The potential of dietary fiber in building immunity against gastrointestinal and respiratory disorders.

The numerous health benefits of dietary fibers (DFs) justify their inclusion in human diets and biomedical products. Given the short- and long-term human impacts of the COVID-19 virus on human health, the potential of DFs in building immunity against gastrointestinal and respiratory disorders is currently receiving high attention. This paper reviews the physicochemical properties of DFs, together with their immune functions and effects on the gastrointestinal tract and respiratory system mainly based on research in the last ten years. Possible modes of action of DFs in promoting health, especially building immunity, are explored. We seek to highlight the importance of understanding the exact physical and chemical characteristics and molecular behaviors of DFs in providing specific immune function. This review provides a perspective beyond the existing recognition of DFs' positive effects on human health, and offers a theoretical framework for the development of special DFs components and their application in functional foods and other therapeutic products against gastrointestinal and respiratory disorders. DFs enhance immunity from gastrointestinal and respiratory diseases to promote host health.

Structures and Biological Activities of Secondary Metabolites from the Trichoderma genus (Covering 2018-2022).

Trichoderma, a genus with more than 400 species, has a long history of use as an industrial bioreactor, biofertilizer, and biocontrol agent. It is considered a significant source of secondary metabolites (SMs) that possess unique structural features and a wide range of bioactivities. In recent years, numerous secondary metabolites of Trichoderma, including terpenoids, polyketides, peptides, alkaloids, and steroids, have been identified. Most of these SMs displayed antimicrobial, cytotoxic, and antifungal effects. This review focuses on the structural diversity, biological activities, and structure-activity relationships (SARs) of the SMs isolated from Trichoderma covered from 2018 to 2022. This study provides insights into the exploration and utilization of bioactive compounds from Trichoderma species in the agriculture or pharmaceutical industry.

Ionic liquid-based ultrasonic-assisted extraction coupled with HPLC to analyze isoquercitrin, trifolin and afzelin in Amygdalus persica L. flowers.

This study aimed to establish a method for the simultaneous determination of isoquercitrin, trifolin and afzelin in A. persica flowers by high performance liquid chromatography (HPLC) with ionic liquid as extractant and ultrasonic-assisted extraction. The effects of ionic liquid concentration, solid-liquid ratio, number of crushing mesh, ultrasonic time, extraction temperature, and ultrasonic power on the extraction yield of three target compounds were investigated using the extraction yield of target analytes as the index. According to the results of single factor experiment, the Box-Behnken design-response surface methodology (BBD) was used to optimize the extraction method and compared with the traditional extraction method. The results showed that, calibration curves had excellent linearity (R2 > 0.9990) within the test ranges. In combination with other validation data, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of isoquercitrin, trifolin and afzelinin A. persica flowers. And the contents of isoquercitrin, trifolin and afzelin were 64.08, 20.55 and 75.63 µg/g, respectively. The optimal process obtained by BBD was as follows: ionic liquid concentration was 1.0 mol/L, solid-liquid ratio was 1:40 g/ml, mesh sieve was 50 mesh, ultrasonic time was 40 min, extraction temperature was 50 °C, and ultrasonic power was 400 W. Under the optimal conditions, the theoretical predicted total extraction yield of the three target compounds was 159.77 µg/g, which was close to the actual extraction value (160.26 µg/g, n = 3), this result indicating that the optimal process parameters obtained by response surface methodology analysis were accurate and reliable. The method was simple, accurate and rapid for determination the contents of three active ingredients in A. persica flowers.

Bioactive cytochalasans from the desert soil-derived fungus Chaetomium madrasense 375 obtained via a chemical engineering strategy.

The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives (1-11) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13-16 displayed potent phytotoxic effects on Arabidopsis thaliana, while compounds 1, 2, 5, 10, and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 µM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1.

