NAD+ supplementation prevents STING-induced senescence in CD8+ T cells by improving mitochondrial homeostasis.

Understanding the connection between senescence phenotypes and mitochondrial dysfunction is crucial in aging and premature aging diseases. Loss of mitochondrial function leads to a decline in T cell function, which plays a significant role in this process. However, more research is required to determine if improving mitochondrial homeostasis alleviates senescence phenotypes. Our research has shown an association between NAD+ and senescent T cells through the cGAS-STING pathway, which can lead to an inflammatory phenotype. Further research is needed to fully understand the role of NAD+ in T-cell aging and how it can be utilized to improve mitochondrial homeostasis and alleviate senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in senescent T cells and tumor-bearing mice. Senescence is mediated by a stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD+ levels with nicotinamide mononucleotide (NMN) prevents senescence and SASP by promoting mitophagy. NMN treatment also suppresses senescence and neuroinflammation and improves the survival cycle of mice. Encouraging mitophagy may be a useful strategy to prevent CD8+ T cells from senescence due to mitochondrial dysfunction. Additionally, supplementing with NMN to increase NAD+ levels could enhance survival rates in mice while also reducing senescence and inflammation, and enhancing mitophagy as a potential therapeutic intervention.

Multi-Omics Reveals the Genetic and Metabolomic Architecture of Chirality Directed Stem Cell Lineage Diversification.

Chirality-directed stem-cell-fate determination involves coordinated transcriptional and metabolomics programming that is only partially understood. Here, using high-throughput transcriptional-metabolic profiling and pipeline network analysis, the molecular architecture of chirality-guided mesenchymal stem cell lineage diversification is revealed. A total of 4769 genes and 250 metabolites are identified that are significantly biased by the biomimetic chiral extracellular microenvironment (ECM). Chirality-dependent energetic metabolism analysis has revealed that glycolysis is preferred during left-handed ECM-facilitated osteogenic differentiation, whereas oxidative phosphorylation is favored during right-handed ECM-promoted adipogenic differentiation. Stereo-specificity in the global metabolite landscape is also demonstrated, in which amino acids are enriched in left-handed ECM, while ether lipids and nucleotides are enriched in right-handed ECM. Furthermore, chirality-ordered transcriptomic-metabolic regulatory networks are established, which address the role of positive feedback loops between key genes and central metabolites in driving lineage diversification. The highly integrated genotype-phenotype picture of stereochemical selectivity would provide the fundamental principle of regenerative material design.

A meta-analysis of risk factors for a Dacron-cuffed catheter related infection in hemodialysis.

OBJECTIVE: To provide theoretical basis for prevention of a Dacron-cuffed catheter related infection (CRI), the risk factors of CRI in hemodialysis patients were systematically evaluated. METHODS: Eight databases, including PubMed, Cochrane library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Wanfang Database and Chinese Scientific Journal Database (VIP), were searched to screen out literatures related to the risk factors of long-term indwelling a Dacron-cuffed CRI in hemodialysis. Meta-analysis of risk factors for a Dacron-cuffed CRI in hemodialysis and publication bias test were performed using RevMan 5.4 software. RESULTS: After screening, 13 literatures involving a Dacron-cuffed CRI were included, with a total of 625 patients, and the infection rate was 11.7%. The combined OR value and 95% confidence interval (CI) of all factors were: Combined with Diabetes (1.94, 1.51 ~ 2.50), Hb (1.82, 1.35 ~ 2.44), age (2.38, 1.06 ~ 5.34), catheter indwelling time (1.79, 1.21 ~ 2.66), serum albumin (2.26, 1.25 ~ 4.08), catheter indwelling site (3.29, 1.74 ~ 6.23) and the number of tube placement (5.40, 2.65 ~ 11.02). CONCLUSIONS: The main risk factors for a Dacron-cuffed CRI in hemodialysis were combined with diabetes, hemoglobin level, age, catheter indwelling time, serum albumin level, femoral vein catheter indwelling and catheterization times. In other words, hemodialysis patients are at higher risk of CRI if they have diabetes, or if they have a lower hemoglobin level, or if they are older, or if they have a longer duration of catheterization, or if they have a lower serum albumin level, or if they have a femoral vein catheter, or if they have more catheters.

