Search Results (503)

By examining a novel nanomaterial that has been modified for use in sustainable construction, this study primarily responds to the growing need for environmentally acceptable materials. The primary goal was to improve the functional and aesthetic qualities of building materials by synthesizing and characterizing environmentally friendly clay-based nanomaterials doped with cobalt pyrophosphate (Co₂P₂O₄). The authors employed contemporary experimental methods, such as scanning electron microscopy (SEM) for morphological characterisation, Fourier transform infrared spectroscopy (FT-IR) for molecular bonding assessment, and X-ray diffraction (XRD) for crystal structure research. The published findings show the doped nanomaterials’ potential durability as well as their structural integrity. An economic assessment is part of the investigation. The study is noteworthy for emphasizing the potential of cobalt-doped pyrophosphate nanoparticles as eco-friendly colour pigments for construction materials made of clay. Full article

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D₃ (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using ⁹⁹mTc-pyrophosphate (⁹⁹mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic ⁹⁹mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, ⁹⁹mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article

Background: The number of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been increasing recently, and the early diagnosis and treatment of it are important. ^99mTc pyrophosphate scintigraphy (^99mTc-PYP) plays a key role in the early diagnosis of ATTR-CM. In patients who underwent ^99mTc-PYP, the early diagnosis of ATTR-CM by echocardiography was evaluated, focusing on left ventricular myocardial form and left ventricular wall thickness. Methods: The present study was conducted on 144 patients who underwent ^99mTc-PYP between February 2020 and March 2024. A comparison was made between the ^99mTc-PYP positive (P) and negative (N) groups, and significant factors were subjected to multivariate analysis. Results: 17 of 144 patients were positive (14.9%), and 15 patients were diagnosed with ATTR-CM by myocardial or skin (fat) biopsy. Other positive patients were also clinically considered to have ATTR-CM based on findings such as poor cardiac function and cerebral hemorrhage. ^99mTc-PYP positive had a significantly larger CTR (60.3% in the P group vs. 53.9% in the N group, p = 0.007) and a larger left atrial diameter (42.8 mm in the P group vs. 40.0 mm in the N group, p = 0.047). On the other hand, the mean LV wall thickness was significantly thicker (15.7 mm in the P group vs. 12.8 mm in the N group, p < 0.001); however the LV end-diastolic diameter was smaller (41.9 mm in the P group vs. 48.4 mm in the P group, p < 0.001). The LV mass was similar in both groups, thus the relative left ventricular wall thickness (RWT), which indicates relative wall thickening, was significantly higher in the P group (0.85 in the P group vs. 0.52 mm in the N group, p < 0.001). The receiver operating characteristic curve of RWT for assessing ^99mTc-PYP positivity had a cut-off value of 0.717 (area under the curve 0.862, 95%CI 0.763–0.961). Conclusions: The evaluation of wall thickness and RWT on echocardiography is important for diagnosing ATTR-CM. Full article

Pyruvate decarboxylase (PDC) is an intracellular non-oxidizing enzyme that relies on thiamine pyrophosphate (TPP), which is important for plant survival under anaerobic conditions and increasingly recognized for its role in broader stress reaction. However, the PDC gene family of tomato (Solanum lycopersicum), an important waterlogging-sensitive agricultural product, has not yet been discovered. In this study, eight SlPDC genes were discovered within the tomato genome. Gene structure analysis revealed that SlPDC members exhibited varying intron–exon configurations, with SlPDC8 possessing the most complex structure containing seven introns. Promoter analysis revealed a multitude of cis-acting elements responsive to light, hormones, and various stresses. Particularly, the promoter of SlPDC8 contains both ABRE and TGACG/CGTCA-motif. Tissue-specific expression profiles showed that SlPDC8 was mainly highly expressed in the roots. Expression profiling demonstrated that SlPDC genes respond divergently to different abiotic stresses, including salt, hydrogen peroxide (H₂O₂), drought, waterlogging, cold, heat, darkness, and UV radiation stresses. Notably, SlPDC1, SlPDC7, and SlPDC8 were significantly upregulated by waterlogging, with SlPDC8 showing the most robust induction. Functional validation through VIGS proved that SlPDC8-silenced plants exhibited significantly impaired growth, decreased photosynthetic pigment content, severe leaf wilting, and poor root development under waterlogging conditions compared to control plants. Furthermore, silencing SlPDC8 led to increased malondialdehyde (MDA) levels and decreased antioxidant enzyme activities, indicating heightened oxidative damage under waterlogging stress. We conclusively demonstrate that SlPDC8 plays a critical positive regulatory role in waterlogging tolerance by maintaining cellular homeostasis and enhancing antioxidant capacity. Full article