Background: Currently, there is no satisfactory treatment available for esophageal squamous cell carcinoma (ESCC), and thus, there is a pressing need to develop effective drugs. Chaetoglobosin E, a cytochalasan alkaloid derived from metabolites of Chaetomium madrasense 375, is a chaetoglobosin with intense anti-tumor activity. Therefore, revealing its anti-tumor mechanism for the application of cytochalasans is crucial. Methods: The cytotoxic effect of chaetoglobosin E and cisplatin on esophageal cancer KYSE-30, KYSE-150, and TE-1 cells was detected using cell viability or colony formation assays. The cell cycle, apoptosis, autophagy, invasion, and metastasis were assayed by flow cytometry or western blot. The potential target of chaetoglobosin E was assayed by RNA sequencing (RNA-seq) and large loop prediction software analysis and was assessed by western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of its target on cell pyroptosis was assayed using overexpression and silence experiments. Results: Chaetoglobosin E significantly inhibited the proliferation of KYSE-30, KYSE-150, and TE-1 cells, especially KYSE-30 cells. Our results showed that chaetoglobosin E induced the G2/M phase arrest of KYSE-30 cells, followed by the down-regulation of cyclinB1, CDC2, and p-CDC2, and up-regulation of p21. Moreover, chaetoglobosin E also decreased the anti-apoptotic protein expression of Bcl-2, increased apoptotic expression of Bax, increased autophagy protein expressions of beclin1 and LC3, decreased invasion and metastasis protein expression of E-cadherin, and increased expression of vimentin. The RNA-seq and large loop prediction software analysis results indicated that its potential target might be polo-like kinase 1 (PLK1). Moreover, results also showed that chaetoglobosin E can reverse the PLK1 overexpression plasmid-induced up-regulation of the PLK1 protein. Furthermore, we found that chaetoglobosin E induced pyroptosis via the activation of the gasdermin E (GSDME) protein. Further studies showed that the high expression of PLK1 inactivated the GSDME protein, while the knockdown of PLK1 expression activated the GSDME protein, indicating that chaetoglobosin E induced cell pyroptosis by inhibiting PLK1. Conclusions: This study suggested that chaetoglobosin E may be a novel lead compound to the treatment of ESCC patients by targeting PLK1, and elucidated for the first time that PLK1 was involved in a new pyroptosis mechanism.

Identification of Costimulatory Molecule-Related lncRNAs Associated With Gastric Carcinoma Progression: Evidence From Bioinformatics Analysis and Cell Experiments.

Costimulatory molecules (CMGs) play essential roles in multiple cancers. However, lncRNAs regulating costimulatory molecules have not been fully explored in gastric cancer (GC). Public data of GC patients were obtained from The Cancer Genome Atlas database. R software v4.1.1, SPSS v13.0, and GraphPad Prism 8 were used to perform all the analyses. The Limma package was used for differential expression analysis. The survival package was used for patient prognosis analysis. The gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto encyclopedia of genes and genomes (KEGG) analysis were used for pathway enrichment analysis. qRT-PCR was used to detect the RNA level of target lncRNA. CCK-8 and colony formation assay were used to assess the proliferation ability of GC cells. The transwell assay was used to evaluate the invasion and migration ability of GC cells. We first identified CMG-related lncRNAs (CMLs) through co-expression analysis. Then, an eight-CML-based signature was constructed to predict patient overall survival (OS), which showed satisfactory predictive efficiency (the training cohort: 1-year AUC = 0.764, 3-year AUC = 0.810, 5-year AUC = 0.840; the validation cohort: 1-year AUC = 0.661, 3-year AUC = 0.718, 5-year AUC = 0.822). The patients in the high-risk group tend to have a worse prognosis. GSEA showed that epithelial-mesenchymal transition, KRAS signaling, and angiogenesis were aberrantly activated in high-risk patients. GO and KEGG analyses indicated that the biological difference between high- and low-risk patients was mainly enriched in the extracellular matrix. Immune infiltration analysis showed that macrophages (M1 and M2), dendritic cells, monocytes, Tregs, and T regulatory cells were positively correlated with the risk scores, partly responsible for the worsening OS of high-risk patients. Finally, lncRNA AP000695.2 was selected for further experiments. The result showed that AP000695.2 was upregulated in GC cell lines and could facilitate the proliferation, invasion, and migration of GC cells. In summary, this study established an effective prognosis model based on eight CMLs, which would be helpful for further therapy options for cancer. Also, we found that AP000695.2 could promote GC cell malignant phenotype, making it an underlying therapy target in GC.

Sushi-Repeat-Containing Protein X-Linked 2: A Potential Therapeutic Target for Inflammation and Cancer Therapy.

