Wenxia Zhou

Beijing Institute of Pharmacology and Toxicology, Beijing, China

Cellular transitions hold great promise in translational medicine research. However, therapeutic applications are limited by the low efficiency and safety concerns of using transcription factors. Small molecules provide a temporal and highly tunable approach to overcome these issues. Here, we present PC3T, a computational framework to enrich molecu...

Excessive stress leads to disruptions of the central nervous system. Individuals' responses to stress and trauma differ from person to person. Some may develop various neuropsychiatric disorders, such as post-traumatic stress disorder, major depression, and anxiety disorders, while others may successfully adapt to the same stressful events. These t...

A substantial body of evidence has indicated that intracerebral O-linked N-acetyl-β-D-glucosamine (O-GlcNAc), a generalized post-translational modification, was emerging as an effective regulator of stress-induced emotional and cognitive impairments. Our previous studies showed that the Liuwei Dihuang formula (LW) significantly improved the emotion...

Stress can affect people’s judgment and make them take risky decisions. Abnormal decision-making behavior is a core symptom of psychiatric disorders, such as anxiety, depression, and substance abuse. However, the neuronal mechanisms underlying such impairments are largely unknown. The anterior insular cortex (AIC) is a crucial structure to integrat...

The heterogeneity of tumor immune microenvironment (TIME) plays important roles in the development and immunotherapy response of hepatocellular carcinoma (HCC). Using machine learning algorithms, we introduced the immune index (IMI), a prognostic model based on the HCC immune landscape. We found that IMI low HCCs were enriched in stem cell and prol...

Background Indirectly experiencing traumatic events either by witnessing or learning of a loved one’s suffering is associated with the highest prevalence rates of epidemiological features of PTSD. Social species can develop fear by observing conspecifics in distress. Observational fear learning (OFL) is one of the most widely used paradigms for stu...

Post-traumatic stress disorder (PTSD) can be triggered not only in people who have personally experienced traumatic events but also in those who witness them. Physiological and psychological stress can have different effects on neural activity, but little is known about the underlying mechanisms. There is ample evidence that the insular cortex, esp...

Analysis of drug-induced expression profiles facilitated comprehensive understanding of drug properties. However, many compounds exhibit weak transcription responses though they mostly possess definite pharmacological effects. Actually, as a representative example, over 66.4% of 312,438 molecular signatures in the Library of Integrated Cellular Sig...

The chemical warfare agent sulfur mustard (SM) causes severe cutaneous lesions characterized by epidermal cell death, apoptosis, and inflammation. At present, the molecular mechanisms underlying SM-induced injury are not well understood, and there is no standard treatment protocol for SM-exposed patients. Here, we conducted a high-content screening...

The novel coronavirus disease, COVID-19, has rapidly spread worldwide. Developing methods to identify the therapeutic activity of drugs based on phenotypic data can improve the efficiency of drug development. Here, a state-of-the-art machine-learning method was used to identify drug mechanism of actions (MoAs) based on the cell image features of 11...

Lycium barbarum is widely used as a functional food and medicinal herb to promote health and longevity in China and in some other Asian countries. In modern pharmacological and chemical studies, the most valuable and well-researched component of L. barbarum is a group of unique water-soluble glycoconjugates that are collectively termed Lycium barba...

Background: The toxicity of excessive glutamate release has been implicated in various acute and chronic neurodegenerative conditions. Vesicular glutamate transporters (VGLUTs) are the major mediators for the uptake of glutamate into synaptic vesicles. However, the dynamics and mechanism of this process in glutamatergic neurons are still largely u...

It is pivotal and remains challenge for cancer precision treatment to identify the survival outcome interactions between genes, cells and drugs. Here, we present siGCD, a web-based tool for analysis and visualization of the survival interaction of Genes, Cells and Drugs in human cancers. siGCD utilizes the cancer heterogeneity to simulate the manip...