DCABM-TCM: A Database of Constituents Absorbed into the Blood and Metabolites of Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) not only maintains the health of Asian people but also provides a great resource of active natural products for modern drug development. Herein, we developed a Database of Constituents Absorbed into the Blood and Metabolites of TCM (DCABM-TCM), the first database systematically collecting blood constituents of TCM prescriptions and herbs, including prototypes and metabolites experimentally detected in the blood, together with the corresponding detailed detection conditions through manual literature mining. The DCABM-TCM has collected 1816 blood constituents with chemical structures of 192 prescriptions and 194 herbs and integrated their related annotations, including physicochemical, absorption, distribution, metabolism, excretion, and toxicity properties, and associated targets, pathways, and diseases. Furthermore, the DCABM-TCM supported two blood constituent-based analysis functions, the network pharmacology analysis for TCM molecular mechanism elucidation, and the target/pathway/disease-based screening of candidate blood constituents, herbs, or prescriptions for TCM-based drug discovery. The DCABM-TCM is freely accessible at http://bionet.ncpsb.org.cn/dcabm-tcm/. The DCABM-TCM will contribute to the elucidation of effective constituents and molecular mechanism of TCMs and the discovery of TCM-derived drug-like compounds that are both bioactive and bioavailable.

Activating SIRT1 deacetylates NF-κB p65 to alleviate liver inflammation and fibrosis via inhibiting NLRP3 pathway in macrophages.

Background and aims: Macrophages play a critical role in the development of liver diseases. As an NAD+-dependent histone deacetylase, SIRT1 inhibits liver inflammation and fibrosis, but the mechanisms are not fully understood. Our aim was to investigate the molecular mechanism of SIRT1 in macrophages in liver inflammation and fibrosis. Methods: We employed the CCl4-induced hepatic fibrosis rat models and cultured murine macrophages RAW 264.7 in vitro to explore the anti-fibrosis effect of SIRT1. The content of cytokines was measured with ELISA. The expression of proteins associated with the NF-κB /NLPR3 signaling pathway was detected by Western blot, co-immunoprecipitation, and immunofluorescence. SIRT1, NF-κB, and NLRP3 genes were knocked down in RAW 264.7 cells by small interfering RNA (siRNA) transfection. Results: The expression of NF-κB p65, NLRP3, α-SMA, and iNOS increased in liver tissue, with high plasma LPS level and low expression of SIRT1 in CCl4-induced rat models. Overexpressing SIRT1 could inhibit these protein levels, decrease plasma LPS level, and attenuate liver injury and fibrosis. In vitro, LPS induced cytomorphology changes and up-regulated NF-κB/NLRP3 pathway, with the low expression of SIRT1 in RAW 264.7; meanwhile, the secretion of inflammatory factors increased. Nevertheless, knockdown of NF-κB or NLRP3 and activation of SIRT1 inhibited inflammation of macrophages; inhibition or knockdown of SIRT1 enhanced macrophage inflammation. Furthermore, activation of SIRT1 could inhibit LPS-treated macrophages from activating hepatic stellate cells (HSCs). Conclusions: Activating SIRT1 inhibits the inflammation in macrophages by down-regulating NLRP3 pathway through deacetylating NF-κB p65, which in turn inhibits the activation of HSCs to alleviate hepatic inflammation and fibrosis.

Research progress of natural products and their derivatives against Alzheimer's disease.

Alzheimer's disease (AD), a persistent neurological dysfunction, has an increasing prevalence with the aging of the world and seriously threatens the health of the elderly. Although there is currently no effective treatment for AD, researchers have not given up, and are committed to exploring the pathogenesis of AD and possible therapeutic drugs. Natural products have attracted considerable attention owing to their unique advantages. One molecule can interact with multiple AD-related targets, thus having the potential to be developed in a multi-target drug. In addition, they are amenable to structural modifications to increase interaction and decrease toxicity. Therefore, natural products and their derivatives that ameliorate pathological changes in AD should be intensively and extensively studied. This review mainly presents research on natural products and their derivatives for the treatment of AD.

