Caffeine ingestion compromises thermoregulation and does not improve cycling time to exhaustion in the heat amongst males.

PURPOSE: Caffeine is a commonly used ergogenic aid for endurance events; however, its efficacy and safety have been questioned in hot environmental conditions. The aim of this study was to investigate the effects of acute caffeine supplementation on cycling time to exhaustion and thermoregulation in the heat. METHODS: In a double-blind, randomised, cross-over trial, 12 healthy caffeine-habituated and unacclimatised males cycled to exhaustion in the heat (35 °C, 40% RH) at an intensity associated with the thermoneutral gas exchange threshold, on two separate occasions, 60 min after ingesting caffeine (5 mg/kg) or placebo (5 mg/kg). RESULTS: There was no effect of caffeine supplementation on cycling time to exhaustion (TTE) (caffeine; 28.5 ± 8.3 min vs. placebo; 29.9 ± 8.8 min, P = 0.251). Caffeine increased pulmonary oxygen uptake by 7.4% (P = 0.003), heat production by 7.9% (P = 0.004), whole-body sweat rate (WBSR) by 21% (P = 0.008), evaporative heat transfer by 16.5% (P = 0.006) and decreased estimated skin blood flow by 14.1% (P < 0.001) compared to placebo. Core temperature was higher by 0.6% (P = 0.013) but thermal comfort decreased by - 18.3% (P = 0.040), in the caffeine condition, with no changes in rate of perceived exertion (P > 0.05). CONCLUSION: The greater heat production and storage, as indicated by a sustained increase in core temperature, corroborate previous research showing a thermogenic effect of caffeine ingestion. When exercising at the pre-determined gas exchange threshold in the heat, 5 mg/kg of caffeine did not provide a performance benefit and increased the thermal strain of participants.

Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

Mitigation of caffeine micropollutants in wastewater through Ag-doped ZnO photocatalyst: mechanism and environmental impacts.

Micropollutants, such as caffeine (M-CF), pose a significant threat to ecosystems and human health through water and food sources. The utilization of metal oxide-based photocatalysts has proven to be an effective treatment method for the removal of organic pollutants. This study explores the efficacy of Ag-doped ZnO (Ag/ZnO) for removing M-CF from wastewater. The characterization of Ag/ZnO underscores the crucial role of band gap energy in the photocatalytic degradation process. This parameter influences the separation of electrons and holes (e-/h+) and the generation of reactive radicals. Under solar light, Ag/ZnO demonstrated markedly superior photocatalytic activity, achieving an impressive degradation efficiency of approximately 93.4%, in stark contrast to the 53.2% occurred by ZnO. Moreover, Ag/ZnO exhibited a remarkable degradation efficiency of M-CF in wastewater, reaching 83.5%. A key advantage of Ag/ZnO lies in its potential for recovery and reuse in subsequent treatments, contributing to a reduction in operational costs for industrial wastewater treatment. Impressively, even after five cycles, Ag/ZnO maintained a noteworthy photodegradation rate of M-CF at 78.6%. These results strongly suggest that Ag/ZnO presents a promising solution for the removal of micropollutants in wastewater, with potential scalability for industrial and large-scale applications.

Photophysical Properties of Sinapic Acid and Ferulic Acid and Their Binding Mechanism with Caffeine.

Sinapic acid (SA) and ferulic acid (FA) are bioactive compounds used in the food, pharmaceutical, and cosmetic industries due to their antioxidant properties. In this work, we studied the photophysical properties of SA and FA in different solvents and concentrations and their interactions with caffeine (CF), using ultraviolet-visible (UV-Vis), fluorescence spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The findings show that the quantum yield, fluorescence lifetime, radiative decay rates, and non-radiative decay rates of SA and FA are influenced by the concentrations and solvent polarity. The interaction between SA and FA with CF was also studied using UV-Vis and fluorescence spectroscopy. The results indicate that the CF quenched the fluorescence intensity of SA and FA by static quenching due to the formation of a non-fluorescent complex. The van't Hoff equation suggests that the van der Waals forces and hydrogen bonds force were responsible for the interaction between SA and CF, as indicated by a negative change in enthalpy ( Δ H o  < 0) and a negative change in entropy ( Δ S o  < 0). On the other hand, the interaction between FA and CF was primarily controlled by electrostatic force, as indicated by a negative change in enthalpy ( Δ H o < 0) and a positive change in entropy ( Δ S o > 0). The negative change in Gibbs free energy ( Δ G o ) indicates that both compounds underwent a spontaneous binding process.

Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.

