Development of a new paradigm model for deciphering action mechanism of Danhong injection using a combination of isothermal shift assay and database interrogation.

Background: Identification of active components of traditional Chinese Medicine (TCM) and their respective targets is important for understanding the mechanisms underlying TCM efficacy. However, there are still no effective technical methods to achieve this.

Methods: Herein, we have established a method for rapidly identifying targets of a specific TCM and interrogating the targets with their corresponding active components based on Isothermal Shift Assay (iTSA) and database interrogation.

Flavonoid 4,4'-dimethoxychalcone selectively eliminates senescent cells via activating ferritinophagy.

Flavonoids are bioactive natural polyphenolic compounds with health benefits, including anti-tumor, anti-inflammatory and anti-aging effects. Our previous studies revealed that a flavonoid 4,4'-dimethoxychalcone (DMC) induced ferroptosis via inhibiting ferrochelatase (FECH). However, the effect of DMC on cellular senescence is unknown.

Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistance.

Artemisinins (ART) are critical anti-malarials and despite their use in combination therapy, ART-resistant Plasmodium falciparum is spreading globally. To counter ART resistance, we designed artezomibs (ATZs), molecules that link an ART with a proteasome inhibitor (PI) via a non-labile amide bond and hijack parasite's own ubiquitin-proteasome system to create novel anti-malarials in situ. Upon activation of the ART moiety, ATZs covalently attach to and damage multiple parasite proteins, marking them for proteasomal degradation.

Comprehensive maturity of nuclear pore complexes regulates zygotic genome activation.

Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis.

Nicotinamide -Methyltransferase Remodeled Cell Metabolism and Aggravated Proinflammatory Responses by Activating STAT3/IL1β/PGE Pathway.

Nicotinamide -methyltransferase (NNMT) is a cytosolic methyltransferase, catalyzing -methylation of nicotinamide (NAM) to form 1-methylnicotinamide (1-MNAM), in which S-adenosyl-l-methionine (SAM) is the methyl donor. It has been well documented that NNMT is elevated in multiple cancers and promotes tumor aggressiveness. In the present study, we investigated the effects of NNMT overexpression on cellular metabolism and proinflammatory responses.

Nicotinamide Mononucleotide Administration Restores Redox Homeostasis via the Sirt3-Nrf2 Axis and Protects Aged Mice from Oxidative Stress-Induced Liver Injury.

Altered adaptive homeostasis contributes to aging and lifespan regulation. In the present study, to characterize the mechanism of aging in mouse liver, we performed quantitative proteomics and found that the most upregulated proteins were related to the oxidation-reduction process. Further analysis revealed that malondialdehyde (MDA) and protein carbonyl (PCO) levels were increased, while nuclear Nrf2 and downstream genes were significantly increased, indicating that oxidative stress induced Nrf2 activation in aged mouse liver.

Flavonoid 4,4'-dimethoxychalcone induced ferroptosis in cancer cells by synergistically activating Keap1/Nrf2/HMOX1 pathway and inhibiting FECH.

Flavonoids are widely distributed in plants as secondary metabolites and have various biological benefits such as anti-tumor, anti-oxidant, anti-inflammatory and anti-aging. We previously reported that 4,4'-dimethoxychalcone (DMC) suppressed cancer cell proliferation by aggravating oxidative stress and inducing G2/M cell cycle arrest. In the present study, we explored the underlying mechanisms by which DMC inhibited cancer cell growth.

Nicotinamide reprograms adipose cellular metabolism and increases mitochondrial biogenesis to ameliorate obesity.

Obesity poses a global health challenge and is a major risk factor for diabetes mellitus, cardiovascular diseases, hypertension, stroke and certain kinds of cancers. Although the effects of nicotinamide (NAM) on liver metabolism and diseases were well documented, its effects on adipose tissue are yet to be characterized. Herein, we found that NAM supplementation significantly reduced fat mass and improved glucose tolerance in obese mice.

Complex roles of nicotinamide N-methyltransferase in cancer progression.

Nicotinamide N-methyltransferase (NNMT) is an intracellular methyltransferase, catalyzing the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (1-MNAM), in which S-adenosyl-L-methionine (SAM) is the methyl donor. High expression of NNMT can alter cellular NAM and SAM levels, which in turn, affects nicotinamide adenine dinucleotide (NAD)-dependent redox reactions and signaling pathways, and remodels cellular epigenetic states. Studies have revealed that NNMT plays critical roles in the occurrence and development of various cancers, and analysis of NNMT expression levels in different cancers from The Cancer Genome Atlas (TCGA) dataset indicated that NNMT might be a potential biomarker and therapeutic target for tumor diagnosis and treatment.

Correlation between preoperative psychological personality traits of glioma patients and psychological distress in their primary caregivers.

Objective: To explore the relationship between preoperative psychological personality traits of glioma patients and preoperative psychological distress of their primary caregivers.

Methods: A retrospective analysis was conducted on 85 glioma patients (tumor group) who were admitted to our hospital from February 2016 to December 2018 and 85 primary caregivers. Forty-one healthy volunteers were used as controls.

Overexpression of 15-Hydroxyprostaglandin Dehydrogenase Inhibits A549 Lung Adenocarcinoma Cell Growth via Inducing Cell Cycle Arrest and Inhibiting Epithelial-Mesenchymal Transition.

