Hunan University of Traditional Chinese Medicine

Sensing mechanisms of ZnO nanowire films are investigated by performing transient photocurrent measurements. The current jumps upon ultraviolet or green laser illumination. The amplitude in the jump is strongly dependent on the ambient atmosphere. The decay rate is much more sensitive to the ambient atmosphere than the rise rate. The fast rise is due to rapid photogenerated carriers and the slow decay is controlled by slow surface process. Our experimental results indicate that the oxygen physisorption rate is slower than the chemisorption rate.

Inflammation is a natural defence response of the immune system against environmental insult, stress and injury, but hyper- and hypo-inflammatory responses can trigger diseases. Accumulating evidence suggests that inflammation is involved in multiple psychiatric disorders. Using inflammation-related factors as biomarkers of psychiatric disorders requires the proof of reproducibility and specificity of the changes in different disorders, which remains to be established. We performed a cross-disorder study by systematically evaluating the meta-analysis results of inflammation-related factors in eight major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depression disorder (MDD), post-trauma stress disorder (PTSD), sleeping disorder (SD), obsessive-compulsive disorder (OCD) and suicide. A total of 43 meta-analyses involving 704 publications on 44 inflammation-related factors were included in the study. We calculated the effect size and statistical power for every inflammation-related factor in each disorder. Our analyses showed that well-powered case-control studies provided more consistent results than underpowered studies when one factor was meta-analysed by different researchers. After removing underpowered studies, 30 of the 44 inflammation-related factors showed significant alterations in at least one disorder based on well-powered meta-analyses. Eleven of them changed in patients of more than two disorders when compared with the controls. A few inflammation-related factors showed unique changes in specific disorders (e.g., IL-4 increased in BD, decreased in suicide, but had no change in MDD, ASD, PTSD and SCZ). MDD had the largest number of changes while SD has the least. Clustering analysis showed that closely related disorders share similar patterns of inflammatory changes, as genome-wide genetic studies have found. According to the effect size obtained from the meta-analyses, 13 inflammation-related factors would need <50 cases and 50 controls to achieve 80% power to show significant differences (p < 0.0016) between patients and controls. Changes in different states of MDD, SCZ or BD were also observed in various comparisons. Studies comparing first-episode SCZ to controls may have more reproducible findings than those comparing pre- and post-treatment results. Longitudinal, system-wide studies of inflammation regulation that can differentiate trait- and state-specific changes will be needed to establish valuable biomarkers.

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.

Importance: The long-term prophylactic effects of acupuncture for migraine are uncertain. Objective: To investigate the long-term effects of true acupuncture compared with sham acupuncture and being placed in a waiting-list control group for migraine prophylaxis. Design, Setting, and Participants: This was a 24-week randomized clinical trial (4 weeks of treatment followed by 20 weeks of follow-up). Participants were randomly assigned to true acupuncture, sham acupuncture, or a waiting-list control group. The trial was conducted from October 2012 to September 2014 in outpatient settings at 3 clinical sites in China. A total of 249 participants 18 to 65 years old with migraine without aura based on the criteria of the International Headache Society, with migraine occurring 2 to 8 times per month. Interventions: Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions. Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial. Main Outcomes and Measures: Participants used diaries to record migraine attacks. The primary outcome was the change in the frequency of migraine attacks from baseline to week 16. Secondary outcome measures included the migraine days, average headache severity, and medication intake every 4 weeks within 24 weeks. Results: A total of 249 participants 18 to 65 years old were enrolled, and 245 were included in the intention-to-treat analyses. One hundred eighty-nine (77.1%) were women. Baseline characteristics were comparable across the 3 groups. The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization (P < .001); the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P < .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95% CI, -0.1 to 1.4; P = .07). Conclusions and Relevance: Among patients with migraine without aura, true acupuncture may be associated with long-term reduction in migraine recurrence compared with sham acupuncture or assigned to a waiting list. Trial Registration: clinicaltrials.gov Identifier: NCT01687660.

