Diet with different concentrations of lychee peel flour modulates oxidative stress parameters and antioxidant activity in zebrafish.

The agri-food industry generates substantial waste, leading to significant environmental impacts. Lychee (Litchi chinensis Sonnerat), which is rich in bioactive compounds in its peel, pulp, and seeds, offers an opportunity for waste use. This study aimed to evaluate the effects of supplementing a high-carbohydrate diet with varying levels of lychee peel flour on lipid metabolism biomarkers and oxidative stress in a zebrafish (Danio rerio) model. A total of 225 zebrafish, approximately four months old, were divided into five groups: control, high-carbohydrate (HC), HC2%, HC4%, and HC6%. The study did not find significant differences in the growth performance of zebrafish in any group. However, the HC6% group exhibited a significant decrease in glucose and triglyceride levels compared with the HC group. Furthermore, this group showed enhanced activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), along with reduced levels of malondialdehyde (MDA). Increased antioxidant activity was also evidenced by DPPH-, ABTS+, and ß-carotene/Linoleic acid assays in the HC6% group. A positive correlation was identified between SOD/CAT activity and in vitro antioxidant assays. These findings suggest that dietary supplementation with 6% lychee peel flour can significantly modulate glucose homeostasis, lipid metabolism, and antioxidant activity in zebrafish.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Isolated and combined effects of cobalt and nickel on the microalga Raphidocelis subcapitata.

Aquatic organisms are exposed to several compounds that occur in mixtures in the environment. Thus, it is important to investigate their impacts on organisms because these combined effects can be potentiated. Cobalt (Co) and nickel (Ni) are metals that occur in the environment and are used in human activities. To the best of our knowledge, there are no studies that investigated the combined effects of these metals on a freshwater Chlorophyceae. Therefore, this study analyzed the isolated and combined effects of Co and Ni in cell density, physiological and morphological parameters, reactive oxygen species (ROS), carbohydrates and photosynthetic parameters of the microalga Raphidocelis subcapitata. Data showed that Co affected the cell density from 0.25 mg Co L-1; the fluorescence of chlorophyll a (Chl a) (0.10 mg Co L-1); ROS production (0.50 mg Co L-1), total carbohydrates and efficiency of the oxygen evolving complex (OEC) at all tested concentrations; and the maximum quantum yield (ΦM) from 0.50 mg Co L-1. Ni exposure decreased ROS and cell density (0.35 mg Ni L-1); altered Chl a fluorescence and carbohydrates at all tested concentrations; and did not alter photosynthetic parameters. Regarding the Co-Ni mixtures, our data best fitted the concentration addition (CA) model and dose-ratio dependent (DR) deviation in which synergism was observed at low doses of Co and high doses of Ni and antagonism occurred at high doses of Co and low doses of Ni. The combined metals affected ROS production, carbohydrates, ΦM, OEC and morphological and physiological parameters.

Effect of ultra-violet light radiation on Scenedesmus vacuolatus growth kinetics, metabolic performance, and preliminary biodegradation study.

This study presents the effect of ultra-violet (UV) light radiation on the process kinetics, metabolic performance, and biodegradation capability of Scenedesmus vacuolatus. The impact of the UV radiation on S. vacuolatus morphology, chlorophyll, carotenoid, carbohydrates, proteins, lipid accumulation, growth rate, substrate affinity and substrate versatility were evaluated. Thereafter, a preliminary biodegradative potential of UV-exposed S. vacuolatus on spent coolant waste (SCW) was carried out based on dehydrogenase activity (DHA) and total petroleum hydrocarbon degradation (TPH). Pronounced structural changes were observed in S. vacuolatus exposed to UV radiation for 24 h compared to the 2, 4, 6, 12 and 48 h UV exposure. Exposure of S. vacuolatus to UV radiation improved cellular chlorophyll (chla = 1.89-fold, chlb = 2.02-fold), carotenoid (1.24-fold), carbohydrates (4.62-fold), proteins (1.44-fold) and lipid accumulations (1.40-fold). In addition, the 24 h UV exposed S. vacuolatus showed a significant increase in substrate affinity (1/Ks) (0.959), specific growth rate (µ) (0.024 h-1) and biomass accumulation (0.513 g/L) by 1.50, 2 and 1.9-fold respectively. Moreover, enhanced DHA (55%) and TPH (100%) degradation efficiency were observed in UV-exposed S. vacuolatus. These findings provided major insights into the use of UV radiation to enhance S. vacuolatus biodegradative performance towards sustainable green environment negating the use of expensive chemicals and other unfriendly environmental practices.