Multi-signal aptasensor for thrombin detection based on catalytically active gold nanoparticles and fluorescent silicon quantum dots.

A multi-signal aptasensor for thrombin determination is proposed based on catalytically active gold nanoparticles (AuNPs) and fluorescent silicon quantum dots (SiQDs). Yellow 4-Nitrophenol (4-NP) could be converted to colorless 4-Aminophenol (4-AP) by catalytically active aptamer-modified AuNPs (S1-AuNPs). The SiQDs emitted strong blue fluorescence at 455 nm at the excitation wavelength of 367 nm. When thrombin was absent, S1-AuNPs could catalytically reduce yellow 4-NP to colorless 4-AP. When thrombin was added, the aptamer could be transformed into a G-quadruplex structure, which masked the surface-active catalytic sites of AuNPs and restrained the reduction of 4-NP. Thus, the fluorescence of SiQDs was greatly quenched by 4-NP through the inner filter effect (IFE), and the solution color remained yellow. As the concentration of thrombin increased, the catalytic activity of S1-AuNPs decreased. The concentration of 4-NP that was converted to 4-AP declined and the unconverted 4-NP increased. In this process, the absorption peak of 4-NP at 400 nm increased while the fluorescence emission of SiQDs at 455 nm decreased. The linear ranges of the fluorometric and colorimetric aptasensor were 0.5-30 nM and 0.3-30 nM, respectively. The limits of detection (LOD) for the two modes were 0.15 nM and 0.13 nM. Furthermore, a portable sensing platform was constructed by combining the smartphone-based device with the software ImageJ for the determination of thrombin. With the advantages of cost-effectiveness, simplicity of operation and broad applicability, this aptasensor provided a new perspective for on-site determination of thrombin in the clinical field.

Study on diverse pathological characteristics of heart failure in different stages based on proteomics.

Heart failure is a process characterized by significant disturbance of protein turnover. To elucidate the alterations in cardiac protein expression during the various phases of heart failure and to understand the nature of the processes involved, we analysed the proteome in an established heart failure model at different time points to monitor thousands of different proteins simultaneously. Here, heart failure was induced by transverse aortic constriction (TAC) in KM mice. At 2, 4 and 12 weeks after operation, protein expression profiles were determined in sham-operated (controls) and TAC mice, using label-free quantitative proteomics, leading to identification and quantification of almost 4000 proteins. The results of the KEGG pathway enrichment analysis and GO function annotation revealed critical pathways associated with the transition from cardiac hypertrophy to heart failure, such as energy pathways and matrix reorganization. Our study suggests that in the pathophysiology of heart failure, alterations of protein groups related to cardiac energy substrate metabolism and cytoskeleton remodelling could play the more dominant roles for the signalling that eventually results in contractile dysfunction and heart failure.

Clinical characteristics and misdiagnosis of spontaneous isolated superior mesenteric artery dissection.