Purpose: Lung cancer is one of the most commonly diagnosed cancer as well as the leading cause of cancer-related mortality worldwide, among which lung adenocarcinoma (LUAD) is the most frequent form of lung cancer. Previous studies have shown that 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of prostaglandins to reduce their biological activities and behaves as a tumor suppressor in various cancers. Thus, we aimed to systematically examine the effects of 15-PGDH overexpression on cellular processes in lung adenocarcinoma cells.

Caregiver burden and influencing factors among family caregivers of patients with glioma: A cross-sectional survey.

Objective: The main responsibility of caring for patients with glioma is assumed by family caregivers who experience a considerable burden during the care process. This study aimed to investigate the level of caregiver burden and explore its associated factors among family caregivers of patients with glioma.

Methods: We conducted a cross-sectional study among 131 family caregivers of glioma patients from October 2017 to November 2019.

Flavonoid 4,4'-dimethoxychalcone suppresses cell proliferation via dehydrogenase inhibition and oxidative stress aggravation.

Flavonoids are natural polyphenolic compounds with a diverse array of biological activities and health-promoting effects. Recent studies have found that 4,4'-dimethoxychalcone (DMC) promoted longevity via autophagy; however, its targets are currently unknown. Herein, we employed an unbiased thermal proteome profiling (TPP) method and identified multiple targets of DMC, including ALDH1A3, ALDH2, and PTGES2.

Nicotinamide Mononucleotide Alleviates LPS-Induced Inflammation and Oxidative Stress Decreasing COX-2 Expression in Macrophages.

Macrophage activation is an important process in controlling infection, but persistent macrophage activation leads to chronic inflammation and diseases, such as tumor progression, insulin resistance and atherosclerosis. Characterizing metabolic signatures of macrophage activation is important for developing new approaches for macrophage inactivation. Herein, we performed metabolomic analysis on lipopolysaccharide (LPS)-activated macrophages and identified the associated changes in metabolites.

Clinical study of preoperative psychological distress and its related factors in the primary caregivers of patients with glioma.

Objective: To investigate the preoperative psychological distress in the primary caregivers of glioma patients and its influencing factors and to determine the relationship between preoperative psychological states of glioma patients and their caregivers.

Methods: Using a mixed methods design, the caregivers of patients with malignant glioma were interviewed and completed questionnaires about anxiety/depression and family function during preoperative period.

Results: Caregivers of glioma patients had different types of psychological distress before surgery.

Nicotinamide mononucleotide inhibits hepatic stellate cell activation to prevent liver fibrosis via promoting PGE degradation.

Liver fibrosis is a reversible wound-healing response to acute or chronic liver injury that can progress to cirrhosis and liver cancer. Finding new strategies for prevention and management of liver fibrosis is urgently needed. It is known that hepatic stellate cell (HSC) is the primary source of extracellular matrix that drives liver fibrosis progression.

Effect of backward walking training on knee osteoarthritis: protocol of a systematic review and meta-analysis.

Introduction: Backward walking (BW) is otherwise known as retrowalking. As opposed to forward walking, BW is a countersequential exercise and is a common method of rehabilitation training and disease-assisted treatment. Studies have shown that BW has a helpful effect on improving lower limb proprioception, gait synergy and improving limb balance.

An autoimmune disease variant of IgG1 modulates B cell activation and differentiation.

The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here we identify a variant of human immunoglobulin G1 (IgG1) with a Gly→Arg substitution (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog Gly→Arg (G390R) knockin mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies.

Decreased NAD Activates STAT3 and Integrin Pathways to Drive Epithelial-Mesenchymal Transition.

Nicotinamide adenine dinucleotide (NAD) plays an essential role in all aspects of human life. NAD levels decrease as humans age, and supplementation with NAD precursors plays a protective role against aging and associated disease. Less is known about the effects of decreased NAD on cellular processes, which is the basis for understanding the relationship between cellular NAD levels and aging-associated disease.

Construction of armored RNA containing long-size chimeric RNA by increasing the number and affinity of the pac site in exogenous rna and sequence coding coat protein of the MS2 bacteriophage.

Objectives: To construct a one-plasmid expression system of the armored RNA containing long chimeric RNA by increasing the number and affinity of the pac site.

Methods: The plasmid pET-MS2-pac was constructed with one C-variant pac site, and then the plasmid pM-CR-2C containing 1,891-bp chimeric sequences and two C-variant pac sites was produced. Meanwhile, three plasmids (pM-CR-C, pM-CR-2W and pM-CR-W) were obtained as parallel controls with a different number and affinity of the pac site.

A novel real-time multiplex reverse transcriptase-polymerase chain reaction for the detection of HIV-1 RNA by using dual-specific armored RNA as internal control.

Objective: Transmission of HIV-1 and diagnosis of infection in hospitals and public health settings remains a worldwide concern. HIV-1 detection is sometimes not possible using current commercial assays, probably due to mismatches between the selected primers and probes.

Methods: By screening primers and probes, we developed a dual-specificity probe real-time reverse transcriptase-polymerase chain reaction (DSPrtRT-PCR) assay using dual-specific armored RNA as the internal control.

RNase-resistant virus-like particles containing long chimeric RNA sequences produced by two-plasmid coexpression system.

RNase-resistant, noninfectious virus-like particles containing exogenous RNA sequences (armored RNA) are good candidates as RNA controls and standards in RNA virus detection. However, the length of RNA packaged in the virus-like particles with high efficiency is usually less than 500 bases. In this study, we describe a method for producing armored L-RNA.