of the gut microbiota was analyzed using 16S rRNA gene sequencing. Additionally, the Wekell technique was employed to measure the levels of TMAO in the three groups. Application of network pharmacology to search for intersection targets of DAPA, DIR, and ferroptosis, and RT-PCR experimental verification. Ultimately, the overlapping targets that were acquired were subjected to molecular docking analysis with TMAO. The changes of Bacteroidetes and Firmicutes in the gut microbiota of DIR rats were most significantly affected by DAPA. Escherichia-Shigella and Prevotella_9 within the phylum Bacteroidetes could be identified as the primary effects of DAPA on DIR. Compared with the normal group, the TMAO content in the DIR group was significantly increased, while the TMAO content in the DAPA group was decreased compared to the DIR group. For the network pharmacology analysis, DAPA and DIR generated 43 intersecting target genes, and then further intersected with ferroptosis-related genes, resulting in 11 overlapping target genes. The mRNA expression of ALB, HMOX1, PPARG, CBS, LCN2, and PPARA decreased in the DIR group through reverse transcription polymerase chain reaction (RT-PCR) validation, while the opposite trend was observed in the DAPA group. The docking score between TMAO and DPP4 was - 5.44, and the MM-GBSA result of - 22.02 kcal/mol. It epitomizes the finest docking performance among all the target genes with the lowest score. DAPA could reduce the levels of metabolite TMAO produced by gut microbiota, thereby regulating related target genes to decrease ferroptosis in DIR cardiomyocytes.
Topics: Animals; Ferroptosis; Gastrointestinal Microbiome; Male; Myocardial Reperfusion Injury; Benzhydryl Compounds; Methylamines; Rats; Glucosides; Rats, Sprague-Dawley; Molecular Docking Simulation; Diabetes Mellitus, Experimental
PubMed: 38879701
DOI: 10.1038/s41598-024-64909-5 -
Scientific Reports Jun 2024The purpose of this research was to examine the potential effects of bentonite (BN) supplemented diets on growth, feed utilization, blood biochemistry, and...
Bentonite-supplemented diets improved fish performance ammonia excretion haemato-biochemical analyses immunity antioxidants and histological characteristics of European seabass Dicentrarchus labrax.
The purpose of this research was to examine the potential effects of bentonite (BN) supplemented diets on growth, feed utilization, blood biochemistry, and histomorphology of Dicentrarchus labrax. Six treatments in triplicate were tested: B0, B0.5, B1.0, B1.5, B3.0, and B4.5, which represented fish groups fed diets supplemented with 0, 0.5, 1, 1.5, 3, and 4.5% BN, respectively. For 84 days, juveniles' seabass (initial weight = 32.73 g) were fed diets containing 46% protein, three times daily at 3% of body weight. With a 5% daily water exchange, underground seawater (32 ppt) was used. Findings revealed significant improvements in water quality (TAN and NH3), growth (FW, WG and SGR) and feed utilization (FCR, PER and PPV) in fish fed BN-supplemented diets, with the best values in favor of the B1.5 group. Additional enhancements in kidney function indicators (urea and uric acid) and liver enzymes were observed in fish of the BN-treated groups along with a decrease in cholesterol level in the B1.5 group. Further improvements in fish innate immunity (hemoglobin, red blood cells, glucose, total protein, globulin, and immunoglobulin IgM), antioxidant activity (total antioxidative capacity and catalase), and decreased cortisol levels in fish of the BN-treated groups. Histological examinations of the anterior and posterior intestines and liver in groups B1.5 and B3 revealed the healthiest organs. This study recommends BN at a concentration of 1.5% as a feed additive in the Dicentrarchus labrax diet.
Topics: Animals; Bass; Antioxidants; Dietary Supplements; Bentonite; Ammonia; Animal Feed; Diet
PubMed: 38879696
DOI: 10.1038/s41598-024-63936-6 -
Communications Biology Jun 2024Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our...
Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms. Employing single-cell RNA-seq and 16 s rRNA amplicon sequencing to analyze distinct cell clusters and microbiomes in the mouse colon at different time points after induction with dextran sodium sulfate. We observe a significant reduction in epithelial populations during acute colitis, indicating tissue damage, with a partial recovery observed in chronic inflammation. Analyses of cell-cell interactions demonstrate shifts in networking patterns among different cell types during disease progression. Notably, macrophage phenotypes exhibit diversity, with a pronounced polarization towards the pro-inflammatory M1 phenotype in chronic conditions, suggesting the role of macrophage heterogeneity in disease severity. Increased expression of Nampt and NOX2 complex subunits in chronic UC macrophages contributes to the inflammatory processes. The chronic UC microbiome exhibits reduced taxonomic diversity compared to healthy conditions and acute UC. The study also highlights the role of T cell differentiation in the context of dysbiosis and its implications in colitis progression, emphasizing the need for targeted interventions to modulate the inflammatory response and immune balance in colitis.
Topics: Animals; Colitis, Ulcerative; Gastrointestinal Microbiome; Macrophages; Dextran Sulfate; Mice; Single-Cell Analysis; RNA-Seq; Mice, Inbred C57BL; Disease Models, Animal; DNA Barcoding, Taxonomic; RNA, Ribosomal, 16S; Male; Single-Cell Gene Expression Analysis
PubMed: 38879692
DOI: 10.1038/s42003-024-06409-w -
Scientific Reports Jun 2024Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects...
Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8-10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [C]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.
Topics: Animals; Acute Kidney Injury; Liver; Glutathione; Energy Metabolism; Kidney; Male; Mice; Mice, Inbred C57BL; Ischemia; Metabolomics; Disease Models, Animal; Oxidative Stress; Glycolysis; Metabolome
PubMed: 38879688
DOI: 10.1038/s41598-024-64586-4 -
NPJ Precision Oncology Jun 2024Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin,... (Review)
Review
Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin, radixin, and moesin (ERM) family of proteins, merlin, which is encoded by NF2, regulates diverse cellular events and signalling pathways, such as the Hippo, mTOR, RAS, and cGAS-STING pathways. However, the biological role of NF2 in tumorigenesis has not been fully elucidated. Furthermore, cross-cancer mutations may exert distinct biological effects on tumorigenesis and treatment response. In addition to the functional inactivation of NF2, the codeficiency of other genes, such as cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), BRCA1-associated protein-1 (BAP1), and large tumor suppressor 2 (LATS2), results in unique tumor characteristics that should be considered in clinical treatment decisions. Notably, several recent studies have explored the metabolic and immunological features associated with NF2, offering potential insights into tumor biology and the development of innovative therapeutic strategies. In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin-deficient malignancies. This review may provide a deeper understanding of the biological roles of NF2 and guide possible therapeutic avenues.
PubMed: 38879686
DOI: 10.1038/s41698-024-00627-5 -
Scientific Reports Jun 2024Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a...
Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a serious health risk due to emerging variants of concern. DNA vaccines gained importance during the pandemic due to their advantages such as induction of both arms of immune response, rapid development, stability, and safety profiles. Here, we report the immunogenicity and protective efficacy of a DNA vaccine encoding spike protein with D614G mutation (named pcoSpikeD614G) and define a large-scale production process. According to the in vitro studies, pcoSpikeD614G expressed abundant spike protein in HEK293T cells. After the administration of pcoSpikeD614G to BALB/c mice through intramuscular (IM) route and intradermal route using an electroporation device (ID + EP), it induced high level of anti-S1 IgG and neutralizing antibodies (P < 0.0001), strong Th1-biased immune response as shown by IgG2a polarization (P < 0.01), increase in IFN-γ levels (P < 0.01), and increment in the ratio of IFN-γ secreting CD4 (3.78-10.19%) and CD8 (5.24-12.51%) T cells. Challenging K18-hACE2 transgenic mice showed that pcoSpikeD614G administered through IM and ID + EP routes conferred 90-100% protection and there was no sign of pneumonia. Subsequently, pcoSpikeD614G was evaluated as a promising DNA vaccine candidate and scale-up studies were performed. Accordingly, a large-scale production process was described, including a 36 h fermentation process of E. coli DH5α cells containing pcoSpikeD614G resulting in a wet cell weight of 242 g/L and a three-step chromatography for purification of the pcoSpikeD614G DNA vaccine.
Topics: Vaccines, DNA; Spike Glycoprotein, Coronavirus; Animals; Humans; SARS-CoV-2; Mice; COVID-19; HEK293 Cells; Mice, Inbred BALB C; COVID-19 Vaccines; Mutation; Antibodies, Viral; Antibodies, Neutralizing; Female; Immunogenicity, Vaccine; Immunoglobulin G
PubMed: 38879684
DOI: 10.1038/s41598-024-64690-5