Low-dose immune tolerance induction for severe hemophilia A inhibitor patients: Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL.

Importance: It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS200 regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS40 regimen). Objective: To compare the efficacy of the LD-ITI-IS200 regimen with that of the LD-ITI-IS40 regimen for SHA patients with high-titer inhibitors. Methods: A prospective cohort study on patients receiving LD-ITI-IS200 compared to those receiving LD-ITI-IS40 from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS200 regimen and ≥40 BU/mL in the LD-ITI-IS40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected. Results: We enrolled 30 patients on LD-ITI-IS200 and 64 patients on LD-ITI-IS40, with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS200 regimen compared to the LD-ITI-IS40 regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS200 vs. LD-ITI-IS40) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS200 than for LD-ITI-IS40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS200 regimen) and 28 IS-using (on LD-ITI-IS40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months). Interpretation: In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL.

[Application of convolutional neural networks for the classification of metaphase chromosomes].

OBJECTIVE: To train a deep convolutional neural networks (CNN) using a labeled data set to classify the metaphase chromosomes and test its accuracy for chromosomal identification. METHODS: Three thousand and three hundred individuals undergoing surveillance for chromosomal disorders at the Laboratory for Comprehensive Prevention and Treatment of Birth Defects, Ningbo Maternal and Child Health Care Hospital from January 2013 to July 2019 were enrolled. A total of 3 300×46 chromosome images were included, of which 70% were used as the training set and 30% were used as the test set for the deep CNN. The accuracy of chromosome counting and "cutting + recognition + arrangement + automatic analysis" of the model were respectively evaluated. Another 80 images were collected to record the time and accuracy of chromosome classification by geneticists and the model, respectively, so as to assess the practical value of the model. RESULTS: The CNN model was used to count the chromosomes with an accuracy of 61.81%, and the "cutting + recognition + arrangement + automatic analysis" accuracy of the model was 96.16%. Compared with manual operation, the classification time of the CNN model has been greatly reduced, and its karyotyping accuracy was only 3.58% lower than that of geneticists. CONCLUSION: The CNN model has a high performance for chromosome classification and can significantly reduce the work load involved with the segmentation and classification and improve the efficiency of chromosomal karyotyping, thereby has a broad application prospect.

Effectiveness of bevacizumab in the treatment of metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the benefit of bevacizumab under the comprehensive treatment strategy and its advantages over other drugs, so as to provide reference for the formulation of clinical plans. METHODS: As of October 1, 2022, the randomized controlled clinical trials of bevacizumab in combination with metastatic colorectal cancer published in PubMed, Cochrane Library and Medline databases were searched. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the short-term disease control effect and long-term survival of the treatment strategy. RESULTS: 21 RCTs (6665 patients; 3356 patients in the experimental group and 3309 patients in the control group; average age, 55-75 years) were treated with bevacizumab as the experimental group for metastatic colorectal cancer. BEV has stronger anti-tumor activity than the single treatment scheme (OR = 1.30, 95% CI: 1.11-1.52). And Benefits of the BEV group were 0.73 (0.55, 0.96), 1.26 (0.71, 2.24), 1.63 (0.92, 2.87) and 0.07 (0.02, 0.25) compared with CET, VAN, CED and PAN respectively. The disease control of BEV combined therapy was better (OR = 1.36, 95% CI: 1.04-1.78). The same as compared with cediranib (OR = 1.94, 95% CI: 1.06-3.55). However, the long-term prognosis of BEV, including the overall survival (HRs = 0.98, 95% CI: 0.84-1.15) and progression-free survival (HRs = 1.05,95% CI: 0.97-1.13) were not prolonged. The survival benefits of cetuximab and panitumumab were not reflected. CONCLUSION: The addition of BEV can enhance the anti-tumor ability and disease control, while cetuximab and panitumumab may have stronger ability. However, it did not effectively improve the survival of patients. A more reasonable and effective treatment plan needs more clinical experimental support.

The pertinence of gastric cancer and interleukin 10-819 single nucleotide polymorphisms: a meta-analysis and systematic review.

PURPOSE: Cytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter-819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10-819 by meta-analysis via five statistical models. METHODS: Databases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary. RESULTS: Eventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer. CONCLUSIONS: In our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.

Disrupted Effective Connectivity within the Fronto-Thalamic Circuit in Pontine Infarction: A Spectral Dynamic Causal Modeling Study.

