Search Results (122)

The aim of the present study is to evaluate the impact of chromium (Cr) supplementation on glucose and lipid metabolism in breast muscle in broilers under heat stress. A total of 220 day-old broiler chicks were reared in cages. At 29 days old, 180 birds were randomly assigned to three treatments (0, 400, and 800 µg Cr/kg, as chromium picolinate) and transferred to climate chambers (31 ± 1 °C, 60 ± 7% humidity) for 14 days. Growth performance, carcass traits, serum biochemical indices, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), as well as muscle metabolomic profiles and gene expression related to energy and lipid metabolism were analyzed. The results showed that, compared with the heat stress group, the groups supplemented with 400 and 800 µg Cr/kg showed higher dry matter intake and average daily gain, breast muscle ratio, and lower feed conversion ratio and abdominal fat ratio; chickens supplemented with 400 and 800 µg Cr/kg showed significantly lower serum corticosterone (CORT), free fatty acids, and cholesterol levels compared with the heat stress (HS) group (p < 0.05). Fasting blood glucose and HOMA-IR were also significantly reduced, while fasting insulin was significantly increased in the Cr-supplemented groups (p < 0.05). Metabolomic analysis revealed that Cr supplementation regulated lipid and amino acid metabolism by altering key metabolites such as citric acid, L-glutamine, and L-proline, and modulating pathways including alanine, aspartate, and glutamate metabolism, and glycerophospholipid metabolism. Furthermore, Cr supplementation significantly upregulated the expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), ATP Binding Cassette Subfamily A Member 1 (ABCA1), Peroxisome Proliferator-Activated Receptor α (PPARα), and ATP Binding Cassette Subfamily G Member 1 (ABCG1) in both the hepatic and muscle tissue. This paper suggested that chromium supplementation may enhance energy metabolism and lipid transport like the findings of our study suggested. Full article

Calcium (Ca) is one of the most important elements determining vegetable yield, but the driving factors that regulate microbial community structure, microbial network system stability, and metabolic pathways along the soil Ca gradient remain unclear. In this work, the relationship between soil physicochemical properties and bacterial and fungal communities was investigated under distinct Ca gradients in well-established Chinese cabbage fields located in Shijiazhuang, Hebei Province, China, with sites named Group 1 (G1), Group 2 (G2), and Group 3 (G3) from lowest to highest along the soil Ca gradient. This study demonstrated that Ca exerts dual effects by modulating pH, electrical conductivity (EC), and soil organic carbon (SOC) dynamics, enhancing bacterial diversity while reinforcing fungal network stability through distinct metabolic adaptations. Bacterial networks showed reduced stability despite increased diversity, perhaps linked to the downregulation of ATP-binding cassette (ABC) transporters. Notably, Fe-Mn oxides counteracted Ca influences through selective nutrient adsorption, creating antagonistic selection pressures. Under calcium stress, both Ca and total P (TP) emerge as key drivers of microbial community restructuring, with fungal networks exhibiting significantly greater stability compared to their bacterial counterparts. This study bridges the knowledge gap in the driving mechanisms of microbial communities under soil Ca stress and provides a theoretical basis for improving vegetable yields, with implications for soil management in Ca-rich ecosystems. Full article

Familial hypercholesterolemia (FH) is a genetic disorder marked by significantly elevated levels of low-density lipoprotein cholesterol (LDL-C) since childhood, substantially increasing the risk of premature atherosclerosis and cardiovascular disease. While dysfunction of hepatic LDL-C receptors is the main underlying cause, the gastrointestinal tract plays a key role in cholesterol homeostasis and represents an important therapeutic target. Inhibition of intestinal cholesterol absorption has emerged as an effective strategy in the management of pediatric FH, particularly in patients for whom statins may not be the ideal first-line treatment. Ezetimibe, an inhibitor of the Niemann-Pick C1-like 1 (NPC1L1) protein, has been shown to reduce LDL-C levels in children with FH, with a greater efficacy observed when used in combination with statins. Bile acid sequestrants also enhance cholesterol excretion but are often limited by gastrointestinal side effects, while dietary interventions, such as phytosterol supplementation and fiber-enriched diets, provide additional benefits in lowering LDL-C and are generally well tolerated. Emerging therapies, including microbiota-targeted strategies and novel cholesterol absorption inhibitors, show promise for expanding future treatment options. This review explores the mechanisms of intestinal cholesterol absorption and their relevance to pediatric FH. We examine key pathways, including dietary cholesterol uptake through NPC1L1, bile acid reabsorption, and cholesterol efflux mediated by ATP-binding cassette transporters, while also discussing clinical and experimental evidence on pharmacological and dietary interventions that modulate these pathways. A deeper understanding of cholesterol metabolism, the emerging role of the gut microbiota, and innovative therapeutic agents can support the development of more effective and personalized approaches to the treatment of children with FH. Full article