Accumulating evidence has showed that sushi-repeat-containing protein X-linked 2 (SRPX2) is an abnormal expression in a variety of cancers and involved in cancer carcinogenesis, chemosensitivity, and prognosis, which mainly promote cancer cell metastasis, invasion, and migration by regulating the uPAR/integrins/FAK signaling pathway, epithelial-mesenchymal transition (EMT), angiogenesis, and glycosylation. Inflammation has been regarded as a key role in regulating cancer initiation, progression, EMT, and therapeutics. Furthermore, SRPX2 exhibited excellent antifibrosis effect via the TGFßR1/SMAD3/SRPX2/AP1/SMAD7 signaling pathway. Therefore, this review provides compelling evidence that SRPX2 might be a therapeutic target for inflammation and cancer-related inflammation for future cancer therapeutics.

Diversified Polyketides With Anti-inflammatory Activities From Mangrove Endophytic Fungus Daldinia eschscholtzii KBJYZ-1.

In total, five new polyketide derivatives: eschscholin B (2), dalditone A and B (3 and 4), (1R, 4R)-5-methoxy-1,2,3,4-tetrahydronaphthalene-1,4-dio (5), and daldilene A (6), together with 10 known as analogs (1, 7-15) were isolated from the mangrove endophytic fungus Daldinia eschscholtzii KBJYZ-1. Their structures and absolute configurations were established by extensive analysis of NMR and HRESIMS spectra data combined with ECD calculations and the reported literature. Compounds 2 and 6 showed significant cell-based anti-inflammatory activities with IC50 values of 19.3 and 12.9 µM, respectively. In addition, western blot results suggested that compound 2 effectively inhibits the expression of iNOS and COX-2 in LPS-induced RAW264.7 cells. Further molecular biology work revealed the potential mechanism of 2 exerts anti-inflammatory function by inactivating the MAPK and NF-κB signaling pathways.

A glucomannogalactan from Pleurotus geesteranus: Structural characterization, chain conformation and immunological effect.

A water-soluble glucomannogalactan was isolated from P. geesteranus fruit bodies by hot water extraction and column chromatography method. The structure, chain conformation and immune effect of PGP-1c (20.9 kDa) were investigated comprehensively based on high purity and neutral sugar content (94.7 ± 0.5%). Confirmed by monosaccharide composition, methylation and NMR analysis, PGP-1c was composed of unsubstituted (1,6-α-Gal and 1,6-α-3-OMe-Gal) and monosubstituted (1,2,6-α-Gal and 1,2,6-α-3-OMe-Gal) galactose units in the backbone through α-(1 â†’ 6) glycosidic bonds and the possible branches that a long-branched chain composed of →3)-Glc-(1 â†’ Man and a few fucoses were connected at the O-2 of galactose with a branching degree of 48%. Through the conformational behavior of the molecular chain, it was observed that PGP-1c might have a long-branched or stacked macromolecular network caused by O-CH3 groups. Moreover, PGP-1c could promote the secretion of NO and cytokines significantly in a dose-dependent manner, which indicated a good immune-enhancing effect.

Nomogram for predicting the 12-year risk of ADL disability among older adults.

OBJECTIVES: Previous studies have identified plenty of risk factors for activities of daily living (ADL). However, there are no reliable and widely available prediction models for ADL disability up to now. This study aimed to develop and validate a nomogram for predicting the 12-year risk of ADL disability in older adults. METHODS: Data from 4,809 participants in the English Longitudinal Study of Ageing (ELSA) and 18,620 participants in the Survey of Health, Ageing and Retirement in Europe (SHARE) were used as training set and validation set, respectively. We used the least absolute shrinkage and selection operator (LASSO) and Cox regression to screen the predictors and develop the nomogram. The P value, concordance index (C-index), integrated area under the ROC (receiver operating characteristic) curve (AUC) and calibration curves were used to validate the nomogram. RESULTS: During 12 years, 30.0% (n = 1,441) participants developed ADL disability in the training set, while the corresponding percentages were 18.5% in the validation set (n = 3,445). After screening, 13 variables were contained in the final prediction model. In ADL nomogram, the C-index and AUC were 0.744 ± 0.013 and 0.793 in internal valid ation, respectively, while in external validation, the C-index and AUC were 0.755 ± 0.009 and 0.796. CONCLUSIONS: This study developed and validated a nomogram that predicts functional disability. The application of the predictive model could have important implications for patient prognosis and health care.

