Integration of liquid biopsy and immunotherapy: opening a new era in colorectal cancer treatment.

Immunotherapy has revolutionized the conventional treatment approaches for colorectal cancer (CRC), offering new therapeutic prospects for patients. Liquid biopsy has shown significant potential in early screening, diagnosis, and postoperative monitoring by analyzing circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). In the era of immunotherapy, liquid biopsy provides additional possibilities for guiding immune-based treatments. Emerging technologies such as mass spectrometry-based detection of neoantigens and flow cytometry-based T cell sorting offer new tools for liquid biopsy, aiming to optimize immune therapy strategies. The integration of liquid biopsy with immunotherapy holds promise for improving treatment outcomes in colorectal cancer patients, enabling breakthroughs in early diagnosis and treatment, and providing patients with more personalized, precise, and effective treatment strategies.

Optimizing Thermoelectric Performance of Tellurium via Doping with Antimony and Selenium.

Forming solid solutions is one of the most effective strategies to suppress the thermal conductivity of thermoelectric materials. However, the accompanying increase in impurity ion scattering usually results in an undesirable loss in hall mobility, negatively impacting the electrical transport properties. In this work, a tellurium-selenium (Te-Se) solid solution with trace antimony (Sb) doping was synthesized via the high pressure and high temperature method. It was found that slight Se doping into the Te sites not only had no impact on the hall mobility and carrier concentration, but also enhanced the density-of-state effective mass of Sb0.003Te0.997, leading to an enhanced power factor near room temperature. Additionally, the presence of Se doping caused a significant reduction in the phonon thermal conductivity of Te due to fluctuations in the mass and strain field. The lowest phonon thermal conductivity was as low as ~0.42 Wm-1K-1 at 600 K for Sb0.003Se0.025Te0.972, which approached the theoretical minimum value of Te (~0.28 Wm-1K-1). The effects of Se doping suppressed thermal conductivity, while Sb doping enhanced the power factor, resulting in a larger ZT of ~0.94 at 600 K. Moreover, these findings demonstrate that Sb and Se doping can effectively modulate the electrical and thermal transport properties of Te in a synergistic manner, leading to a significant increase in the average ZT across a wide temperature range.

It's high-time to re-evaluate the value of induced-chemotherapy for reinforcing immunotherapy in colorectal cancer.

Immunotherapy has made significant advances in the treatment of colorectal cancer (CRC), revolutionizing the therapeutic landscape and highlighting the indispensable role of the tumor immune microenvironment. However, some CRCs have shown poor response to immunotherapy, prompting investigation into the underlying reasons. It has been discovered that certain chemotherapeutic agents possess immune-stimulatory properties, including the induction of immunogenic cell death (ICD), the generation and processing of non-mutated neoantigens (NM-neoAgs), and the B cell follicle-driven T cell response. Based on these findings, the concept of inducing chemotherapy has been introduced, and the combination of inducing chemotherapy and immunotherapy has become a standard treatment option for certain cancers. Clinical trials have confirmed the feasibility and safety of this approach in CRC, offering a promising method for improving the efficacy of immunotherapy. Nevertheless, there are still many challenges and difficulties ahead, and further research is required to optimize its use.

Could immunoscore improve the prognostic and therapeutic management in patients with solid tumors?

The Immunoscore (ISc) is an emerging immune-based scoring system that has shown potential in improving the prognostic and therapeutic management of patients with solid tumors. The ISc evaluates the immune infiltrate within the tumor microenvironment (TME) and has demonstrated superior predictive ability compared to traditional histopathological parameters. It has been particularly promising in colorectal, lung, breast, and melanoma cancers. This review summarizes the clinical evidence supporting the prognostic value of the ISc and explores its potential in guiding therapeutic decisions, such as the selection of adjuvant therapies and recognizing patients likely to profit from immune checkpoint inhibitors (ICIs). The challenges and future directions of ISc implementation are also discussed, including standardization and integration into routine clinical practice.

From organ preservation to selective surgery: How immunotherapy changes colorectal surgery?

The emergence of immunotherapy has revolutionized the traditional treatment paradigm of colorectal cancer (CRC). Among them, immune checkpoint blockade has become the first-line treatment for metastatic colorectal cancer (mCRC) and has made significant progress in the treatment of locally advanced colorectal cancer (LACRC). We reviewed a series of clinical trials that have made breakthrough progress. We will emphasize the breakthrough progress in achieving organ preservation in patients with high microsatellite instability or DNA mismatch repair deficiency (MSI-H/dMMR), and based on this, we propose the concept of selective surgery, which includes selectively removing or preserving lymph nodes, with the aim of proving our idea through more research in the future.

Multifunctional nanocarriers for targeted drug delivery and diagnostic applications of lymph nodes metastasis: a review of recent trends and future perspectives.

