Metabolomics Reveals the Mechanisms for the Pulmonary Toxicity of Siegesbeckia orientalis L. and the Toxicity-Reducing Effect of Processing

Siegesbeckia orientalis L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO–induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO–induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.

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The Role of Cell Metabolism in Innate Immune Memory

Journal of Innate Immunity ◽

10.1159/000512280 ◽

2020 ◽

pp. 1-9

Author(s):

Anaisa Valido Ferreira ◽

Jorge Domiguéz-Andrés ◽

Mihai Gheorghe Netea

Keyword(s):

Metabolic Pathways ◽

Tricarboxylic Acid Cycle ◽

Cell Metabolism ◽

Innate Immune ◽

Immune Memory ◽

Functional Changes ◽

Trained Immunity ◽

Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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Long-term Diet Quality and Gut Microbiome Functionality: A Prospective, Shotgun Metagenomic Study among Urban Chinese Adults

Current Developments in Nutrition ◽

10.1093/cdn/nzab026 ◽

2021 ◽

Vol 5 (4) ◽

Author(s):

Danxia Yu ◽

Yaohua Yang ◽

Jirong Long ◽

Wanghong Xu ◽

Qiuyin Cai ◽

...

Keyword(s):

Diet Quality ◽

Gut Microbiome ◽

Metabolic Pathways ◽

Gene Families ◽

Diet Group ◽

Healthy Diet ◽

Chinese Adults ◽

Α Diversity ◽

Unhealthy Diet

ABSTRACT Background Diet is known to affect human gut microbiome composition; yet, how diet affects gut microbiome functionality remains unclear. Objective We compared the diversity and abundance/presence of fecal microbiome metabolic pathways among individuals according to their long-term diet quality. Methods In 2 longitudinal cohorts, we assessed participants’ usual diets via repeated surveys during 1996–2011 and collected a stool sample in 2015–2018. Participants who maintained a healthy or unhealthy diet (i.e., stayed in the highest or lowest quintile of a healthy diet score throughout follow-up) were selected. Participants were excluded if they reported a history of cancer, cardiovascular disease, diabetes, or hypertension; had diarrhea or constipation in the last 7 d; or used antibiotics in the last 6 mo before stool collection. Functional profiling of shotgun metagenomics was performed using HUMAnN2. Associations of dietary variables and 420 microbial metabolic pathways were evaluated via multivariable-adjusted linear or logistic regression models. Results We included 144 adults (mean age = 64 y; 55% female); 66 had an unhealthy diet and 78 maintained a healthy diet. The healthy diet group had higher Shannon α-diversity indexes of microbial gene families and metabolic pathways (both P < 0.02), whereas β-diversity, as evaluated by Bray-Curtis distance, did not differ between groups (both P > 0.50). At P < 0.01 [false discovery rate (FDR) <0.15], the healthy diet group showed enriched pathways for vitamin and carrier biosynthesis (e.g., tetrahydrofolate, acetyl-CoA, and l-methionine) and tricarboxylic acid (TCA) cycle, and increased degradation (or reduced biosynthesis) of certain sugars [e.g., cytidine monophosphate (CMP)-legionaminate, deoxythymidine diphosphate (dTDP)-l-rhamnose, and sucrose], nucleotides, 4-aminobutanoate, methylglyoxal, sulfate, and aromatic compounds (e.g., catechol and toluene). Meanwhile, several food groups were associated with the CMP-legionaminate biosynthesis pathway at FDR <0.05. Conclusions In a small longitudinal study of generally healthy, older Chinese adults, we found long-term healthy eating was associated with increased α-diversity of microbial gene families and metabolic pathways and altered symbiotic functions relevant to human nutrition and health.

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Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

International Journal of Molecular Sciences ◽

10.3390/ijms22126274 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6274

Author(s):

María Fernández ◽

Alicia de de Coo ◽

Inés Quintela ◽

Eliane García ◽

Márcio Diniz-Freitas ◽

...

Keyword(s):

Down Syndrome ◽

Metabolic Pathways ◽

Nominal Significance ◽

Severe Periodontitis ◽

Gene Level ◽

Individual Marker ◽

The Individual ◽

Control Study ◽

Marker Level

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10−05, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10−05, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10−05, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10−05, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10−05, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10−02, p = 5.1 × 10−03, p = 1.2 × 10−02, respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.

