Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Neuroprotective Effects of the Nutraceutical Dehydrozingerone and Its C2-Symmetric Dimer in a Drosophila Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons responsible for unintended or uncontrollable movements. Mutations in the leucine-rich repeat kinase 2 locus contribute to genetic forms of PD. The fruit fly Drosophila melanogaster carrying this mutation (LRRK2-Dm) is an in vivo model of PD that develops motor impairment and stands for an eligible non-mammalian paradigm to test novel therapeutic approaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger and presents anti-inflammatory, antioxidant and neuroprotective properties, making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1 mM for 14 and 21 days in the LRRK2-Dm, with the aim of assessing changes in rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-bars). The shorter treatment with both molecules revealed efficacy at the higher dose, improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-bars failure was observed with the DHZ-DIM. Our data indicate that the DHZ-DIM exerts a more potent neuroprotective effect with respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

The anti-urolithiasis activity and safety of strangury-relieving herbs: A comparative study based on fruit fly kidney stone model.

ETHNOPHARMACOLOGICAL RELEVANCE: Urolithiasis is one of the oldest and most widespread urological diseases suffered globally. In the long history of Traditional Chinese Medicine, there're numerous herbs documented with strangury-relieving properties playing crucial roles in treating various urological disorders, including dysuria, hematuria, and renal colic, etc., which may be caused by urolithiasis. Exploring these herbs may reveal safer, more effective, and cost-efficient drugs and therapies for urolithiasis. AIM OF THE STUDY: This study aims to assess the anti-urolithiasis efficacy and safety of 46 Chinese traditional and folk herbal drugs using the fruit fly (Drosophila melanogaster) kidney stone model, in order to identify the most valuable ethnomedicinal materials. MATERIALS AND METHODS: Water extract and 50% ethanol extract of each herb were prepared respectively. 0.2% (w/w) sodium oxalate was chosen as appropriate lithogenic agent through fruit fly life span study. Male fruit-flies within three days of emergence were aged for an additional three days, then were randomly divided into experimental groups, model group and control groups (n = 20). The flies in blank control group, model group and positive control group were fed with standard food, standard food containing 0.2% sodium oxalate, standard food containing 0.2% sodium oxalate and 3% (w/w) Garcinia cambogia extract, respectively. Meanwhile, flies in the experimental groups were raised on standard food containing 0.2% sodium oxalate and 3% (w/w) herbal extract. The anti-urolithiasis capability of the extracts was evaluated using stone area ratio (the stone area divided by the area of the Malpighian tubule) and stone-clearing rate. Additionally, the 7-day mortality rate was employed as an indicator of safety. RESULTS: Out of the 46 herbs, 24 exhibited significant anti-urolithiasis effects in their water extracts. Among them, Herba Nephrolepidis, Herba Humuli, Herba Desmodii Styracifolii, Cortex Plumeriae Rubrae, and Herba Mimosae Pudicae showed us a low 7-day mortality rate of fruit-flies as well. However, only a limited number of herbal extracts (8 out of 46) showed obvious anti-urolithiasis activity in their 50% ethanol extracts. CONCLUSION: Highly potential anti-urolithiasis candidates were discovered from strangury-relieving herbs recorded in classical Traditional Chinese Medicine works, highlighting the significant value of traditional and folk ethnopharmacological knowledge.

Ginseng Extract Attenuates the Injury from Ultraviolet Irradiation for Female Drosophila melanogaster through the Autophagy Signaling Pathway.

Ginseng is an ancient medicinal and edible plant with many health benefits, and can serve as a drug and dietary supplement, but there are few relevant studies on its use to ease ultraviolet (UV) irradiation damage. After 0.8 mg/mL ginseng extract (GE) was added to the medium of female Drosophila melanogaster subjected to UV irradiation, the lifespan, climbing ability, sex ratio, developmental cycle, and antioxidant capacity of flies were examined to evaluate the GE function. In addition, the underlying mechanism by which GE enhances the irradiation tolerance of D. melanogaster was explored. With GE supplementation, female flies subjected to UV irradiation exhibited an extension in their lifespan, enhancement in their climbing ability, improvement in their offspring sex ratio, and restoration of the normal development cycle by increasing their antioxidant activity. Finally, further experiments indicated that GE could enhance the irradiation tolerance of female D. melanogaster by upregulating the gene expressions of SOD, GCL, and components of the autophagy signaling pathway. Finally, the performance of r4-Gal4;UAS-AMPKRNAi flies confirmed the regulatory role of the autophagy signaling pathway in mitigating UV irradiation injury.

Probiotic Lactobacillus spp. improves Drosophila memory by increasing lactate dehydrogenase levels in the brain mushroom body neurons.

Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body ß and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.