Structural Characterization and Anticoagulant Activity of a 3-O-Methylated Heteroglycan From Fruiting Bodies of Pleurotus placentodes.

Pleurotus placentodes, a fungus, belongs to the Pleurotaceae family. The aim of the present study was to characterize the structure of a novel polysaccharide from fruiting bodies of P. placentodes (PPp-W) and evaluate its anticoagulant activity in vitro. The high-performance liquid chromatography and GC-MS analysis indicated that PPp-W with a molecular weight of 27.4 kDa was mainly composed of mannose (17.56%), glucose (6.37%), galactose (44.89%), and fucose (1.22%) with a certain amount of 3-O-methyled galactose. SEM, XRD, and AFM combined with Congo red test revealed that PPp-W was an irregular curly sheet with triple-helix conformation. The FT-IR, methylation, and nuclear magnetic resonance analysis indicated that PPp-W contained→6)-α-D-Galp-(1→, →6)-3-O-Me-α-D-Galp-(1→and →2, 6)-α-D-Galp-(1→ as main chain, partially substituted at O-2 and O-6 by non-reducing ends of ß-D-Manp-(1→ and ß-L-Fucp-(1→ with a small amount of α-1,3-linked-Glcp in backbone. PPp-W could significantly prolong APTT (12.9 ± 0.42 s, p < 0.001) and thrombin time (39.9 ± 0.28 s, p < 0.01) compared with the control group (11.45 ± 0.071 s and 38.05 ± 0.21 s), which showed that PPp-W had anticoagulant activity. These studies suggested that PPp-W was a 3-O-methylated heteroglycan and might be suitable for functional foods and natural drugs as an anticoagulant ingredient, which provided a basis for the application of polysaccharides from P. placentodes.

Establishment of a nomogram model to predict macrosomia in pregnant women with gestational diabetes mellitus.

AIM: To establish a nomogram model to predict the risk of macrosomia in pregnant women with gestational diabetes mellitus in China. METHODS: We retrospectively collected the medical records of 783 pregnant women with gestational diabetes who underwent prenatal examinations and delivered at the Affiliated Hospital of Qingdao University from October 2019 to October 2020. The pregnant women were randomly divided into two groups in a 4:1 ratio to generate and validate the model. The independent risk factors for macrosomia in pregnant women with gestational diabetes mellitus were analyzed by multivariate logistic regression, and the nomogram model to predict the risk of macrosomia in pregnant women with gestational diabetes mellitus was established and verified by R software. RESULTS: Logistic regression analysis showed that prepregnancy body mass index, weight gain during pregnancy, fasting plasma glucose, triglycerides, biparietal diameter and amniotic fluid index were independent risk factors for macrosomia (P < 0.05). The areas under the ROC curve for internal and external validation of the model were 0.813 (95 % confidence interval 0.754-0.862) and 0.903 (95 % confidence interval 0.588-0.967), respectively. The calibration curve was a straight line with a slope close to 1. CONCLUSIONS: In this study, we constructed a nomogram model to predict the risk of macrosomia in pregnant women with gestational diabetes mellitus. The model has good discrimination and calibration abilities, which can help clinical healthcare staff accurately predict macrosomia in pregnant women with gestational diabetes mellitus.

Optimization of Nonlinear Lamb Wave Detection System Parameters in CFRP Laminates.

Carbon fiber reinforced polymer (CFRP) laminates, as unique multifunctional materials, are widely applied in various aircraft, such as airliners, fighter planes, and space shuttles. To ensure aircraft safety during the production and application of CFRP laminates, it is necessary to improve the accuracy of nonlinear Lamb wave nondestructive testing to assess the damage in CFRP laminates caused by impact, high temperature, friction, corrosion, etc. In this study, the accuracy of nonlinear ultrasonic nondestructive testing was found to highly depend on the cycle number, output level and gain of the nonlinear ultrasonic detection system. Based on a single-factor experiment that considered the cycle number, output level, and gain of the amplifier as independent variables, a regression analysis was carried out on the fundamental wave amplitude value (A1) and second harmonic amplitude value (A2). Two response surface surrogate models were established to improve the accuracy of nonlinear Lamb wave nondestructive testing and to optimize the detection system parameters. The response surface models were verified via an analysis of variance (ANOVA), significance tests and an error statistical analysis. The results revealed the significant influence of these three factors on A1 and A2. Optimization of the response surface was achieved at eight cycles, an output level of 42 and a gain of 32 dB. Moreover, the nonlinear ultrasonic detection system achieved good operational stability, high accuracy and reliability under the above optimal parameter conditions. This approach provides scientific guidance for the accurate assessment of CFRP laminate damage.