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Subthreshold Micropulse Laser Modulates Retinal Neuroinflammatory Biomarkers in Diabetic Macular Edema

Journal of Clinical Medicine ◽

10.3390/jcm10143134 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3134

Author(s):

Luisa Frizziero ◽

Andrea Calciati ◽

Giulia Midena ◽

Tommaso Torresin ◽

Raffaele Parrozzani ◽

...

Keyword(s):

Macular Edema ◽

Laser Treatment ◽

Diabetic Macular Edema ◽

Metabolic Pathways ◽

Treatment Method ◽

Micropulse Laser ◽

Subthreshold Micropulse Laser ◽

Inflammatory Processes ◽

Standardized Parameters

Subthreshold micropulse laser treatment has become a recognized option in the therapeutic approach to diabetic macular edema. However, some yet undefined elements pertaining to its mechanism of action and most effective treatment method still limit its clinical diffusion. We reviewed the current literature on subthreshold micropulse laser treatment, particularly focusing on its effects on the modulation of retinal neuroinflammation. Subthreshold micropulse laser treatment seems to determine a long-term normalization of specific retinal neuroinflammatory metabolic pathways, contributing to the restoration of retinal homeostasis and the curtailing of local inflammatory processes. Optimized and standardized parameters ensure effective and safe treatment.

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Leaf proteome modulation and cytological features of seagrass Cymodocea nodosa in response to long-term high CO2 exposure in volcanic vents

Scientific Reports ◽

10.1038/s41598-020-78764-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Amalia Piro ◽

Letizia Bernardo ◽

Ilia Anna Serra ◽

Isabel Barrote ◽

Irene Olivé ◽

...

Keyword(s):

Metabolic Pathways ◽

Total Protein Content ◽

Cymodocea Nodosa ◽

Cell Respiration ◽

Strong Reduction ◽

Vulcano Island ◽

Leaf Tissues ◽

Cytological Features ◽

Harvesting Process

AbstractSeagrass Cymodocea nodosa was sampled off the Vulcano island, in the vicinity of a submarine volcanic vent. Leaf samples were collected from plants growing in a naturally acidified site, influenced by the long-term exposure to high CO2 emissions, and compared with others collected in a nearby meadow living at normal pCO2 conditions. The differential accumulated proteins in leaves growing in the two contrasting pCO2 environments was investigated. Acidified leaf tissues had less total protein content and the semi-quantitative proteomic comparison revealed a strong general depletion of proteins belonging to the carbon metabolism and protein metabolism. A very large accumulation of proteins related to the cell respiration and to light harvesting process was found in acidified leaves in comparison with those growing in the normal pCO2 site. The metabolic pathways linked to cytoskeleton turnover also seemed affected by the acidified condition, since a strong reduction in the concentration of cytoskeleton structural proteins was found in comparison with the normal pCO2 leaves. Results coming from the comparative proteomics were validated by the histological and cytological measurements, suggesting that the long lasting exposure and acclimation of C. nodosa to the vents involved phenotypic adjustments that can offer physiological and structural tools to survive the suboptimal conditions at the vents vicinity.

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Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

10.22541/au.160655409.95797246/v1 ◽

2020 ◽

Author(s):

Zhenhua Dang ◽

Yuanyuan Jia ◽

Yunyun Tian ◽

Jiabin Li ◽

Yanan Zhang ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Pathways ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Grazing Intensity ◽

Glycolate Oxidase ◽

Bisphosphate Carboxylase ◽

Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

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Effects of 5-Ion Beam Irradiation and Hindlimb Unloading on Metabolic Pathways in Plasma and Brain of Behaviorally Tested WAG/Rij Rats

Frontiers in Physiology ◽

10.3389/fphys.2021.746509 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jacob Raber ◽

Sarah Holden ◽

Reetesh Sudhakar ◽

Reed Hall ◽

Breanna Glaeser ◽

...

Keyword(s):

Total Body Irradiation ◽

Metabolic Pathways ◽

Ion Beam ◽

Cognitive Testing ◽

Hindlimb Unloading ◽

Ion Beam Irradiation ◽

Behavioral Measures ◽

Mixed Beam ◽

Total Body

A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham-irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.