Protective effect of Bougainvillea glabra Choisy bract in toxicity induced by Paraquat in Drosophila melanogaster.

Paraquat (PQ) is a herbicide widely used in agriculture to control weeds. The damage caused to health through intoxication requires studies to combating its damage to health. Bougainvillea glabra Choisy is a plant native to South America and its bracts contain a variety of compounds, including betalains and phenolic compounds, which have been underexplored about their potential applications and benefits for biological studies to neutralize toxicity. In this study, we evaluated the antioxidant and protective potential of the B. glabra bracts (BBGCE) hydroalcoholic extract against Paraquat-induced toxicity in Drosophila melanogaster. BBGCE demonstrated high antioxidant capacity in vitro through the assays of ferric-reducing antioxidant power (FRAP), radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), free radical ABTS and quantification of phenolic compounds, confirmed through identifying the main compounds. Wild males of D. melanogaster were exposed to Paraquat (1.75 mM) and B. glabra Choisy (1, 10, 50 and 100 µg/mL) in agar medium for 4 days. Flies exposed to Paraquat showed a reduction in survival rate and a significant decrease in climbing capacity and balance test when compared to the control group. Exposure of the flies to Paraquat caused a reduction in acetylcholinesterase activity, an increase in lipid peroxidation and production of reactive species, and a change in the activity of the antioxidant enzymes. Co-exposure with BBGCE was able to block toxicity induced by PQ exposure. Our results demonstrate that bract extract has a protective effect against PQ on the head and body of flies, attenuating behavioral deficit, exerting antioxidant effects and blocking oxidative damage in D. melanogaster.

Drosophila expressing mutant human KCNT1 transgenes make an effective tool for targeted drug screening in a whole animal model of KCNT1-epilepsy.

Mutations in the KCNT1 potassium channel cause severe forms of epilepsy which are poorly controlled with current treatments. In vitro studies have shown that KCNT1-epilepsy mutations are gain of function, significantly increasing K+ current amplitudes. To investigate if Drosophila can be used to model human KCNT1 epilepsy, we generated Drosophila melanogaster lines carrying human KCNT1 with the patient mutation G288S, R398Q or R928C. Expression of each mutant channel in GABAergic neurons gave a seizure phenotype which responded either positively or negatively to 5 frontline epilepsy drugs most commonly administered to patients with KCNT1-epilepsy, often with little or no improvement of seizures. Cannabidiol showed the greatest reduction of the seizure phenotype while some drugs increased the seizure phenotype. Our study shows that Drosophila has the potential to model human KCNT1- epilepsy and can be used as a tool to assess new treatments for KCNT1- epilepsy.

Exploring the Efficient Natural Products for the Therapy of Parkinson's Disease via Drosophila Melanogaster (Fruit Fly) Models.

Parkinson's disease (PD) is a severe neurodegenerative disorder, partly attributed to mutations, environmental toxins, oxidative stress, abnormal protein aggregation, and mitochondrial dysfunction. However, the precise pathogenesis of PD and its treatment strategy still require investigation. Fortunately, natural products have demonstrated potential as therapeutic agents for alleviating PD symptoms due to their neuroprotective properties. To identify promising lead compounds from herbal medicines' natural products for PD management and understand their modes of action, suitable animal models are necessary. Drosophila melanogaster (fruit fly) serves as an essential model for studying genetic and cellular pathways in complex biological processes. Diverse Drosophila PD models have been extensively utilized in PD research, particularly for discovering neuroprotective natural products. This review emphasizes the research progress of natural products in PD using the fruit fly PD model, offering valuable insights into utilizing invertebrate models for developing novel anti-PD drugs.

Artemisia argyi extract exerts antioxidant properties and extends the lifespan of Drosophila melanogaster.

BACKGROUND: Chinese mugwort (Artemisia argyi) possesses extensive pharmacological activities associated with anti-tumour, antioxidative and anti-inflammatory effects. The present study aimed to investigate the antioxidant and anti-ageing effects of A. argyi extract (AAE) on the fruit fly (Drosophila melanogaster) ageing model by detecting antioxidant enzyme activities and the mRNA level of antioxidant genes. RESULTS: AAE could significantly lengthen the mean lifespan, 50% survival days, and maximum lifespan of D. melanogaster, especially when the amount of AAE added reached 6.68 mg mL-1, the mean lifespan of both female and male flies increased by 23.74% and 22.30%, respectively, indicating the effective life extension effect of AAE. At the same time, AAE could improve the climbing ability and tolerance to hydrogen peroxide in D. melanogaster. In addition, the addition of AAE effectively increased the activities of copper-zinc-containing superoxide dismutase, manganese-containing superoxide dismutase and catalase in D. melanogaster and reduced the contents of malondialdehyde. Moreover, when reared with diets containing AAE, the expression of antioxidant-related genes SOD1, SOD2 and CAT was up-regulated in D. melanogaster and down-regulated for MTH genes. CONCLUSION: The study indicates that AAE effectively enhances the antioxidant capacity of D. melanogaster and has potential applications as an antioxidant and anti-ageing agent in the nutraceutical industry. © 2024 Society of Chemical Industry.