SAD rats: Effects of short photoperiod and carbohydrate consumption on sleep, liver steatosis, and the gut microbiome in diurnal grass rats.

Seasonal affective disorder (SAD) is a recurrent depression triggered by exposure to short photoperiods, with a subset of patients reporting hypersomnia, increased appetite, and carbohydrate craving. Dysfunction of the microbiota - gut - brain axis is frequently associated with depressive disorders, but its role in SAD is unknown. Nile grass rats (Arvicanthis niloticus) are potentially useful for exploring the pathophysiology of SAD, as they are diurnal and have been found to exhibit anhedonia and affective-like behavior in response to short photoperiods. Further, given grass rats have been found to spontaneously develop metabolic syndrome, they may be particularly susceptible to environmental triggers of metabolic dysbiosis. We conducted a 2 × 2 factorial design experiment to test the effects of short photoperiod (4 h:20 h Light:Dark (LD) vs. neutral 12:12 LD), access to a high concentration (8%) sucrose solution, and the interaction between the two, on activity, sleep, liver steatosis, and the gut microbiome of grass rats. We found that animals on short photoperiods maintained robust diel rhythms and similar subjective day lengths as controls in neutral photoperiods but showed disrupted activity and sleep patterns (i.e. a return to sleep after an initial bout of activity that occurs ~ 13 h before lights off). We found no evidence that photoperiod influenced sucrose consumption. By the end of the experiment, some grass rats were overweight and exhibited signs of non-alcoholic fatty liver disease (NAFLD) with micro- and macro-steatosis. However, neither photoperiod nor access to sucrose solution significantly affected the degree of liver steatosis. The gut microbiome of grass rats varied substantially among individuals, but most variation was attributable to parental effects and the microbiome was unaffected by photoperiod or access to sucrose. Our study indicates short photoperiod leads to disrupted activity and sleep in grass rats but does not impact sucrose consumption or exacerbate metabolic dysbiosis and NAFLD.

Central effects of mouth rinses on endurance and strength performance.

Rinsing the mouth with a carbohydrate (CHO) solution has been shown to enhance exercise performance while reducing neuromuscular fatigue. This effect is thought to be mediated through the stimulation of oral receptors, which activate brain areas associated with reward, motivation, and motor control. Consequently, corticomotor responsiveness is increased, leading to sustained levels of neuromuscular activity prior to fatigue. In the context of endurance performance, the evidence regarding the central involvement of mouth rinse (MR) in performance improvement is not conclusive. Peripheral mechanisms should not be disregarded, particularly considering factors such as low exercise volume, the participant's fasting state, and the frequency of rinsing. These factors may influence central activations. On the other hand, for strength-related activities, changes in motor evoked potential (MEP) and electromyography (EMG) have been observed, indicating increased corticospinal responsiveness and neuromuscular drive during isometric and isokinetic contractions in both fresh and fatigued muscles. However, it is important to note that in many studies, MEP data were not normalised, making it difficult to exclude peripheral contributions. Voluntary activation (VA), another central measure, often exhibits a lack of changes, mainly due to its high variability, particularly in fatigued muscles. Based on the evidence, MR can attenuate neuromuscular fatigue and improve endurance and strength performance via similar underlying mechanisms. However, the evidence supporting central contribution is weak due to the lack of neurophysiological measures, inaccurate data treatment (normalisation), limited generalisation between exercise modes, methodological biases (ignoring peripheral contribution), and high measurement variability.Trial registration: PROSPERO ID: CRD42021261714.

