Search Results (1,974)

Amyloid-β peptides (Aβ) are considered a main culprit of Alzheimer’s disease (AD), leading to synaptic dysfunction and memory deficits. Although studies in animal models of AD converge to show alterations of synaptic plasticity, namely of long-term potentiation (LTP), the mechanisms through which Aβ affects synaptic function remain to be unveiled. In this study, we established experimental conditions showing that the acute exposure of mouse hippocampal slices to optimized concentrations of Aβ impaired short-term (PPF-paired-pulse facilitation) and long-term (LTP-long-term potentiation) plasticity without altering basal synaptic transmission. We observed that the elimination of extracellular adenosine with adenosine deaminase abrogated the impact of Aβ on synaptic plasticity, showing a mandatory involvement of extracellular adenosine in the neurophysiological effects of Aβ. Additionally, inhibiting adenosine receptor function with caffeine, as well as selectively blocking adenosine A₁ receptors (A₁R) with DPCPX, or adenosine A_2A receptor (A_2AR) with either an antagonist SCH58261 or through knocking out A_2AR, demonstrated that acute Aβ modified mouse hippocampal PPF via A₁R and LTP through A_2AR. Furthermore, the use of slices from mice bearing forebrain-neuron A_2AR deletion, along with the application of α,β-methylene ADP, a CD73 inhibitor, confirmed that the neurophysiological actions of Aβ on hippocampal LTP occur selectively through the overfunction of neuronal A_2AR via CD73-mediated formation of extracellular adenosine. Overall, the exploitation of a neurophysiological model of early AD, based on the acute administration of Aβ to hippocampal slices, confirmed the critical involvement of adenosine signaling in the impact of Aβ on synaptic plasticity. Full article

Background/Objectives: Humans have at least 26 bitter taste receptors (T2Rs), and among these, bitter taste receptor 14 (T2R14) is highly expressed in both oral and extraoral tissues. Over 100 bitter ligands can activate T2R14, including hormones, vitamins, plant compounds, and peptides. Previous studies suggest that bitter tastants such as quinine and caffeine can inhibit G protein-coupled receptor kinases (GRKs) and delay T2R signal termination. Our earlier research showed that peptides from alcalase and chymotrypsin hydrolysates of beef proteins inhibited quinine-dependent calcium release through T2R4, with AGDDAPRAVF and ETSARHL showing the greatest effectiveness. However, the effect of these antagonistic peptides on other T2Rs, such as T2R14 signaling, remains unknown. This study aimed to evaluate the ability of these beef protein-derived peptides to activate or inhibit T2R14 signaling and the involvement of GRK2 in signal termination. Methods and Results: Our results indicate that the above two antagonist peptides significantly inhibit T2R14 activity. Furthermore, GRK2 knockout in HEK cells stably expressing T2R14 decreases intracellular calcium release, as measured by the area under the curve (AUC), and also delays the fall time (indication of desensitization) of the calcium response when exposed to the T2R14 agonist diphenhydramine (DPH) or beef protein-derived agonist peptide TMTL. Next, we measured the effects of these ligands on cAMP accumulation, and our results suggest no significant change in cAMP levels upon treatment with beef protein-derived peptides. Conclusions: Thus, this study showed that beef protein-derived peptides can function as both T2R inhibitors and mediate T2R14 desensitization through GRK2 signaling. These antagonistic food protein-derived peptides inform strategies to enhance nutrition, such as promoting healthier food choices by reducing bitterness and thereby improving the palatability of health-promoting bitter foods, such as fruit and vegetable extracts, as well as bitter medications. Full article