Lymph node metastasis is a frequent occurrence in a variety of tumour forms and poses an enormous challenge to cancer treatment. This process is critical to the development of the disease and is frequently linked to a poor prognosis. Over 90% of cancerous cells move through lymph nodes, making them important entry routes for the spread of cancer cells. The prognosis of cancer patients is significantly impacted by lymph node metastases, which also affects treatment choices. Targeting lymph node metastases presents numerous difficulties for conventional medication delivery techniques. It is still very difficult to selectively target cancer cells in lymph nodes without risking injury to healthy organs and unforeseen consequences. Additionally, systemic delivery of drugs is hampered by the slow flow rate of lymphatic vessels. Chemotherapeutic medicines' poor solubility and stability further reduce their effectiveness when taken orally. Additionally, the extracellular matrix that surrounds lymph node tumours is extensive, which makes it difficult for conventional pharmaceutical delivery systems to reach cancer cells. The development of nanocarriers for precise drug delivery to LNs has attracted a lot of interest to overcome these obstacles. Most solid tumours first spread through the lymphatic system, hence effective drug administration to these tissues is essential for better therapeutic results. Nanocarriers have several benefits, including the capacity to pass through barriers like blood-brain barriers and membranes to reach the lymphatic system. High medication dosages can be enclosed thanks to the physicochemical characteristics of nanocarriers, such as their higher surface-to-volume ratio. Additionally, ligands, antibodies, polymers, or biological molecules can be attached to nanocarrier surfaces to change their properties, allowing for the targeted delivery of lymph node epithelial cells. This use of nanocarriers for drug delivery maximizes on-target effects and related adverse effects while improving the effectiveness of medication delivery to target locations. More research and development in this field is needed to optimize nanocarrier design, increase targeting capabilities, and expand clinical applications for better cancer care.

First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.

BACKGROUND: QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. CONCLUSIONS: QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis.

BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.

Drought priming mechanisms in wheat elucidated by in-situ determination of dynamic stomatal behavior.

Stomata play a critical role in balancing photosynthesis and transpiration, which are essential processes for plant growth, especially in response to abiotic stress. Drought priming has been shown to improve drought tolerance. Lots of studies have been done with the response of stomatal behavior to drought stress. However, how the stomatal dynamic movement in intact wheat plants response to drought priming process is not known. Here, a portable microscope was used to take microphotographs in order to in-stiu determination of stomatal behavior. Non-invasive micro-test technology was used for measurements of guard cell K+, H+ and Ca2+ fluxes. Surprisingly, the results found that primed plants close stomatal much faster under drought stress, and reopening the stomatal much quicker under recovery, in relation to non-primed plants. Compared with non-primed plants, primed plants showed higher accumulation of ABA and Ca2+ influx rate in guard cells under drought stress. Furthermore, genes encoding anion channels were higher expressed and K+ outward channels activated, leading to enhanced K+ efflux, resulting in faster stomatal closure in primed plants than non-primed plants. During recovery, both guard cell ABA and Ca2+ influx of primed plants were found to be significantly reducing K+ efflux and accelerating stomatal reopening. Collectively, a portable non-invasive stomatal observation of wheat found that priming promoted faster stomatal closure under drought stress and faster reopening during post-drought recovery in relation to non-primed plants, thereby enhancing overall drought tolerance.

N-Ethylnorketamine has anesthetic and analgesic effects with abuse liability.

Arylcyclohexylamines is an ever-growing class of new psychoactive substances, including an increasing number of ketamine analogs. N-Ethylnorketamine (NENK) is a new synthetic ketamine analog that has emerged as an abused drug, but little is known about the pharmacological profile of NENK. In this study, we investigated the anesthetic and analgesic activity, abuse liability of NENK compared with ketamine. The ED50 values of anesthetic activity for NENK and ketamine were 96.9, 69.4 mg/kg, respectively. The ED50 values of analgesic activity for NENK and ketamine were 45.9 and 23.6 mg/kg, respectively. NENK induced significant conditioned place preference at a minimum dose of 10.0 mg/kg in mice, an effect comparable to that of ketamine (3.0 mg/kg). Acute injections of NENK or ketamine at 30.0 mg/kg enhanced locomotor activity, and repeated treatments with this dose induced locomotor sensitization after withdrawal. Taken together, these results clearly demonstrated that NENK has lower anesthetic and analgesic activity compared to ketamine, but has significant abuse liability.

Fucoxanthin has potential for therapeutic efficacy in neurodegenerative disorders by acting on multiple targets.

