Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

The burden of non-alcoholic fatty liver disease among working-age people in the Western Pacific Region, 1990-2019: an age-period-cohort analysis of the Global Burden of Disease study.

BACKGROUND: The growing prevalence of non-alcoholic fatty liver disease (NAFLD) in younger populations, particularly those of working age (15-64 years), has become a public health concern. Being diagnosed at a younger age implies a greater likelihood of accruing disability-adjusted life years (DALYs) later in life due to potential progression to conditions such as cirrhosis or hepatocellular carcinoma. This study aims to analyze NAFLD prevalence trends over three decades globally, regionally, and nationally, with a focus on age, period, and birth cohort associations. METHODS: Global, regional, and country time trends in the prevalence of NAFLD among working-age people from 1990 to 2019: Age-period-cohort analysis based on Global Burden of Disease Study 2019 estimates and 95% uncertainty interval (UI) of NAFLD prevalence in the working age population was extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. Age-period-cohort models were used to estimate the prevalence within each age group from 1990 to 2019 (local drift, % per year), fitted longitudinal age-specific rates adjusted for period bias (age effect), and period/cohort relative risk (period/cohort effect). RESULTS: The global age-standardized prevalence (ASPR) of NAFLD increased significantly from 1990 (14,477.6 per 100 000) to 2019 (19,837.6 per 100 000). In the Western Pacific, there were 42,903.8 NAFLD cases in 2019, 54.15% higher than in 1990. The ASPR also increased significantly in the region over the past three decades. At the national level, Palau had the highest ASPR while Brunei Darussalam had the lowest. Age-period-cohort analysis showed that in the Western Pacific, unlike globally, the risk of NAFLD declined after age 60-64 years. Relative to 1980-1989, incidence and DALY risks decreased but prevalence increased in subsequent birth cohorts. Future predictions indicate an upward trend in NAFLD burden, especially among women and medium (SDI) regions like China. CONCLUSION: Non-alcoholic fatty liver disease imparts an immense health burden that continues to grow globally and in the Asia Pacific region. Our work highlights working age adults as an at-risk group and calls attention to socioeconomic gradients within Western Pacific countries. Upward future projections demonstrate that NAFLD prevention is an urgent priority.

Global, regional, national epidemiology and trends of neglected tropical diseases in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019.

BACKGROUND: In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. METHODS: Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. RESULTS: In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. CONCLUSION: NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019-exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.

The global burden of cardiovascular disease attributable to diet low in fiber among people aged 60 years and older, 1990-2019: an age-period-cohort analysis of the global burden of disease study.

OBJECTIVES: This study aimed to quantify the global cardiovascular disease (CVD) burden attributable to diet low in fiber among adults aged 60 years and older using data from the Global Burden of Disease (GBD) Study 2019. METHODS: We extracted data on CVD mortality, disability-adjusted life-years (DALYs), and risk-factor exposures from the GBD 2019 study for people aged 60 and older. Age-period-cohort models were used to estimate the overall annual percentage change in mortality and DALY rate (net drift, % per year), mortality and DALY rate for each age group from 1990 to 2019 (local drift, % per year), longitudinal age-specific rate corrected for period bias (age effect), and mortality and Daly rate for each age group from 1990 to 2019 (local drift, % per year). And period/cohort relative risk (period/cohort effect). RESULTS: From 1990 to 2019, global age-standardized cardiovascular disease (CVD) mortality rates attributable to low dietary fiber intake decreased by 2.37% per year, while disability-adjusted life years (DALYs) fell by 2.48% annually. Decreases were observed across all sociodemographic index regions, with fastest declines in high and high-middle SDI areas. CVD mortality and DALY rates attributable to low fiber increased exponentially with age, peaking at 85-89 years, and were higher in men than women. Regarding period effects, mortality and DALY rates declined since 2000, reaching nadirs in 2015-2019. For birth cohort patterns, risks attributable to low fiber intake peaked among early 1900s births and subsequently fell, with more pronounced reductions over time in women. CONCLUSIONS: Low dietary fiber intake is a leading contributor to the global cardiovascular disease burden, accounting for substantial mortality and disability specifically among older adults over recent decades.

Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification.