This study aims to investigate alterations in effective connectivity (EC) within the fronto-thalamic circuit and their associations with motor and cognitive declines in pontine infarction (PI). A total of 33 right PI patients (RPIs), 38 left PI patients (LPIs), and 67 healthy controls (HCs) were recruited. The spectral dynamic causal modeling (spDCM) approach was used for EC analysis within the fronto-thalamic circuit, including the thalamus, caudate, supplementary motor area (SMA), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC). The EC differences between different sides of the patients and HCs were assessed, and their correlations with motor and cognitive dysfunctions were analyzed. The LPIs showed increased EC from the mPFC to the R-SMA and decreased EC from the L-thalamus to the ACC, the L-SMA to the R-SMA, the R-caudate to the R-thalamus, and the R-thalamus to the ACC. For RPIs, the EC of the R-caudate to the mPFC, the L-thalamus and L-caudate to the L-SMA, and the L-caudate to the ACC increased obviously, while a lower EC strength was shown from the L-thalamus to the mPFC, the LSMA to the R-caudate, and the R-SMA to the L-thalamus. The EC from the R-caudate to the mPFC was negatively correlated with the MoCA score for RPIs, and the EC from the R-caudate to the R-thalamus was negatively correlated with the FMA score for LPIs. The results demonstrated EC within the fronto-thalamic circuit in PI-related functional impairments and reveal its potential as a novel imaging marker.

Spleen-targeted neoantigen DNA vaccine for personalized immunotherapy of hepatocellular carcinoma.

Neoantigens are emerging as attractive targets to develop personalized cancer vaccines, but their immunization efficacy is severely hampered by their restricted accessibility to lymphoid tissues where immune responses are initiated. Leveraging the capability of red blood cells (RBCs) to capture and present pathogens in peripheral blood to the antigen-presenting cells (APCs) in spleen, we developed a RBC-driven spleen targeting strategy to deliver DNA vaccine encoding hepatocellular carcinoma (HCC) neoantigen. The DNA vaccine-encapsulating polymeric nanoparticles that were intentionally hitchhiked on the preisolated RBCs could preferentially accumulate in the spleen to promote the neoantigen expression by APCs, resulting in the burst of neoantigen-specific T-cell immunity to prevent tumorigenesis in a personalized manner, and slow down tumor growth in the established aggressively growing HCC. Remarkably, when combined with anti-PD-1, the vaccine achieved complete tumor regression and generated a robust systemic immune response with long-term tumor-specific immunological memory, which thoroughly prevented tumor recurrence and spontaneous lung metastasis. This study offers a prospective strategy to develop personalized neoantigen vaccines for augmenting cancer immunotherapy efficiency in immune "cold" HCC.

The effectiveness of blood-activating and stasis-transforming traditional Chinese medicines (BAST) in lung cancer progression-a comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Blood-activating and stasis-transforming traditional Chinese medicines (BAST) are a class of herbs that have the effect of dilating blood vessels and dispersing stagnation. Modern pharmaceutical research has demonstrated that they are capable of improving hemodynamics and micro-flow, resist thrombosis and promote blood flow. BAST contain numerous active ingredients, which can theoretically regulate multiple targets at the same time and have a wide range of pharmacological effects in the treatment of diseases including human cancers. Clinically, BAST have minimal side effects and can be used in combination with Western medicine to improve patients' quality of life, lessen adverse effects and minimize the risk of recurrence and metastasis of cancers. AIM OF THE REVIEW: We aimed to summarize the research progression of BAST on lung cancer in the past five years and present a prospect for the future. Particularly, this review further analyzes the effects and molecular mechanisms that BAST inhibit the invasion and metastasis of lung cancer. MATERIALS AND METHODS: Relevant studies about BSAT were collected from PubMed and Web of science. RESULTS: Lung cancer is one of the malignant tumors with the highest mortality rate. Most patients with lung cancer are diagnosed at an advanced stage and are highly susceptible to metastasis. Recent studies have shown that BAST, a class of traditional Chinese medicine (TCM) with the function of opening veins and dispersing blood stasis, significantly improve hemodynamics and microcirculation, prevent thrombosis and promote blood flow, and thereby inhibiting the invasion and metastasis of lung cancer. In the current review, we analyzed 51 active ingredients extracted from BAST. It was found that BAST and their active ingredients contribute to the prevention of invasion and metastasis of lung cancer through multiple mechanisms, such as regulation of EMT process, specific signaling pathway and metastasis-related genes, tumor blood vessel formation, immune microenvironment and inflammatory response of tumors. CONCLUSIONS: BSAT and its active ingredients have showed promising anticancer activity and significantly inhibit the invasion and metastasis of lung cancer. A growing number of studies have realized their potential clinical significance in the therapy of lung cancer, which will provide substantial evidences for the development of new TCM for lung cancer therapy.