Background/Objective: Coffee is the most highly consumed beverage worldwide, and coffee drinkers exhibit decreased mortality and protection from aging-related diseases. This study investigates the role of orphan nuclear receptor 4A1 (NR4A1) in mediating the effects of brewed coffee and the major polyphenolic and polyhydroxy compounds in brewed coffee and also in determining their binding to NR4A1. Methods: The interactions of brewed coffee and several of the major individual compounds in brewed coffee with the ligand-binding domain of NR4A1 were determined using a fluorescent binding assay. For specific compounds, binding was also carried out by surface plasmon resonance, and molecular docking studies were also performed. NR4A1-responsive Rh30 cancer cells were used as models to determine NR4A1-dependent transactivation, cell growth inhibition and inhibition of specific gene products, and in some studies, knockdown of NR4A1 by RNA interference was also determined. Inhibition of lipopolysaccharide-induced IkBα by key polyphenolics was also investigated in RAW264.7 macrophages. Results: Brewed coffee and several polyphenolics, including caffeic acid, ferulic acid, chlorogenic acid, p-coumaric acid, several cinnamic acid derivatives, kahweol, and cafestrol, bound NR4A1 in binding assays, and most Kd values were <10 µM. Brewed coffee and the major polyphenolics inhibited growth of NR4A1-responsive Rh30 cells, and this was attenuated in NR4A1-deficient Rh30 cells. These same compounds also exhibited NR4A1-dependent effects on transactivation and gene product responses in Rh30 and RAW264.7 macrophages and exhibited inverse NR4A1 agonist activity. In contrast, the NR4A1-dependent activity of caffeine and quinic acid was highly variable, suggesting that they are selective NR4A1 ligands. Conclusions: The results of this study demonstrate that brewed coffee and its major polyphenolics and polyhydroxy constituents are NR4A1 ligands and that NR4A1 may play an important role in the health-protective effects of coffee. These results, coupled with recent studies, indicate that NR4A1 and its ligands may play an important role in diet and health. Full article

This study developed an optimized processing strategy for γ-aminobutyric acid (GABA) instant white tea (GABA-IT) using GABA-enriched white tea as raw material, systematically characterizing its chemical composition and volatile profile. In contrast to the conventional instant tea production process, this work integrates response surface methodology with spray-drying parameter optimization. This integrated approach enables the simultaneous enhancement of functional components and sensory quality. A response surface design was employed to refine the extraction and spray-drying variables following preliminary single-factor trials, and the optimal parameter combination was subsequently determined (40% ethanol concentration, material-to-liquid ratio of 1:15, extraction time of 3 days, atomization speed of 300 rpm, and inlet temperature of 120 °C); the resulting GABA-IT exhibited significantly improved quality characteristics. Specifically, the GABA content increased by 209% (reaching 4.42 mg/g), and theanine, catechins, and caffeine were enriched by 200–300%. Regarding volatile profiles, processing led to a reduction in esters but an increase in aldehydes and hydrocarbons. Relative odor activity value (rOAV) analysis revealed that epoxy-β-ionone and linalool were the key contributors to the characteristic aroma of GABA-IT. Collectively, this study demonstrates the technical feasibility of producing GABA-rich instant tea with enhanced functional components and improved sensory quality, providing practical guidance for the large-scale industrial production of functional tea beverages. Full article

Mental fatigue is a psychobiological state induced by sustained effortful cognitive efforts during daily life activities. Yet research efforts in exercise science have focused primarily on performance implications for athletes to the point of exclusion of vulnerable populations for which mental fatigue may be a health risk. This narrative review aims to clarify the role of mental fatigue on population health. Evidence suggest mental fatigue predisposes people to acute events related to temporary performance impairments (e.g., falls), and chronic diseases related to sedentarism (e.g., stroke, diabetes), as mental fatigue de-motivates people to engage in physical activity. Major risks are experienced by people with higher fatigability (i.e., people for whom mental fatigue is induced by less effortful tasks) and lower performance capacity. However, the few available information about moderators of fatigability and the lack of a normative protocol to assess mental fatigue are limiting the prevention of mental fatigue. Several strategies are used to counter mental fatigue acutely (e.g., caffeine ingestion); however, enduring countermeasures intended to alter psychobiological sequelae of mental fatigue, such as Brain Endurance and other trainings, are the only proved long-term countermeasures for mental fatigue. Yet the effectiveness of these interventions should be tested in populations with major risk for mental fatigue. We present a model identifying putative pathways through which mental fatigue may contribute to health risks to guide future investigations seeking to (a) evaluate the role of mental fatigue as a threat to health and well-being and (b) design interventions to mitigate the effects of mental fatigue in vulnerable populations. Full article