Anthracyclines have been clinically well established in cancer chemotherapy for decades. The main limitations of this drug class are the development of resistance and severe side effects. In the present investigation, we analyzed 30 anthracyclines in a panel of 59 cell lines of the National Cancer Institute, USA. The log₁₀IC₅₀ values varied from −10.49 M (3′-deamino-3′-(4″-(3″-cyano)morpholinyl)-doxorubicin, 1) to −4.93 M (N,N-dibenzyldaunorubicin hydrochloride, 30). Multidrug-resistant NCI-ADR-Res ovarian cancer cells revealed a high degree of resistance to established anthracyclines (between 18-fold to idarubicin (4) and 166-fold to doxorubicin (13) compared to parental, drug-sensitive OVCAR8 cells). The resistant cells displayed only low degrees of resistance (1- to 5-fold) to four other anthracyclines (7, 18, 28, 30) and were even hypersensitive (collaterally sensitive) to two compounds (1, 26). Live cell time-lapse microscopy proved the cross-resistance of the three chosen anthracyclines (4, 7, 9) on sensitive CCRF/CEM and multidrug-resistant CEM/ADR5000 cells. Structure–activity relationships showed that the presence of tertiary amino functions is helpful in avoiding resistance, while primary amines rather increased resistance development. An α-aminonitrile function as in compound 1 was favorable. Investigating the mRNA expression of 49 ATP-binding cassette (ABC) transporter genes showed that ABCB1/MDR1 encoding P-glycoprotein was the most important one for acquired and inherent resistance to anthracyclines. Molecular docking demonstrated that all anthracyclines bound to the same binding domain at the inner efflux channel side of P-glycoprotein with high binding affinities. Kaplan–Meier statistics of RNA sequencing data of more than 8000 tumor biopsies of TCGA database revealed that out of 23 tumor entities high ABCB1 expression was significantly correlated with worse survival times for acute myeloid leukemia, multiple myeloma, and hepatocellular carcinoma patients. This indicates that ABCB1 may serve as a prognostic marker in anthracycline-based chemotherapy regimens in these tumor types and a target for the development of novel anthracycline derivatives. Full article

The present work reports the synthesis and structural design of three novel Zn(II) complexes [Zn(L¹)(CH₃COO)(H₂O)] (1), [Zn(L²)₂] (2), and [Zn(L³)₂] (3) with carbazate ligands, 2-acetylpyridine-methylcarbazate (HL¹), 2-acetylpyridine-ethylcarbazate (HL²), and 2-acetylpyridine-benzylcarbazate (HL³). All compounds were characterized by spectroscopic methods, and the crystal structures of the complexes were elucidated by single-crystal X-ray. Based on the analysis, distorted square pyramid geometry is suggested for complex (1) and an octahedral geometry is suggested for complexes (2) and (3) with the ligands exhibiting an NNO-donor system. The 3D Hirshfeld surface and the 2D fingerprint plot were used to study the non-covalent interactions in the crystal structures. The in vitro antibacterial investigation of the free ligands and their complexes was performed against different strains of periodontopathogen bacteria. The Zn(II) complexes showed more potent antibacterial activity than the free ligand. Molecular docking studies showed the metal complexes as promising candidates for further therapeutic exploration, particularly in targeting the ATP-binding cassette transporter with peptidase domain of the cariogenic bacteria S. mutans (PDB code 5XE9) and the prolyl tripeptidyl aminopeptidase from P. gingivalis anaerobic bacteria (PDB code 2EEP) inhibition. Full article

