Search Results (76,238)

Extracellular vesicles (EVs), as key mediators of intercellular communication, play multifaceted roles in the pathogenesis, treatment, drug resistance, and monitoring of B-cell non-Hodgkin lymphomas (B-NHLs), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). EVs derived from lymphoma cells or tumor microenvironment cells carry diverse cargoes such as proteins, microRNAs (miRNAs), and viral oncoproteins, which regulate tumor progression by modulating signaling pathways related to cell proliferation, invasion, apoptosis, autophagy, and immune suppression. In terms of treatment, accumulating evidence suggests that EVs may be associated with the efficacy of classical regimens such as R-CHOP, and they also hold potential as therapeutic targets and drug delivery vehicles for B-NHL. They contribute to drug resistance by altering the expression of key molecules or reshaping the tumor niche. Additionally, EV-derived biomarkers enable non-invasive diagnosis and monitoring of treatment response and prognosis. This review summarizes the latest research progress on the roles of EVs in major B-NHL subtypes, aiming to provide new insights for the development of innovative diagnostic and therapeutic strategies for B-NHL. Full article

This review examines the role of sulfate-reducing bacteria in the anaerobic degradation of hydrocarbons in marine sediments, where they contribute to the mineralization of organic matter under anoxic conditions. The metabolic diversity of these microorganisms is described, including their ability to degrade various classes of hydrocarbons such as short-chain (C₂–C₅), medium-chain (C₆–C₁₂), and long-chain (C₁₃–C₂₀₊) alkanes, alkenes, and aromatic compounds like naphthalene and phenanthrene. The primary mechanisms involved in the initial activation of these hydrocarbons—fumarate addition and carboxylation—are discussed, along with key enzymes, including alkylsuccinate synthase and benzylsuccinate synthase. Syntrophic interactions are also considered, particularly in which archaea initiate the oxidation of short-chain alkanes (e.g., ethane and butane), with sulfate-reducing bacteria serving as terminal electron acceptors via sulfate reduction. The potential application of these anaerobic processes in bioremediation strategies for oil-contaminated marine sediments is discussed. This microbially mediated degradation may offer a complementary approach to aerobic methods, particularly in oxygen-limited environments. Understanding the activity of sulfate-reducing bacteria activity is relevant to several areas: the development of remediation techniques for anoxic zones, the assessment of methane emissions from marine sediments, the management of microbiologically influenced corrosion, and potential biotechnological applications. Current research directions include the study of syntrophic microbial consortia and the exploration of bioelectrochemical systems. Full article

Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical challenge, driven in part by resistance–nodulation–division (RND) efflux pumps that reduce intracellular antibiotic concentrations and limit the efficacy of many antibacterial agents, including fluoroquinolones. The aim of this study was to identify and characterize TXA11114 as a small-molecule efflux pump inhibitor (EPI) capable of restoring the activity of the fluoroquinolone levofloxacin against MDR P. aeruginosa. Methods: The antibacterial activity of the TXA11114–levofloxacin combination was evaluated using minimum inhibitory concentration (MIC) assays against panels of clinical isolates. Mechanistic studies included levofloxacin accumulation assays, ethidium bromide accumulation assays, outer-membrane permeability measurements, and whole-genome sequencing of mutants with altered potentiation phenotypes. In vivo efficacy was evaluated in murine thigh and lung infection models, while preliminary safety and drug-like properties were assessed using cytotoxicity assays and in vitro ADME profiling. Results: The TXA11114–levofloxacin combination produced > 1 log₁₀ CFU reductions in bacterial burden in murine thigh and lung infection models, exceeding the activity of levofloxacin monotherapy. TXA11114 markedly potentiated levofloxacin activity, producing substantial reductions in levofloxacin MIC values across multiple MDR clinical isolates, and also enhanced the activity of several additional efflux pump substrates, including β-lactams, tetracyclines, chloramphenicol, and trimethoprim–sulfamethoxazole. Mechanistic experiments demonstrated increased intracellular accumulation of efflux substrates without evidence of nonspecific membrane disruption, and mutations in ompH were associated with altered potentiation phenotypes. Conclusions: The TXA11114–levofloxacin combination produced significantly greater bacterial reductions than levofloxacin monotherapy in murine infection models. Levofloxacin was selected because fluoroquinolone resistance in P. aeruginosa is frequently driven by efflux-mediated mechanisms. While this study focused on levofloxacin potentiation, future work will evaluate additional efflux pump substrates and further define the molecular target of TXA11114. Full article