Insoluble/soluble fraction ratio determines effects of dietary fiber on gut microbiota and serum metabolites in healthy mice.

Both soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) play pivotal roles in maintaining gut microbiota homeostasis; whether the effects of the different ratios of IDF and SDF are consistent remains unclear. Consequently, we selected SDFs and IDFs from six representative foods (apple, celery, kale, black fungus, oats, and soybeans) and formulated nine dietary fiber recipes composed of IDF and SDF with a ratio from 1 : 9 to 9 : 1 (NDFR) to compare their impact on microbial effects with healthy mice. We discovered that NDFR treatment decreased the abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes at the phylum level. The α diversity and relative richness of Parabacteroides and Prevotella at the genus level showed an upward trend along with the ratio of IDF increasing, while the relative abundance of Akkermansia at the genus level and the production of acetic acid and propionic acid exhibited an increased trend along with the ratio of SDF increasing. The relative abundance of Parabacteroides and Prevotella in the I9S1DF group (the ratio of IDF and SDF was 9 : 1) was 1.72 times and 5.92 times higher than that in the I1S9DF group (the ratio of IDF and SDF was 1 : 9), respectively. The relative abundance of Akkermansia in the I1S9DF group was 17.18 times higher than that in the I9S1DF group. Moreover, a high ratio of SDF (SDF reaches 60% or more) enriched the glycerophospholipid metabolism pathway; however, a high ratio of IDF (IDF reaches 80% or more) regulated the tricarboxylic acid cycle. These findings are helpful in the development of dietary fiber supplements based on gut microbiota and metabolites.

Preventive effect of low-carbohydrate high-fat dietary pattern on liver disease caused by alcohol consumption via a 6pgd-involved mechanism in mice.

A low-carbohydrate high-fat (LCHF) dietary pattern has been reported to improve chronic metabolic diseases. However, whether and how the LCHF diet affects the pathological progression in patients with alcohol-related liver diseases (ALD) is largely unknown. This study was conducted to evaluate the effect of the LCHF diet on ALD and clarify its potential mechanism(s). The ALD model was established by feeding C57BL/6N mice with a Lieber-DeCarli liquid alcohol diet with a modified carbohydrate/fat ratio under an isoenergetic pattern. After an eight-week intervention, we observed that the LCHF diet significantly reduced alcohol-induced hepatic steatosis and liver injury, along with improved lipid metabolic-related gene disorders and redox imbalance. The alcohol-stimulated increase in pro-inflammatory cytokine cytokines expression, including TNF-α, IL-1ß, and IL-6, was markedly reversed by the LCHF diet. Liver transcriptome sequencing and qPCR validation showed that twenty-four alcohol-disturbed genes were significantly reversed by LCHF-diet intervention. The top differentially expressed genes were selected for further investigation. Among them, 6-phosphogluconate dehydrogenase (6PGD) was significantly up-regulated by alcohol treatment in both the liver and cultured hepatocytes. Spearman correlation analysis revealed that 6PGD was positively associated with hepatic steatosis, liver injury, and oxidative stress indexes. In vitro, the 6PGD knockdown ameliorated alcohol-induced hepatotoxicity and intracellular lipid accumulation, as well as lipid metabolic-related gene disorders, implying the involvement of 6PGD in LCHF-protected ALD. In conclusion, LCHF diet intervention alleviated chronic alcohol consumption-induced liver dysfunction in mice. 6PGD is a potential novel target for ALD prevention that contributes to LCHF-improved ALD. A LCHF diet might be a promising choice for ALD management.

Structure-Controllable and Mass-Produced Glycopolymersomes as a Template of the Carbohydrate@Ag Nanobiohybrid with Inherent Antibacteria and Biofilm Eradication.

