Mechanisms of a novel regulatory light chain-dependent cardiac myosin inhibitor.

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart characterized by thickening of the left ventricle (LV), hypercontractility, and impaired relaxation. HCM is caused primarily by heritable mutations in sarcomeric proteins, such as ß myosin heavy chain. Until recently, medications in clinical use for HCM did not directly target the underlying contractile changes in the sarcomere. Here, we investigate a novel small molecule, RLC-1, identified in a bovine cardiac myofibril high-throughput screen. RLC-1 is highly dependent on the presence of a regulatory light chain to bind to cardiac myosin and modulate its ATPase activity. In demembranated rat LV trabeculae, RLC-1 decreased maximal Ca2+-activated force and Ca2+ sensitivity of force, while it increased the submaximal rate constant for tension redevelopment. In myofibrils isolated from rat LV, both maximal and submaximal Ca2+-activated force are reduced by nearly 50%. Additionally, the fast and slow phases of relaxation were approximately twice as fast as DMSO controls, and the duration of the slow phase was shorter. Structurally, x-ray diffraction studies showed that RLC-1 moved myosin heads away from the thick filament backbone and decreased the order of myosin heads, which is different from other myosin inhibitors. In intact trabeculae and isolated cardiomyocytes, RLC-1 treatment resulted in decreased peak twitch magnitude and faster activation and relaxation kinetics. In conclusion, RLC-1 accelerated kinetics and decreased force production in the demembranated tissue, intact tissue, and intact whole cells, resulting in a smaller cardiac twitch, which could improve the underlying contractile changes associated with HCM.

Gastrodia elata polysaccharide alleviates Parkinson's disease via inhibiting apoptotic and inflammatory signaling pathways and modulating the gut microbiota.

Parkinson's disease (PD) is a common, chronic, and progressive degenerative disease of the central nervous system for which there is no effective treatment. Gastrodia elata is a well-known food and medicine homologous resource with neuroprotective potential. Gastrodia elata polysaccharide (GEP), which is a highly active and safe component in Gastrodia elata, is an important ingredient in the development of functional products. In this study, GEP was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice over 3 weeks to investigate its neuroprotective effects. The results showed that GEP significantly alleviated the motor dysfunction of PD mice, inhibited the accumulation of α-synuclein, and reduced the loss of dopaminergic neurons in the brain. Moreover, GEP increased the Bcl-2/Bax ratio and decreased the cleaved-caspase-3 level, suggesting that GEP may ameliorate PD by preventing MPTP-induced mitochondrial apoptosis. GEP also significantly inhibited the increase of GFAP and decreased the levels of TNF-α, IL-1ß, and IL-6 in the brain of PD mice, which may be the result of the inhibition of neuroinflammation by the inactivation of the TLR4/NF-κB pathway. Furthermore, the neuroprotective effects of GEP involve the gut-brain axis, as it has been shown that GEP regulated the dysbiosis of PD-related gut microbiota such as Akkermansia, Lactobacillus, Bacteroides, Prevotella, and Faecalibacterium, increased the content of microbial metabolites SCFAs in the colon and increased the level of occludin that repairs the intestinal barrier of PD mice. In conclusion, this study is expected to provide a theoretical basis for the development and application of functional products with GEP from the perspective of neuroprotective effects.

An alkaloid from Menispermum dauricum, dauricine mediates Ca2+ influx and inhibits NF-κB pathway to protect chondrocytes from IL-1ß-induced inflammation and catabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Dauricine (DA) is a natural plant-derived alkaloid extracted from Menispermum dauricum. Menispermum dauricum has been used in traditional Chinese medicine as a classic remedy for rheumatoid arthropathy and is believed to be effective in alleviating swelling and pain in the limbs. AIM OF THE STUDY: Osteoarthritis (OA) is a classic degenerative disease involving chondrocyte death, and there is still a lack of effective therapeutic agents that can reverse the progression of the disease. Here we explored the therapeutic effects of DA against OA and further explored the mechanism. MATERIALS AND METHODS: The effect of DA on cell viability was assessed by CCK-8. IL-1ß-treated mouse chondrocytes were used as an in vitro model of OA, and apoptosis was detected by flow cytometry. QRT-PCR, western blotting, cell staining, and immunofluorescence were used to detect relevant inflammatory factors and cartilage-specific expression. RNA sequencing was used to identify pertinent signaling pathways. The therapeutic effect of DA was verified by micro-CT, histological analysis and immunohistochemical analysis in a mouse OA model. RESULTS: DA demonstrated a high safety profile on chondrocytes, significantly reversing the inflammatory response induced by IL-1ß, and promoting factors associated with cartilage regeneration. Moreover, DA exhibited a significant protective effect on the knee joints of mice undergoing ACLT-DMM, effectively preventing cartilage degeneration and subchondral bone tissue destruction. These positive therapeutic effects were achieved through the modulation of the NF-κB pathway and the Ca2+ signaling pathway by DA. CONCLUSION: Being derived from a traditional herb, DA exhibits remarkable therapeutic potential and safety in OA treatment, presenting a promising option for patients dealing with osteoarthritis.