Background: The G2019S mutation of LRRK2, which enhances kinase activity of the protein, confers a substantial risk of developing Parkinson's disease (PD). However, the mutation demonstrates incomplete penetrance, suggesting the involvement of other genetic or environmental modulating factors. Here, we investigated whether LRRK2 G2019S knock-in (KI) mice treated with the inflammogen lipopolysaccharide (LPS) could model LRRK2 PD. Results: We found that short-term (2 weeks) treatment with LPS did not result in the loss of dopaminergic neurons in either LRRK2 G2019S KI or wild-type (WT) mice. Compared with WT mice, LRRK2 G2019S-KI mice showed incomplete recovery from LPS-induced weight loss. In LRRK2 G2019S KI mice, LPS treatment led to upregulated phosphorylation of LRRK2 at the autophosphorylation site Serine 1292, which is known as a direct readout of LRRK2 kinase activity. LPS treatment caused a greater increase in the activated astrocyte marker glial fibrillary acidic protein (GFAP) in the striatum and substantia nigra of LRRK2 G2019S mice than in those of WT mice. The administration of caffeine, which was recently identified as a biomarker of resistance to developing PD in individuals with LRRK2 mutations, attenuated LPS-induced astrocyte activation specifically in LRRK2 G2019S KI mice. Conclusions: Our findings suggest that 2 weeks of exposure to LPS is not sufficient to cause dopaminergic neuronal loss in LRRK2 G2019S KI mice but rather results in increased astrocyte activation, which can be ameliorated by caffeine.

Porous sulfur polymers for effective aqueous-phase organic contaminant removal.

Sulfur polymers produced through 'inverse vulcanization' exhibit various attributes, such as photocatalytic activity and a high capacity to adsorb heavy metals. Nevertheless, there is a lack of research investigating the use of sulfur polymers as materials for the removal of organic contaminants. In this work, porous sulfur polymers (PSPs) were synthesized from elemental sulfur and 1,3-diisopropenylbenzene, with porosity introduced via salt templating. The result is a material that can strongly adsorb and chemically neutralize a model organic contaminant (caffeine). PSPs show adsorption up to 5 times higher than a leading adsorption material (activated carbon). Furthermore, either the adsorption or degradation processes can govern the removal efficiency depending on the synthesis parameters of PSPs. This is the first-ever report demonstrating sulfur polymers as effective materials for removing emerging contaminants from water. The versatile synthesis of sulfur polymers offers variation, which means that there is much more to explore in this exciting research area.

Coffee Consumption Among Adolescents: A Cross-Sectional Study.

The purpose of this cross-sectional study is to analyze and perform a model analysis of the scope of caffeine consumption in adolescents in Turkey. The prevalence of caffeine consumption was 65.5% (321/490), with 22% of boys and 38.45% of girls consuming foodstuffs or beverages containing it. The mean daily caffeine intake was 85.8 mg. Girls consumed all types of coffee more frequently, while boys consumed black tea and energy drinks such as Red Bull and Burn more frequently than girls. Coffee was most frequently consumed to boost concentration, and tea and energy drinks out of habit. Individuals who lived in the city center, smokers, and individuals with high income levels consumed more caffeine (P = .000, P = .000, and P = .000). The level at which energy drinks were consumed by mixing with alcohol in a party setting was 11.5%, and this was more common among boys (P = .000). Greater efforts should be made to inform parents and adolescents of the potential harm resulting from misuse of caffeine.

Estimate the prevalence of daily caffeine consumption, caffeine use disorder, caffeine withdrawal and perceived harm in Iran: a cross-sectional study.

One of the informal diagnoses in DSM-5 is Caffeine Use Disorder (CUD). CUD and high levels of caffeine consumption could impact mental health conditions. This study aimed to estimate the prevalence of CUD, caffeine consumption, caffeine-related harms, and related psychiatric symptoms in Iran. A cross-sectional survey with a convenience sample of 1228 adults were conducted in Iran. Caffeine consumption was assessed across 20 products in Iran. Caffeine Use Disorder Questionnaire (CUDQ), Caffeine Withdrawal Symptoms Questionnaire (CWSQ), 14-item Caffeine-related Harm Screening (CHS), and Symptom Checklist-25 (SCL-25) were used in the present study. We used SPSS (desktop version 26.0) to analyze the data using descriptive statistics, chi-square, and the least significant difference (LSD) post hoc test. The daily average caffeine consumption was 146.67 mg. The prevalence of CUD and caffeine withdrawal (C.W.) were estimated at 19.5% and 46.62%, respectively. Also, 12.9% of responders received CUD and C.W.s simultaneously. The prevalence of CUD was higher in men than females (25.08% vs. 13.93%). 95% of participants (n = 1166) reported using at least one caffeine product yesterday. Moreover, the most reported caffeine-related harms were the desire for sugar (42.9%), insomnia (39.3%), and caffeine dependence (38.3%). Age significantly correlates with CUD (- 0.07) and daily caffeine intake (0.08). Moreover, all SCL-90 subscales had a significant correlation with daily caffeine intake. Finally, responders at younger ages reported higher levels of CUD and caffeine consumption than older adults(P < 0.05). High rates of C.W. and CUD in the Iranian population suggest that it is necessary to develop evidence-based treatments.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