Glycopolymer-supported silver nanoparticles (AgNPs) have demonstrated a promising alternative to antibiotics for the treatment of multidrug-resistant bacteria-infected diseases. In this contribution, we report a class of biohybrid glycopolymersome-supported AgNPs, which are capable of effectively killing multidrug-resistant bacteria and disrupting related biofilms. First of all, glycopolymersomes with controllable structures were massively fabricated through reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly (PISA) in an aqueous solution driven by complementary hydrogen bonding interaction between the pyridine and amide groups of N-(2-methylpyridine)-acrylamide (MPA) monomers. Subsequently, Ag+ captured by glycopolymersomes through the coordination between pyridine-N and Ag+ was reduced into AgNPs stabilized by glycopolymersomes upon addition of the NaBH4 reducing agent, leading to the formation of the glycopolymersome@AgNPs biohybrid. As a result, they showed a wide-spectrum and enhanced removal of multidrug-resistant bacteria and biofilms compared to naked AgNPs due to the easier adhesion onto the bacterial surface and diffusion into biofilms through the specific protein-carbohydrate recognition. Moreover, the in vivo results revealed that the obtained biohybrid glycopolymersomes not only demonstrated an effective treatment for inhibiting the cariogenic bacteria but also were able to repair the demineralization of caries via accumulating Ca2+ through the recognition between carbohydrates and Ca2+. Furthermore, glycopolymersomes@AgNPs showed quite low in vitro hemolysis and cytotoxicity and almost negligible acute toxicity in vivo. Overall, this type of biohybrid glycopolymersome@AgNPs nanomaterial provides a new avenue for enhanced antibacterial and antibiofilm activities and the effective treatment of oral microbial-infected diseases.

FGF21 Improves Glycolipid Metabolism in Rainbow Trout (Oncorhynchus mykiss) Fed a High-Carbohydrate Diet by Inhibiting Inflammatory Responses and Activating Autophagy.

In this study, the coding region of rainbow trout fgf21 was cloned and sequenced to synthesize a recombinant protein (rFGF21) and investigate its potential role in improving glycolipid metabolism. Acute injection of rFGF21 into rainbow trout effectively reduced serum glucose levels. To investigate the effect of rFGF21 on high-carbohydrate diet (HCD)-induced metabolic disorders in rainbow trout, a 31-day feeding experiment was conducted. At the end of the third week, fish were injected with either PBS or rFGF21. The results showed that the final body weight (FBW) significantly increased in rainbow trout on an HCD (P < 0.05), but there were potential risks including disturbances in glycolipid metabolism and increased inflammatory responses. However, these effects were altered by rFGF21 treatment. In addition, rFGF21 promotes glucose uptake by increasing the phosphorylation levels of AKT (protein kinase B) and GSK3ß (glycogen synthase kinase 3ß), increasing hepatic glycogen, thereby lowering serum glucose. Notably, the rFGF21 did not exacerbate the inflammatory response but downregulated the expression of inflammatory factors. Interestingly, the activation of autophagy and the AMPK pathway may contribute to the positive effect of rFGF21, where rFGF21 injection significantly increased the levels of LC3I/II protein and phosphorylate AMPKα (P < 0.05).

Influence of in vitro gastrointestinal digestion and colonic fermentation on carbonyl scavenging capacity of fiber-bound polyphenols from quinoa.