Here, we described the generation of human induced pluripotent stem cells (iPSC) from peripheral blood mononuclear cells (PBMCs) of a 87-year-old female patient with sporadic Alzheimer's disease(sAD) having APOE3 (ε3/ε3) genotype. iPSC line were generated from PBMCs with four factors of OCT4, SOX2, c-MYC and KLF4 using episomal system. The pluripot...

Background Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for bi...

The cell-type-specific response of neural cells to oxidative stress, a crucial mechanism for accelerating aging and cognitive dysfunction in Alzheimer's disease (AD) is still far from understood. Here, we employed human induced pluripotent stem cells (hiPSC)-derived neural stem cells (hiPSC-NSCs), neurons (hiPSC-Neurons) and microglia-like cells (h...

Two healthy elderly donated their peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell lines (IPTi005-A and IPTi007-A) were reprogrammed by episomal vector system with Yamanaka factors OCT4, SOX2, C-MYC and KLF4. Both the two iPSC lines can differentiate into three germ layers determined by embryoid bodies (EBs) differentia...

Aging is a natural biological process associated with cognitive decline and neuroendocrine–immune system changes; the neuroendocrine–immune system plays crucial role in brain aging and neurodegeneration, and it is essential to discern beneficial attempts to delay the aging progress based on immunological aging. In this study, we have investigated t...

LW-AFC is a new formula derived from the Liuwei Dihuang decoction, a classical traditional Chinese medicine prescription. Based on our research, LW-AFC is a promising drug for Alzheimer's disease (AD). The studies were conducted primarily in two typical AD mouse models: SAMP8 and APP/PS1 mice. The results showed that LW-AFC could improve many cogni...

Fungal bioactive polysaccharides are well known and have been widely used in Asia as a part of the traditional diet and medicine. In fact, some biopolymers (mainly β-glucans or glycoconjugate) have already made their way to the market as antitumor or immunostimulating drugs. In the last decades, the relationship between structure and activity of po...

A 62-year old sporadic Alzheimer's disease (sAD) male patient with APOE3 (ε3/ε3) genotype donated his peripheral blood mononuclear cells (PBMCs). The induced pluripotent stem cell (iPSC) line was established by episomal vector system with the four factors OCT4, SOX2, C-MYC and KLF4. EB differentiation in vitro showed that iPSC line had a potential...

Neuroinflammation is known as a typical feature associated with many neurodegenerative diseases including Alzheimer’s disease (AD) and impairs the synaptic plasticity of the hippocampus. LW-AFC is an active fraction combination being extracted from Liuwei Dihuang decoction, a classic traditional Chinese medicine prescription. This study aimed to in...

Mounting evidence points to alterations in the gut microbiota-neuroendocrine immunomodulation (NIM) network that might drive Alzheimer's Disease (AD) pathology. In previous studies, we found that Liuwei Dihuang decoction (LW) had beneficial effects on the cognitive impairments and gastrointestinal microbiota dysbiosis in an AD mouse model. In parti...

The Supplemenantry data can be found online at: www.aginganddisease.org/EN/10.14336/AD.2018.0910

Neuroinflammation and activation of microglia have been recognized as important pathological events in Alzheimer's disease (AD). LW‐active fraction combination (LW‐AFC) is extracted from Liuwei Dihuang decoction (LW), a classic traditional Chinese medicinal prescription. It has been demonstrated that LW‐AFC had neuroprotective effects on AD animal...

Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are beneficial in treating AD; however, no significant clinical effects have been shown. Furthermore, no study has investigated the efficacy of combining t...

Microglia constitute the majority of innate immune cells in the brain, and their dysfunction is associated with various central nervous system diseases. Human microglia are extremely difficult to obtain experimentally, thereby limiting studies on their role in complex diseases. Microglia derived from human stem cells provide new tools to assess the...

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling mo...

