Search Results (1,675)

Phosphine (PH₃) is a fumigant often used to control insect pests, but its metabolic effects on insect physiology remain unclear. In this study, a comparative metabolomics analysis was performed to elucidate the physiological metabolic pathways affected by PH₃ exposure in Planococcus citri, and significant changes in the metabolic profiles induced by PH₃ treatment were identified. Principal component analysis and correlation analysis revealed different metabolic changes, and a total of 45 metabolites were identified and mapped to metabolic pathways using the KEGG database. PH₃ exposure inhibited energy metabolism by down-regulating riboflavin and flavin adenine dinucleotide, which are important cofactors in oxidative phosphorylation and reactive oxygen species generation. In addition, purine and pyrimidine metabolism, essential for nucleotide synthesis and cellular energy homeostasis, were also suppressed. Notably, lipid metabolism was significantly altered, and the juvenile hormone biosynthesis pathway was down-regulated. These results suggest that PH₃ inhibits electron transport chain activity, induces oxidative stress, and disrupts lipid homeostasis. This study enhances our understanding of the potential biomarkers of PH₃ exposure, the metabolic processes involved, and the resistance mechanisms that pests may develop in response to such exposure. Full article

Variegated Cymbidium lancifolium is a highly valued ornamental plant sought after in local and international markets. The commercial production of variegated C. lancifolium through traditional propagation methods faces significant challenges, such as low propagation rates and prolonged growth periods. This study aims to develop effective in vitro propagation techniques for variegated C. lancifolium through asymbiotic seed germination to enhance production efficiency and meet market demand. We examined the effects of various plant growth regulators and coconut water (CW) on in vitro seed germination. The highest germination percentage (46.8%) was recorded in Murashige and Skoog (MS) medium supplemented with 50 mL/L CW, 4.0 µM α-naphthalene acetic acid (NAA), 2.3 µM kinetin (KN), and 2.9 µM gibberellic acid (GA₃). Seed-derived rhizomes were placed on MS medium containing indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), and NAA for proliferation. Among the auxins, NAA was the most effective, significantly increasing rhizome proliferation, with the highest number (17.4) and length (2.1 cm) observed at 5.0 µM. The rhizome explants were cultured in MS medium enriched with kinetin (KN), N⁶-(2-isopentenyl)adenine (2-IP), and N⁶-benzyladenine (BA) to promote plantlet regeneration. Of the cytokinins tested, BA at 10.0 µM resulted in the highest rate of plantlet regeneration (79.4%), the greatest number of plantlets (4.4 per culture), and notable plantlet height (8.5 cm). We obtained plantlets with dark green leaves, light green leaves, and distinct variegation patterns. They were transferred to three different substrate mixtures for acclimatization. The substrate made of orchid stone (30%), wood bark (30%), coconut husk chips (20%), and perlite (20%) supported the highest survival rate (95.9%). This study successfully established optimized in vitro propagation techniques for variegated C. lancifolium, enabling enhanced germination, rhizome proliferation, and plantlet regeneration to meet the growing market demand. Full article

Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition. Full article

Adenosine deaminase (ADA) is one of the most important enzymes in nucleoside metabolism, regulating the levels of adenosine and deoxyadenosine triphosphate (ADT/dATP) on either side of the cell membrane. This small protein (weighing approximately 40 kDa) exhibits deamination properties towards other pharmaceuticals built on adenine as the leading structure, which requires co-administration of ADA inhibitors. 3′-deoxyadenosine (Cordycepin, Cord) is an active compound isolated from the fungus Cordyceps, which has been used in traditional Chinese medicine for over 2000 years. Its anticancer activity is likely related to the inhibition of primer elongation of lagging strands during genetic information replication. Unfortunately, Cord is rapidly deaminated by ADA into inactive 3′-deoxyinosine, necessitating its co-administration with ADA inhibitors. Here, for the first time, the synthesis and discussion of the oxidised form of Cord are presented. The 7,8-dihydro-8-oxo-3′-deoxyadenosine (Cord^OXO) exhibits high resistance to ADA because of its syn conformation, as shown experimentally by UV spectroscopy and RP-HPLC monitoring. Theoretical Density Functional based Tight Binding (DFTB) studies of the Michaelis complex ADA-Cord^OXO have revealed significant distance increases between the “active” H₂O molecule and C6 of the 8-oxo-adenine moiety of Cord^OXO, i.e., 4 Å as opposed to 2.7 Å in the cases of ADA-dAdo and Cord. In conclusion, it can be postulated that the conversion of Cord to Cord^OXO enhances its therapeutic potential; however, this needs to be verified in vitro and in vivo. It should be emphasised that the therapeutic effect, if any, can be achieved theoretically without ADA inhibitors, e.g., pentostatin, thus reducing adverse effects. These promising preliminary results, presented here, warrant further investigations. Full article