Whole grain insoluble dietary fiber (IDF) is a good source of bound-form polyphenols. In the present study, insoluble dietary fiber rich in bound polyphenols (BP-IDF) from quinoa, rye and wheat was prepared. The carbonyl scavenging capacities of these three BP-IDFs and the effects of in vitro gastrointestinal (GI) digestion and colonic fermentation on their scavenging activities were studied. The results indicated that the fiber-bound polyphenols from quinoa showed the highest carbonyl scavenging capacity compared to those from rye and wheat. After colonic fermentation, more than 73% of the bound polyphenols were still retained in the fermented residues of the quinoa BP-IDF. The fiber-bound polyphenols in the GI-digested residues of quinoa retained considerable carbonyl scavenging activities. During the fermentation process, the residual fiber-bound polyphenols in the fermented residues still scavenged 35.8% to 45.2% of methylglyoxal, 19.3% to 25.4% of glyoxal, 50.7% to 60.5% of acrolein and 5.2% to 9.7% of malondialdehyde, showing a critical role in the scavenging of carbonyl compounds compared to the released and metabolized polyphenols. These findings confirm the capacity of fiber-bound polyphenols from three whole grains to scavenge carbonyls during in vitro digestion and fermentation processes, suggesting that they could be used as functional ingredients to maintain continuous defenses against carbonyls along the digestive tract.

Effects of exogenous melatonin on sugar and organic acid metabolism in early-ripening peach fruits.

To evaluated the effects melatonin (MT) on the sugar and acid metabolism of early-ripening peach fruits, the concentration of 150 µmol/L MT was sprayed on the leaves of peach trees. MT increased the contents of total soluble sugar and sucrose in peach fruits during the whole ripening period, and increased the contents of glucose and sorbitol at the mature stage. During the whole ripening period, MT also increased the activities of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase and the relative expression levels of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase genes, while decreased the activity of sorbitol oxidase and the relative expression level of sorbitol dehydrogenase to some extent. Moreover, MT decreased the contents of total organic acid, malic acid, and citric acid at mature stage. At mature stage, MT decreased the activities of citrate synthetase and phosphoenolpyruvate carboxylase and the relative expression levels of citrate synthetase and phosphoenolpyruvate carboxylase genes, while increased the relative expression levels of Nicotinamide adenine dinucleotide phosphate (NADP+)-malic enzyme, malate dehydrogenase, and aconitase genes. Therefore, MT promotes the sugar accumulation and organic acid degradation in early-ripening peach fruits.

Effects of exogenous zinc on the physiological characteristics and enzyme activities of Passiflora edulis Sims f. edulis seedlings.

Passionflower (Passiflora edulis Sims) is widely distributed in tropical and subtropical areas for edible, medicinal and skin care product processing, and the market demand is large. Zinc (Zn) is a necessary trace element for plant growth and development. In many countries, the content of Zn in soil is low and/or bioavailability is low. The exogenous application of Zn has become a common agronomic measure in agriculture. However, the effect of Zn on the physiological characteristics and enzyme activity of passionflower seedlings is not clear. In this study, pot experiments were conducted to analyse the effects of different concentrations of Zn (0, 200, 400, 800 mg kg-1) on the plant growth, photosynthetic pigments, osmotic regulators, membrane system and antioxidant enzyme system of purple passionflower (Passiflora edulis Sims f. edulis) seedlings, and Pearson correlation and principal component analyses were performed. The results showed that (1) the 200 mg kg-1 Zn treatment increased the contents of chlorophyll a (37.65%), chlorophyll b (41.22%), chlorophyll a+b (38.59%) and carotenoids (29.74%). The value of chlorophyll a/b changed little and had no effect on leaf growth. (2) The contents of proline (Pro) and malondialdehyde (MDA) in P. edulis Sims f. edulis seedlings treated with 400 mg kg-1 Zn increased significantly by 116.84% and 42.69%, respectively. The activities of catalase (CAT) and peroxidase (POD) increased by 16.82% and 18.70%, respectively. Superoxide dismutase (SOD), leaf area (LA), leaf perimeter (LP) and leaf width (LW) decreased significantly by 47.20%, 19.75%, 8.32% and 11.97%, respectively. (3) 800 mg kg-1 Zn significantly increased the contents of Pro (202.56%) and MDA (26.7%) and the activities of CAT (16.00%) and POD (67.00%), while the soluble sugar (SS), SOD, LA, LP and LW decreased significantly by 36.67%, 32.86%, 23.36%, 8.32% and 11.18%, respectively. (4) There was a significant positive correlation between Pro and photosynthetic pigments and between SOD and leaf growth and a significant negative correlation between POD and SS and between SOD and MDA. (5) A low concentration (200 mg kg-1) of Zn promoted the growth of P. edulis Sims f. edulis seedlings and allowed stress caused by high Zn concentrations to be tolerated. The results of this study can provide a reference for the application of Zn fertilizer to P. edulis Sims f. edulis.