Ischemic stroke remains one of the leading causes of death worldwide, thereby highlighting the urgent necessary to identify new therapeutic targets. Deoxyhypusine hydroxylase (DOHH) is a fundamental enzyme catalyzing a unique posttranslational hypusination modification of eukaryotic translation initiation factor 5A (eIF5A) and is highly involved in the progression of several human diseases, including HIV-1 infection, cancer, malaria, and diabetes. However, the potential therapeutic role of pharmacological regulation of DOHH in ischemic stroke is still poorly understood. Our study first discovered a natural small-molecule brazilin (BZ) with an obvious neuroprotective effect against oxygen-glucose deprivation/reperfusion insult. Then, DOHH was identified as a crucial cellular target of BZ using HuProt™ human proteome microarray. By selectively binding to the Cys232 residue, BZ induced a previously undisclosed allosteric effect to significantly increase DOHH catalytic activity. Furthermore, BZ-mediated DOHH activation amplified mitophagy for mitochondrial function and morphology maintenance via DOHH/eIF5A hypusination signaling pathway, thereby protecting against ischemic neuronal injury in vitro and in vivo. Collectively, our study first identified DOHH as a previously unreported therapeutic target for ischemic stroke, and provided a future drug design direction for DOHH allosteric activators using BZ as a novel molecular template.

LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis.

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.

Puerarin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of inflammation.

Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus complications. Inflammation factors may be one reason for the damage from DM. The purpose of this research is to study the potential protective effects of puerarin on DM and the possible mechanisms of action related to NF-κB signal pathway. Following administration of puerarin to the disease model rat, several changes were observed including the changes of serum biochemical index, improved diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities, further NF-κB signaling activation. Puerarin showed cardio-protective effects on DCM by inhibiting inflammation, and it might be a potential candidate for the treatment of DCM.

MYBL2 is a Potential Prognostic Marker that Promotes Cell Proliferation in Gallbladder Cancer.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive and highly lethal biliary tract malignancy, with extremely poor prognosis. In the present study, we analyzed the potential involvement of MYBL2, a member of the Myb transcription factor family, in the carcinogenesis of human GBC. METHODS: MYBL2 expression levels were measured in GBC and cholecystitis tissue specimens using quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) assays. The effects of MYBL2 on cell proliferation and DNA synthesis were evaluated using Cell Counting Kit-8 assay (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) retention assay, flow cytometry analysis, western blot, and a xenograft model of GBC cells in nude mice. RESULTS: MYBL2 expression was increased in GBC tissues and associated with histological differentiation, tumour invasion, clinical stage and unfavourable overall survival in GBC patients. The downregulation of MYBL2 expression resulted in the inhibition of GBC cell proliferation, and DNA replication in vitro, and the growth of xenografted tumours in nude mice. Conversely, MYBL2 overexpression resulted in the opposite effects. CONCLUSIONS: MYBL2 overexpression promotes GBC cell proliferation through the regulation of the cell cycle at the S and G2/M phase transitions. Thus, MYBL2 could serve as a potential prognostic and therapeutic biomarker in GBC patients.

A new use for an old index: preoperative high-density lipoprotein predicts recurrence in patients with hepatocellular carcinoma after curative resections.

BACKGROUND: Hepatocellular carcinoma has high incidence and mortality worldwide. Liver is the site of most metabolic biotransformation, which could reflect the status of cells. Most plasma apolipoproteins, endogenous lipids and lipoproteins are synthesized in the liver. Therefore, the effects of lipid metabolites on prognosis of HCC deserved to be explored. METHODS: We prospectively included 58 healthy donors (HD), 50 chronic hepatitis (CH) patients and a training cohort of 189 patients with HCC who underwent curative resections at Zhongshan Hospital from January 2012 to August 2012. We identified the optimal HDLPO cutoff value at 0.98 mmol/L and used it to stratify patients into low- or high-HDLPO groups for the entire cohort and four low-recurrent-risk subgroups. We also included an independent validation group of 182 HCC patients to validate this cutoff value. Prognostic values of HDLPO and other factors were determined by Kaplan-Meier curves and the Cox proportional hazards model. RESULTS: The low-HDLPO group had a higher median tumor grade (P = 0.020) and a higher recurrence rate (P = 0.032). Results of multivariate analysis showed that preoperative γ-glutamyl transpeptidase (GGT) and HDLPO were independent predictors of recurrence. Moreover, the predictive value of HDLPO was retained in four low-recurrent-risk subgroups. As expected, clinicopathologic characteristics and predictive values were similar in the validation and training cohorts. CONCLUSIONS: HDLPO is an accessible predictor of HCC recurrence after liver resections that can help identify patients who need more careful monitoring and follow-up care.