The development of resistance to standard cytostatics, such as 5-fluorouracil (5-FU), significantly limits the efficacy of colon cancer therapy, prompting the search for novel anticancer agents, particularly among natural compounds. This study evaluated the anticancer effects of isorhamnetin, a plant-derived flavonol, and its ability to modulate the expression of drug-resistance-related biomarkers in SW-480 and HT-29 colon cancer cells, with a focus on ATP-binding cassette (ABC) transporters. Isorhamnetin demonstrated strong cytotoxic and proapoptotic activity on both cell lines, while showing lower toxicity toward normal HaCaT cells. In addition to suppressing the mRNA expression of drug-metabolizing enzymes (CYP1A1 and CYP1B1), isorhamnetin significantly reduced the mRNA levels of multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5), as well as the P-glycoprotein (P-gp) level in SW-480 and HT-29 cells. Molecular docking analysis revealed a high binding affinity of isorhamnetin to CYP1A1, CYP1B1, P-gp, MRP1, MRP5, and glutathione S-transferase (GST) proteins, with stronger interactions than those observed for 5-FU, suggesting potential interference with their function. These results provide a solid basis for future investigations to confirm the therapeutic potential of isorhamnetin as a modulator of drug resistance in colon cancer cells. Full article

Background: Hyperuricemia is a prevalent metabolic disorder characterized by elevated serum uric acid (UA) levels. Methods: In this study, hydrolysate (SPP) derived from silkworm pupae protein was isolated and identified, demonstrating anti-hyperuricemic activity. The research aimed to investigate its anti-hyperuricemic and nephroprotective effects, along with potential mechanisms, through in vitro assays and in vivo experiments using potassium oxonate/hypoxanthine-induced hyperuricemic mice. Results: The SPP exhibited significant xanthine oxidase (XOD) inhibitory activity, with an IC₅₀ value of 7.41 mg/mL. Furthermore, SPP administration effectively reduced serum UA, blood urea nitrogen (BUN), creatinine levels, and renal pro-inflammatory cytokines in hyperuricemic mice. Mechanistic studies revealed that the anti-hyperuricemic effects of SPP may involve XOD inhibition and the modulation of renal UA transporters, specifically upregulating organic anion transporter 1 (OAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression. Histopathological analysis and inflammatory cytokine profiling further demonstrated that SPP alleviated renal inflammation and pathological damage. Conclusions: These findings suggest that SPP possesses a notable urate-lowering efficacy and renal protective properties, highlighting its potential as a therapeutic agent for the management and prevention of hyperuricemia (HUA). Full article

Chalcones, potential anticancer agents, have shown promise in the suppression of multidrug resistance due to the inhibition of drug efflux driven by certain adenosine triphosphate (ATP)-binding cassette (ABC) transporters. The gene and protein expression of chosen ABC transporters (multidrug resistance protein 1, ABCB1; multidrug resistance-associated protein 1, ABCC1; and breast cancer resistance protein, ABCG2) in human colorectal cancer cells (COLO 205 and COLO 320, which overexpress active ABCB1) was mainly studied in this work under the influence of a novel synthetic acridine-based chalcone, 1C. While gene expression dropped just at 24 h, compound 1C selectively suppressed colorectal cancer cell growth and greatly lowered ABCB1 protein levels in COLO 320 cells at 24, 48, and 72 h. It also reduced ABCC1 protein levels after 48 h. Molecular docking and ATPase tests show that 1C probably acts as an allosteric modulator of ABCB1. It also lowered galectin-1 (GAL1) expression in COLO 205 cells at 24 h. Functional tests on COLO cells revealed ABCB1 and ABCC1/2 to be major contributors to multidrug resistance in both. Overall, 1C transiently lowered GAL1 in COLO 205 while affecting important functional ABC transporters, mostly ABCB1 and to a lesser extent ABCC1 in COLO 320 cells. COLO 320’s absence of GAL1 expression points to a possible yet unknown interaction between GAL1 and ABCB1. Full article

Familial Mediterranean fever (FMF) is an autoinflammatory genetic disorder characterized by recurrent fevers and inflammation of the serous membranes in the abdomen, lungs, and joints. Currently, the standard treatment of FMF includes colchicine, which is an alkaloid, derived from Colchicum autumnale. Colchicine’s efficacy in FMF is well-established as it is used both to prevent acute attacks and reduce the risk of long-term complications. However, despite these available treatments, 5–10% of patients exhibit resistance to the drug. It has been demonstrated that polymorphisms in several genes involved in inflammation can influence treatment outcomes and the risk of FMF complications like amyloidosis. Among them, some research focused on polymorphism affecting adenosine triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1) gene encoding for P-glycoprotein. P-glycoprotein is considered a key transporter protein as it regulates the absorption, distribution, and excretion of several drugs, including colchicine. In diseases like FMF, ABCB1 polymorphisms have been shown to affect the response to colchicine, potentially leading to treatment resistance or altered toxicity. Based on this evidence, this systematic review aims to analyze available evidence on ABCB1-mediated colchicine transport and its clinical implications in FMF, showing how relevant ABCB1 variants are in response to therapy. Full article