Fucoxanthin, one of the most abundant carotenoids from edible brown seaweeds, for years has been used as a bioactive dietary supplement and functional food ingredient. Recently, fucoxanthin was reported to penetrate the blood-brain barrier, and was superior to other carotenoids to exert anti-neurodegenerative disorder effects via acting on multiple targets, including amyloid protein aggregation, oxidative stress, neuroinflammation, neuronal loss, neurotransmission dysregulation and gut microbiota disorder. However, the concentration of fucoxanthin required for in vivo neuroprotective effects is somewhat high, and the poor bioavailability of this molecule might prevent its clinical use. As such, new strategies have been introduced to overcome these obstacles, and may help to develop fucoxanthin as a novel lead for neurodegenerative disorders. Moreover, it has been shown that some metabolites of fucoxanthin may produce potent in vivo neuroprotective effects. Altogether, these studies suggest the possibility for future development of fucoxanthin as a one-compound-multiple-target or pro-drug type pharmaceutical or nutraceutical treatment for neurodegenerative disorders.Trial registration: ClinicalTrials.gov identifier: NCT03625284.Trial registration: ClinicalTrials.gov identifier: NCT02875392.Trial registration: ClinicalTrials.gov identifier: NCT03613740.Trial registration: ClinicalTrials.gov identifier: NCT04761406.

Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an ß-amyloid (Aß) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aß1-42 aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aß1-42 pentamers. Moreover, 13a effectively attenuated Aß1-42 oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.

PLGA-PEG Nanoparticles Facilitate In Vivo Anti-Alzheimer's Effects of Fucoxanthin, a Marine Carotenoid Derived from Edible Brown Algae.

The marine natural product fucoxanthin has been reported previously to produce anti-Alzheimer's disease (AD) neuroprotective effects in vitro and in vivo. Fucoxanthin was also demonstrated to be safe in preclinical and small population clinical studies, but the low bioavailability of fucoxanthin in the central nervous system (CNS) has limited its clinical applications. To overcome this, poly lactic-co-glycolic acid-block-polyethylene glycol loaded fucoxanthin (PLGA-PEG-Fuc) nanoparticles with diameter at around 200 nm and negative charge were synthesized and suggested to penetrate into the CNS. Loaded fucoxanthin could be liberated from PLGA-PEG nanoparticles by sustained released in the physiological environment. PLGA-PEG-Fuc nanoparticles were shown to significantly inhibit the formation of Aß fibrils and oligomers. Moreover, these nanoparticles were taken up by both neurons and microglia, leading to the reduction of Aß oligomers-induced neurotoxicity in vitro. Most importantly, intravenous injection of PLGA-PEG-Fuc nanoparticles prevented cognitive impairments in Aß oligomers-induced AD mice with greater efficacy than free fucoxanthin, possibly via acting on Nrf2 and NF-κB signaling pathways. These results altogether suggest that PLGA-PEG nanoparticles can enhance the bioavailability of fucoxanthin and potentiate its efficacy for the treatment of AD, thus potentially enabling its future use for AD therapy.

Long noncoding RNA LINC01287 promotes proliferation and inhibits apoptosis of lung adenocarcinoma cells via the miR-3529-5p/RNASEH2A axis under the competitive endogenous RNA pattern.

Lung adenocarcinoma (LUAD) is regarded as the most common type of lung cancer. The molecular targeted therapies for LUAD have being extensively studied. Ribonuclease H2 subunit A (RNASEH2A) is a nucleotide degrading enzyme gene that exerts great influence on cell proliferation, DNA replication and genomic stability. According to bioinformatics analysis, RNASEH2A expression in LUAD tissues is predicted to be upregulated and high expression of RNASEH2A might be related to lower survival rate in LUAD patients. In the present study, we investigated functions of RNASEH2A in LUAD. The mRNA RNASEH2A showed high expression in LUAD cells, and its knockdown inhibited proliferation and induced apoptosis in LUAD cells. RNASEH2A was found to be a target gene of microRNA miR-3529-5p after their expression levels and interaction being examined. Long noncoding RNA LINC01287 upregulated RNASEH2A expression in LUAD cells by combining with miR-3529-5p in a competitive way. Rescue assays revealed that the overexpression of RNASEH2A reversed the suppression of cell proliferation and the promotion of cell apoptosis induced by miR-3529-5p overexpression or LINC01287 knockdown. Finally, forkhead box A1 (FOXA1) interacted with RNASEH2A promoter and LINC01287 promoter to upregulate the expression levels of RNASEH2A and LINC01287 in LUAD cells. Overall, FOXA1-induced LINC01287 serves as a competing endogenous RNA to promote proliferation and inhibit apoptosis of LUAD cells via upregulation of RNASEH2A expression at the posttranscriptional level by competitively combining with miR-3529-5p.

Long non-coding RNA GATA6-AS1 upregulates GATA6 to regulate the biological behaviors of lung adenocarcinoma cells.