Diet supplementation with sodium pyruvate increases sleep time and lifespan in Drosophila model.

Sodium pyruvate is a natural metabolite commonly used in biological fields, including cell culture. This study investigated the effects of sodium pyruvate on the lifespan and other physiological characters of Drosophila melanogaster, by measuring feeding, fecundity, and spontaneous activity. The results indicated that 0.2 mol/L of sodium pyruvate increased the median lifespan of female flies by 8.33%. Moreover, the group sleep duration of female flies significantly increased by 53.98% when exposed to the sodium pyruvate concentration. However, the intake of sodium pyruvate did not significantly affect the fecundity or food intake of female flies. Our results also show that the effect of extending lifespan and increasing sleep time was dose-dependent and sex-specific. Our data provides the role of sodium pyruvate as an insect culture additive by enhancing survival.

Exploring the Fluconazole-Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from Caryocar coriaceum Wittm. (Caryocaraceae) against Candida Species.

The fixed oil from the inner mesocarp of Caryocar coriaceum Wittm. is used in the Chapada do Araripe region of Brazil for the treatment of genitourinary candidiasis. This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of C. coriaceum tested against three Candida yeasts. The oil was characterized by gas chromatography (GC-MS and GC-FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub-inhibitory concentrations (MIC/8). The mechanism of action of C. coriaceum fixed oil was determined by evaluating the inhibition of morphological transition in Candida spp. The chemical composition of the fixed oil of C. coriaceum comprised both unsaturated and saturated fatty acids. Oleic (61 %) and palmitic (33 %) acids were the major constituents. Regarding its anti-Candida activity, the oil inhibited the growth of C. albicans (IC50 : 371 µg/mL) and C. tropicalis (IC50 : 830 µg/mL). Furthermore, the oil reversed the antifungal resistance of C. albicans and C. tropicalis, restoring the susceptibility to fluconazole and reducing their IC50 from 12.33 µg/mL and 362 µg/mL to 0.22 µg/mL and 13.93 µg/mL, respectively. The fixed oil of C. coriaceum completely inhibited the morphological transition of C. albicans and C. tropicalis at a concentration of 512 µg/mL, but exhibited limited low antifungal potential against C. krusei. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the Drosophila melanogaster in vivo model. The fixed oil from the inner mesocarp of C. coriaceum emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by Candida spp.

Glutamine enhances sucrose taste through a gut microbiota-gut-brain axis in Drosophila.

AIMS: Amino acids (AAs) are known to play important roles in various physiological functions. However, their effect on sweet taste perception remains largely unknown. MAIN METHODS: We used Drosophila to evaluate the effect of each AA on sucrose taste perception. Individual AA was supplemented into diets and male flies were fed on these diets for 6 days. The proboscis extension response (PER) assay was applied to assess the sucrose taste sensitivity of treated flies. We further utilized the RNA-seq and germ-free (GF) flies to reveal the underlying mechanisms of sucrose taste sensitization induced by glutamine (Gln). KEY FINDINGS: We found that supplementation of Gln into diets significantly enhances sucrose taste sensitivity. This sucrose taste sensitization is dependent on gut microbiota and requires a specific gut bacterium Acetobacter tropicalis (A. tropicalis). We further found that CNMamide (CNMa) in the gut and CNMa receptor (CNMaR) in dopaminergic neurons are required for increased sucrose taste sensitivity by Gln diet. Finally, we demonstrated that a gut microbiota-gut-brain axis is required for Gln-induced sucrose taste sensitization. SIGNIFICANCE: These findings can advance understanding of the complex interplay between host physiology, dietary factors, and gut microbiota.

Antioxidant and anti-Alzheimer's potential of Tetragonisca angustula (Jataí) stingless bee pollen.

Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.

Iron chelation and supplementation: A comparison in the management of inflammatory bowel disease using drosophila.