Background: Oral iron supplementation or food fortification is essential for managing or preventing iron deficiency but often causes gastrointestinal side effects. While solubility has traditionally been considered a requirement for iron uptake via the DMT1 transporter, recent evidence shows that insoluble iron can also be absorbed through endocytosis, raising questions about particle size and epithelial responses. Methods: Human intestinal cell lines (Hutu-80 and Caco-2) were exposed to physiologically relevant but elevated iron levels (0.5 mM Fe, 48 h) as ferric pyrophosphate, ferrous fumarate (both prone to precipitation), and soluble ferric EDTA. Cell survival and COX-2 protein were quantified by ELISA, solubility by ICP-OES, and particle size in cell culture medium by dynamic light scattering analyses. Results: Ferric pyrophosphate (0.62–3.8 μm) markedly increased COX-2 expression in Hutu-80 cells (254% ± 37%, n = 3, p = 4.11 × 10⁻⁵) and in Caco-2 cells (78% ± 8%, n = 3, p = 0.01) compared to the control. Ferrous fumarate (237–866 nm) also induced COX-2, but only in Hutu-80 cells (62% ± 11%, n = 3, p = 0.04), whereas ferric EDTA showed no effect in either cell line. COX-2 induction was associated with larger particles in the medium (≥237 nm), whereas smaller particles (<146 nm) were not. Conclusions: Particle size appears to be a critical determinant of cell survival and iron-induced epithelial COX-2 expression. Iron compounds that present as both soluble and particulate forms may optimize bioavailability, but controlling aggregate size (<146 nm) could reduce inflammatory signaling. These findings may have important implications for cell culture systems and warrant in vivo validation in iron supplemental studies. Full article

Background/Objectives: Cutaneous leishmaniasis (CL) is a prevalent vector-borne disease characterized by a broad spectrum of clinical manifestations resulting from protozoan parasites belonging to the genus Leishmania. The challenges associated with the treatment of CL are attributable to various factors, including but not limited to: drug resistance, the adverse effects of conventional therapeutic interventions and the imperative for novel therapeutic alternatives to address the global health burden posed by this neglected tropical disease. Methods: In this study, The therapeutic efficacy of two silver(I)-N-heterocyclic carbene (NHC) complexes, namely chloro[1-methallyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2a) and chloro[1-methallyl-3-(4-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2b), was evaluated against promastigotes in vitro and in vivo in an experimentally induced CL model in Balb/c mice. Results: The findings of this study indicated that these compounds possess the potential to function as effective therapeutic agents, particularly in the treatment of CL. Subsequently, the silver(I) complexes were analyzed by means of molecular docking against LaGP63, LaARG, N-myristoyltransferase and farnesyl pyrophosphate synthase. Conclusions: According to the docking evaluations, complex 2a emerged as the most notable molecule in terms of its potential antileishmanial activity. Full article

The investigation aimed to use selected waste plant materials as thiamine matrices for fortification purposes. Thiamine hydrochloride (TCh) and thiamine pyrophosphate (TP) constituted the sources of thiamine. The waste vegetable variables (carrots (crowns, peel), cauliflower, and broccoli (stems, leaves)) were used as a matrix for the thiamine. The peeled carrots, without crowns, as well as the florets of cauliflower and broccoli, were also used as a matrix for thiamine, serving as a reference for the waste used. Fortification effectiveness was analysed based on thiamine content analysis in the product immediately after freeze-drying and after storage (230 days at 4, 21, and 40 °C). The results confirmed that after six months of storage, these products contained thiamine at 55 to 90% of the level found in samples immediately after drying. The results confirm the effectiveness of using analysed waste plant materials as matrices for thiamine. The highest effectiveness was confirmed for broccoli and cauliflower leaves. The analysis of the influence of all predictors on thiamine changes revealed that storage temperature significantly affected thiamine loss in all carriers. It was confirmed that the lower the storage temperature, the lower the dynamics of thiamine loss. It was also confirmed that TP had a lower thiamine retention. Full article