Appropriate body mass index cutoffs for type 2 diabetes in Xinjiang population: defining the influence of liver aminotransferase.

BACKGROUND/PURPOSE: Recent study suggested that type 2 diabetes (T2DM) attributed to body mass index (BMI) could be influenced by liver aminotransferase. We aim to ascertain the cut-off point of BMI associated with T2DM and the influence of both elevated aminotransferase (AST) and alanine aminotransferase (ALT). MATERIALS AND METHODS: In our retrospective cohort study, T2DM was diagnosed when FBS ≥ 7.0 mmol/L, BMI of participants with baseline fasting (FBS) < 7.0 mmol/L was divided by percentiles and by aminotransferanse (ALT and AST ≥ 20 U/L, ALT or AST < 20 U/L). Hazard ratios and the turning point of BMI of high T2DM risk was estimated in totality and different aminotransferanse groups. RESULTS: During an average follow-up time of 3.71 years of 33346 participants, 1486 developed T2DM, and the average baseline BMI of participants who developed T2DM was 26.22 kg/m2. Cumulative incidence of T2DM was more than 5% when ALT and AST ≥ 20U/L, age over 44, male sex or BMI over 25.39 kg/m2; The risk of T2DM incidence increased as the BMI grow. The turning point of BMI at high risk of T2DM was 25.0 kg/m2 in totality, 25.1 kg/m2 when ALT or AST < 20 U/L and 26.1 kg/m2 when ALT and AST ≥ 20U/L. CONCLUSIONS: BMI of 25.0 kg/m2 was the cutoff point for T2DM development, and there is greater association between BMI and T2DM when ALT or AST < 20 U/L.

Loneliness mediates the relationships between perceived neighborhood characteristics and cognition in middle-aged and older adults.

OBJECTIVES: We aimed to examine whether loneliness mediates these associations between perceived neighborhood characteristics and cognition among middle-aged and older adults. METHODS: Data from wave 10 (2010-2012) to wave 13 (2016-2017) of the Health and Retirement Study were analyzed. Perceived neighborhood characteristics were self-reported. Loneliness was measured by Revised University of California Los Angeles (R-UCLA) Loneliness Scale. Cognition was evaluated by the modified version of Telephone Interview for Cognitive Status. Baron and Kenny's causal steps and multiple linear regression models based on Karlson/Holm/Breen (KHB) method were used to examine the mediating effect. RESULTS: At baseline, 15,142 participants had no cognitive impairment, and 11,413 individuals were finally included in our analysis after 6-year follow-up. Multiple linear regression models suggested that lower perceived neighborhood physical disorder (ß = 0.073, p = 0.033) and greater perceived neighborhood safety (ß = 0.350, p = 0.009) were associated with better cognition. KHB test identified the significant mediating effect of loneliness on the relationships between perceived neighborhood physical disorder (ß = 0.011, p = 0.016) and perceived neighborhood safety (ß = 0.023, p = 0.026) and cognition. CONCLUSIONS: Perceived neighborhood characteristics are associated with cognition among middle-aged and older American adults. Loneliness mediated associations between perceived neighborhood physical disorder and perceived neighborhood safety and cognition.

Hydrazine-Containing Heterocycle Cytochalasan Derivatives From Hydrazinolysis of Extracts of a Desert Soil-Derived Fungus Chaetomium madrasense 375.

"Diversity-enhanced extracts" is an effective method of producing chemical libraries for the purpose of drug discovery. Three rare new cytochalasan derivative chaetoglobosins B1-B3 (1-3) were obtained from chemically engineered crude broth extracts of Chaetomium madrasense 375 prepared by reacting with hydrazine monohydrate and four known metabolite chaetoglobosins (4-7) were also identified from the fungus. The structures were identified by NMR and MS analysis and electronic circular dichroism simulation. In addition, the antiproliferative activities of these compounds were also evaluated, and the drug-resistant activities of cytochalasans were evaluated for the first time. Compound 6 possessed potent activity against four human cancer cells (A549, HCC827, SW620, and MDA-MB-231), and two drug-resistant HCC827 cells (Gefitinib-resistant, Osimertinib-resistant) compared with the positive controls.