Atherosclerosis, a leading contributor to cardiovascular diseases (CVDs), is characterized by foam cell formation driven by excessive lipid accumulation in macrophages and vascular smooth muscle cells. This study elucidates the anti-atherosclerotic potential of AWLNH (P3) and PHDL (P4) peptides by assessing their effects on foam cell formation, lipid metabolism, and oxidative stress regulation. P3 and P4 effectively suppressed intracellular lipid accumulation in RAW264.7 macrophages and human aortic smooth muscle cells (hASMCs), thereby mitigating foam cell formation. Mechanistically, both peptides modulated cholesterol homeostasis by downregulating cholesterol influx mediators, cluster of differentiation 36 (CD36), and class A1 scavenger receptor (SR-A1), while upregulating cholesterol efflux transporters ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1). The activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α) further substantiated their role in promoting cholesterol efflux and restoring lipid homeostasis. Additionally, P3 and P4 peptides exhibited potent antioxidative properties by attenuating reactive oxygen species (ROS) generation through activation of the HO-1/Nrf2 signaling axis. HO-1 silencing via siRNA transfection abolished these effects, confirming HO-1-dependent regulation of oxidative stress and lipid metabolism. Collectively, these findings highlight P3 and P4 peptides as promising therapeutic agents for atherosclerosis by concurrently targeting foam cell formation, cholesterol dysregulation, and oxidative stress, warranting further exploration for potential clinical applications. Full article

Background: Berberine has extremely low oral bioavailability, but shows a potent lipid-lowering effect, indicating its potential role in regulating intestinal microbiota, which has not been investigated. Methods: In the present study, five experimental diets, a control diet (Con), a high-lipid diet (HL), and high-lipid·diets·supplemented with an antibiotic cocktail (HLA), berberine (HLB), or both (HLAB) were fed to zebrafish (Danio rerio) for 30 days. Results: The HLB group showed significantly greater weight gain and feed intake than the HLA and other groups, respectively (p < 0.05). Hepatic triglyceride (TG) and total cholesterol (TC) levels, lipogenesis, and proinflammatory cytokine gene expression were significantly upregulated by the high-lipid diet, but significantly downregulated by berberine supplementation. Conversely, the expression levels of intestinal and/or hepatic farnesoid X receptor (fxr), Takeda G protein-coupled receptor 5 (tgr5), lipolysis genes, and zonula occludens 1 (zo1) exhibited the opposite trend. Compared with the HLB group, the HLAB group displayed significantly greater hepatic TG content and proinflammatory cytokine expression, but significantly lower intestinal bile salt hydrolase (BSH) activity and intestinal and/or hepatic fxr and tgr5 expression levels. The HL treatment decreased the abundance of certain probiotic bacteria (e.g., Microbacterium, Cetobacterium, and Gemmobacter) and significantly increased the pathways involved in cytochrome P450, p53 signaling, and ATP-binding cassette (ABC) transporters. The HLB group increased some probiotic bacteria abundance, particularly BSH-producing bacteria (e.g., Escherichia Shigella). Compared with the HLB group, the abundance of BSH-producing bacteria (e.g., Bifidobacterium and Enterococcus) and pathways related to Notch signaling and Wnt signaling were reduced in the HLAB group. Conclusions: This study revealed that berberine’s lipid-lowering and intestine-protective effects are closely related to the intestinal microbiota, especially BSH-producing bacteria. Full article

Multidrug resistance (MDR) development against cytotoxic drugs by tumor cells is one of the main causes of treatment failure in gastrointestinal cancers, a group of cancers of great relevance due to their prevalence and/or mortality. This phenomenon is mediated by diverse mechanisms, including the overexpression of members of the superfamily of membrane transporters of the ATP-binding cassette (ABC). Most of these molecules, including P-glycoprotein (P-gp or MDR1/ABCB), MDR-associated protein 1 (MRP1/ABCC1), MRP2, and breast cancer resistance protein (BCRP/ABCG2), are integrated in the cell membrane, acting as drug efflux pumps. Despite the use of various MDR modulators as adjuvants to improve the chemotherapy response, the results have not been satisfactory. Natural products from plants, such as flavonoids, alkaloids, terpenoids, and coumarins, are capable of modifying drug resistance, suggesting an improvement in the antitumoral effect of the current treatments without generating side effects. This review aims to provide an overview of the most recent studies in relation to plant-derived molecules and extracts that modulate resistance to antitumor drugs and that could be applied in the future in clinical practice to improve the treatment of patients with gastrointestinal cancer. Full article