Effects of Calendula officinalis extract on liver histopathology, lipid profile, and oxidative stress in rats submitted to a diet rich in cholesterol and carbohydrates.

PURPOSE: To evaluate the modulatory properties of Calendula officinalis L. (Asteraceae) (C. officinalis) extract on cafeteria diet-fed rats. METHODS: A cafeteria diet was administered ad libitum for 45 days to induce dyslipidemia. Then, the rats were treated with the formulations containing C. officinalis in the doses of 50, 100, and 150 mg/kg or only with the vehicle formulation; the control group received a commercial ration. RESULTS: The cafeteria diet decreased glutathione S-transferase activity and high-density lipoprotein plasmatic levels and damaged the hepatic architecture. The C. officinalis extract was able to reduce lipid infiltration in liver tissue and to modulate oxidative stress and lipid profile markers. CONCLUSIONS: The correlations between the variables suggest a pathological connection between oxidative stress markers and serum lipid profile.

Effects of pre-sleep protein supplementation on plasma markers of muscle damage and inflammatory cytokines resulting from sprint interval training in trained swimmers.

BACKGROUND: Pre-sleep protein has been shown to improve muscle recovery overnight following exercise-induced muscle damage. Whether such an approach affects recovery from sprint interval training (SIT) has yet to be elucidated. This study examined the effects of protein supplementation every night before sleep on early (45 min post-SIT) and late (24 and 48 h after SIT) responses of creatine kinase (CK) and inflammatory cytokines, including interleukin-6 and 10 (IL-6 and IL-10) and tumor necrosis factor-alpha (TNFα). METHODS: Twenty trained swimmers underwent a 2-week in-water swimming SIT (two sets of 12 × 50-m all-out swims, interspersed by 1:1 recovery between each sprint and 3 min of rest between sets) and were randomized to two intervention groups receiving either 0.5 g kg-1 day-1 protein beverage (PRO) or the same amount of carbohydrate (CHO) preceding going to bed every night. For initial and final training sessions, CK and cytokine responses were analyzed at different time points, including resting, immediately after completion, 45 min post-SIT, and 24 and 48 h after SIT. RESULTS: CK concentrations elevated from resting point to 24 and 48 h post-SIT for both PRO and CHO groups (p < 0.05). In both training groups, the peak levels of IL-6 and 10 were observed 45 min post-SIT on both occasions. TNFα levels significantly elevated from rest to immediately after SIT (p < 0.001) and returned to values equivalent to the baseline afterward in both groups and on both occasions. In both groups, swimming SIT also switched the cytokine response 48 hours after exercise to an anti-inflammatory status by decreasing the ratio of IL-6 to IL-10 (p < 0.04) in the last training session. CONCLUSIONS: Pre-sleep protein ingestion failed to ameliorate blood markers of muscle damage. The late anti-inflammatory profile of cytokines and exercise-induced muscle damage improved after two weeks of swimming SIT with either protein or carbohydrate ingestion before sleep.

Galectin-targeting glycocalix[4]arenes can enter the cells.

Elevated levels of galectin-3 are associated with tumorigenesis. Its inhibition with high-affinity carbohydrate ligands opens new therapeutic routes. Targeting of intracellular galectin-3 is challenging for polar inhibitors like carbohydrates. We demonstrate the potential of novel biomedical research tools, glycocalix[4]arenes, to enter epithelial cells, which may allow their interaction with galectin-3.

Carbohydrate derivatives fight against malaria parasite as anti-plasmodial agents.