Background/Objectives: Linezolid is an oxazolidinone antibiotic whose prolonged use is associated with peripheral neuropathy, hyperlactatemia, and metabolic acidosis. These adverse effects are primarily linked to the inhibition of mitochondrial protein synthesis, respiratory chain dysfunction, and oxidative stress. Given the central role of impaired energy metabolism and redox imbalance in drug-induced peripheral neuropathy, therapeutic strategies targeting mitochondrial function are of particular interest. Accordingly, this study aimed to comparatively evaluate the effects of adenosine triphosphate (ATP), coenzyme Q10 (CoQ10), pyridoxine, and thiamine pyrophosphate (TPP) on linezolid-induced peripheral neuropathic pain in rats. Methods: Sixty male albino Wistar rats were assigned to ten groups: healthy (HG); ATP-only (ATPG, 5 mg/kg, intraperitoneally); CoQ10-only (CQ10G, 10 mg/kg, orally); pyridoxine-only (PDXG, 50 mg/kg, orally); TPP-only (TPPG, 20 mg/kg, intraperitoneally); linezolid-only (LZDG, 125 mg/kg, orally); linezolid+ATP (ATLG); linezolid+CoQ10 (CQLG); linezolid+pyridoxine (PXLG); and linezolid+TPP (TPLG). Treatments were administered once daily for ATP, CoQ10, and TPP, and twice daily for linezolid and pyridoxine for 14 days. Oxidative stress indices (MDA, tGSH, SOD, CAT) were quantified in the sciatic nerve using ELISA. Serum lactate dehydrogenase (LDH) activity and blood lactate levels were determined to evaluate metabolic disturbances. Mechanical paw withdrawal thresholds were measured using the Randall–Selitto test both before and after treatment. Results: Linezolid significantly reduced paw withdrawal thresholds and induced oxidative stress, antioxidant depletion, increased LDH activity, and hyperlactatemia. Co-treatment with ATP and CoQ10 attenuated oxidative stress but did not significantly improve linezolid-induced reductions in nociceptive thresholds. In contrast, pyridoxine partially alleviated linezolid-induced neuropathic pain and improved biochemical parameters. Notably, TPP exerted the most robust protective effect, preserving nociceptive thresholds and effectively normalizing oxidative stress and metabolic indices. Conclusions: These findings identify TPP as a promising therapeutic strategy for mitigating linezolid-induced peripheral neuropathic pain by targeting mitochondrial energy metabolism and pyruvate–lactate homeostasis. Full article

Magnesium alloys require protective surface coatings for widespread application, with micro-arc oxidation (MAO) being a prominent technique. However, conventional MAO coatings are typically gray or light-colored, necessitating secondary treatments for specific colors like black, which complicates the process. This study aims to develop a one-step method for fabricating black MAO coatings on AZ31 magnesium alloy by introducing cupric pyrophosphate (Cu₂P₂O₇) as a colorant into a silicate-based electrolyte. As the Cu₂P₂O₇ concentration increased from 0 to 5 g/L, the coating color transitioned from grayish-white to pink, then brownish-black, achieving a uniform black appearance at 4–5 g/L. XPS and EDS analyses confirmed the incorporation of copper as CuO, identified as the primary coloring agent. XRD indicated that the phase composition remained MgO, MgSiO₃, and Mg, although the MgO content decreased. Microstructural analysis showed that an optimal concentration of 4 g/L enhanced coating compactness by thickening the dense layer and reducing pore size. However, electrochemical tests revealed that the incorporation of CuO significantly increased the corrosion current density, thereby reducing the coating’s corrosion resistance compared to the unmodified coating. This work successfully demonstrates the one-step fabrication of black MAO coatings, elucidates the coloration mechanism involving CuO formation, and provides insights into the trade-off between aesthetic functionalization and corrosion performance. Full article