Kucha, a unique tea germplasm rich in theacrine, imparts its fresh leaves with a particularly bitter taste and multiple bioactivities. However, systematic studies on processed Kucha—especially white tea—remain limited. In this study, white teas were produced from two Yunnan Kucha accessions (YLKC1, YLKC2) and two conventional cultivars. Their quality characteristics and non-volatile metabolic profiles were systematically compared using sensory evaluation, targeted quantification and widely targeted metabolomics. Results indicated that Kucha white teas displayed pronounced bitterness, with YLKC1 presenting a richer, well-layered flavor, indicating promising quality potential. Targeted quantification demonstrated a remarkably high theacrine content (~30 mg/g) in Kucha white teas, whereas caffeine and several catechin monomers were significantly lower than those in conventional cultivars. Widely targeted metabolomic analysis identified 3376 non-volatile metabolites. PCA and OPLS-DA demonstrated a clear separation in metabolic profiles between Kucha and control groups. In total, 601 significantly differential metabolites were identified. Taste-driven annotation against ChemTastesDB revealed 17 known bitter compounds, 10 of which were significantly accumulated in Kucha white tea—including theacrine, theophylline, theobromine, L-arginine, neohesperidin, pinocembrin, kaempferol-3-O-(6”-malonyl)glucoside, fraxin, adenosine, and xanthine. Among these compounds, theacrine showed the highest upregulation (9.30-fold). In addition, several galloylated flavonoid glycosides also exhibited significant accumulation. KEGG enrichment analysis further indicated that flavonoid biosynthesis and caffeine metabolism were crucial pathways contributing to these metabolic differences. Collectively, these findings demonstrate that the characteristic bitterness of Kucha white tea arises from the coordinated accumulation of a specific set of bitter phytochemicals rather than a single compound and provide a prioritized panel of candidate compounds for flavor-oriented breeding and processing. Full article

Photocatalytic processes have been studied as promising solutions to mitigate the impact of pollutants on aquatic environments. Here, the enhancement of photocatalytic performance and stability of titanate nanostructures (TNS), a well-established photocatalyst, were investigated through Sr modification. Structural characterization confirmed Sr in-corporation in the crystalline structure, mainly in the interlayers. The sample Sr(5%)TNS, synthesized with 5% (wt.), exhibited fine lamellar morphology, different from the elongated nanowires of pristine TNS. The photocatalytic performance of the Sr-modified sample was studied for the removal of a model pollutant, caffeine, under UV-Vis and visible irradiation. A clear enhancement in the caffeine removal rate was observed using Sr(5%)TNS as a photocatalyst, when compared with the pristine material. Further improvement in the photocatalytic performance was obtained by combining Sr(5%)TNS with graphitic-like carbon nitride (g-C₃N₄) as a novel composite film. This proved to be a promising strategy for enhancing both the visible-light photocatalytic efficiency and the stability of the films, while also facilitating their reuse. Various configurations of the hybrid system were tested, and the best results for caffeine degradation and catalyst robustness were achieved with a 4:1 ratio of Sr(5%)TNS to g-C₃N₄. Mechanisms for charge transfer in irradiated Sr(5%)TNS particles, and in Sr(5%)TNS/g-C₃N₄ composite films are proposed and discussed. Full article