Malaria, a prevalent fatal disease around the world is caused by Plasmodium sp. and is transmitted by the bite of female Anopheles mosquito. It is leading cause of death in this century among most infectious diseases. Drug resistance was reported for almost every front-line drug against the deadliest species of the malarial parasite, i.e., Plasmodium falciparum. In the evolutionary arms race between parasite and existing arsenals of drugs new molecules having novel mechanism of action is urgently needed to overcome the drug resistance. In this review, we have discussed the importance of carbohydrate derivatives of different class of compounds as possible antimalarials with emphasis on mode of action, rational design, and SAR with improved efficacy. Carbohydrate-protein interactions are increasingly important for medicinal chemists and chemical biologists to understand the pathogenicity of the parasite. Less is known about the carbohydrate-protein interactions and pathogenicity in the Plasmodium parasite. With the increased knowledge on protein-sugar interaction and glycomics of Plasmodium parasites, carbohydrate derivatives can surpass the existing biochemical pathways responsible for drug resistance. The new candidates with novel mode of action will prove to be a potent antimalarial drug candidate without any parasitic resistance.

Adrenomedullin Enhances Mouse Gustatory Nerve Responses to Sugars via T1R-Independent Sweet Taste Pathway.

On the tongue, the T1R-independent pathway (comprising glucose transporters, including sodium-glucose cotransporter (SGLT1) and the KATP channel) detects only sugars, whereas the T1R-dependent (T1R2/T1R3) pathway can broadly sense various sweeteners. Cephalic-phase insulin release, a rapid release of insulin induced by sensory signals in the head after food-related stimuli, reportedly depends on the T1R-independent pathway, and the competitive sweet taste modulators leptin and endocannabinoids may function on these two different sweet taste pathways independently, suggesting independent roles of two oral sugar-detecting pathways in food intake. Here, we examined the effect of adrenomedullin (ADM), a multifunctional regulatory peptide, on sugar sensing in mice since it affects the expression of SGLT1 in rat enterocytes. We found that ADM receptor components were expressed in T1R3-positive taste cells. Analyses of chorda tympani (CT) nerve responses revealed that ADM enhanced responses to sugars but not to artificial sweeteners and other tastants. Moreover, ADM increased the apical uptake of a fluorescent D-glucose derivative into taste cells and SGLT1 mRNA expression in taste buds. These results suggest that the T1R-independent sweet taste pathway in mouse taste cells is a peripheral target of ADM, and the specific enhancement of gustatory nerve responses to sugars by ADM may contribute to caloric sensing and food intake.

Sugar restriction and blood ingestion shape divergent immune defense trajectories in the mosquito Aedes aegypti.

Immune defense is comprised of (1) resistance: the ability to reduce pathogen load, and (2) tolerance: the ability to limit the disease severity induced by a given pathogen load. The study of tolerance in the field of animal immunity is fairly nascent in comparison to resistance. Consequently, studies which examine immune defense comprehensively (i.e. considering both resistance and tolerance in conjunction) are uncommon, despite their exigency in achieving a thorough understanding of immune defense. Furthermore, understanding tolerance in arthropod disease vectors is uniquely relevant, as tolerance is essential to the cyclical transmission of pathogens by arthropods. Here, we tested the effect(s) of dietary sucrose concentration and blood ingestion on resistance and tolerance to Escherichia coli infection in the yellow fever mosquito Aedes aegypti. Resistance and tolerance were measured concurrently and at multiple timepoints. We found that mosquitoes from the restricted sugar treatment displayed enhanced resistance at all timepoints post-infection compared to those from the laboratory standard sugar treatment. Blood also improved resistance, but only early post-infection. While sucrose restriction had no effect on tolerance, we show that consuming blood prior to bacterial infection ameliorates a temporal decline in tolerance that mosquitoes experience when provided with only sugar meals. Taken together, our findings indicate that different dietary components can have unique and sometimes temporally dynamic impacts on resistance and tolerance.

Macronutrients effects on satiety and food intake in older and younger adults: A randomised controlled trial.

Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the 13C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.