The association between wet overactive bladder and consumption of tea, coffee, and caffeine: Results from 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.

Total fermentable oligo-, di-, monosaccharides and polyols intake, carbohydrate malabsorption and gastrointestinal symptoms during a 56 km trail ultramarathon event.

AIMS: To explore the relationship between nutritional intake, fermentable oligo-, di, monosaccharides and polyols, and carbohydrate malabsorption, with gastrointestinal symptoms during a 56 km trail ultramarathon event and identify differences in nutritional intake between runners with severe and non-severe gastrointestinal symptoms. METHODS: Forty-four ultramarathoners recorded and self-reported dietary intake 3 days before, morning of, and during the ultramarathon with gastrointestinal symptoms obtained retrospectively and nutrient analysis via FoodWorks. Carbohydrate malabsorption was determined via breath hydrogen content pre- and post-race. Spearman's rank-order and Mann-Whitney U-tests were used to identify relationships and differences between groups. RESULTS: Total fermentable oligo-, di, monosaccharides and polyols intake were not associated with gastrointestinal symptoms, but weak associations were observed for lower energy (rs = -0.302, p = 0.044) and fat intake (rs = -0.340, p = 0.024) 3 days before with upper gastrointestinal symptoms and higher caffeine intake 3 days before with overall gastrointestinal symptoms (rs = 0.314, p = 0.038). Total fermentable oligo-, di-, monosaccharides and polyols intake and breath hydrogen were not different between those with severe versus non-severe symptoms (p > 0.05). Although those with severe symptoms had higher caffeine (p = 0.032), and total polyols intake (p = 0.031) 3 days before, and higher % energy from fat (p = 0.043) and sorbitol intake (p = 0.026) during the race, and slower ultramarathon finish times (p = 0.042). CONCLUSION: Total fermentable oligo-, di-, and monosaccharides intake and carbohydrate malabsorption were not associated with gastrointestinal symptoms. Additional research on the effect of fat, caffeine, and polyol intake on exercise-associated gastrointestinal symptoms is warranted and presents new nutritional areas for consideration when planning nutritional intake for ultramarathoners.

Assessment of restriction measures implemented during COVID pandemics on community lifestyle choices via wastewater-based epidemiology.

SARS-CoV-2 pandemic affected lifestyle habits, and the mental health and wellbeing of people around the world. In this manuscript, two towns (Paulton and Radstock) and two cities (Bath and Bristol) in Southwest England (> 1 million people) were monitored for two years using Wastewater-Based Epidemiology to assess impacts of COVID (including management measures such as lockdowns and movement restrictions) on community lifestyle choices: illicit drugs, legal stimulants, abused pharmaceuticals and pain pharma usage. Results were triangulated with key dates captured during the pandemic (national lockdowns, restrictions and social distancing measures, etc.). This highlighted a reduction in cocaine intake (as benzoylecgonine) (community average: -36 %) during the first lockdown and an increase in illicit drugs usage after the 3rd national lockdown (community averages for amphetamine: +8 %, cocaine/benzoylecgonine: +39 %, ketamine:+70 %) when restrictions were removed, and social interaction and recreational activities increased. There was a reduction in the intake of caffeine (as 1,7-dimethylxanthine) (community average:-39 %) after 3rd national lockdown coinciding with pubs reopening while nicotine intake (via cotinine) remained stable indicating lack of impact of COVID on smoking habits. Pain pharma often used in pain management resulting from injuries linked with sport activities (naproxen and diclofenac) showed decrease in usage due to lockdown restrictions in physical exercise and access to gyms/sport facilities.

The association of caffeine and nandrolone decanoate modulates aversive memory and nociception in rats.