Spatial proteomics landscape and immune signature analysis of renal sample of lupus nephritis based on laser-captured microsection.

OBJECTIVE: We aimed to reveal a spatial proteomic and immune signature of kidney function regions in lupus nephritis (LN). MATERIAL AND METHODS: The laser capture microdissection (LCM) was used to isolate the glomerulus, tubules, and interstitial of the kidney from paraffin samples. The data-independent acquisition (DIA) method was used to collect proteomics data. The bioinformatic analysis was performed. RESULTS: A total of 49,658 peptides and 4056 proteins were quantitated. Our results first showed that a high proportion of activated NK cells, naive B cells, and neutrophils in the glomerulus, activated NK cells in interstitial, and resting NK cells were accumulated in tubules in LN. The immune-related function analysis of differential expression proteins in different regions indicated that the glomerulus and interstitial were major sites of immune disturbance and regulation connected with immune response activation. Furthermore, we identified 7, 8, and 9 hub genes in LN's glomerulus, renal interstitial, and tubules. These hub genes were significantly correlated with the infiltration of immune cell subsets. We screened out ALB, CTSB, LCN2, A2M, CDC42, VIM, LTF, and CD14, which show higher performance as candidate biomarkers after correlation analysis with clinical indexes. The function within three regions of the kidney was analyzed. The differential expression proteins (DEGs) between interstitial and glomerulus were significantly enriched in the immune-related biological processes, and myeloid leukocyte-mediated immunity and cellular response to hormone stimulus. The DEGs between tubules and glomerulus were significantly enriched in cell activation and leukocyte-mediated immunity. While the DEGs between tubules and interstitial were enriched in response to lipid, antigen processing, and presentation of peptide antigen response to oxygen-containing compound, the results indicated a different function within kidney regions. CONCLUSIONS: Collectively, we revealed spatial proteomics and immune signature of LN kidney regions by combined using LCM and DIA.

Relationship between nightmare distress and depressive symptoms in Chinese emergency department nurses: A cross-sectional study.

BACKGROUND: Most of the recent research on nightmare distress and depressive symptoms has focused on adolescents and students, with less research on the nurse population. Emergency department nurses are at high risk for nightmare distress and depressive symptoms, but no studies have been conducted to explore the relationship between the two; thus, further investigation is needed. AIM: To understand the relationship between nightmare distress and depressive symptoms among emergency department nurses in China. METHODS: A convenience sampling method was used to select 280 emergency department nurses from nine provinces, including Jiangxi, Sichuan, Jiangsu, and Shanxi Provinces. The Chinese version of the Nightmare Distress Questionnaire and the Center for Epidemiological Studies Depression Scale (CES-D) were administered. RESULTS: Emergency department nurses' nightmare distress scores were positively associated with depressive symptom scores (r = 0.732), depressed affect (r = 0.727), somatic symptoms (r = 0.737), and interpersonal difficulty (r = 0.647). Further multiple linear regression analyses showed that education level, work pressure, self-reported health, and CES-D scores were factors that influenced nightmare distress among Chinese emergency department nurses (P < 0.05). CONCLUSION: Nightmare distress is closely associated with depressive symptoms in Chinese emergency department nurses, and early intervention is recommended for professionals with this type of sleep disorder to reduce the occurrence of depressive symptoms.

Clinical findings, diagnosis and therapy of patent ductus venosus in children: a case series.