BACKGROUND: Sub-therapeutic antibiotics are widely used as growth promoters in the poultry industry; however, the resulting antibiotic resistance threatens public health. A plant-derived growth promoter, Macleaya cordata extract (MCE), with effective ingredients of benzylisoquinoline alkaloids, is a potential alternative to antibiotic growth promoters. Altered intestinal microbiota play important roles in growth promotion, but the underlying mechanism remains unknown. RESULTS: We generated 1.64 terabases of metagenomic data from 495 chicken intestinal digesta samples and constructed a comprehensive chicken gut microbial gene catalog (9.04 million genes), which is also the first gene catalog of an animal's gut microbiome that covers all intestinal compartments. Then, we identified the distinctive characteristics and temporal changes in the foregut and hindgut microbiota. Next, we assessed the impact of MCE on chickens and gut microbiota. Chickens fed with MCE had improved growth performance, and major microbial changes were confined to the foregut, with the predominant role of Lactobacillus being enhanced, and the amino acids, vitamins, and secondary bile acids biosynthesis pathways being upregulated, but lacked the accumulation of antibiotic-resistance genes. In comparison, treatment with chlortetracycline similarly enriched some biosynthesis pathways of nutrients in the foregut microbiota, but elicited an increase in antibiotic-producing bacteria and antibiotic-resistance genes. CONCLUSION: The reference gene catalog of the chicken gut microbiome is an important supplement to animal gut metagenomes. Metagenomic analysis provides insights into the growth-promoting mechanism of MCE, and underscored the importance of utilizing safe and effective growth promoters.

Copper is king! A convenient method for the synthesis of trifluoromethylated heteroaromatic compounds under mild conditions has been developed based on the observation that 1 can be reduced by certain metals (see scheme). Substrate 1 is assumed to be reduced by copper via a single-electron transfer mechanism, and CuCF3 is the most probable intermediate in this reaction. DMF=N,N-dimethylformamide, Tf=triflate. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti‑inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.

Ohne viel Aufwand dank Kupfer: Ausgehend von der Beobachtung, dass 1 durch bestimmte Metalle reduziert werden kann, wurde eine einfache Methode zur Synthese von trifluormethylierten Heteroarenen unter milden Bedingungen entwickelt (siehe Schema). Es wird angenommen, dass Kupfer das Substrat 1 über einen Einelektronentransfermechanismus reduziert, und CuCF3 ist die wahrscheinlichste Zwischenstufe dieser Reaktion.

Copper (Cu) is an essential micronutrient involved in a variety of fundamental biological processes. Recently, disorder of Cu homeostasis can be observed in many malignancies. Elevated Cu levels in serum and tissue are correlated with cancer progression. Hence, targeting Cu has emerged as a novel strategy in cancer treatment. This review provides an overview of physiological Cu metabolism and its homeostasis, followed by a discussion of the dysregulation of Cu homeostasis in cancer and the effects of Cu on cancer progression. Finally, recent therapeutic advances using Cu coordination complexes as anticancer agents, as well as the mechanisms of their anti-cancer action are discussed. This review contributes full comprehension to the role of Cu in cancer and demonstrates the broad application prospect of Cu coordination compounds as potential therapeutic agents.

The disorder of lipid metabolism is pathologically linked to hyperlipidemia, lipid storage disease, obesity and other related diseases. Intriguingly, recent studies have revealed that lipid metabolism disorders play an important role in carcinogenesis and development as well, since they cause abnormal expression of various genes, proteins, and dysregulation of cytokines and signaling pathways. More importantly, lipid-lowering drugs and anti-lipid per-oxidation treatment have been showing their advantages in clinic, in comparison with other anti-cancer drugs with high toxicity. Thus, further elucidation of molecular mechanism between lipid metabolism and cancer is essential in developing novel diagnostic biomarkers and therapeutic targets of human cancers.