Glycerophosphocholine (GPC) and glycerophosphoinositol (GPI) are phospholipid metabolites generated by phospholipase-mediated deacylation. In budding yeast, they enter cells via the Git1 permease; in fission yeast, the homolog is Tgp1. This study investigates why GPC is toxic to asp1-STF mutants, where Tgp1 is upregulated due to loss of Asp1 pyrophosphatase, resulting in elevated inositol pyrophosphate 1,5-IP₈. We show that S. pombe Tgp1 specifically transports GPC, explaining why GPC, but not GPI, impairs growth. Increased GPC uptake slows doubling time but does not reduce viability. Toxicity is relieved by deletion of Gde1, a phosphodiesterase that hydrolyzes GPC to choline and glycerol-3-phosphate. Mutations in either the Gde1 active site or SPX domain also suppress toxicity, and radiolabeling confirms both domains are required for enzymatic activity. GPC is toxic in cells vastly overexpressing Tgp1 even without elevated IP₈, but Gde1 loss does not suppress this effect. Similarly, in S. cerevisiae overexpressing the Candida albicans Git3 transporter, GPC provision causes toxicity independent of Gde1. Loss of Gpc1, the acyltransferase converting GPC to lysophosphatidylcholine, does not alter toxicity in either yeast. These findings highlight a conserved process by which GPC regulates growth and reveal a role for IP₈ in modulating this process. Full article

Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine pyrophosphate (TPP) remain poorly defined. This study aimed to evaluate whether ATP and TPP mitigate metformin-induced renal injury through biochemical and histopathological assessments. Wistar rats were randomly divided into six groups: control, ATP, TPP, metformin, ATP + metformin, and TPP + metformin. Metformin (50 mg/kg, oral), ATP (4 mg/kg, intraperitoneal), or TPP (20 mg/kg, intraperitoneal) was administered daily for 10 days. Oxidative stress markers, inflammatory cytokines, renal histopathology, and serum creatinine, BUN, lactate, and LDH levels were evaluated. Metformin induced significant oxidative stress, inflammation, metabolic disturbance, and renal injury. ATP provided partial protection, whereas TPP markedly restored redox balance, reduced inflammation, and preserved renal histology. TPP confers superior protection against metformin-induced renal injury compared with ATP by modulating oxidative, inflammatory, and metabolic pathways, highlighting its therapeutic potential in preventing metformin-related nephrotoxicity. Full article

The uterus is a dynamic organ in which the endometrium undergoes cyclic processes of proliferation, shedding, and regeneration under the influence of estrogen and progesterone. In particular, estrogen regulates the proliferation and differentiation of the endometrium and plays an important role in the development of gynecological diseases such as endometrial cancer. Farnesyl diphosphate synthase (FDPS) is a key enzyme involved in the mevalonate pathway, catalyzing the synthesis of farnesyl pyrophosphate (FPP), which plays an essential role in cholesterol biosynthesis and protein prenylation. In this study, we demonstrated using an in vivo mouse model that the expression of FDPS is regulated by estrogen. FDPS expression was specifically elevated during the proestrus stage of the estrous cycle and subsequently decreased. In ovariectomized (OVX) mice, FDPS expression was significantly increased 24 h after estrogen treatment, whereas this response was suppressed by treatment with the estrogen receptor alpha (ERα) antagonist, ICI 182,780. Although FDPS expression has been reported in various cancers, its role in endometrial cancer remains unclear. Histological and cellular analyses revealed that FDPS is highly expressed in human endometrial cancer tissues and in the endometrial cancer cell line Ishikawa, where it contributes to cell proliferation. These findings suggest that FDPS may play a role in the survival and growth of endometrial cancer cells. This study provides new insights into the potential function of FDPS in the uterus and suggests that targeting FDPS may represent a promising therapeutic strategy for endometrial cancer. Full article