Background: Patent ductus venosus (PDV) is a rare form of congenital portosystemic shunt. Because of the diversity of clinical symptoms and insufficient knowledge of this condition, clinicians often fail to perform targeted examinations, resulting in missed diagnoses and misdiagnoses. This study summarized the clinical and radiological findings, as well as surgical methods, of PDV with the aim of improving early diagnosis and guiding treatment. Methods: Clinical, laboratory, and radiologic data of patients with PDV were analyzed retrospectively. In all, 9 patients with PDV were included in the study (7 male, 2 female; median age 1.6 years, age range 16 days to 16.5 years). Results: Data for all 9 patients with PDV were reviewed. The most common initial clinical presentations were jaundice and respiratory symptoms. Laboratory data revealed hypoxemia in 5 patients, hyperammonemia in 2, hyperbilirubinemia in 7, abnormal coagulation function in 6, abnormal myocardial enzymes in 4, hepatic dysfunction in 8, and renal dysfunction in 3. The direct imaging sign of PDV was a vascular structure connecting the left branch of the portal vein (LPV) to the inferior vena cava. Secondary imaging findings observed in all 9 patients were dilated right heart, pulmonary artery, and LPV, and an atrophic right branch of the portal vein. The main portal vein was dilated in 8 patients and shrunk in 1. Moreover, 8 patients had enlarged livers, and 3 presented with hypoperfusion in the right lobe of the liver. The spleen was enlarged in 8 patients but shrunk in 1. Renal imaging was abnormal in 2 patients. Hepatic encephalopathy was found in 4 patients; 7 patients had PDV combined with other malformations, with congenital heart disease and vascular abnormalities being the most common; 3 patients successfully underwent surgical ligation of PDV. Conclusions: PDV can lead to multisystem damage. Secondary radiological signs of PDV play an important role in early diagnosis and preoperative evaluation. Complications and coexisting malformations were common and should not be missed during preoperative evaluation. Early surgical closure for PDV is recommended.

Cranial fasciitis in children: clinicoradiology features and management.

BACKGROUND: Cranial fasciitis (CF) is a rare benign fibroproliferative lesion of the skull. To date, the summarized radiologic characteristics and the subtype of the disease have not been reported. our purpose was to summarize the characteristic clinicoradiology features and management of CF and to improve the knowledge of radiologists and clinicians. METHODS: We searched our institution's database and retrieved the clinical and radiologic data of CF patients confirmed by histopathological examination. The clinicoradiology features and management of CF were analysed retrospectively. RESULTS: A total of 14 CF patients were included. A total of 85.7% of the patients presented with a painless, firm, nonmobile and single mass. Tenderness and multiple masses were found in 14.3% of the patients. The mass was clearly increased in 2 patients and gradually increased in 5 patients in the short term. We divided these patients into three types based on the CT characteristics. The characteristic features of type I (9 patients) presented as an expansive and osteolytic bone destruction with a soft tissue mass. Type II (2 patients) presented as a scalp mass with mild erosion of the outer skull plate. Type III (3 patients) presented as a scalp mass without skull destruction. All patients underwent surgical resection. For type I patients, craniectomy and cranioplasty were performed. For type II patients, complete excision of the scalp mass with local skull curettage was performed. For type III patients, complete excision of the scalp mass was performed. There were no cases of recurrence after follow-up. CONCLUSIONS: CF usually presents as a painless, firm, nonmobile and single mass with a clear boundary. There are generally three types of MSCT findings: bone destruction with a soft tissue mass, a scalp mass with erosion of the skull and a scalp mass. Different management strategies should be utilized for the various types of CF.

Echocardiographic evaluation of total anomalous pulmonary venous connection: Comparison of obstructed and unobstructed type.

ABSTRACT: This study aims to compare the differences between obstructed and unobstructed total anomalous pulmonary venous connection (TAPVC) using echocardiography, and to evaluate the clinical and echocardiographic parameters associated with pulmonary venous obstruction (PVO).We conducted a retrospective study of 70 patients with TAPVC between 2014 and 2019. The morphologic and hemodynamic echocardiographic parameters of patients were observed and measured, and the parameters between obstructed and unobstructed TAPVC were compared. The clinical and echocardiographic parameter differences between the two groups were used for ROC curve analysis.Obstructed TAPVC was found in 30 (42.9%) of 70 patients. Between obstructed and unobstructed TAPVC, there were significant differences in atrial septal defect size, pulmonary artery maximum velocity (PA Vmax ), peak E velocity of mitral valve, left ventricular fractional shortening, left ventricular ejection fraction, stroke volume and the incidence of patent ductus arteriosus, but there was no significant difference in birth weight. The first diagnosis age of obstructed TAPVC was earlier than unobstructed type. The ROC curve analysis for the first diagnosis age showed the sensitivity and specificity were 76.7%, 80% respectively. The ROC curve analysis for the PA Vmax showed the sensitivity and specificity were 88.5%, 67.6% respectively.Patients with TAPVC had a high incidence of PVO. The presence of PVO can affect the size of atrial septal defect and the closure of the ductus arteriosus, cause significant changes in PA Vmax, peak E velocity of mitral valve, left ventricular fractional shortening, left ventricular ejection fraction, stroke volume, lead to earlier symptoms and earlier first diagnosis age. The first diagnosis age and PA Vmax were excellent values since they associated with PVO.