BACKGROUND: Spontaneous isolated superior mesenteric artery (SMA) dissection (SISMAD) is a rare disease with a potentially fatal pathology. Due to the lack of specificity of clinical characteristics and laboratory tests, misdiagnosis and missed diagnosis are often reported. Therefore, the aim of this study was to investigate the clinical characteristics and misdiagnosis of SISMAD. METHODS: In a registry study from January 2013 to December 2020, 110 patients with SISMAD admitted to the First Affiliated Hospital of Wenzhou Medical University were enrolled. Descriptive methods were used to analyse clinical characteristics, laboratory data, diagnostic method or proof, misdiagnosed cases, plain computed tomography (CT) findings and dissection features. To study the relationship between dissection features and treatment modality, the selected patients were classified into the conservative group (n = 71) and the non-conservative group (n = 39). The Chi-square test and Student's t-test were used to compare the conservative and non-conservative groups. RESULTS: One hundred ten patients with SISMAD, including 100 (90.9%) males and 10 (9.1%) females, with a mean age of 52.4 ± 7.6 years, were enrolled in the study. Relevant associated comorbidities included a history of hypertension in 43 cases (39.1%), smoking in 46 cases (41.8%), and alcohol consumption in 34 cases (30.9%). One hundred four patients (94.5%) presented with abdominal pain. Abnormalities in the C-reactive protein lever, white blood cells count and D-dimer lever were the 3 most common abnormal findings. There were 32 misdiagnosis or missed diagnosis. Fourteen cases were misdiagnosed because of insufficient awareness. Twelve cases were misdiagnosed because of disease features. Twenty cases were misdiagnosed as SMA embolism. Among them, There were 15 cases of Yun type IIb SISMAD. Sixty-six patients underwent plain CT. The maximum SMA diameter was 12.1 (11.3-13.1) mm, and the maximum SMA diameter was located on the left renal vein (LRV) plane in 68.2% of cases. Dissection features observed on contrast-enhanced CT (CECT), CT angiography (CTA), or digital subtraction angiography (DSA) showed that there were 70 cases (63.6%) of Yun type IIb SISMAD, the maximum SMA diameter was 13.0 ± 2.4 mm, the location of the maximum SMA diameter was on the LRV plane in 64.5% of cases, and 7.3% of cases were complicated with intestinal obstruction, including bowel necrosis in 3.6% of cases. There were differences between the conservative group and non-conservative groups in the residual true lumen diameter or degree of true lumen stenosis and the presence of intestinal obstruction or bowel necrosis (all P < 0.05). CONCLUSION: For SISMAD, misdiagnosis and missed diagnosis were usually caused by insufficient awareness and disease features. SISMAD should be considered in the differential diagnosis of patients presenting with unexplained abdominal pain, especially males, patients in the 5th decade of life, patients with hypertension, and patients with an enlarged SMA diameter or a maximum SMA diameter located on the LRV plane on plain CT. Mesenteric CTA or CECT should be recommended for the investigation of these conditions.

The roles of primary care doctors in the COVID-19 pandemic: consistency and influencing factors of doctor's perception and actions and nominal definitions.

BACKGROUND: At the end of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic broke out. As front-line health professionals, primary care doctors play a significant role in screening SARS-CoV-2 infection and transferring suspected cases. However, the performance of primary care doctors is influenced by their knowledge and role perception. A web-based cross-sectional survey was conducted to assess the consistency and influencing factors of primary care doctor's role perception and expert advice in the guidelines (regulatory definition). METHODS: We designed the questionnaire using "Wenjuanxing" platform, distributed and collected the questionnaire through WeChat social platform, and surveyed 1758 primary care doctors from 11 community health service stations, community health service centers and primary hospitals in Zhejiang Province, China. After the questionnaire was collected, descriptive statistics were made on the characteristics of participants, and univariate analysis and multivariate analysis were used to determine the relevant factors affecting their role cognition. RESULTS: In the reporting and referral suspected cases and patients receiving treatment, most participants' cognition of their roles were consistent with the requirements of guidelines. However, 49.54% and 61.43% of participant doctors were not in line with the government guidelines for diagnosing and classifying COVID-19 and treating suspected cases, respectively. Having a middle or senior professional title and participating in front-line COVID-19 prevention and control work is beneficial to the accurate role perception of diagnosis and classification of COVID-19, the reporting and transfer of suspected cases, and the treatment of suspected cases. CONCLUSIONS: Primary care doctors' role perceptions in the COVID-19 pandemic are not always consistent with government guidelines in some aspects, such as transferring and diagnosing suspected cases. Therefore, it is essential to guide primary care doctors in performing their duties, especially those with lower professional titles.

Supramolecular Hydrogels with Tunable Chirality for Promising Biomedical Applications.