AIMS: Inflammatory Bowel Disease (IBD) is associated with systemic iron deficiency and has been managed with iron supplements which cause adverse side effects. Conversely, some reports highlight iron depletion to ameliorate IBD. The underlying intestinal response and comparative benefit of iron depletion and supplementation in IBD is unknown. The aims of this work were to characterize and compare the effects of iron supplementation and iron depletion in IBD. MAIN METHODS: IBD was induced in Drosophila melanogaster using 3 % dextran sodium sulfate (DSS) in diet for 7 days. Using this model, we investigated the impacts of acute iron depletion (using bathophenanthroline disulfonate, BPS) and supplementation (using ferrous sulphate, FS), before and after IBD induction, on gut iron homeostasis, cell death, gut permeability, inflammation, antioxidant defence, antimicrobial response and several fly phenotypes. KEY FINDINGS: DSS decreased fly mass (p < 0.001), increased gut permeability (p < 0.001) and shortened lifespan (p = 0.035) compared to control. The DSS-fed flies also showed significantly elevated lipid peroxidation (p < 0.001), and the upregulated expression of apoptotic marker- drice (p < 0.001), tight junction protein - bbg (p < 0.001), antimicrobial peptide - dpta (p = 0.002) and proinflammatory cytokine - upd2 (p < 0.001). BPS significantly (p < 0.05) increased fly mass and lifespan, decreased gut permeability, decreased lipid peroxidation and decreased levels of drice, bbg, dpta and upd2 in IBD flies. This iron chelation (using BPS) showed better protection from DSS-induced IBD than iron supplementation (using FS). Preventive and curative interventions, by BPS or FS, also differed in outcomes. SIGNIFICANCE: This may inform precise management strategies aimed at tackling IBD and its recurrence.

Reduced iron and cobalt levels in response to curcumin supplementation are not responsible for the prolonged larval development and do not affect the oxidative stress tolerance and polyamine status of D. melanogaster.

Recent reports indicated that the phytochemical curcumin possesses iron-chelating activity. Here, by employing the fruit fly Drosophila melanogaster, we conducted feeding studies supplementing curcumin or, as a control, the iron chelator bathophenanthroline (BPA). First, the absorption and further metabolization of dietary curcuminoids were proved by metabolomics analyses. Next, we found that 0.2% dietary curcumin, similar to BPA, lowered the iron but also the cobalt content, and to a lesser extent affected the manganese and zinc status. Supplementation during larval stages was required and sufficient for both compounds to elicit these alterations in adult animals. However, curcumin-induced retarded larval development was not attributable to the changed trace metal status. In addition, a reduction in the iron content of up to 70% by curcumin or BPA supplementation did not reduce heme-dependent catalase activity and tolerance toward H2 O2 in D. melanogaster. Moreover, polyamines were not influenced by curcumin treatment and decreased iron levels. This was confirmed for selected organs from 0.2% curcumin-treated mice, except for the spleen. Here, elevated spermidine level and concomitant upregulation of genes involved in polyamine production were associated with a putatively anemia-derived increased spleen mass. Our data underline that the metal-chelating property of curcumin needs to be considered in feeding studies.

NOTCH Signaling Pathway: Occurrence, Mechanism, and NOTCH-Directed Therapy for the Management of Cancer.

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.

Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis.

Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment of mitochondrial proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, is enriched in the mitochondrial matrix of muscle tissues and is an NADPH oxidoreductase. Interactome analysis and in vitro enzymatic assays revealed an essential role for RTN4IP1 in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3. Rtn4ip1-knockout myoblasts had markedly decreased CoQ9 levels and impaired cellular respiration. Furthermore, muscle-specific knockdown of dRtn4ip1 in flies resulted in impaired muscle function, which was reversed by dietary supplementation with soluble CoQ. Collectively, these results demonstrate that RTN4IP1 is a mitochondrial NAD(P)H oxidoreductase essential for supporting mitochondrial respiration activity in the muscle tissue.

Transcriptomic and metabolomic analyses reveal that lemon extract prolongs Drosophila lifespan by affecting metabolism.

Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.

Fractionation and antioxidation activities of polysaccharides from Zanthoxylum bungeanum Maxim.

Zanthoxylum bungeanum has a lengthy history of widespread use as a food ingredient in China. However, the composition of Zanthoxylum bungeanum polysaccharide remains ambiguous, and the antioxidant effect has received limited attention. This study aimed to extract water-soluble polysaccharide from the dried pericarp of Zanthoxylum bungeanum, referred to as WZBP, which was fractionated into a neutral component (WZBP-N) and three pectic components (WZBP-A-I, WZBP-A-II, WZBP-A-III). The findings indicated that WZBP-A-III is a pectic polysaccharide "smooth region" without many side chains. All components of WZBP exhibited a notable capacity for scavenging free radicals, with WZBP-A-III demonstrating the most potent antioxidation activity, and WZBP-A-III also observed to effectively extend the lifespan of Drosophila melanogaster and enhanced the activity of antioxidant enzymes. These results provide valuable insight and direction for future research on Zanthoxylum bungeanum polysaccharide as an antioxidant agent.