Nucleic acid aptamers are single-stranded DNA or RNA of 20-100 nucleotides in length that have attracted substantial scientific interest due to their ability to specifically bind to target molecules via the formation of three-dimensional structures. Compared to traditional protein antibodies, aptamers have several advantages, such as their small size, high binding affinity, specificity, flexible structure, being chemical synthesizable and modifiable, good biocompatibility, high stability and low immunogenicity, which all contribute to their widely applications in the biomedical field. To date, much progress has been made in the study and applications of aptamers, however, detailed information on how aptamers bind to their targets is still scarce. Over the past few decades, many methods have been introduced to investigate the aptamer-target binding process, such as measuring the main kinetic or thermodynamic parameters, detecting the structural changes of the binding complexes, etc. Apart from traditional physicochemical methods, various types of molecular docking programs have been applied to simulate the aptamer-target interactions, while these simulations also have limitations. To facilitate the further research on the interactions, herein, we provide a brief review to illustrate the recent advances in the study of aptamer-target interactions. We summarize the binding targets of aptamers, such as small molecules, macromolecules, and even cells. Their binding constants (KD) are also summarized. Methods to probe the aptamer-target binding process, such as surface plasmon resonance (SPR), circular dichroism spectroscopy (CD), isothermal titration calorimetry (ITC), footprinting assay, truncation and mutation assay, nuclear magnetic resonance spectroscopy (NMR), X-ray crystallography and molecular docking simulation are indicated. The binding forces mediating the aptamer-target interactions, such as hydrogen bonding, electrostatic interaction, the hydrophobic effect, π-π stacking and van der Waals forces are summarized. The challenges and future perspectives are also discussed.

IMPORTANCE: The effects of acupuncture as adjunctive treatment to antianginal therapies for patients with chronic stable angina are uncertain. OBJECTIVE: To investigate the efficacy and safety of acupuncture as adjunctive therapy to antianginal therapies in reducing frequency of angina attacks in patients with chronic stable angina. DESIGN, SETTING, AND PARTICIPANTS: In this 20-week randomized clinical trial conducted in outpatient and inpatient settings at 5 clinical centers in China from October 10, 2012, to September 19, 2015, 404 participants were randomly assigned to receive acupuncture on the acupoints on the disease-affected meridian (DAM), receive acupuncture on the acupoints on the nonaffected meridian (NAM), receive sham acupuncture (SA), and receive no acupuncture (wait list [WL] group). Participants were 35 to 80 years of age with chronic stable angina based on the criteria of the American College of Cardiology and the American Heart Association, with angina occurring at least twice weekly. Statistical analysis was conducted from December 1, 2015, to July 30, 2016. INTERVENTIONS: All participants in the 4 groups received antianginal therapies as recommended by the guidelines. Participants in the DAM, NAM, and SA groups received acupuncture treatment 3 times weekly for 4 weeks for a total of 12 sessions. Participants in the WL group did not receive acupuncture during the 16-week study period. MAIN OUTCOMES AND MEASURES: Participants used diaries to record angina attacks. The primary outcome was the change in frequency of angina attacks every 4 weeks from baseline to week 16. RESULTS: A total of 398 participants (253 women and 145 men; mean [SD] age, 62.6 [9.7] years) were included in the intention-to-treat analyses. Baseline characteristics were comparable across the 4 groups. Mean changes in frequency of angina attacks differed significantly among the 4 groups at 16 weeks: a greater reduction of angina attacks was observed in the DAM group vs the NAM group (difference, 4.07; 95% CI, 2.43-5.71; P < .001), in the DAM group vs the SA group (difference, 5.18; 95% CI, 3.54-6.81; P < .001), and in the DAM group vs the WL group (difference, 5.63 attacks; 95% CI, 3.99-7.27; P < .001). CONCLUSIONS AND RELEVANCE: Compared with acupuncture on the NAM, SA, or no acupuncture (WL), acupuncture on the DAM as adjunctive treatment to antianginal therapy showed superior benefits in alleviating angina. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01686230.

BACKGROUND: Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with the targets involved in UC has not been elucidated yet. AIM: A network pharmacology-based approach combined with molecular docking and in vitro validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HHS against UC. MATERIALS AND METHODS: Bioactives and potential targets of HHS, as well as UC-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro experiments were conducted to further verify the findings. RESULTS: A total of 28 bioactive ingredients of HHS and 421 HHS-UC-related targets were screened. Bioinformatics analysis revealed that quercetin, luteolin, and nobiletin may be potential candidate agents. JUN, TP53, and ESR1 could become potential therapeutic targets. PI3K-AKT signaling pathway might play an important role in HHS against UC. Moreover, molecular docking suggested that quercetin, luteolin, and nobiletin combined well with JUN, TP53, and ESR1, respectively. Cell experiments showed that the most important ingredient of HHS, quercetin, could inhibit the levels of inflammatory factors and phosphorylated c-Jun, as well as PI3K-Akt signaling pathway in LPS-induced RAW264.7 cells, which further confirmed the prediction by network pharmacology strategy and molecular docking. CONCLUSION: Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HHS against UC. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.