Chirality exits from molecular-level, supramolecular, and nanoscaled helical structures to the macroscopic level in biological life. Among these various levels, as the central structural motifs in living systems (e.g., double helix in DNA, α-helix, ß-sheet in proteins), supramolecular helical systems arising from the asymmetrical spatial stacking of molecular units play a crucial role in a wide diversity of biochemical reactions (e.g., gene replication, molecular recognition, ion transport, enzyme catalysis, and so on). However, the importance of supramolecular chirality and its potential biofunctions has not yet been fully explored. Thus, generating chiral assembly to transfer nature's chiral code to artificial biomaterials is expected to be utilized for developing novel functional biomaterials. As one of the most commonly used biomaterials, supramolecular hydrogels have attracted considerable research interest due to their resemblance to the structure and function of the native extracellular matrix (ECM). Therefore, the performance and manipulation of chiral assembled nanoarchitectures in supramolecular hydrogels may provide useful insights into understanding the role of supramolecular chirality in biology.In this Account, recent progress on chiral supramolecular hydrogels is presented, including how to construct and regulate assembled chiral nanostructures in hydrogels with controllable handedness and then use them to develop chiral hydrogels that could be applied in biology, biochemistry, and medicine. First, a brief introduction is provided to present the basic concept related to supramolecular chirality and the importance of supramolecular chirality in living systems. The chiral assemblies in supramolecular hydrogels are strongly driven by noncovalent interactions between molecular building blocks (such as hydrogen bonding, π-π stacking, hydrophobic, and van der Waals interactions). Consequently, the handedness of these chiral assemblies can be regulated by many extra stimuli including solvents, temperature, pH, metal ions, enzymes, and photoirradiation, which is presented in the second section. This manipulation of the chirality of nanoarchitectures in supramolecular hydrogels can result in the development of potential biofunctions. For example, specific supramolecular chirality-induced biological phenomena (such as controlled cell adhesion, proliferation, differentiation, apoptosis, protein adsorption, drug delivery, and antibacterial adhesion) are presented in detail in the third section. Finally, the outlook of open challenges and future developments of this rapidly evolving field is provided. This account that highlights the diverse chirality-dependent biological phenomena not only helps us to understand the importance of chirality in life but also provides new ideas for designing and preparing chiral materials for more bioapplications.

Integration of magnetic separation and real-time ligation chain reaction for detection of uracil-DNA glycosylase.

Uracil-DNA glycosylase (UDG) is a protein enzyme that initiates the base excision repair pathway for maintaining genome stability. Sensitive detection of UDG activity is important in the study of many biochemical processes and clinical applications. Here, a method for detecting UDG is proposed by integrating magnetic separation and real-time ligation chain reaction (LCR). First, a DNA substrate containing uracil base is designed to be conjugated to the magnetic beads. By introducing a DNA complementary to the DNA substrate, the uracil base is recognized and removed by UDG to form an apurinic/apyrimidinic (AP) site. The DNA substrate is then cut off from the AP site by endonuclease IV, releasing a single-strand DNA (ssDNA). After magnetic separation, the ssDNA is retained in the supernatant and then detected by real-time LCR. The linear range of the method is 5 × 10-4 to 5 U/mL with four orders of magnitude, and the detection limit is 2.7 × 10-4 U/mL. In the assay, ssDNA template obtained through magnetic separation can prevent other DNA from affecting the subsequent LCR amplification reaction, which provides a simple, sensitive, specific, and universal way to detect UDG and other repair enzymes. Furthermore, the real-time LCR enables the amplification reaction and fluorescence detection simultaneously, which simplifies the operation, avoids post-contamination, and widens the dynamic range. Therefore, the integration of magnetic separation and real-time LCR opens a new avenue for the detection of UDG and other DNA repair enzymes.

A fluorometric assay for α-glucosidase activity based on quaternary AgInZnS QDs.