Preventive Effects of Different Black and Dark Teas on Obesity and Non-Alcoholic Fatty Liver Disease and Modulate Gut Microbiota in High-Fat Diet Fed Mice.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading public health challenge and is closely associated with metabolic syndromes, such as obesity. Intestinal microbiota dysbiosis could play a vital role in the pathogenesis and progression of NAFLD. Tea is the second most popular health drink in the world behind water, and exhibits many health-promoting effects. In this study, the protective effects of different black and dark teas on NAFLD induced by long-term high-fat diet (HFD) exposure and their regulation of gut microbiota were evaluated and explored. The results indicated that supplementation with different black and dark tea extracts could significantly suppress the energy intake, alleviate abnormal accumulation of visceral fat, and prevent obesity, hepatic abnormal lipid deposition and liver steatosis in HFD-fed mice at varying degrees. In addition, Dianhong tea and Liupao tea interventions could significantly decrease the ratio of Firmicutes to Bacteroidetes, and selenium-enriched black tea and selenium-enriched dark rea supplementation could remarkably reduce the relative abundance of Actinobacteria compared to the model group. Moreover, these teas could partly shift the relative abundances of Allobaculum, Roseburia and Dubosiella. Taken together, black teas and dark teas could prevent HFD-induced features of obesity and NAFLD, which might partly be due to the modulation of gut microbiota.

Self-assembled traditional Chinese nanomedicine modulating tumor immunosuppressive microenvironment for colorectal cancer immunotherapy.

Colorectal cancer (CRC), mostly categorized as a low immunogenic microsatellite-stable phenotype bearing complex immunosuppressive tumor microenvironment (TME), is highly resistant to immunotherapy. Seeking safe and efficient alternatives aimed at modulating tumor immunosuppressive TME to improve outcome of CRC is highly anticipated yet remains challenging. Methods: Enlightened from the drug complementary art in traditional Chinese medicine, we designed a self-assembled nanomedicine (termed LNT-UA) by the natural active ingredients of ursolic acid (UA) and lentinan (LNT) through a simple nano-precipitation method, without any extra carriers, for CRC immunotherapy. Results: UA induces immunogenic cell death (ICD), while LNT further promotes dendritic cell (DC) maturation and repolarizes tumor-associated macrophage (TAM) from a protumorigenic M2 to an antitumor M1 phenotype. Co-delivery of UA and LNT by LNT-UA effectively reshapes the immunosuppressive TME and mobilizes innate and adaptive immunity to inhibit tumor progression in the CT26 CRC tumor model. Following the principle of integrative theoretical system of traditional Chinese medicine (TCM) on overall regulation, the further combination of LNT-UA and anti-CD47 antibody (αCD47) would reinforce the antitumor immunity by promoting phagocytosis of dying tumor cells and tumor-associated antigens (TAAs), leading to effective suppression of both primary and distant tumor growth with 2.2-fold longer of median survival time in the bilateral tumor model. Most notably, this combination effect is also observed in the spontaneous CRC model induced by chemical carcinogens, with much less and smaller size of tumor nodules after sequential administration of LNT-UA and αCD47 through gavage and intraperitoneal injection, respectively. Conclusions: This study provides a promising self-assembled traditional Chinese nanomedicine to improve immunotherapy for CRC, which might be applicable for future clinical translation.

Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway.