Insulin resistance is the major pathological characteristic of type 2 diabetes, and the elderly often develop insulin resistance. However, the deep-seated mechanisms for aging-related insulin resistance remain unclear. Here, we showed that nanosized exosomes released by bone marrow mesenchymal stem cells (BM-MSCs) of aged mice could be taken up by adipocytes, myocytes, and hepatocytes, resulting in insulin resistance both in vivo and in vitro. Using microRNA (miRNA) array assays, we found that the amount of miR-29b-3p was dramatically increased in exosomes released by BM-MSCs of aged mice. Mechanistically, SIRT1 (sirtuin 1) was identified to function as the downstream target of exosomal miR-29b-3p in regulating insulin resistance. Notably, utilizing an aptamer-mediated nanocomplex delivery system that down-regulated the level of miR-29b-3p in BM-MSCs-derived exosomes significantly ameliorated the insulin resistance of aged mice. Meanwhile, BM-MSCs-specific overexpression of miR-29b-3p induced insulin resistance in young mice. Taken together, these findings suggested that BM-MSCs-derived exosomal miR-29b-3p could modulate aging-related insulin resistance, which may serve as a potential therapeutic target for aging-associated insulin resistance.

BACKGROUND: Ferroptosis is an emerging iron-dependent programmed cell death mode characterized by lipid peroxidation and iron accumulation, closely associated with Hepatocellular Carcinoma (HCC) progression. Although the impact of Polyphyllin I (PPI), a prominent bioactive constituent derived from Paris polyphylla, on diverse malignancies has been established, the specific role and potential mechanistic pathways through which PPI modulates ferroptosis in HCC remain elusive. PURPOSE: This study aimed to elucidate the anti-cancer properties and potential mechanisms of PPI in inducing ferroptosis and triggering mitochondrial injury in HCC. METHODS: Cell viability was assessed using CCK-8 assays. EdU proliferation and colony formation assays were employed to evaluate cell proliferation. A wound-healing assay was performed to assess cell migration. Transwell assay was utilized to evaluate cell invasion. Ferroptosis was evaluated through the utilization of a FerroOrange fluorescent probe, malondialdehyde (MDA) and reduced glutathione (GSH) assay kits, DCFH-DA fluorescent probe, western blotting, and transmission electron microscopy (TEM) analysis. Molecular docking, immunofluorescence, and western blotting were employed to predict and validate the binding and interaction of PPI with Nrf2, HO-1, xCT, and GPX4. Mitochondrial structure and membrane potential changes were evaluated using JC-1 and Mito Tracker Green fluorescent probes. A nude mice xenograft model was constructed to determine the inhibitory effects and the levels of ferroptosis of PPI on HCC through hematoxylin and eosin (H&E), Prussian blue reaction, immunofluorescence staining, immunohistochemistry, and western blotting analysis, in vivo. RESULTS: accumulation, depleting GSH, and suppressing the expression of xCT and GPX4, thereby inducing ferroptosis in HCC. The induction of ferroptosis by PPI was associated with the binding of PPI to Nrf2, HO-1, and GPX4 proteins, modulating the Nrf2/HO-1/GPX4 antioxidant axis. PPI also induced mitochondrial structural damage and decreased mitochondrial membrane potential (MMP). Inhibition of ferroptosis by ferrostatin-1 (Fer-1) mitigated the mitochondrial disruption induced by PPI. In vivo, PPI inhibited Nrf2/HO-1/GPX4 axis-induced ferroptosis, impeding HCC growth similar to the effects of sorafenib. CONCLUSION: These results demonstrated that PPI intervention can suppress the proliferation, invasion, and metastasis of HCC cells by enhancing mitochondrial disruption and inducing ferroptosis via the Nrf2/HO-1/GPX4 axis. Consequently, our research advances the frontiers of pharmacodynamics and deepens our comprehension of the intricate mechanisms underpinning PPI. Furthermore, it has yielded an innovative treatment stratagem rooted in the tenets of Traditional Chinese Medicine (TCM), thereby furnishing a novel therapeutic avenue for addressing HCC.