A sensitive fluorescence strategy was constructed for the detection of α-glucosidase activity based on AgInZnS QDs. The AIZS QDs which were synthesized by hydrothermal method have a fluorescence emission wavelength of 554 nm. Ce4+ was able to oxidize p-phenylenediamine (PPD) to generate oxPPD, which can quench the fluorescence of AIZS QDs through dynamic quenching. When α-glucosidase was introduced into the system, L-ascorbic acid-2-O-α-D-glucopyranosyl (AAG) could be hydrolyzed to form ascorbic acid (AA), which can reduce Ce4+ and prevent the oxidation of PPD. Thus, the dynamic quenching process was blocked accompanying with the fluorescence recovery of AIZS QDs. The developed detection system for α-glucosidase displayed a good linear relationship between 0.01 and 0.16 U·mL-1 with a detection limit of 0.0073 U·mL-1. The sensing platform with high feasibility and anti-interference is a competitive alternative applied to α-glucosidase-related diagnostics.

Visible Enantiomer Discrimination via Diphenylalanine-Based Chiral Supramolecular Self-Assembly on Multiple Platforms.

The development of enantioselective recognition is of great significance in medical science and pharmaceutical industry, which associates with the molecular recognition phenomenon widely observed in biological systems. In particular, the facile and straight achievement of visual enantioselective recognition has been drawing increasing consideration, but it is still a challenge. Herein, a heterochiral diphenylalanine-based gelator (LFDF) is synthesized, presenting left-handed nanofibers during self-assembly in ethanol, which accomplishes the phenylalaninol enantiomer recognition on multiple platforms. When adding l- or d-phenylalaninol into LFDF supramolecular solution followed by ultrasonic treatment, precipitate and gel are formed, respectively. Meanwhile, LFDF supramolecular gel completely collapses in a minute after dropping l-phenylalaninol, while the gel almost remains when d-type is employed. Moreover, a fluorescent supramolecular xerogel (ThT-LFDF) is fabricated by combining the LFDF gelator with thioflavine T (ThT), which could detect l-phenylalaninol accompanying with fluorescence quenching while d-type with barely decreasing. And the ThT-LFDF xerogel system shows a good sensitivity (reaches to ppm) for the detection of l-phenylalaninol. It is found that the chirality of the assembled nanofibers, as well as amino and carboxyl of phenylalaninol, plays a critical role on the discrimination process. The multiple and visible enantioselective recognition of phenylalaninol through chiral supramolecular self-assemblies shows potential applications in the fields of medical science and pharmaceutical industry.

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF-α-induced injury via inhibiting NF-κB and JNK signals.

The traditional Chinese herb Lonicerae Japonicae Flos has shown significant clinical benefits in the treatment of heart failure, but the mechanism remains unclear. As the main active ingredient found in the plasma after oral administration of Lonicerae Japonicae Flos, chlorogenic acid (CGA) has been reported to possess anti-inflammatory, anti-oxidant and anti-apoptosis function. We firstly confirmed the cardioprotective effects of CGA in transverse aortic constriction (TAC)-induced heart failure mouse model, through mitigating the TNF-α-induced toxicity. We further used TNF-α-induced cardiac injury in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to elucidate the underlying mechanisms. CGA pre-treatment could reverse TNF-α-induced cellular injuries, including improved cell viability, increased mitochondrial membrane potential and inhibited cardiomyocytes apoptosis. We then examined the NF-κB/p65 and major mitogen-activated protein kinases (MAPKs) signalling pathways involved in TNF-α-induced apoptosis of hiPSC-CMs. Importantly, CGA can directly inhibit NF-κB signal by suppressing the phosphorylation of NF-κB/p65. As for the MAPKs, CGA suppressed the activity of only c-Jun N-terminal kinase (JNK), but enhanced extracellular signal-regulated kinase1/2 (ERK1/2) and had no effect on p38. In summary, our study revealed that CGA has profound cardioprotective effects through inhibiting the activation of NF-κB and JNK pathway, providing a novel therapeutic alternative for prevention and treatment of heart failure.

iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.

BACKGROUND: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. METHODS: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. RESULTS: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. CONCLUSIONS: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

A label-free fluorescent sensor based on silicon quantum dots-MnO2 nanosheets for the detection of α-glucosidase and its inhibitor.