Ajuga bracteosa is a herb with high medicinal value and a low range of distribution. It is used in several herbal and traditional medicines, including diabetes. In the present study, we designed the methodology for the micropropagation of A. bracteosa from internodal segments. The highest shoot multiplication was achieved on Murashige and Skoog (MS) medium supplemented with 6-benzyl-amino-purine (BAP) (5.0 µM) + indole-3-acetic acid (IAA) (1.5 µM) + adenine sulphate (ADS) (15.0 µM), which produced the maximum number of 20.45 ± 0.12 shoots/explants with 6.43 ± 0.006 cm shoot length. Rooting in the microshoots was attained on half-strength MS medium containing indole-3-butyric acid (IBA) (1.5 µM), with the highest root number of 16.44 ± 0.015 roots/shoot, and root length of 2.25 ± 0.011 cm. To assess genetic fidelity, SCoT marker analysis was performed on nine randomly selected in vitro regenerated plantlets and the mother plant, all of which exhibited monomorphic banding patterns, confirming genetic stability. Scanning electron microscopy (SEM) reveals normal stomatal structure in the regenerated plants post-acclimatization, indicating successful physiological recovery. Furthermore, Gas Chromatography–Mass Spectrometry (GC-MS) analysis confirms the presence of major phytocompounds in both the in vitro regenerated plants and the mother plant, supporting the conservation of phytochemical integrity. Given the restricted distribution and overharvesting pressure on this species, the established protocol provides an efficient strategy for rapid, large-scale, and genetically stable propagation to support conservation and pharmaceutical utilization. Full article

The relationship between periodontitis and cardiovascular diseases (CVDs) extends beyond epidemiological associations, as demonstrated by meta-analyses showing a significantly increased risk for coronary heart disease development. At the core of this association lies systemic inflammation, where periodontal pathogens initiate cascades of pro-inflammatory cytokines. This inflammatory response manifests through substantial elevations in interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in periodontitis patients. Oxidative stress plays a crucial role, with Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase 2 (NOX2) activation leading to markedly increased superoxide production compared to healthy controls. The peroxynitrite formed via NO–superoxide interaction accumulates in affected vascular tissues, substantially reducing nitric oxide (NO) bioavailability. Molecular mimicry mechanisms are evidenced by P. gingivalis heat shock protein sharing significant sequence homology with human HSP60, triggering autoimmune responses that affect cardiovascular tissues. Epigenetic modifications show specific alterations, with Nrf2 target gene expression substantially downregulated in chronic periodontal inflammation, particularly affecting heme oxygenase-1 (HO-1) and NAD(P)H:Quinone Oxidoreductase 1 (NQO1) expression. These molecular pathways create a complex network of interactions that fundamentally link periodontal and cardiovascular pathologies. Full article

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

In this study, we investigated the effects of air packaging, vacuum packaging and modified atmosphere packaging (CO₂/N₂: 80/20) on the purine metabolism and enzyme activities of refrigerated large yellow croakers. The results showed that modified atmosphere packaging significantly inhibited microbial growth, delayed adenosine triphosphate degradation and maintained higher IMP content (1.93 μmol/g on day 21) compared to the air packaging group (2.82 μmol/g on day 12). The total purine content increased with storage time, with hypoxanthine content increasing significantly and occupying most of the total content, which was the key factor for the elevation of purine, followed by adenine content showing a significant decreasing trend. Hypoxanthine accumulation was significantly suppressed in the modified atmosphere packaging group (2.31 μmol/g on day 18), which was much lower than that in the air packaging group (5.64 μmol/g), whereas xanthine and guanine did not show significant differences among the groups. The key enzymes xanthine oxidase and purine nucleoside phosphorylase were much less active in modified atmosphere packaging, effectively delaying the cascade reaction of inosine monophosphate → hypoxanthine → xanthine. The study confirmed that modified atmosphere packaging intervenes in purine metabolism through enzyme activity regulation, providing a theoretical basis for the preservation of low purine aquatic products. Full article

Complete mitochondrial DNA genome annotation of an ecologically and commercially important fish species Cirrhinus cirrhosus was executed with next-generation sequencing (NGS) for nucleotide and phylogenetic analyses. The findings of this study showed that the Cirrhinus cirrhosus mitochondrial genome contained 16,593 bp, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and a D-loop region. The overall base composition was 32% adenine, 25% thiamine, 16% guanine, and 27% cytosine. This mitochondrial DNA exhibits an AT biasness, with 56% AT content in its genome. Significant fluctuations were identified in the AT and GC skew values of the ND6 gene, indicating that the selection and mutation forces acting on this gene might be different from those acting on other genes. The Ka/Ks ratios of most protein-coding genes were less than 1, indicating very strong natural selection pressure. Phylogenetic analysis of Cirrhinus cirrhosus with Cirrhinus mrigala and Bangana tungting suggested a closer evolutionary relationship among these species, which might have shared a more recent common ancestor. It has been also found that the genera Labeo and Cirrhinus are not monophyletic. Full article