Caffeine and anabolic-androgenic steroids (AAS) are commonly used to improve muscle mass and athletic performance. Nandrolone Decanoate (ND) is one of the most abused AAS worldwide, leading to behavioral changes in both humans and rodents. Caffeine, the most widely consumed psychostimulant globally, is present in various thermogenic and gym supplements. Low and moderate doses of caffeine antagonize adenosine receptors and have been linked to improved memory and pain relief. We have previously demonstrated that consuming caffeine prevents the risk-taking behavior triggered by nandrolone. In this study, we aimed to investigate the long-term effects of ND and caffeine, either alone or in combination, on passive avoidance memory and nociception. We used the step-down and hot-plate tasks in male and female Lister Hooded rats. Our results confirmed the antinociceptive effect of caffeine and indicated that chronic administration of the ND-caffeine association promotes the evocation of aversive memory in female rats.

Enhancing Sustainability and Antifungal Properties of Biodegradable Composites: Caffeine-Treated Wood as a Filler for Polylactide.

This study investigates the suitability of using caffeine-treated and untreated black cherry (Prunus serotina Ehrh.) wood as a polylactide filler. Composites containing 10%, 20%, and 30% filler were investigated in terms of increasing the nucleating ability of polylactide, as well as enhancing its resistance to microorganisms. Differential scanning calorimetry studies showed that the addition of caffeine-treated wood significantly altered the crystallization behavior of the polymer matrix, increasing its crystallization temperature and degree of crystallinity. Polarized light microscopic observations revealed that only the caffeine-treated wood induced the formation of transcrystalline structures in the polylactide. Incorporation of the modified filler into the matrix was also responsible for changes in the thermal stability and decreased hydrophilicity of the material. Most importantly, the use of black cherry wood treated with caffeine imparted antifungal properties to the polylactide-based composite, effectively reducing growth of Fusarium oxysporum, Fusarium culmorum, Alternaria alternata, and Trichoderma viride. For the first time, it was reported that treatment of wood with a caffeine compound of natural origin alters the supermolecular structure, nucleating abilities, and imparts antifungal properties of polylactide/wood composites, providing promising insights into the structure-properties relationship of such composites.

Combined metabolome and transcriptome analyses reveal that growing under Red shade affects secondary metabolite content in Huangjinya green tea.

Shading treatments impact the tea (Camellia sinensis L.) quality. The sunlight sensitive varieties can be grown under shading nets for better growth and secondary metabolite content. Here, we studied the responses of a sunlight sensitive green tea variety "Huangjinya" by growing under colored shading nets (red, yellow, blue, and black (75% and 95%) shading rates) to find out the most suitable color of the shading net. Red shading was the most promising treatment as it positively affected the weight and length of 100 one-bud-three leaves and reduced the degree and rate of new shoots burn compared to control (natural sunlight). We then explored the comparative metabolomic changes in response to red shading by using UPLC-ESI-MS/MS system. The amino acids and derivatives, flavonoids, and alkaloids were downaccumulated whereas lipids, organic acids, and lignans were upaccumulated in Red shade grown tea samples. The red shading nets caused a decreased catechin, epicatechin, dopamine, and L-tyramine contents but increased caffeine content. We then employed transcriptome sequencing to find key changes in expressions of related genes and pathways. Notably, key genes associated with the phenylpropanoid and flavonoid biosynthesis pathways exhibited complex regulation. These expression changes suggested a potential trend of polymerization or condensation of simple molecules like catechin or pelargonidin into larger molecules like glucoside or proanthocyanidins. Here, Red shading net triggered higher expression of genes enriched in lipid biosynthesis and jasmonic acid biosynthesis, suggesting an interplay of fatty acids and JA in improving tea performance. These findings contribute to the metabolic responses of Huangjinya tea to red shading nets which might have implications for flavor and health benefits. Our data provide a foundation for further exploration and optimization of cultivation practices for this unique tea variety.

Causal association of genetically determined caffeine intake from tea or coffee with bone health: a two-sample Mendelian randomization study.

BACKGROUND: Relationship of caffeine intake and consumption of caffeinated beverages, such as tea and coffee, with bone health remains controversial. This study aimed to evaluate whether genetically determined caffeine intake from tea or coffee has causal effects on overall total body bone mineral density (TB-BMD) and fracture. We also assessed the association with TB-BMD in five age strata. METHODS: Using two-sample Mendelian randomization approach, summary statistics were retrieved from genome-wide association studies (GWAS)/GWAS meta-analyses of caffeine intake from tea (n = 395 866)/coffee (n = 373 522), TB-BMD (n = 66 628), and fracture (n = 426 795). Inverse variance weighted method was adopted as the main univariable analysis. Multivariable analysis was conducted to evaluate whether the causal effect is independent. RESULTS: In univariable analysis, genetically determined caffeine intake from tea had positive association with overall TB-BMD (per SD increase in genetically determined caffeine intake, beta of TB-BMD [in SD]: 0.166; 95% confidence interval (CI): 0.006-0.326) and inverse association with fracture (OR = 0.79; 95% CI: 0.654-0.954). Genetically determined caffeine intake from coffee was also positively associated with overall TB-BMD (beta = 0.231; 95% CI: 0.093-0.369). The association remained significant after adjustment for smoking in multivariable analysis. Genetically determined caffeine intake from tea or coffee was both positively associated with TB-BMD in the age strata of 45-60 years, but we lacked evidence of association in other strata. CONCLUSIONS: Genetically, caffeine intake from tea or coffee may be beneficial to bone health. Due to the ascertainment method of caffeine intake from tea, our study also implied genetically higher tea consumption may improve TB-BMD and lower fracture risk.