Differential Expression Study of Lysine Crotonylation and Proteome for Chronic Obstructive Pulmonary Disease Combined with Type II Respiratory Failure.

Introduction: The modification of lysine crotonylation (Kcr) is another biological function of histone in addition to modification of lysine acetylation (Kac), which may play a specific regulatory role in diseases. Objectives: This study compared the expression levels of Kcr and proteome between patients with chronic obstructive pulmonary disease (COPD) combined with type II respiratory failure (RF) to study the relationship between Kcr, proteome, and COPD. Methods: We tested the Kcr and proteome of COPD combined with type II RF and normal control (NC) using croton acylation enrichment technology and liquid chromatography tandem mass spectrometry (LC-MS/MS) with high resolution. Results: We found that 32 sites of 23 proteins were upregulated and 914 sites of 295 proteins were downregulated. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG), protein domain, and Gene Ontology (GO) analysis on crotonylated protein. In proteomics research, we found that 190 proteins were upregulated and 151 proteins were downregulated. Among them, 90 proteins were both modified by differentially expressed crotonylation sites and differentially expressed in COPD combined with type II RF and NC. Conclusion: Differentially expressed crotonylation sites may be involved in the development of COPD combined with type II RF. 90 proteins modified by crotonylation and differentially expressed in COPD combined with type II RF can be used as markers for the study of the molecular pathogenesis of COPD combined with type II RF.

Zinc(II) Complexes Derived from Schiff Bases: Syntheses, Structures, and Biological Activity.

Three new zinc(II) complexes, [Zn2I2(L1)2] (1), [Zn(HL2)2(NCS)2] (2), and [ZnIL3] (3), where L1 is the anionic form of 2-[(6-methylpyridin-2-ylimino)methyl]phenol (HL1), HL2 is the zwitterionic form of 2-(cyclopropyliminomethyl)-5-fluorophenol (HL2), and L3 is the anionic form of 5-bromo-2-[(3-morpholin-4-ylpropylimino)methyl]phenol (HL3), have been prepared and characterized by elemental analyses, IR, UV and NMR spectra, and single crystal X-ray crystallographic determination. Complex 1 is a dinuclear zinc complex, and complexes 2 and 3 are mononuclear zinc complexes. The Zn atoms in the complexes are in tetrahedral coordination. The effect of the complexes on the antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans were evaluated.

Nanocarrier-based activation of necroptotic cell death potentiates cancer immunotherapy.

Even though immunological checkpoint inhibitors have demonstrated a potent anti-tumor effect in clinical practice, the low immunogenicity of the majority of tumors still results in a lower response rate and a higher resistance to mono-immunotherapy. Recent studies revealed that immunogenic cell death (ICD) augments T cell responses against some cancers, thus indicating that this combination therapy may further improve the anti-tumor immunity produced by anti-PD-1/PD-L1. Herein a robust synergetic strategy is reported to integrate the activation of necroptotic cell death and the subsequent using of immune checkpoint inhibitors. Liposomes have good biocompatibility and are widely used as drug carriers. Using liposomes as TNF-α-loaded nanoplatforms achieves in vivo tumor targeting and long-term retention in the tumor microenvironment. Tumor cells treated with TNF-α-loaded liposomes exhibited the hallmarks of ICD including the release of high mobility group box 1 (HMGB1) and lactate dehydrogenase (LDH). Additionally, the tumor cell necrosis caused by TNF-α induces the in situ release of tumor-specific antigens, thus increasing the dendritic cell (DC) activation and T cell infiltration when combined with the checkpoint blockade therapy. Collectively, significant tumor reduction is accomplishable by this synergetic strategy, in which TNF-α-loaded liposomes convert the tumor cell into an endogenous vaccine and improve the anti-tumor immunity of anti-PD-1/PD-L1.

Synthetic thick filaments: A new avenue for better understanding the myosin super-relaxed state in healthy, diseased, and mavacamten-treated cardiac systems.