Radiation dose reduction and image quality in pediatric paranasal sinus CT: with automatic tube current modulation and iterative reconstruction technique.

Our objective is to evaluate radiation dose and image quality in pediatric paranasal sinus computed tomography (CT) with automatic tube current modulation (ATCM) and sinogram-affirmed iterative reconstruction algorithm (SAFIRE). CT scans from 80 patients were divided into two groups: Group A [80 kVp, pitch 1.5, 40 mAs, the filtered back projection (FBP) algorithm] and Group B (70 kVp, pitch 3, ATCM with reference at 40 mAs, SAFIRE strengths 1-5). We have evaluated image quality and radiation dose. Group B demonstrated significantly lower volume computed tomography dose index, dose-length product, and effective dose than Group A (0.13 ± 0.03 vs. 1.57 ± 0.01 mGy, 2.27 ± 0.82 vs. 19.88 ± 2.01 mGy·cm, and 0.0081 ± 0.0017 vs. 0.079 ± 0.013 mSv, respectively; P < .001). Increasing SAFIRE strengths correlated with noise reduction and SNR enhancement. Group B's noise and SNRsoft at SAFIRE strength 5 were comparable with Group A. Images reconstructed with SAFIRE strength 5 in Group B exhibit comparable image quality with FBP in Group A.

Resveratrol prevents age-related heart impairment through inhibiting the Notch/NF-κB pathway.

Resveratrol (RSV) is a natural polyphenol compound found in various plants that has been shown to have potential benefits for preventing aging and supporting cardiovascular health. However, the specific signal pathway by which RSV protects the aging heart is not yet well understood. This study aimed to explore the protective effects of RSV against age-related heart injury and investigate the underlying mechanisms using a D-galactose-induced aging model. The results of the study indicated that RSV provided protection against age-related heart impairment in mice. This was evidenced by the reduction of cardiac histopathological changes as well as the attenuation of apoptosis. RSV-induced cardioprotection was linked to a significant increase in antioxidant activity and mitochondrial transmembrane potential, as well as a reduction in oxidative damage. Additionally, RSV inhibited the production of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Furthermore, the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), and notch 1 protein were inhibited by RSV, indicating that inhibiting the Notch/NF-κB pathway played a critical role in RSV-triggered heart protection in aging mice. Moreover, further data on intestinal function demonstrated that RSV significantly increased short-chain fatty acids (SCFAs) in intestinal contents and reduced the pH value in the feces of aging mice. RSV alleviated aging-induced cardiac dysfunction through the suppression of oxidative stress and inflammation via the Notch/NF-κB pathway in heart tissue. Furthermore, this therapeutic effect was found to be associated with its protective roles in the intestine.

Cayratia albifolia C.L.Li exerts anti-rheumatoid arthritis effect by inhibiting macrophage activation and neutrophil extracellular traps (NETs).

BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Proliferation and differentiation of neural stem cells co-cultured with cerebral microvascular endothelial cells after oxygen-glucose deprivation.

Various stem cells, including neural stem cells (NSCs), have been extensively studied in stroke models, but how to increase neuronal differentiation rate of NSCs remains unresolved, particularly in a damaged environment. The purpose of this study was to investigate the effects of cerebral microvascular endothelial cells (CMECs) on the neurogenesis of NSCs with or without oxygen-glucose deprivation (OGD). The NSCs acquired from primary culture were immunostained to prove cell purity. Survival and proliferation of NSCs were determined after the co-culture with CMECs for 7 days. After removing the CMECs, NSCs were randomly divided into two groups as follows: OGD and non-OGD groups. Both groups were maintained in differentiation culture for 4 days to evaluate the differentiation rate. Mouse embryo fibroblast (MEF) cells co-cultured with NSCs served as control group. NSCs co-cultured with CMECs had an increase in size (on the 7th day: 89.80±26.12 µm vs. 73.08±15.01 µm, P<0.001) (n=12) and number [on the 7th day: 6.33±5.61/high power objective (HP) vs. 2.23±1.61/HP, P<0.001] (n=12) as compared with those co-cultured with MEF cells. After further differentiation culture for 4 days, NSCs co-cultured with CMECs had an increase in neuronal differentiation rate in OGD and non-OGD groups, but not in the control group (15.16% and 16.07% vs. 8.81%; both P<0.001) (n=6). This study provided evidence that OGD could not alter the effects of CMECs in promoting the neuronal differentiation potential of NSCs. These findings may have important implications for the development of new cell therapies for cerebral vascular diseases.