Cerebral ischemia reperfusion injury (CIRI) is still a serious problem threatening human health. Salidroside (SAL) is a natural phenylpropanoid glycoside compound with antioxidant, anti-inflammatory, and anti-ischemic properties. This study investigated the protective mechanism of SAL on middle cerebral artery occlusion (MCAO)- and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced CIRI via regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/thioredoxin 1 (Trx1) axis. The results indicated that SAL (50 mg/kg or 100 mg/kg, intraperitoneal injection) not only effectively alleviated infarction rate, improved histopathological changes, relieved apoptosis by strengthening the suppression of cleaved caspase-3 and Bax/Bcl-2 proteins and decreased malondialdehyde (MDA) formation, but also increased superoxide dismutase (SOD) and catalase (CAT) activities and upregulated the expressions of Nrf2 and Trx1 on MCAO-induced CIRI rats. SAL also efficiently inhibited apoptosis and decreased oxidative stress in OGD/R-stimulated PC12 cells. Furthermore, blocking the Nrf2/Trx1 pathway using tretinoin, an Nrf2 inhibitor, significantly reversed the protective effect of SAL on OGD/R-induced oxidative stress. Moreover, SAL reduced the expression of apoptosis signal-regulating kinase-1 (ASK1) and mitogen-activated protein kinase (MAPK) family proteins. These results demonstrated that SAL inhibited oxidative stress through Nrf2/Trx1 signaling pathway, and subsequently reduced CIRI-induced apoptosis by inhibiting ASK1/MAPK.

Effects of Different Green Teas on Obesity and Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice.

Non-alcoholic fatty liver disease (NAFLD) and obesity are serious public health problems. Green tea is widely consumed in the world and different green teas could possess different bioactivities. In this study, the effects of 10 selected green teas on obesity and NAFLD were evaluated and compared. The mice fed with a high-fat diet were intervened with green tea extract (200 mg/kg body weight) for 15 weeks. Most of these teas were first evaluated for their effects on obesity and NAFLD. The results showed that Selenium-Enriched Chaoqing Green Tea and Jieyang Chaoqing Tea showed the most prominent inhibition of obesity and body weight gains of mice in these two tea intervention groups and model groups were 5.3, 5.5, and 13.7 g, respectively. In addition, Jieyang Chaoqing Tea, Taiping Houkui Tea, and Selenium-Enriched Chaoqing Green Tea exerted the most notable effect on NAFLD, which was attributed to decreasing body weight, and lipid content and ameliorating oxidative stress. Furthermore, 13 phytochemicals were determined in these teas by high-performance liquid chromatography and the correlation analysis found that epigallocatechin gallate, gallocatechin, and epigallocatechin might contribute to the decrease of hepatic weight, while epicatechin might reduce oxidative stress. In general, several green teas could prevent the development of obesity and NAFLD and could be developed into functional foods. This study was also helpful for the public to select appropriate tea to prevent obesity and NAFLD.

GPC2 deficiency inhibits cell growth and metastasis in colon adenocarcinoma.

Glypican-2 (GPC2) has been reported to promote tumor progression through metabolic pathways. However, the role of GPC2 in colon adenocarcinoma (COAD) remains to be further investigated. This study was designed to evaluate the role of GPC2 in COAD. Based on patients with complete clinical information and GPC2 expression from the Cancer Genome Atlas-COAD database, we found that GPC2 mRNA was highly expressed in COAD tissues, which was associated with poor prognosis and tumornode-metastasis (TNM) stage. The predicted survival probability based on GPC2 mRNA expression and TNM stage was in good agreement with the observed survival probability. Furthermore, the genes coexpressed with GPC2 in COAD tissues were significantly enriched in basal cell carcinoma, Notch signaling pathway, and Hedgehog signaling pathway. After GPC2 was decreased through transfecting short hairpin RNA of GPC2 into HCT-8 and SW620 cells, cell cycle was arrested in G0/G1 phase, proliferation was decreased, apoptosis was increased, and migration and invasion were repressed. In conclusion, decreasing GPC2 significantly inhibited proliferation, migration, and invasion, and enhanced apoptosis, which implied that GPC2 can be considered a promising therapeutic target of COAD in the future.

Genome-wide association study and functional follow-up identify 14q12 as a candidate risk locus for cervical cancer.

Cervical cancer is among the leading causes of cancer-related death in females worldwide. Infection by human papillomavirus (HPV) is an established risk factor for cancer development. However, genetic factors contributing to disease risk remain largely unknown. We report on a genome-wide association study (GWAS) on 375 German cervical cancer patients and 866 healthy controls, followed by a replication study comprising 658 patients with invasive cervical cancer, 1361 with cervical dysplasia and 841 healthy controls. Functional validation was performed for the top GWAS variant on chromosome 14q12 (rs225902, close to PRKD1). After bioinformatic annotation and in silico predictions, we performed transcript analysis in a cervical tissue series of 317 samples and demonstrate rs225902 as an expression quantitative trait locus (eQTL) for FOXG1 and two tightly co-regulated long non-coding RNAs at this genomic region, CTD-2251F13 (lnc-PRKD1-1) and CTD-2503I6 (lnc-FOXG1-6). We also show allele-specific effects of the 14q12 variants via luciferase assays. We propose a combined effect of genotype, HPV status and gene expression at this locus on cervical cancer progression. Taken together, this work uncovers a potential candidate locus with regulatory functions and contributes to the understanding of genetic susceptibility to cervical cancer.