A hallmark feature of myosin-II is that it can spontaneously self-assemble into bipolar synthetic thick filaments (STFs) in low-ionic-strength buffers, thereby serving as a reconstituted in vitro model for muscle thick filaments. Although these STFs have been extensively used for structural characterization, their functional evaluation has been limited. In this report, we show that myosins in STFs mirror the more electrostatic and cooperative interactions that underlie the energy-sparing super-relaxed (SRX) state, which are not seen using shorter myosin subfragments, heavy meromyosin (HMM) and myosin subfragment 1 (S1). Using these STFs, we show several pathophysiological insults in hypertrophic cardiomyopathy, including the R403Q myosin mutation, phosphorylation of myosin light chains, and an increased ADP:ATP ratio, destabilize the SRX population. Furthermore, WT myosin containing STFs, but not S1, HMM, or STFs-containing R403Q myosin, recapitulated the ADP-induced destabilization of the SRX state. Studies involving a clinical-stage small-molecule inhibitor, mavacamten, showed that it is more effective in not only increasing myosin SRX population in STFs than in S1 or HMM but also in increasing myosin SRX population equally well in STFs made of healthy and disease-causing R403Q myosin. Importantly, we also found that pathophysiological perturbations such as elevated ADP concentration weakens mavacamten's ability to increase the myosin SRX population, suggesting that mavacamten-bound myosin heads are not permanently protected in the SRX state but can be recruited into action. These findings collectively emphasize that STFs serve as a valuable tool to provide novel insights into the myosin SRX state in healthy, diseased, and therapeutic conditions.

Clinical and radiologic features of the first cured Coronavirus disease 2019 (COVID-19) patient in Guangzhou City, China.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.

Impact of Red Yeast Rice on Metabolic Diseases: A Review of Possible Mechanisms of Action.

Metabolic diseases constitute a major public health burden and are linked with high morbidity and mortality. They comprise atherosclerosis dyslipidemia, diabetes, hypertension, and obesity. However, there is no single drug that can simultaneously treat multiple diseases with complex underlying mechanisms. Therefore, it is necessary to identify a class of adjuvant drugs that block the development of metabolic diseases from a preventive perspective. Red yeast rice is a food fermentation product widely used to promote blood circulation and remove blood stasis. Modern pharmacology has shown that red yeast rice exerts potential protective effects on the liver, pancreas, blood vessels, and intestines. Therefore, this study was carried out to analyze and summarize the effect of red yeast rice on several metabolic diseases and the mechanisms of action involved. It was found that red yeast rice may be beneficial in the prevention and treatment of metabolic diseases.

Proteomic analysis of differentially expressed proteins in the serum of patients with acute renal allograft rejection using iTRAQ labelling technology.

Transplantation is currently the best treatment for patients with end­stage renal disease. However, acute rejection (AR) is the major source of failure in renal transplantation. The current best practice for the diagnosis of AR involves renal biopsy, but it is invasive, time­consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve allograft function. The present study applied isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry to analyze serum protein expression in patients with AR and healthy controls. Overall, 1,399 proteins were identified. Using a cut­off of Q<0.05 and a fold change of >1.2 for the variation in expression, 109 proteins were identified to be differentially expressed between the AR and control groups, 72 of which were upregulated and 37 were downregulated. Several proteins, including properdin, keratin 1, lipoprotein(a) and vitamin D­binding protein, may have roles in the pathogenesis of AR. The present study focused on iTRAQ­based proteomic profiling of serum samples in AR. Insight from the present study may help advance the understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.

Dynamic Metabolomics Study of the Bile Acid Pathway During Perioperative Primary Hepatic Carcinoma Following Liver Transplantation.

BACKGROUND There are many situations of abnormal metabolism influencing liver graft function. This study aims to provide data for the development of liver function recovery after liver transplantation by dynamically analyzing metabolites of bile acids pathway in serum. MATERIAL AND METHODS A comprehensive metabolomics profiling of serum of 9 liver transplantation patients before transplantation, on the 1st, 3rd, and 7th days after liver transplantation, and healthy individuals were performed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Multivariate data and dynamic analysis were used to search for biomarkers between the metabolomics profiles present in perioperative liver transplantation and normal controls. RESULTS Thirty-three differential endogenous metabolites were screened by the threshold of variable importance in the projection (VIP) from an orthogonal partial least square discriminant analysis (OPLS-DA) greater than 1.0, q-value <0.05, and fold change (FC) ≤0.8 or ≥1.2 between the preoperative group and the normal controls in negative mode. The metabolite intensities of taurocholic acid, taurochenodeoxycholic acid, chenodeoxycholic acid glycine conjugate, and glycocholic acid pre-transplantation were significantly higher than those of normal controls. The average metabolite intensities of taurocholic acid and taurochenodesoxycholic acid on the first day after liver transplantation were lower than those observed pre-transplantation. The average metabolite intensities on day 3 after liver transplantation showed a sudden increase and then decreased after 7 postoperative days. The average metabolite intensities of glycocholic acid and chenodeoxycholic acid glycine conjugate showed an increasing trend on the 1st, 3rd, and 7th days after liver transplantation. CONCLUSIONS Use of taurocholic acid and taurochenodeoxycholic acid-related bile secretion, liver regeneration, and de novo bile acid synthesis may help clinical evaluation and provide data for the development of liver function recovery after liver transplantation.