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus with suboptimal outcomes despite standard management. Emerging evidence suggests that thiamine (vitamin B1) deficiency may play an under-recognized role in DKA pathophysiology and clinical course. This narrative review synthesizes current evidence regarding thiamine deficiency in diabetes and DKA, examining molecular mechanisms, clinical implications, and the rationale for thiamine supplementation as adjunctive therapy. Thiamine deficiency is highly prevalent in diabetes, with plasma concentrations reduced by approximately 75% compared to healthy controls. In DKA specifically, 25–35% of patients present with thiamine deficiency, which often worsens during insulin therapy. The primary mechanism involves hyperglycemia-induced downregulation of renal thiamine transporters (THTR-1 and THTR-2), resulting in 16–24-fold increased renal clearance and massive urinary losses. Thiamine pyrophosphate serves as an essential cofactor for three critical enzymes in glucose metabolism: pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase. Deficiency impairs these pathways, causing pyruvate accumulation with conversion to lactate (resulting in lactic acidosis), compromised TCA cycle function (reducing ATP production by 40–48%), and decreased NADPH generation (increasing oxidative stress). Clinical manifestations include persistent metabolic acidosis despite standard therapy, myocardial dysfunction with elevated cardiac biomarkers, neurological impairment, and prolonged recovery times. Cellular studies demonstrate that thiamine supplementation significantly improves mitochondrial oxygen consumption in DKA patients. The high prevalence of thiamine deficiency in DKA, compelling biochemical rationale, excellent safety profile, and preliminary mechanistic evidence support the urgent need for large-scale randomized controlled trials examining thiamine supplementation to definitively establish efficacy, optimal dosing, and patient selection criteria. Full article

Pathological reduction in enzymatic activity of the tissue-non-specific alkaline phosphatase (TNSALP) is the molecular hallmark of hypophosphatasia (HPP), a group of rare inborn systemic diseases, mainly characterized by pathological affections of calcified tissue mineralization and the musculoskeletal system. The disease, in all clinical forms, is biochemically characterized by variable degrees of chronically reduced activity of circulating total alkaline phosphatase (ALP). Repeated detection of low values of ALP activity is mandatory to diagnose the presence of HPP, but, alone, it is not sufficient for the diagnosis of the disease. Detection of increased circulating levels of one of the main natural substrates of TNSALP, the pyridoxal 5′-phosphate (PLP), is needed to biochemically confirm the diagnosis of HPP. Urinary and/or blood levels of phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi), two other natural substrates of TNSALP, can be elevated in a percentage of HPP patients. The contemporary biochemical evaluation of ALP activity and its target substrates is of great help in the diagnosis of HPP, and also for the monitoring of a patient’s response to enzymatic replacement therapy or other pharmacological treatments. Here, we describe and discuss possibilities and challenges of biochemical screenings for HPP, based also on the experience gained in our analysis laboratory. Full article

Studying the origin of life requires identifying chemical and physical processes that could have supported early self-replicating and evolving molecular systems. Besides the requirement of information storage and transfer, an essential aspect is an energy source that could have thermodynamically driven the formation and replication of these molecular assemblies. Chemical energy sources such as cyclic trimetaphosphate are attractive because they could drive replication with relatively simple catalysts. Here, we focus on cyclic trimetaphosphate (cTmp), and compare its solubility in water to linear triphosphate, pyrophosphate, and phosphite when Mg²⁺ or Ca²⁺ are present. These solubilities are important for facilitating the reactions under prebiotically plausible conditions. The results showed that cTmp was soluble even at molar concentrations of Mg²⁺ and little precipitation with 200 mM Ca²⁺. In contrast, pyrophosphate and linear triphosphate precipitated efficiently even at low divalent metal ion concentrations. The precipitation of phosphate was pH-dependent, showing similar precipitation with Mg²⁺ and Ca²⁺ at a prebiotically plausible pH of 6.5. Phosphite was soluble at high Mg²⁺ concentrations but started precipitating with increasing Ca²⁺ concentration. At conditions that model Archaean seawater, cTmp was the most soluble of these compounds. Together, this experimental overview may help to identify promising conditions for lab-based investigations of phosphate-based energy metabolisms in early life forms. Full article