Identification of a Five-Gene Panel to Assess Prognosis for Gastric Cancer.

METHODS: Two datasets were used as training and validation cohorts to establish the predictive model. We used three types of screening criteria: background analysis, pathway analysis, and functional analysis provided by the cBioportal website. Fisher's exact test and multivariable logistic regression were performed to screen out related genes. Furthermore, we performed receiver operating characteristic (ROC) and Kaplan-Meier curve analyses to evaluate the correlation between the selected genes and overall survival. RESULT: We screened five genes (KNL1, NRXN1, C6, CCDC169-SOHLH2, and TTN) that were highly related to recurrence of GC. The area under the receiver operating characteristic (ROC) curve was 0.813, which was much higher than that of the baseline model (AUC = 0.699). This result suggested that the mutation of five selected genes had a significant effect on the prediction of recurrence compared with other factors (age, stages, history, etc.). Furthermore, the Kaplan-Meier estimator also revealed that the mutation of five genes positively correlated with patient survival. CONCLUSIONS: The patients who have mutations in these five genes may experience longer survival than those who do not have mutations. This five-gene panel will likely be a practical tool for prognostic evaluation and will provide another possible way for clinicians to determine therapy.

Alpinae Oxyphyllae Fructus alleviated LPS-induced cognitive impairments via PI3K/AKT/NF-κB signaling pathway.

Herein, we aim to investigate the effect of Alpinae Oxyphyllae Fructus (AOF) on cognitive impairments and neuroinflammation in a lipopolysaccharide (LPS)-induced models of AD. Mice were injected intracerebroventricularly with LPS, and then administrated AOF using a gavage for 6 weeks. Spatial working memory was assessed using the Y-maze and Morris water maze test, whereas the levels of PI3K, AKT, p-AKT, p-GSK3ß, GSK3ß, NF-κB, IL-1ß, IL-6, and TNF-α were evaluated using western blot and ELISA assay. Our data showed that AOF was able to significantly alleviate the memory decline in LPS-induced AD mice. Moreover, AOF was able to protect neurons through the PI3K/AKT signaling pathway and significantly decrease NF-κB, IL-6, IL-1ß, and TNF-α levels in the hippocampal and cortex tissues, which were reversed through the use of LY294002. Additionally, we discovered that AOF could significantly decrease the high expression of cytokines as well as the expression and translocation of NF-κB induced by LPS in PC12 cells. These results demonstrate the anti-neuroinflammatory effect of AOF in both cell and animal models of AD, thereby slowing down the process and development of the disease.

Protective effects of tea extracts against alcoholic fatty liver disease in mice via modulating cytochrome P450 2E1 expression and ameliorating oxidative damage.

The alcoholic fatty liver disease (AFLD) has been a severe public health problem. Oxidative stress is involved in the initiation and progression of AFLD. Tea is a popular beverage worldwide with strong antioxidant activity. In this research, our purpose is to explore and compare the effects of 12 selected teas on AFLD. The ethanol liquid diet was used to feed the mice, and 12 tea extracts were administrated at 200 mg/kg body weight every day for 4 weeks. The results showed that the application of several tea extracts exhibited different inhibitory effects on lipid accumulation induced by sub-acute alcohol consumption based on the determination of triglyceride concentration and the histological alteration in the liver. In addition, several teas significantly decreased serum alanine aminotransferase and aspartate aminotransferase activities, inhibited the cytochrome P450 2E1 expression, and promoted alcohol metabolism (p < .05). Besides, compared with the model group, several teas obviously elevated superoxide dismutase and glutathione peroxidase activities as well as glutathione content, and remarkably decreased malondialdehyde level (p < .05). In general, Fried Green Tea, Fenghuang Narcissus Oolong Tea, and Pu-erh Dark Tea possessed potential preventive effects on AFLD. Moreover, the main phytochemicals in the three tea extracts were determined and quantified via high-performance liquid chromatography, and the most commonly detected ingredients were catechins and caffeine, which could exert the protective effects on AFLD.

Effects of Tea against Alcoholic Fatty Liver Disease by Modulating Gut Microbiota in Chronic Alcohol-Exposed Mice.