Background/Objectives: Ginger has a long history as both a culinary and medicinal plant and is widely recognized in traditional medicine for its ability to promote health and well-being. The principal bioactive compounds of ginger are present in fresh and dried forms and have been largely studied for their therapeutic potential. These compounds exhibit a wide range of biological activities mediated through various mechanisms. Advances in nanotechnology have enabled the development of innovative delivery systems, thereby enhancing the bioavailability and therapeutic efficacy of ginger-derived compounds in modern medical applications. Methods: A comprehensive literature review was conducted to evaluate the characteristics of ginger and its potential role in disease prevention. Relevant studies were identified through the main research databases, publication screening, manual reference checks, and author consensus was conducted. Results: This narrative review provides an overview of the therapeutic potential of bioactive compounds in ginger for the management and prevention of cardiovascular, arthritis, neurodegenerative, and gastrointestinal diseases, with particular emphasis on the molecular mechanisms. In addition, their potential anti-aging properties are extensively discussed. The evidence reported is predominantly preclinical (in vitro and in vivo models), with more limited and heterogeneous clinical data. Recent studies have also highlighted the role of artificial intelligence (AI) in accelerating the discovery and evaluation of bioactive agents with therapeutic relevance across diverse biological systems. Conclusions: This review highlights the emerging applications of ginger extracts in human health and suggests their applications in both traditional medicine and contemporary drug discovery. Full article

Bitter compounds may function not only as taste substances but also as important active constituents mediating therapeutic effects. Their recognition is primarily mediated by bitter taste receptors (TAS2Rs), which exert pharmacological effects, such as regulating glucose metabolism, anti-inflammatory properties, and immune modulation, aligning closely with the therapeutic effects of bitter Chinese herbal medicine (BCHM). Contemporary pharmacological research has increasingly underscored the therapeutic potential of bitter traditional Chinese medicine (TCM), particularly through their bioactive constituents in the prevention and treatment of diverse pathological conditions. Here, we systematically review the diversity of bitter compounds from TCM and features of TAS2Rs, including their tissue distribution, physiological functions, structural characteristics, signal transduction mechanisms, and single-nucleotide polymorphisms. While numerous bitter phytochemicals have been characterized as agonists of TAS2Rs, the precise physiological functions and underlying molecular mechanisms mediated by TAS2R activation remain incompletely elucidated. This knowledge gap is largely attributable to several methodological and biological challenges, including the widespread tissue distribution of TAS2Rs, the complexity of their downstream signaling cascades, and the structural and functional heterogeneity of bitter compounds. This review outlines theoretical foundations, future perspectives and challenges for the drug development of TAS2R from BCHM. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

Background/Objectives: Salidroside, a bioactive phenylethanol glycoside primarily derived from Rhodiola rosea, and its major in vivo metabolite tyrosol exhibit diverse pharmacological activities. However, their direct molecular targets remain poorly defined. Methods: In the present study, an integrated strategy combining transcriptomic profiling, Connectivity Map (CMap) analysis, and multi-level experimental validation was employed. Transcriptomic signatures derived from A549 cells treated with salidroside or tyrosol were queried against the CMap database. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were performed to predict and validate binding interactions. Functional validation was performed in SH-SY5Y cells. The phosphorylation level of extracellular signal-regulated kinase (ERK), a downstream signaling event of dopamine D2 receptor (DRD2), was detected after salidroside and tyrosol treatment. DRD2 antagonist sulpiride pre-intervention and small interfering RNA (siRNA)-mediated DRD2 knockdown were conducted to verify the receptor dependence of the compounds’ effects. Results: CMap analysis revealed that the transcriptomic signatures of salidroside and tyrosol showed significant similarity to known DRD2 modulators. Molecular docking predicted potential binding interactions between the two compounds and DRD2, which was confirmed by SPR and CETSA to be direct physical binding. Functional studies showed that both compounds rapidly induced DRD2 downstream ERK phosphorylation in SH-SY5Y cells; this effect was abrogated by sulpiride or DRD2 knockdown, indicating DRD2-dependent signaling activation. Conclusions: These findings identify DRD2 as a direct molecular target of salidroside and tyrosol and provide mechanistic insight into their dopaminergic regulatory effects. This study highlights the utility of CMap-guided target discovery combined with rigorous experimental validation for elucidating the molecular mechanisms of natural products. Full article

Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury. Estradiol (E2) and the selective estrogen receptor modulator raloxifene (RAL) reduce organ dysfunction, potentially via heme oxygenase-1 (HO-1)–mediated antioxidant and anti-inflammatory effects. This study examined whether E2 and RAL protect against IRI through G protein-coupled estrogen receptor (GPER)–dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway in ovariectomized (OVX) mice; OVX IRI mice were pretreated for four weeks with E2, RAL, RAL + ML385 (Nrf2 inhibitor), or RAL + G15 (GPER antagonist). Renal histology, inflammatory and oxidative markers, and nuclear Nrf2 levels were assessed; OVX IRI increased interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH); nuclear Nrf2 was low in sham and OVX IRI groups. E2 and RAL improved renal function and histology, reduced inflammation and oxidative stress, restored GPER expression, increased nuclear Nrf2, and upregulated HO-1 and NAD(P)H:quinone oxidoreductase 1 (NQO1). Co-treatment with ML385 or G15 reversed RAL’s benefits, reduced nuclear Nrf2, and worsened injury; E2 and RAL exert renoprotective effects against OVX-related renal IRI in a manner consistent with GPER-dependent Nrf2 nuclear translocation, which suggests involvement of the downstream antioxidant gene activation pathway. Full article

Background/Objectives: The valorization of bioactive compounds from food industry by-products aligns with sustainable development goals and represents a strategy for obtaining functional ingredients. Hazelnut (Corylus avellana L.) skins are a phenolic-rich residue with high antioxidant potential, but their extraction conditions and cellular mechanisms of action remain insufficiently explored. Methods: Ultrasound-assisted extraction was optimized using a 3³ Full Factorial Design (FFD) by investigating temperature (30–50–70 °C), extraction time (1–2–3 h), and solvent composition (water/ethanol). Antioxidant activity was evaluated using multiple in vitro assays, including Total Phenolic Content (TPC), DPPH, ABTS, FRAP, and β-carotene bleaching (BCB) assays. The optimized extract (OE) was chemically characterized by UHPLC–MS/MS and its activity was evaluated in HepG2 cells for biocompatibility, modulation of intracellular ROS levels, and antioxidant pathway activation. Results: Optimal extraction conditions were identified as 30 °C, 70.86 min (1.181 h), and 21.13% ethanol (v/v), yielding an extract with enhanced antioxidant capacity. UHPLC–MS/MS analysis revealed 25 bioactive compounds, mainly flavonoids and phenolic acids, relevant for oxidative stress modulation. The extract significantly reduced tert-butyl hydroperoxide (TBH)-induced intracellular ROS levels, restoring antioxidant proteins involved in the Nuclear Factor erythroid 2-related factor 2 (NRF-2)-mediated defense pathway. Conclusions: The optimized hazelnut skin extract combines strong antioxidant efficacy with cellular compatibility, supporting its potential application as a functional ingredient for nutraceutical and pharmaceutical strategies targeting oxidative stress-related conditions. Full article