Role of intelligent/interactive qualitative and quantitative analysis-three-dimensional estimated model in donor-recipient size mismatch following deceased donor liver transplantation.

BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation for Osteoblast Differentiation.

Osteoblasts play an important role in the regulation of bone homeostasis throughout life. Thus, the damage of osteoblasts can lead to serious skeletal diseases, highlighting the urgent need for novel pharmacological targets. This study introduces chemical genetics strategy by using small molecule forskolin (FSK) as a probe to explore the druggable targets for osteoporosis. Here, this work reveals that transglutaminase 2 (TGM2) served as a major cellular target of FSK to obviously induce osteoblast differentiation. Then, this work identifies a previously undisclosed allosteric site in the catalytic core of TGM2. In particular, FSK formed multiple hydrogen bonds in a saddle-like domain to induce an "open" conformation of the ß-sandwich domain in TGM2, thereby promoting the substrate protein crosslinks by incorporating polyamine. Furthermore, this work finds that TGM2 interacted with several mitochondrial homeostasis-associated proteins to improve mitochondrial dynamics and ATP production for osteoblast differentiation. Finally, this work observes that FSK effectively ameliorated osteoporosis in the ovariectomy mice model. Taken together, these findings show a previously undescribed pharmacological allosteric site on TGM2 for osteoporosis treatment, and also provide an available chemical tool for interrogating TGM2 biology and developing bone anabolic agent.

Epigallocatechin-3-gallate alleviates galactose-induced aging impairment via gut-brain communication.

The study aimed to determine whether gut-brain communication could be modulated by epigallocatechin-3-gallate (EGCG) in a mouse aging model that was established by daily injection of D-galactose (D-gal) for 10 weeks. Our results showed that EGCG could improve aging-associated changes by increasing the immune organ indexes, brain index, and learning and memory ability in vivo. EGCG-triggered aging prevention was associated with the reduction of lipid peroxidation and elevation of enzymatic and non-enzymatic antioxidant activities in the brain. Concomitantly, treatment of D-gal-induced aging in mice with EGCG significantly reduced corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone, suggesting that EGCG-exerted protection of the aging brain was involved in the inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. Further data concerning intestinal function showed that EGCG could enhance fecal moisture in vitro and reduce the pH value of feces in aging mice when compared to the D-gal group, suggesting that EGCG played beneficial roles in the intestine of aging mice. Moreover, short-chain fatty acids (SCFAs), the mediators of gut-brain communication, were significantly increased in the intestinal contents of aging mice by treatment with EGCG. Therefore, the tea polyphenol EGCG showing anti-aging properties was demonstrated to be implicated in modulating gut-brain communication by attenuating the HPA axis and enhancing the content of SCFAs.

Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity.

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared to natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from natural resources, especially daily food, implies a promising direction for exploring treatment strategies for human diseases. Here, we report a CQDs-based biocompatible nanozyme prepared from chlorogenic acid (ChA), a major bioactive natural product from coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation of GPX4-catalyzed lipid repair systems. In vivo, ChA CQDs dramatically suppressed the tumor growth in HepG2-tumor-bearing mice with negligible side toxicity. Particularly, in hepatoma H22-bearing mice, ChA CQDs recruited massive tumor-infiltrating immune cells including T cells, NK cells, and macrophages, thereby converting "cold" to "hot" tumors for activating systemic antitumor immune responses. Taken together, our study suggests that natural product-derived CQDs from coffee can serve as biologically safe nanozymes for anticancer therapeutics and may aid the development of nanotechnology-based immunotherapeutic.