Identification of novel autophagy-related lncRNAs associated with a poor prognosis of colon adenocarcinoma through bioinformatics analysis.

LncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57-0.78; 3 years: AUC = 0.71, 95% Cl = 0.6-0.8; 5 years: AUC = 0.76, 95% Cl = 0.66-0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58-0.8; 3 years: AUC = 0.73, 95% Cl = 0.63-0.82; 5 years: AUC = 0.68, 95% Cl = 0.5-0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor = - 0.15, P < 0.001; stromal score, cor = - 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.

Activation of RAW264.7 cells by PCp-I, a polysaccharide from Psoralea corylifolia L, through NF-κB/MAPK signalling pathway.

PCp-I is a polysaccharide isolated and identified from the Psoralea corylifolia L. by our research group. In this study, the immunomodulatory effects of PCp-I on RAW264.7 cells was evaluated. PCp-I could enhance the level of NO along with up-regulation of iNOS mRNA in RAW264.7 cells. The PCp-I could significantly up-regulate the mRNA expression of TNF-α and IL-6 in RAW264.7 cells, and then the expression of TNF-α, IL-6, ROS and the phagocytic activity were increased. Additionally, PCp-I could significantly up-regulate the phosphorylation level of p65, p38, ERK and JNK proteins, which proved that PCp-I could activate the macrophages by MAPKs and NF-κB signalling pathway and the TLR4 may be one of the receptors of PCp-I regulate the RAW264.7 cells.

Systematic profiling of early regulators during tissue regeneration using zebrafish model.

Great progresses have been made in comprehension of tissue regeneration process. However, one of the central questions in regeneration research remains to be deciphered is what factors initiate regenerative process. In present study, we focused on systematic profiling of early regulators in tissue regeneration via high-throughput screening on zebrafish caudal fin model. Firstly, 53 GO-annotated regeneration-related genes, which were specifically activated upon fin amputation, were identified according to the transcriptomic analysis. Moreover, qRT-PCR analysis of a couple of randomly selected genes from the aforementioned gene list validated our sequencing results. These studies confirmed the reliability of transcriptome sequencing analysis. Fibroblast growth factor 20a (fgf20a) is a key initial factor in the regeneration of zebrafish. Through a gene expression correlation analysis, we discovered a collection of 70 genes correlating with fgf20a, whose expression increased promptly at 2 days post amputation (dpa) and went down to the basal level until the completion of fin regeneration. In addition, two genes, socs3b and nppc, were chosen to investigate their functions during the fin regeneration. Inhibition of either of those genes significantly delayed the regenerative process. Taken together, we provided a simple and effective time-saving strategy that may serve as a tool for identifying early regulators in regeneration and identified 71 genes as early regulators of fin regeneration.

Anticancer Effects and Mechanisms of Action of Plumbagin: Review of Research Advances.

Plumbagin (PLB), a natural naphthoquinone constituent isolated from the roots of the medicinal plant Plumbago zeylanica L., exhibited anticancer activity against a variety of cancer cell lines including breast cancer, hepatoma, leukemia, melanoma, prostate cancer, brain tumor, tongue squamous cell carcinoma, esophageal cancer, oral squamous cell carcinoma, lung cancer, kidney adenocarcinoma, cholangiocarcinoma, gastric cancer, lymphocyte carcinoma, osteosarcoma, and canine cancer. PLB played anticancer activity via many molecular mechanisms, such as targeting apoptosis, autophagy pathway, cell cycle arrest, antiangiogenesis pathway, anti-invasion, and antimetastasis pathway. Among these signaling pathways, the key regulatory genes regulated by PLB were NF-kß, STAT3, and AKT. PLB also acted as a potent inducer of reactive oxygen species (ROS), suppressor of cellular glutathione, and novel proteasome inhibitor, causing DNA double-strand break by oxidative DNA base damage. This review comprehensively summarizes the anticancer activity and mechanism of PLB.