This work aims to solve the problem of product quality fluctuations caused by batch-to-batch variations in the adsorption capacity of activated carbon during the production of traditional Chinese medicine (TCM) injections. In this work, Shenqi Fuzheng injection was selected as an example. Diluted Shenqi Extract (DSE), an intermediate in the production process of Shenqi Fuzheng injection, was adsorbed with different batches of activated carbon. The adsorption capacities of adenine, adenosine, calycosin-7-glucoside, and astragaloside IV in DSE were selected as evaluation indices for activated carbon absorption. Characterization methods such as nitrogen adsorption, X-ray photoelectron spectrum (XPS), and Fourier transform infrared (FTIR) were chosen to explore the quantitative relationships between the properties of activated carbon (i.e., specific surface area, pore volume, surface elements, and spectrum) and the adsorption capacities of these four components. It was found that the characteristic wavelengths from FTIR characterization, i.e., 1560 cm⁻¹, 2325 cm⁻¹, 3050 cm⁻¹, and 3442 cm⁻¹, etc., showed the strongest correlation with the adsorption capacities of these four components. Prediction models based on the transmittance at characteristic wavelengths were successfully established via multiple linear regression. In validation experiments of models, the relative errors of predicted adsorption capacities of activated carbon were mostly within 5%, indicating good predictive ability of the models. The results of this work suggest that the prediction method of adsorption capacity based on the mid-infrared spectrum can provide a new way for the quality control of activated carbon. Full article

Gut microbiota-derived trimethylamine N-oxide (TMAO) has been implicated in both intestinal and renal diseases; however, its specific role in modulating gut–kidney interactions remains unclear. This study aimed to investigate the effects of TMAO on gut–kidney crosstalk using a mouse model of diarrhea. Mice were divided into four groups: normal, model, TMAO, and TMAO + model. The normal group received sterile water, while the other groups were administered adenine + Folium sennae, TMAO, or a combination of TMAO and adenine + Folium sennae. Samples were collected to assess morphological changes in the colon and kidney, evaluate the colonic mucosal barrier and renal function, and measure NLRP3 inflammasome activity and inflammatory cytokine levels in colonic and renal tissues. TMAO levels and the gut microbiota composition were analyzed using 16S rRNA sequencing. The model group exhibited altered stool morphology, which was further aggravated by TMAO intervention. Both the model and TMAO + model groups exhibited significant damage to intestinal and renal tissues, along with compromised intestinal mucosal barriers and impaired renal function compared to controls. Inflammatory markers were elevated in these groups, with the TMAO + model group showing the most pronounced increases. Correlation analysis indicated significant relationships among TMAO levels, inflammasome activation, and inflammatory cytokines. The genera Mucispirillum and Anaerotruncus negatively correlated with TMAO, whereas Parabacteroides and Parasutterella genera positively correlated with TMAO. In conclusion, TMAO plays a critical role in modulating gut–kidney crosstalk by promoting inflammation, disrupting mucosal and renal integrity, and altering the gut microbial ecosystem. Full article

Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca²⁺ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca²⁺ elevation was detected, chelation of intracellular Ca²⁺ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca²⁺-depleted conditions. CEP activates Ca²⁺-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article

This pilot study investigated the metabolic responses of five selected bacteria to physiological stress. Surface-enhanced Raman spectroscopy was used to analyze spectral changes associated with the release of adenine, a key metabolite indicative of stress conditions. Laboratory-synthesized spherical silver and gold nanoparticles, which remained stable over an extended period, were employed as enhanced surfaces. Bacterial cultures were analyzed under standard conditions and in the presence of a selected stressor—demineralized water—inducing osmotic stress. The results showed that the adenine signal originated from metabolites released into the surrounding environment rather than directly from the bacterial cell wall. The study confirms the suitability of these cost-effective and easily synthesized stable nanoparticles for the qualitative detection of bacterial metabolites using a commercially available Raman instrument. Full article

Sarcopenia, the progressive loss of muscle mass, strength, and regenerative capacity with age, is driven by interconnected processes such as oxidative stress, chronic inflammation, mitochondrial dysfunction, and reduced activity of muscle stem cells. As the population ages, nutritional strategies that target these mechanisms are becoming increasingly important. This review focuses on nicotinamide (vitamin B3) and pyridoxine (vitamin B6), two essential micronutrients found in functional foods, which play complementary roles in redox regulation, immune balance, and muscle repair. Nicotinamide supports nicotinamide adenine dinucleotide (NAD⁺) metabolism, boosts mitochondrial function, and activates sirtuin pathways involved in autophagy and stem cell maintenance. Pyridoxine, via its active form pyridoxal 5′-phosphate (PLP), is key to amino acid metabolism, antioxidant defense, and the regulation of inflammatory cytokines. We summarize how these vitamins influence major molecular pathways such as Sirtuin1 (SIRT1), protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), Nuclear factor-κB (NF-κB), and Nrf2, contributing to improved myogenic differentiation and protection of the aging muscle environment. We also highlight emerging preclinical and clinical data, including studies suggesting possible synergy between B3 and B6. Finally, we discuss how biomarkers such as PLP, nicotinamide mononucleotide (NMN), and C-reactive protein (CRP) may support the development of personalized nutrition strategies using these vitamins. Safe, accessible, and mechanistically grounded, nicotinamide and pyridoxine offer promising tools for sarcopenia prevention and healthy aging. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article