Background/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine–cold interaction in transitional menopause, focusing on water homeostasis and the estrogen–transient receptor potential melastatin 8 (TRPM8) cold-sensory axis, and to propose potentially actionable, nutrition-centered intervention candidates for future testing. Methods: Structured narrative review of PubMed, Embase, Web of Science, and citation tracking (inception–January 2026). Evidence was mapped into a mechanistic framework distinguishing established from hypothesis-generating links; no formal systematic-review study selection or meta-analysis was performed. Results: Caffeine can increase urine output via renal mechanisms (adenosine receptor antagonism and natriuresis) and may lower bladder sensory thresholds. Because half-life is long and variable, afternoon intake can extend into sleep, potentially increasing awakenings and nocturnal voids. Human studies link colder indoor environments to nocturia/overactive bladder, and passive pre-bedtime heating is associated with fewer nocturnal voids. We propose that repeated nighttime cold may amplify caffeine-related diuresis and may shift urine production toward the night, while estradiol decline may heighten TRPM8-mediated cold sensory gain, potentially contributing to urgency/frequency flares. A testable 2 × 2 cold × caffeine framework can operationalize dose, timing, and metabolism, pairing voiding diaries and bedroom temperature sensing with copeptin profiling. Conclusions: Transitional menopause may represent a susceptibility window in which endocrine instability and estradiol decline could plausibly increase sensitivity to indoor cold exposure and caffeine intake, potentially contributing to nocturia and urgency. The hypothesis label ‘dual hormone suppression’ (attenuated nocturnal AVP signal plus estradiol decline) may provide a mechanistic substrate for cold-exacerbated nocturnal polyuria, while an estrogen–TRPM8 axis may amplify cold-evoked urgency. Potentially actionable candidates include chronobiological caffeine timing/management and low-burden thermal strategies; nevertheless, menopause-stage-specific epidemiologic and clinical evidence for a caffeine × cold interaction remains limited and several mechanistic links are extrapolated, so prospective diary- and biomarker-enabled studies and controlled trials are needed to validate mechanisms and refine cold-sensitive endotypes. Full article

Background: Red/blue- light-emitting diode (LED)-assisted withering provides a controllable spectral input to steer tea quality, yet metabolite-level evidence linking spectrum composition to quantitative taste phenotypes in white tea remains insufficient. Methods: Fresh leaves were withered under supplemental red/blue LEDs—S0, S1, S2, S3, S4, and S5—and the resulting white teas were evaluated by quantitative descriptive analysis (QDA), untargeted metabolomics, weighted gene co-expression network analysis (WGCNA), and high-performance liquid chromatography (HPLC) quantification of caffeine, gallic acid, and eight catechin monomers. Results: Red/blue-mixed spectrum enhanced the overall sensory quality relative to the incandescent lamp; S3 maximized sweetness and freshness, whereas S4 minimized bitterness and astringency and achieved the highest overall score. Untargeted metabolomics showed the largest deviation for S0 vs. S4. A total of 18 common metabolites were identified between the S0 and light-supplemented withering treatments, dominated by saccharides and related derivatives. WGCNA linked a saccharide-centered module to higher sweetness/freshness/smoothness and a lipid-oxylipin-centered module to stronger bitterness/astringency. HPLC independently confirmed that S4 contained the lowest catechins and caffeine, supporting its reduced bitter/astringent attributes. Conclusions: Overall, the application of mixed red-blue spectra offered a promising approach to enhancing the palatability of white tea by coordinately intensifying saccharide metabolism while simultaneously suppressing key bitter and astringent components. Our study provided a scientific basis for standardizing white tea processing to enhance sensory quality. Full article

Background: Long-haul travel and jet lag can disrupt athletes’ circadian, physiological, and performance systems, potentially impairing competition outcomes. This review aimed to study the effects of long-haul travel on athletes’ health and performance, differentiate travel fatigue from jet lag, and review mitigation strategies. Methods: A systematic narrative review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched for studies on jet lag, travel fatigue, and long-haul travel in athletes. Eligibility included studies reporting physiological, hemodynamic, or performance outcomes in athletes of any level and sex. Data were extracted on travel characteristics, interventions, physiological and performance markers, and risk of bias. Results: Overall, 284 records were identified, with 89 studies included. Travel directions were equally distributed between eastward and westward journeys, crossing 1–12 time zones. Interventions to mitigate travel effects were reported in 17 studies, primarily melatonin, caffeine, and light exposure. Common physiological changes included sleep disturbances (n = 36), body temperature alterations (n = 18), blood pressure changes, hormonal shifts (n = 9), heart rate variability (n = 4), and immune alterations (n = 4). Travel effects comprised fatigue (n = 25), sleep changes (n = 21), decreased physical performance (n = 18), mood changes (n = 15), and cognitive impairments (n = 9). Physical performance outcomes included anaerobic power (n = 18), strength (n = 14), velocity (n = 12), aerobic capacity (n = 10), coordination (n = 8), and reaction time (n = 7). Risk of bias was low in 49%, moderate in 17%, and high in 34% of studies. Conclusions: Long-haul travel negatively affects multiple physiological and performance domains in athletes, including sleep, hormonal balance, autonomic function, and physical performance. The magnitude of these effects seems to be influenced by travel direction, number of time zones crossed, and individual susceptibility. Eastward travel is generally associated with stronger circadian disruption and impaired aerobic capacity, coordination, and technical performance, whereas westward travel often induces greater fatigue and adversely affects team-sport outcomes. Monitoring key markers such as heart rate variability, sleep, and cortisol, combined with personalized strategies including circadian management, sleep hygiene, nutrition, recovery interventions, and training load adjustments, is essential to mitigate travel-related impairments and optimize performance. Full article