Modulation of Apoptosis by Plant Polysaccharides for Exerting Anti-Cancer Effects: A Review.

Cancer has become a significant public health problem with high disease burden and mortality. At present, radiotherapy and chemotherapy are the main means of treating cancer, but they have shown serious safety problems. The severity of this problem has caused further attention and research on effective and safe cancer treatment methods. Polysaccharides are natural products with anti-cancer activity that are widely present in a lot of plants, and many studies have found that inducing apoptosis of cancer cells is one of their important mechanisms. Therefore, this article reviews the various ways in which plant polysaccharides promote apoptosis of cancer cells. The major apoptotic pathways involved include the mitochondrial pathway, the death receptor pathway, and their upstream signal transduction such as MAPK pathway, PI3K/AKT pathway, and NF-κB pathway. Moreover, the paper has also been focused on the absorption and toxicity of plant polysaccharides with reference to extant literature, making the research more scientific and comprehensive. It is hoped that this review could provide some directions for the future development of plant polysaccharides as anticancer drugs in pharmacological experiments and clinical researches.

Differential expression profile study and gene function analysis of maternal foetal-derived circRNA for screening for Down's syndrome.

Recent studies have shown that circular RNAs (circRNAs) exhibit differential expression in certain diseases. However, to the best of our knowledge, maternal fetal-derived circRNAs and mRNAs associated with Down's syndrome (DS) have not yet been investigated. A total of 12 umbilical cord blood samples were collected from pregnant women, including six women carrying fetuses with DS (diagnosed by G-banding karyotype analysis), and six women carrying fetuses without DS. In addition, 12 peripheral blood samples were obtained from children, including six children with DS and six children without DS. Gene chip technology was used to screen for differentially expressed circRNAs and mRNAs in the cord blood samples, and were subsequently verified by reverse transcription-quantitative polymerase chain reaction in peripheral blood from the children to identify potential biomarkers. Furthermore, circRNA/microRNA (miRNA) interactions were predicted using Arraystar miRNA target prediction software. There was a significant difference in the expression of hsa_circRNA_103127, hsa_circRNA_103112 and hsa_circRNA_104907 between cord blood obtained from the women carrying fetuses with and without DS, and between peripheral blood obtained from children with and without DS (P<0.01). As hsa_circRNA_103112 exhibited significant differences in expression between cord blood obtained from the women carrying fetuses with and without DS and between peripheral blood obtained from children with and without DS, its corresponding gene, ubiquitin specific peptidase 25, may be involved in the pathogenesis of the condition. These results suggested that hsa_circRNA_103112 may be upregulated in individuals with DS, resulting in an expression imbalance of diploid genes through interactions among circRNA, miRNA and mRNA. Therefore, the level of hsa_circRNA_103112 in the peripheral blood of a pregnant woman may serve as potential biomarker of fetal DS during non-invasive prenatal screening.

Quercetin pretreatment enhances the radiosensitivity of colon cancer cells by targeting Notch-1 pathway.

Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 µM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.

Syntheses, Crystal Structures, Antimicrobial Activity and Thermal Behavior of Copper(II) Complexes Derived from 1-Naphthylacetic Acid and Diamines.

Two copper(II) complexes, [CuL2(EA)] (1) and [Cu2L4(PA)2]·2H2O (2·2H2O), where L is 1-naphthylacetate, EA is N,N-diethylethane-1,2-diamine, PA is propane-1,3-diamine, have been prepared and characterized. Structures of the complexes have been characterized by single-cyrstal X-ray diffraction. Complex 1 is a mononuclear copper(II) compound, with the Cu atoms coordinated in square planar geometry. Complex 2·2H2O is a centrosymmetric dinuclear copper(II) compound, with the Cu atoms coordinated in square pyramidal geometry. Single crystals of the complexes are stabilized by hydrogen bonds. The effects of the compounds on the antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, as well as thermal behavior of the complexes were studied.