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Evaluation of Acute Hematologic and Long-Term Pulmonary Toxicities of Radioimmunotherapy of Cryptococcus neoformans Infection in Murine Models

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.1004-1006.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 1004-1006 ◽

Cited By ~ 20

Author(s):

E. Dadachova ◽

R. A. Bryan ◽

A. Frenkel ◽

T. Zhang ◽

C. Apostolidis ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Cryptococcus Neoformans ◽

Pulmonary Toxicity ◽

Murine Models ◽

Radiation Fibrosis

ABSTRACT We evaluated acute hematological and long-term pulmonary toxicity of radioimmunotherapy in murine models of Cryptococcus neoformans infection. Activities up to 250 μCi were well tolerated by healthy A/JCr mice for 213Bi-18B7 and 188Re-18B7 monoclonal antibodies. In infected mice, doses up to 150 μCi produced only transient toxicity. The lungs of treated mice had no evidence of radiation fibrosis.

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Analiza obrazu klinicznego niedokrwistości z niedoboru witaminy B12 u dzieci

Nowa Pediatria ◽

10.25121/np.2019.23.1.40 ◽

2019 ◽

Vol 23 (1) ◽

Author(s):

Aleksandra Pankiewicz ◽

Anna Adamowicz-Salach ◽

Marek W. Karwacki ◽

Katarzyna Pawelec ◽

Katarzyna Albrecht ◽

...

Keyword(s):

Vitamin B12 ◽

Metabolic Pathways ◽

Essential Role ◽

Vitamin B12 Deficiency ◽

Neurological Damage ◽

Laboratory Findings ◽

Delay In Diagnosis ◽

B12 Deficiency ◽

Late Manifestation

Diagnosis of vitamin B12 deficiency could be difficult due to various and rather unspecific symptoms and often late manifestation in hematological findings. B12 has a crucial role as cofactor of many metabolic pathways and has essential role in many processes such as DNA synthesis, neuron myelination and gluconeogenesis. Blood smear has a huge role in early diagnosis and should be performed. B12 deficiency is not very common, however could be underestimated especially in developing countries. In children main cause of deficiency is exclusively breastfeeding by vitamin B12 depleted mothers. Consequences of low intake in children are more severe than in adults, because of lower liver storage. Early detection and treatment is very important, because long term deficiency could result in persistent neurological damage. Coexistence iron or folate deficiencies could result delay in diagnosis. In this article different manifestation and laboratory findings in group of children with B12 deficiency is described.

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One Step Chip Attach Materials (OSCA) for Conventional Mass Reflow Processing

International Symposium on Microelectronics ◽

10.4071/isom-tp35 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 000262-000267

Author(s):

Daniel J. Duffy ◽

Lin Xin ◽

Jean Liu ◽

Bruno Tolla

Keyword(s):

Flip Chip ◽

Polymeric Materials ◽

Cure Kinetics ◽

Filler Loading ◽

Single Step ◽

Seamless Integration ◽

Device Reliability ◽

One Step ◽

Traditional Processing

One step chip attach (OSCA) materials are dispensable polymeric materials for flip chip assembly, which are designed to flux metallic interconnections and subsequently turn into an underfill upon curing. OSCA materials enable a drastic simplification of the assembly process by combining the reflow (fluxing/soldering), defluxing and capillary underfilling steps used in traditional processing into a single step. One key challenge for the design of OSCA materials is timing the cure kinetics with fluxing activity and solder reflow during processing. A second key challenge is to factor a process-friendly rheological design into the formulation. The OSCA material rheology must allow for high filler loading levels, seamless integration with standard dispensing equipment, flow control during and after dispense (avoid keep out zones), flow during die placement (elimination of voids), after placement (fillet formation) and during reflow. The final key requirements for a functional device are defect-free interconnections combined with optimal thermo-mechanical and water resistant properties of the final underfill to guarantee the long-term reliability of the assembly in various environmental conditions. This paper presents the properties of materials designed by Kester for use in mass reflow processing (OSCA-R). The rheological design principles behind a seamless integration into customer-friendly processes will be presented In addition results illustrating the timing of cure kinetics with fluxing and soldering events during processing will be discussed. Preliminary device reliability results will also be presented for several types of test vehicles including; Si-Si and Si-FR4.

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