(1) Background: Medication-related problems (MRPs) are a significant burden on health care systems. Pharmacists play an important role in preventing and reducing MRPs through clinical review, education, and policy governance. This study analyzed pharmacist interventions within a 92-bed neonatal clinical care unit to better understand MRPs and guide targeted medication safety initiatives. (2) Methods: All pharmacist interventions documented in REDCap^® between 1 July 2022 and 30 June 2025 were analyzed identifying MRP incidence, types, and acceptability following interventions. (3) Results: A total of 873 pharmacist interventions were recorded during the study period. The most common MRPs were related to dosing errors (320/873, 36.7%), compliance with hospital policy (152/873, 17.4%), no indication apparent (106/873, 12.1%), drug interactions (66/873, 7.6%), and inadequate laboratory monitoring (40/873, 4.6%). Of these, 545/873, 62.4% were accepted by prescribers, while 228/873, 26.1% had unknown outcomes at the time of data entry. 343/873, 39.3% of interventions documented were from the Neonatal Intensive Care Unit, involving medications such as gentamicin (n = 46/343, 13.4%), benzylpenicillin (n = 37/343, 10.8%), caffeine (n = 34/343, 9.9%), parenteral nutrition (n = 23/343, 6.7%), and morphine (n = 16/343, 4.7%) and meropenem (n = 16/343, 4.7%)). (4) Conclusions: Regular analysis of pharmacist interventions provides valuable insights into local MRP trends and highlights opportunities for quality improvement and education. Full article

Background: Caffeine is widely used as an ergogenic aid to enhance strength performance; however, its effects on perceptual accuracy during submaximal force regulation remain unclear, particularly in multi-joint isometric tasks. This study examined whether caffeine ingestion influences maximal isometric force production and the accuracy of voluntary submaximal force estimation during complex isometric exercises. Methods: Seventeen recreationally trained participants completed a randomized, double-blind, placebo-controlled crossover study. Participants ingested either caffeine (4 mg·kg⁻¹ body mass) or a placebo before performing an isometric squat test (ISqT) and an isometric mid-thigh pull test (IMTP). Maximal voluntary contractions were assessed, followed by freely estimated submaximal efforts at 50% and 75% of perceived maximal force. Relative peak force and discrepancies between prescribed and exerted force (estimation error) were analyzed, with discrepancies calculated as the difference between exerted force and the prescribed target intensity. Results: Caffeine ingestion did not significantly affect relative peak force during maximal isometric efforts nor improve the accuracy of voluntary submaximal force estimation. Regardless of supplementation conditions, participants consistently misestimated submaximal efforts, tending to overproduce force, particularly at lower intensities. The IMTP showed a closer approximation to prescribed submaximal targets than the ISqT. Conclusions: Ingesting 4 mg·kg⁻¹ of caffeine does not enhance maximal isometric force output or perceptual accuracy during voluntary submaximal force regulation in multi-joint isometric tasks. Prescribing isometric intensity based solely on perceived effort may therefore be unreliable under these specific testing conditions, particularly at lower intensities. Full article