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, and its dysregulation is implicated in HF pathophysiology. Traditional Chinese Medicine (TCM) has been investigated in HF management, but a systematic synthesis of preclinical evidence on TCM-mediated AMPK modulation is lacking. Methods: PubMed and Web of Science were searched from January 2020 to December 2025 using a comprehensive strategy combining terms for AMPK, HF, and TCM. Studies were included if they were original research investigating TCM-derived compounds or formulas in HF models and reporting AMPK modulation. Study quality and evidence levels were assessed using predefined criteria. The review was conducted in accordance with PRISMA 2020 guidelines. Results: Of 243 records identified, 56 studies met the inclusion criteria (7 from database search and 49 from manual screening). Direct evidence for AMPK-dependent cardioprotection was limited. Cinnamaldehyde and paeoniflorin showed the most rigorous validation with confirmed target engagement and loss-of-function rescue. Berberine, crocin, ginsenoside Rb1, and honokiol demonstrated pathway-specific effects validated by pharmacological or genetic approaches. Most complex herbal formulas provided correlative evidence only, with Fuyu Decoction being a notable exception where AMPK agonist EX229 confirmed pathway involvement. Conclusions: Current evidence for TCM-mediated AMPK modulation in HF remains predominantly preliminary and correlative. Future research should prioritize causality validation using genetic models and human-relevant systems. Full article

The rapid integration of generative artificial intelligence (GAI) tools into academic and professional contexts has raised concerns regarding unethical use and the potential development of problematic usage patterns. Drawing on personality and moral psychology frameworks, the present study examined the associations between antagonistic personality traits (narcissism, Machiavellianism, and psychopathy) and problematic (i.e., addictive) GAI use (PGAIU), as well as the chain mediating effect of moral disengagement and unethical GAI use (UGAIU). Data were collected from an adult sample (N = 491; 52% men; M_age = 43.92) using validated self-report measures. Path analysis indicated that narcissism exhibited significant direct and indirect associations with PGAIU. In contrast, Machiavellianism and psychopathy were indirectly related to PGAIU via moral disengagement and UGAIU but demonstrated non-significant total and direct effects. Multi-group analyses revealed broadly similar structural patterns across men and women, although some paths involving moral disengagement were significant only among men. A comparable pattern was also observed across age groups, with only minor variations in the mediation pathways. Overall, the findings highlight the central role of moral disengagement and unethical GAI-related behaviors in linking antagonistic personality traits to PGAIU. Full article

As social media campaigns become increasingly important in grocery and supermarket retail communication strategies, there is little research on how consumers view campaign performance throughout their decision-making process, rather than isolated behavioral outcomes. This study examines how the five-stage decision-making process is influenced by consumer-perceived social media performance effectiveness (CP-SMPE), grounded in consumer decision-making theory and social media performance literature. The study uses a mixed-methods research design, combining qualitative interviews with the consumers and a quantitative survey of 300 grocery shoppers in Greece. Perceived return on investment, revenue contribution, lead generation, engagement, reach, cost efficiency, and quality of electronic word-of-mouth are components of social media performance conceptualized as a multidimensional construct. Exploratory factor analysis and PLS-SEM were employed to analyze quantitative data. The findings show that high perceived social media campaign performance influences all stages of the consumer decision-making process, both directly and indirectly, through sequential intermediate stages. It ultimately enhances purchase decisions and post-purchase outcomes. By adopting a consumer-centric, process-based perspective, this study contributes to research on digitally mediated retail decision-making by demonstrating how effective social media communication can support more informed, structured consumer choices. The findings suggest that social media communication can lead to more informed and potentially responsible consumption choices by improving information environments and decision support, even though sustainability outcomes are not directly measured. Full article