Gut microbiota dysbiosis has been a crucial contributor to the pathogenesis of alcoholic fatty liver disease (AFLD). Tea is a popular beverage worldwide and exerts antioxidant and anti-inflammatory activities, as well as hepatoprotective effects. However, the potential role of gut microbiota regulated by tea in the prevention and management of AFLD remains unclear. Here, the protective effects of oolong tea, black tea, and dark tea on AFLD and its regulation of gut microbiota in chronic alcohol-exposed mice were explored and investigated. The results revealed that tea supplementation significantly prevented liver steatosis, decreased oxidative stress and inflammation, and modulated gut microbiota in chronic alcohol-exposed mice, especially oolong tea and dark tea. However, black tea showed less effectiveness against liver injury caused by alcohol. Moreover, the diversity, structure and composition of chronic alcohol-disrupted gut microbiota were restored by the supplementation of oolong tea and dark tea based on the analysis of gut microbiota. Furthermore, the relationship between liver injury biochemical indicators and gut microbiota indicated that some specific bacteria, such as Bacteroides, Alloprevotella, and Parabacteroides were closely associated with AFLD. In addition, the phytochemical components in tea extracts were measured by high-performance liquid chromatography, which could contribute to preventive effects on AFLD. In summary, oolong tea and dark tea could prevent chronic alcohol exposure-induced AFLD by modulating gut microbiota.

Effects of several tea extracts on nonalcoholic fatty liver disease in mice fed with a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD) is considered as a severe threat to human health. It has been reported that tea has abundant bioactive compounds and beneficial effects. In our study, the effects of 12 tea extracts on NAFLD were assessed and compared at the dose of 200 mg/kg body weight in mice fed with a high-fat diet (HFD) for 15 weeks. Enshi Yulu Tea, Fenghuang Narcissus Tea, and Yihong Tea showed strong effects in suppressing the accumulation of epididymal and perirenal adipose tissue as well as the increases of body weight and liver weight. The histopathological analysis revealed that hepatic steatosis and adipocyte hypertrophy induced by a HFD could be ameliorated by tea supplementation. In addition, Enshi Yulu Tea and Qing Brick Tea exerted more remarkable functions on decreasing the level of serum triglyceride and preventing hepatic fat accumulation, respectively. Furthermore, Fenghuang Narcissus Tea, Enshi Yulu Tea, and Qing Brick Tea could reverse the abnormal change in the levels of glutathione and superoxide dismutase. Moreover, 13 phytoconstituents were detected and quantified in these teas with high-performance liquid chromatography (HPLC) method. The correlation analysis demonstrated that gallic acid might decrease MDA level, and the reduction of liver weight might be attributed to ellagic acid. However, it should be paid attention to some teas that showed hepatotoxicity with elevated levels of aspartate transaminase and alanine aminotransferase. Several teas showed strong effects in the prevention of NAFLD, which could be developed into functional foods against NAFLD.

Schisandra chinensis protects against dopaminergic neuronal oxidative stress, neuroinflammation and apoptosis via the BDNF/Nrf2/NF-κB pathway in 6-OHDA-induced Parkinson's disease mice.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a disorder of both the motor and nonmotor systems due to a loss of dopaminergic (DA) neurons. Herein, we aimed to investigate the potential neuroprotective role of Schisandra chinensis (Sch) and to determine the mechanism by which Sch functions to ameliorate PD in a 6-hydroxydopamin (6-OHDA)-induced PD model. The open field test, sucrose preference test, and Y-maze test were utilized to evaluate the motor and nonmotor symptoms. We found that administration of Sch improved both disorders and DA neurodegeneration in 6-OHDA-induced mice. Additional data confirmed that Sch treatment significantly increased BDNF expression and decreased the activity of GSK-3ß in the striatum and hippocampus. Moreover, Sch was able to alleviate the abnormal levels of ROS and increase SOD by boosting Nrf2 expression. The nuclear translocation of NF-κB was inhibited by Sch, which subsequently led to a downregulation of proinflammatory cytokines. Sch effectively suppressed apoptosis by decreasing expressions of caspase 3, caspase 9, and p53 in the PD mouse model. Our findings demonstrate that Sch protects against DA neurodegeneration in 6-OHDA-induced PD mice by suppressing oxidative stress, neuroinflammation and apoptosis through the involvement of the BDNF/Nrf2/NF-κB signaling pathway.