α-Glucosidase and its inhibitors play a key role in diagnosis and treatment of diabetes. In the present work, we established a facile, sensitive and selective fluorescence method based on silicon quantum dots (SiQDs) and MnO2 nanosheets for the determination of α-glucosidase and one of its inhibitors acarbose. The fluorescence of SiQDs was greatly quenched by MnO2 nanosheets due to the inner filter effect. α-Glucosidase could easily catalyze the hydrolysis of l-ascorbic acid-2-O-α-d-glucopyranosyl (AAG) to produce ascorbic acid (AA), which could reduce MnO2 nanosheets to Mn2+, resulting in dramatic recovery of the fluorescence of SiQDs. The proposed sensing platform could provide a good linear relationship between the fluorescence intensity of SiQDs and the concentration of α-glucosidase in the range of 0.02-2.5 U mL-1 with a detection limit of 0.007 U mL-1. In addition, the sensing platform could be used for α-glucosidase inhibition. Acarbose was one of the most common and typical inhibitors, and this sensing platform can be utilized to detect acarbose in the range of 1-1000 µM. The developed fluorescence method was successfully validated for the determination of α-glucosidase in human serum samples.

Co-Assembled Supramolecular Nanostructure of Platinum(II) Complex through Helical Ribbon to Helical Tubes with Helical Inversion.

We demonstrated the morphology transformation of co-assemblies based on terpyridine-based ligands (1R and 1S) possessing R- or S-alanine analogues and their platinum(II) complex (2R-Pt and 2S-Pt). The right-handed helical ribbon of the co-assembly formed with 0.5 equivalents of 2R-Pt to 1R was converted into the left-handed helical ribbon with 0.6 equivalents of 2R-Pt. The left-handed helical ribbon structure of the co-assembly became a tubular structure in the presence of 0.8-1.0 equivalents of 2R-Pt. The morphology transformation via helical inversion at the supramolecular level was due to an orientation change of the amide groups caused by non-covalent Pt⋅⋅⋅Pt interactions between the terpyridine of 2R-Pt and that of 2R-Pt. This study provides insights into controlling the morphology of the transformation of helical ribbons into tubular structures through helicity inversion in co-assembled supramolecular nanostructures based on platinum(II) complexes.

Anticancer activity of cucurbitacin-A in ovarian cancer cell line SKOV3 involves cell cycle arrest, apoptosis and inhibition of mTOR/PI3K/Akt signaling pathway.

PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation. DAPI staining using fluorescence microscopy was used to evaluate the effects of the compound on apoptosis. Flow cytometry was used to study the effects on cell cycle phase distribution, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) loss. RESULTS: Cucurbitacin-A exhibited an IC50 of 40 µM against ovarian SKVO3 cancer cell line. It also caused DNA damage in SKVO3 cells and also prompted ROS mediated alterations in MMP. On the other hand, it triggered cell cycle arrest of SKVO3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that cucurbitacin-A considerably inhibited the expression levels of key proteins of PI3K/Akt/ mTOR signaling pathway. CONCLUSION: The study showed that cucurbitacin-A is a potent agent against ovarian cancer cells, can be considered for further in vivo research and can also be developed as a possible lead molecule.

The Cooperative Effect of Both Molecular and Supramolecular Chirality on Cell Adhesion.

Although helical nanofibrous structures have great influence on cell adhesion, the role played by chiral molecules in these structures on cells behavior has usually been ignored. The chirality of helical nanofibers is inverted by the odd-even effect of methylene units from homochiral l-phenylalanine derivative during assembly. An increase in cell adhesion on left-handed nanofibers and weak influence of cell behaviors on right-handed nanofibers are observed, even though both were derived from l-phenylalanine derivatives. Weak and negative influences on cell behavior was also observed for left- and right-handed nanofibers derived from d-phenylalanine, respectively. The effect on cell adhesion of single chiral molecules and helical nanofibers may be mutually offset.