BACKGROUND: Lung adenocarcinoma (LUAD) is known to be one of the leading causes of cancer-related deaths globally. In recent decades, long non-coding RNAs (lncRNAs) have been indicated to exert pivotal regulating functions in multiple biological behaviors in the initiation and development of LUAD. However, the functional mechanism of lncRNA GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in LUAD has not been explored. METHODS: In the current study, GATA6-AS1 expression in LUAD tissues was revealed. Meanwhile, GATA6-AS1 expression in LUAD cells was investigated via RT-qPCR analysis. After A549 and H1975 cells were transfected with GATA6-AS1 overexpression plasmids, EdU and colony formation assays, TUNEL assays and flow cytometry analyses, as well as wound healing and Transwell assays were conducted to detect cell proliferation, apoptosis, migration and invasion. Afterwards, bioinformatic tools, western blot analyses, dual-luciferase reporter assays, and RNA immunoprecipitation (RIP) assays were performed to investigate the correlation of microRNA-4530 (miR-4530), GATA6-AS1 and GATA6. RESULTS: We found that GATA6-AS1 expression was low-expressed in LUAD tissues and cells. Furthermore, the upregulation of GATA6-AS1 suppressed the proliferative, migration and invasion abilities, as well as promoted apoptotic rate of A549 and H1975 cells. Moreover, the mechanistic investigations revealed that GATA6-AS1 upregulated the expression of its cognate sense gene GATA6 by binding with miR-4530, thereby modulating the malignant progression of LUAD cells. CONCLUSIONS: GATA6-AS1 repressed LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via regulation of the miR-4530/GATA6 axis, indicating GATA6-AS1 as a new prognostic biomarker for LUAD.

Evans Blue Might Produce Pathologically Activated Neuroprotective Effects via the Inhibition of the P2X4R/p38 Signaling Pathway.

The main pathological features of ischemic stroke include neuronal damage and blood-brain barrier (BBB) dysfunction. Previous studies have shown that Evans Blue, a dye used to probe BBB integrity, could enter the brain only during the pathological status of ischemic stroke, indicating the potential pathologically activated therapeutic use of this chemical to treat ischemic stroke. In this study, we have reported that Evans Blue could produce in vitro neuroprotective effects against iodoacetic acid (IAA)-induced hypoxia neuronal death in HT22 cells. We further found that P2X purinoreceptor 4 (P2X4R), a subtype of ATP-gated cation channel, was expressed in HT22 cells. Evans Blue could prevent IAA-induced increase of P2X4R mRNA and protein expression. Interestingly, shRNA of P2X4R could protect against IAA-induced activation of p38, and SB203580, a specific inhibitor of p38, could reverse IAA-induced neurotoxicity, indicating that p38 is a downstream signaling molecule of P2X4R. Molecular docking analysis further demonstrated the possible interaction between Evans Blue and the ATP binding site of P2X4R. Most importantly, pre-treatment of Evans Blue could largely reduce neurological and behavioral abnormity, and decrease brain infarct volume in middle cerebral artery occlusion/reperfusion (MCAO) rats. All these results strongly suggested that Evans Blue could exert neuroprotective effects via inhibiting the P2X4R/p38 pathway, possibly by acting on the ATP binding site of P2X4R, indicating that Evans Blue might be further developed as a pathologically activated therapeutic drug against ischemic stroke.

Retinal Levels of Amyloid Beta Correlate with Cerebral Levels of Amyloid Beta in Young APPswe/PS1dE9 Transgenic Mice before Onset of Alzheimer's Disease.

OBJECTIVES: Retina abnormalities are related to cognitive disorders in patients with Alzheimer's disease (AD). Retinal amyloid beta (Aß) can be labeled by curcumin. We measured Aß content in the cerebrum and retina of APPswe/PS1dE9 (APP) transgenic mice with early age to investigate the correlation between cerebrum and retina. METHODS: APP mice and age-matched wild-type mice were investigated every month from age 2 months to 6 months to assess changes in Aß content in the retina and cerebrum. At the beginning of each month, mice were fed a curcumin diet (50 mg/kg/day) for 7 consecutive days. The Aß levels in the retina and cerebrum were measured by ELISAs. Correlations were identified between retinal and cerebral Aß contents using Pearson's correlation. RESULTS: In the absence of curcumin, there was a significant correlation between Aß contents in the retina and cerebrum of APP mice (r = 0.7291, P = 0.0014). With increasing age, Aß-mediated degenerative change in the cerebrum (P < 0.001 in 5 months) and retina (P < 0.01 in 5 months) increased significantly. The inhibitory effect of curcumin on the Aß level was significant in the cerebrum (P < 0.001) and retina (P < 0.01) of older APP mice in the early stage of life. CONCLUSION: We observed a significant correlation between the Aß content in the retina and Aß content in the cerebrum of APP mice. Our data suggest an appropriate time to measure retinal Aß. Although curcumin can label Aß in the retina, it also suppresses Aß levels and weakens the degree of correlation between Aß in cerebrum and retina tissues.