Exosomes are small extracellular vesicles 40-160 nm in diameter that are secreted by almost all cell types. Exosomes can carry diverse cargo including RNA, DNA, lipids, proteins, and metabolites. Exosomes transfer substances and information between cells by circulating in body fluids and are thus involved in diverse physiological and pathological processes in the human body. Recent studies have closely associated exosomal microRNAs (miRNAs) with various human diseases, including diabetes mellitus (DM), which is a complex multifactorial metabolic disorder disease. Exosomal miRNAs are emerging as pivotal regulators in the progression of DM, mainly in terms of pancreatic β-cell injury and insulin resistance. Exosomal miRNAs are closely associated with DM-associated complications, such as diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic cardiomyopathy (DCM), etc. Further investigations of the mechanisms of action of exosomal miRNAs and their role in DM will be valuable for the thorough understanding of the physiopathological process of DM. Here, we have summarized recent findings regarding exosomal miRNAs associated with DM to provide a new strategy for identifying potential diagnostic biomarkers and drug targets for the early diagnosis and treatment, respectively, of DM.

Many cancer patients suffer from severe fatigue when treated with chemotherapy or radiotherapy; however, the etiology and pathogenesis of this kind of fatigue remains unknown. Fatigue is associated with cancer itself, as well as adjuvant therapies and can persist for a long time. Cancer patients present a high degree of fatigue, which dramatically affects the quality of their everyday life. There are various clinical research studies and reviews that aimed to explore the mechanisms of cancer-related fatigue (CRF). However, there are certain limitations in these studies: For example, some studies have only blood biochemical texts without histopathological examination, and there has been insufficient systemic evaluation of the dynamic changes in relevant indexes. Thus, we present this narrative review to summarize previous studies on CRF and explore promising research directions. Plenty of evidence suggests a possible association between CRF and physiological dysfunction, including skeletal muscular and mitochondrial dysfunction, peripheral immune activation and inflammation dysfunction, as well as central nervous system (CNS) disorder. Mitochondrial DNA (mtDNA), mitochondrial structure, oxidative pressure, and some active factors such as ATP play significant roles that lead to the induction of CRF. Meanwhile, several pro-inflammatory and anti-inflammatory cytokines in the peripheral system, even in the CNS, significantly contribute to the occurrence of CRF. Moreover, CNS function disorders, such as neuropeptide, neurotransmitter, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, tend to amplify the sense of fatigue in cancer patients through various signaling pathways. There have been few accurate animal models established to further explore the molecular mechanisms of CRF due to different types of cancer, adjuvant therapy schedules, living environments, and physical status. It is imperative to develop appropriate animal models that can mimic human CRF and to explore additional mechanisms using histopathological and biochemical methods. Therefore, the main purpose of this review is to analyze the possible pathogenesis of CRF and recommend future research that will clarify CRF pathogenesis and facilitate the formulation of new treatment options.

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), but the effects of secondary carbonyl lesions receive less emphasis. In inflammatory conditions, reactive oxygen species (ROS), such as superoxide anion free radical (O2 (∙-)), hydrogen peroxide (H2O2), and hydroxyl radical (HO(∙)), are produced at high levels and accumulated to cause oxidative stress (OS). In oxidative status, accumulated ROS can cause protein dysfunction and DNA damage, leading to gene mutations and cell death. Accumulated ROS could also act as chemical messengers to activate signaling pathways, such as NF-κB and p38 MAPK, to affect cell proliferation, differentiation, and apoptosis. More importantly, electrophilic carbonyl compounds produced by lipid peroxidation may function as secondary pathogenic factors, causing further protein and membrane lesions. This may in turn exaggerate oxidative stress, forming a vicious cycle. Electrophilic carbonyls could also cause DNA mutations and breaks, driving malignant progression of UC. The secondary lesions caused by carbonyl compounds may be exceptionally important in the case of host carbonyl defensive system deficit, such as aldo-keto reductase 1B10 deficiency. This review article updates the current understanding of oxidative stress and carbonyl lesions in the development and progression of UC and CAC.

Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.