Objectives: To determine whether caffeine supplementation and its expectancy influence muscle strength (ST) and muscle endurance (ME) using a balanced-placebo design. Methods: Using a randomized, double-blind, balanced-placebo design, resistance-trained men (18–30 years; n = 16) participated in two assessment/familiarization visits (demographics; one repetition maximum (1RM) followed by four counterbalanced sessions: C/C (informed caffeine/used caffeine), P/C (informed placebo/used caffeine), C/P (informed caffeine/used placebo), P/P (informed placebo/used placebo). Caffeine dose was 5 mg/kg. Peak torque (PT) and maximum work (MW) were measured in the knee extensors at 0, 60, 180, and 300°/s, which was followed by ME testing (three sets of maximal repetitions using 60%1RM). Capillary blood lactate was measured after ME testing. Results: Caffeine increased PT only during static and 60°/s contractions (4%; p ≤ 0.003; d = 0.3 for both speeds), while MW increased across all speeds (4%; p < 0.001; d = 0.2). Caffeine did not increase ME (3%; p = 0.184; d = 0.1), but it did increase blood lactate levels (1.2 mmol/L; p < 0.001; d = 0.7). Caffeine expectation did not improve ST or ME, but increased blood lactate levels (0.7 mmol/L; p = 0.003; d = 0.4). Across ST and ME, responses to caffeine were markedly heterogeneous, with 50–88% of individuals considered responders (∆ > 0), and improvements in responders ranged from 1–16%. Conclusions: Caffeine significantly increased ST, despite ME increasing in 50% of participants, this was not significant. No placebo effect was observed in ST or ME, but it significantly increased lactate. Further research is necessary to elucidate the mechanisms behind this variability in the ME response, especially the role of fiber-type predominance. Full article

Background: Caffeine is an ergogenic aid shown to delay fatigue, increase arousal, and improve performance. Recommended doses are 3–6 mg/kg BM, although evidence supports lower doses (<3 mg/kg). Some conflicting results have highlighted that lower doses may still be ergogenic, and with new pouch and gum products, further research is warranted. Method: This study investigated the effects of novel low-dose caffeine products on muscular endurance, strength, and power. A repeated-measure, crossover design (pouch 80 mg, gum 80 mg, control gum 0 mg) was employed, recruiting nineteen participants (age 22.4 + 4.8 yrs; weight 72.8 + 16.9 kg; relative caffeine dose 1.1 mg/kg). Participants completed a battery of tests, including 60% 1 RM single leg press (LP) and shoulder press (SP) to exhaustion, counter-movement jump, and isometric mid-thigh pull, in addition to providing ratings of perceived exertion (RPE) during endurance tests. One-way repeated measures ANOVA was conducted on all measures associated with physical tasks, with a two-way repeated measures ANOVA conducted for RPE. Results: No significance was observed among conditions for physical tests. However, effect sizes, employing Cohen’s D classification, identified a moderate (d = 0.55) and small (d = 0.45) effect for the caffeine pouch compared to the placebo and caffeine gum for the LP respectively. Further, small effects for the pouch compared to the placebo were observed (d = 0.33) for the SP. Significant differences were produced for RPE during the LP (p = 0.022), with post hoc analysis identifying significant differences between the placebo vs. caffeine pouch (p = 0.032). Conclusion: Low-dose caffeine has the potential to produce meaningful effects on strength endurance, likely linked to caffeine mechanisms reducing RPE. Full article

This study focuses on the storage process of coffee beans, employing electron beam irradiation (EBI) to investigate the comprehensive effects of different irradiation doses on coffee beans and their storage process, including physicochemical indicators, microbial abundance, and flavor compounds. The results showed that a 2 kGy dose of EBI could effectively reduce the total number of bacteria, molds, and yeasts in green coffee beans (GCBs), while a dose of 4 kGy can completely inactivate the bacteria and maintain this effect for one month. Compared with the control sample that has not undergone processing by EBI (CK), the crude fat content of the irradiated samples decreased, accompanied by a significant increase in acid value. After 30 days of storage, compared with the CK-30 sample, EBI treatment significantly reduced both the moisture content and overall brightness value of GCB. The analysis of aroma compounds in roasted coffee beans (RCBs) revealed that substances related to Maillard reaction, caramelization reaction and sugar degradation, such as 2-Furanmethanol and acetic acid, changed in the irradiated samples, but had no significant effect on the characteristic components like caffeine and the aroma detected by the electronic nose. The obtained results provide a scientific basis for applying irradiation technology to the preservation of coffee beans. Full article