ATP-binding cassette (ABC) transporters are a large family of proteins that transport various substances across cell membranes using energy from ATP hydrolysis. ATP-binding cassette sub-family G member 1 (ABCG1) is a member of the ABCG subfamily of transporters and performs many important functions, such as the export of cholesterol and some other lipids across the membranes of various cells. Cholesterol transport is the mechanism that links metabolism and the innate immune system. Due to its lipid transport function, ABCG1 may contribute to the prevention of atherosclerosis and is involved in the functioning of the lung, pancreas, and other organs and systems. However, the full clinical significance of ABCG1 is still unknown and is a promising area for future research. Full article

Brown planthoppers (BPHs, Nilaparvata lugens Stål) are a major threat to rice cultivation in Asia, necessitating the development of pest-resistant varieties for effective management. However, the adaptability of BPHs has resulted in the development of virulent populations, such as biotype Y BPHs, which exhibit significant virulence against the rice variety YHY15 that harbors the resistance gene Bph15. The various response mechanisms of BPH populations to resistant rice varieties are critical yet underexplored. Via RNA sequencing, the present study identified distinct transcriptional profiles in avirulent (biotype 1) and virulent (biotype Y) BPH nymphs both before and after feeding on YHY15 rice. Our findings revealed differential expression patterns of gene clusters involved in protein synthesis, hydrolysis, fatty acid biosynthesis, metabolism, cuticle composition, and translocation. Further analysis elucidated changes in the expression of genes associated with longevity and structural components of cuticles, highlighting specific disruptions in both biotype 1 and biotype Y BPHs. Moreover, the two biotypes showed differences in the expression level of genes involved in ATP-binding cassette (ABC) transporters. A functional assessment of ABC transporter genes revealed a role of NlABCG14 in the honeydew production of biotype Y BPHs to YHY15 rice, without impacting their survival and developmental dynamics. These insights deepen our understanding of the mechanisms of virulent BPHs response to resistant rice varieties and highlight potential targets for improving pest management strategies. Full article

Atherosclerosis is caused by the accumulation of cholesterol within intimal smooth muscle cells (SMCs) and macrophages. However, the transporter ATP-binding cassette subfamily A, member 1 (ABCA1), can remove cholesterol from these intimal, cells reducing atherosclerosis. Antagomir-mediated inhibition of miR-33a-5p, a microRNA that represses ABCA1 translation, promotes ABCA1-dependent cholesterol efflux and may impede atherosclerosis development. In our previous work, transducing cultured endothelial cells (ECs) with a helper-dependent adenoviral vector (HDAd) that expresses X-motif-tagged anti-miR-33a-5p enhanced antagomir packaging into EC-derived exosomes, which delivered the antagomir to cultured SMCs and macrophages. In this present study, we tested whether in vivo transduction of rabbit carotid artery endothelium can deliver an X-motif-tagged anti-miR-33a-5p to subendothelial cells. Rabbit carotid endothelial cells were transduced in vivo with an HDAd expressing anti-miR-33a-5p either with or without the X-motif (n = 11 arteries per vector). Contralateral carotids received HDAd that express scrambled oligonucleotides. Three days after transduction, the antagomir—without the X-motif—was detected in the intima but not in the media of transduced carotids (p = 0.062). The X-motif antagomir was detected in 82% of the intimal extracts (9 out of 11 carotids) and 27% of medial samples (3 out of 11 carotids, p = 0.031). However, the X-motif did not significantly enhance antagomir delivery to the media (p = 0.214 vs. non-X-motif antagomir). Expression of the antagomirs—with and without the X-motif—was sub-stoichiometric in ECs and SMCs. No antagomir-related changes in miR-33a-5p or ABCA1 expressions were detected. Despite its potential as a therapeutic strategy, our exosome-targeted gene transfer system requires further improvements to enhance antagomir expression and delivery to the subendothelial cells. Full article