Dose-Response Study of Caffeine on Postnatal Weight Gain in Premature Neonates-A Retrospective Cohort Study.

Background: Caffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses' effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5 mg/kg/day as the standard regimen. Method: This retrospective cohort study included neonates of ≤36 weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I=(5 mg/kg/day), group-II=(>5-7 mg/kg/day), and group-III=(>7 mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard. Results: The study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88 g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88 g/kg/d vs 16.7 ± .71, P < .001). During 29-42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d, P = .003) and comparable with group-II. During 15-28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29-42 DOL was significant only in group-III. Conclusion: Exposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.

Non-invasive caffeinated-nanovesicles as adipocytes-targeted therapy for cellulite and localized fats.

Caffeine (CAF) is a non-selective adenosine A1 receptor antagonist which predominates in fat cells. When CAF binds to adenosine receptors, it increases cyclic adenosine monophosphate; inhibiting adipogenesis and inducing fat lipolysis. Resveratrol (RSV) is an antioxidant polyphenol possessing different anti-obesity mechanisms. Topical application of both hydrophilic CAF and lipophilic RSV is limited. This study aimed to develop novel caffeinated-resveratrol bilosomes (CRB) and caffeine-bilosomes (CB) that could non-invasively target and deposit in fat cells. RSV bilosomes (RB) were prepared as a non-targeted system for comparison. CRB showed nanosize (364.1 nm ±6.5 nm) and high entrapment for both active compounds. Rats treated topically with CRB revealed a significant decrease (P = 0.039) in body weight. Histological analysis of the excised skin demonstrated a reduction in the subcutaneous fatty layer thickness and a decrease in the size of connective tissue-imbedded fat cells. Kidney histological examination of RB-treated rats showed subcapsular tubular epithelial cells with cytoplasmic vacuolation. This reflects a systemic effect of RSV from the non-targeted RB compared to CRB, which had a targeting effect on the adipose tissue. In conclusion, CAF in CRB significantly enhanced RSV deposition in adipose tissue and assisted its local-acting effect for managing obesity and cellulite.

Therapeutic Effects of Tretinoin and Caffeine-Treated Bone Marrow-Derived Mesenchymal Stem Cell on Immunological Features of Ulcerative Colitis: An Animal Model Study.

Background: Ulcerative colitis (UC) is one of the inflammatory gastrointestinal diseases. It causes irritation, inflammation, and ulcers in the digestive tract. UC is distinguished clinically by abdominal and rectal pain and intestinal secretion abnormalities. Mesenchymal stem cell (MSC) therapy could be the underlying treatment for UC. This study aimed to compare the results of MSC therapy with tretinoin and caffeine in an animal model. Materials and Methods: Sixty male BALB/c mice were randomly divided into six equal groups. Five groups were exposed to acetic acid-induced colitis, and one healthy negative control group was designed. The positive control group was UC-induced mouse model with no treatment. Besides, treatment groups were MSCs (n = 2×106) that received tretinoin and caffeine. The treatment group was given mesalazine orally. The decision to begin treatment was taken after monitoring the symptoms of the UC. Results: MSCs, tretinoin, and caffeine-treated MSCs significantly decrease inflammatory cytokines (interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α) and inflammatory mediators (myeloperoxidase (MPO) and nitric oxide (NO)) compared with the positive control group. However, the alleviated effects of tretinoin-treated MSCs significantly were more than those of MSCs and caffeine-treated MSCs. Conclusion: MSC therapy is an effective option for UC and can prevent disease progression. The results represented a high developmental rate and simple cell application of MSC therapy in UC patients. Also, MSC therapy's ability for immunomodulation is strengthened by drugs that improve their microenvironment by binding to their receptors.

Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation.

The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms "Caffeine" and "Hepatocellular Carcinoma." Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.