Background: Extracellular vesicles (EVs) released from skeletal muscle mediate metabolic communication via microRNAs (miRNAs). While both circadian rhythms and exercise influence metabolism, the joint modulation of the muscle-derived EV miRNA landscape by circadian rhythms and chronic exercise remains undefined, particularly under the metabolic stress of obesity. Methods: Employing a 2×2 factorial design (Phase: ZT3 vs. ZT15; Condition: sedentary vs. exercise; ZT, Zeitgeber Time), EV-enriched fractions were isolated from ex vivo quadriceps muscle (QUA) cultures of high-fat diet-fed mice following an 8-week treadmill training regimen using polymer-based precipitation, and comprehensive miRNA profiling was performed by small RNA sequencing. Results: Principal component analysis (PCA) revealed that circadian phase accounted for a greater proportion of global variance in EV miRNA profiles than exercise. Differential expression analysis identified miR-1a-3p and miR-1b-5p as upregulated across both composite phase and exercise contrasts; however, condition-specific analyses indicated that this signal was primarily driven by the sedentary-phase comparison (ZT15-sed vs. ZT3-sed), in which the miR-29 family was also prominently co-upregulated, rather than constituting independent phase and exercise effects; this phase-associated signature was absent in the corresponding exercise-condition comparison. Exploratory functional enrichment of experimentally validated targets revealed phase-preferential association with metabolic and iron–heme pathways, whereas exercise-associated miRNAs mapped to signaling, inflammatory, and transcription-related networks. Conclusions: Circadian phase was the dominant contributor to global variance in muscle-derived EV-enriched miRNA profiles in obesity, as reflected by the phase-associated separation along principal component 1 (PC1, 33.47% of total variance), with exercise introducing context-dependent adaptive modulation. This study provides a foundational basis for investigating the temporal regulation of muscle secretome dynamics under high-fat diet conditions, highlighting temporal specificity as a key dimension in EV-mediated exercise physiology research. Full article

Under global climate change, analyzing carbon storage dynamics and their drivers is essential for understanding regional carbon sink capacity. Human activities and land-use change have substantially affected regional carbon storage. However, in China, most existing studies emphasize specific driving pathways, and integrated analyses of the combined effects of climate, natural, human, and landscape factors remain limited. This study aims at clarifying the integrated mechanisms by which multiple driving factors influence regional carbon storage. The InVEST model was used to analyze the carbon storage spatiotemporal changes. OPGD was then applied to evaluate the explanatory power of driving factors and their interactions, quantifying their contributions to carbon storage spatial patterns. Based on PLS-SEM, the direct and indirect effects of LULC, climate, natural, human, and landscape factors were quantified to elucidate the driving pathways of carbon storage. This study focuses on Shaanxi Province, which is a key ecological restoration region in the core area of the Loess Plateau. The main results are as follows: (1) From 2000 to 2020, carbon storage in Shaanxi Province showed a continuous increasing trend, rising from 2.97 × 10¹⁰ Mg C to 3.03 × 10¹⁰ Mg C. (2) LULC was identified as the most important direct and predominantly negative driving factor of carbon storage. (3) Natural factors had a strong positive influence on carbon storage, among which slope and NDVI exhibited the highest explanatory power; in contrast, climate factors showed weaker but still positive effects. (4) Human activities affected carbon storage through both direct and indirect pathways associated with LULC, with positive effects driven by landscape factors and negative effects driven by natural factors, while climate factors exhibited mixed but weak effects. Overall, carbon storage dynamics in Shaanxi Province reflect a hierarchical and path-dependent process shaped by the combined effects of natural constraints, human activities, and policy guidance through LULC pathways, providing important evidence for systematically understanding the driving structure and pathways of regional carbon storage. These findings highlight the importance of aligning land-use policies with regional biophysical constraints to enhance carbon sequestration efficiency. Full article

Sustainable development has become an important global goal for environmental protection and economic growth. Promoting environmental sustainability and green development has become an inevitable trend for global economic transformation. The carbon emission trading market (carbon market) is a crucial market-based mechanism for pricing greenhouse gas emissions, where carbon trading prices signal the costs of emission reduction and drive firms to engage in green technology innovation for a low-carbon transition. Using a sample of A-share listed companies in China’s eight carbon pilot regions from 2013 to 2024, this study employs a two-way fixed effects model to examine how carbon prices affect both the quantity and quality of corporate green technological innovation. Baseline regressions show that a one-unit increase in carbon prices significantly boosts green patent quantity (GreNum) by 0.018 and quality (GreQua) by 0.361, both at the 1% significance level. Mechanism analysis reveals that financing constraints act as a partial mediator, while environmental regulation and media attention further amplify the positive impact of carbon prices on corporate green technological innovation. Heterogeneity analysis further indicates that this positive effect is more pronounced in non-high-tech enterprises, China’s northern and eastern regions, and state-owned enterprises. This study provides empirical evidence for optimizing carbon market allocation, supporting corporate low-carbon transition, and promoting global environmental sustainability and green development. Full article