It is highly valuable to study the pharmacokinetics of herbal components under the pathological condition of liver dysfunction for safe and rational use of herbal medicines. In this study, the pharmacokinetic profiles of four effective lignans from Schisandra chinensis (SC), schisandrin, schisantherin A, deoxyshisandrin and γ-schisandrin, were inve...

Traditional Chinese medicine (TCM) have been long and widely used in prevention and treatment of diseases in China for thousands of years, which made a great contribution to health care of Chinese people. Prescriptions or formula are the main form of TCM and the compatibility and composition of them are made up following the theory of TCM among whi...

Alzheimer's disease (AD) is the leading cause of dementia that affects millions of elderly people worldwide. The currently available therapies have limited efficacy. Liuwei Dihuang decoction (LW), a classical traditional Chinese medicine (TCM) formula, has long been used to treat various diseases, including dementia. A large number of pharmacologic...

Alzheimer's disease (AD) is a neurodegenerative disease which cannot be effectively prevented, halted or cured. The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a robust experimental model for developing preventative and therapeutic treatments for AD. LW-AFC is a new formula derived from the classical traditional Chinese medici...

Objective: Alzheimer’s disease (AD) causes progressive hippocampus dysfunctions leading to the impairment of learning and memory ability and a reduced uptake rate of glucose in the hippocampus. LW-AFC is a new formula derived from the classical traditional Chinese medicinal prescription Liuwei Dihuang decoction. In this study, we investigated the b...

Alzheimer’s disease (AD) is the leading cause of dementia that affects millions of elderly people worldwide. The currently available therapies have limited efficacy. Liuwei Dihuang decoction (LW), a classical traditional Chinese medicine (TCM) formula, has long been used to treat various diseases, including dementia. A large number of pharmacologic...

Oxidative stress, DNA damage repair, and inflammation are three important reactions of sulfur mustard (SM) exposure. But molecular related chronological events in the earlier stage of SM exposure model are still unclear. In the research, reactive oxygen species (ROS) was measured by using flow cytometry. Cytokines were tested in Luminex method. Mye...

The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a robust experimental model for developing preventative and therapeutic treatments for Alzheimer's disease (AD), a neurodegenerative disease which cannot be effectively prevented, halted, or cured. Our previous studies showed that LW-AFC, a new formula derived from the classical...

Microbes have deserved broader attention as causal factors in Alzheimer's disease (AD), a neurodegenerative disorder. The senescence-accelerated mouse prone 8 (SAMP8) strain, a spontaneous mice of accelerated aging, are considered a robust model for sporadic AD. LW-AFC, an herbal medicine, was prepared from LiuweiDihuang decoction, which is a class...

Background: Alzheimer's disease (AD), the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang decoction (LW), a classical traditional Chinese medicinal prescription, possesses potential therapeutic effects on AD. LW-AFC is...

Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight,...

Toll-like receptor (TLR) 4 is an important polysaccharide receptor; however, the relationships between the structures and biological activities of TLR4 and polysaccharides remain unknown. Many recent findings have revealed the primary structure of TLR4/MD-2-related polysaccharides, and several three-dimensional structure models of polysaccharide-bi...

Liuwei Dihuang decoction (LW) has been used in traditional Chinese medicine (TCM) for more than 900years to prevent and treat various diseases with characteristic features of kidney yin deficiency. To date, LW has been commonly prescribed in TCM as therapy or adjuvant therapy against various diseases. To elucidate the pharmacological characteristic...

There are currently no approved effective therapies for Alzheimer's disease (AD). AD is a classic, multifactorial, complex syndrome. Thus, a polypharmacological or multitargeted approach to AD might provide better therapeutic benefits than monotherapies. However, it remains elusive which biological processes and biomolecules involved in the pathoph...

It is well known that GnRH analogs can self-assemble into amyloid fibrils and that the duration of action of GnRH analogs depends on the ability of the amyloid to slowly release active peptides. The aim of this study was to investigate the influence of the amino acid residues at position 7 of GnRH analogues on peptide self-assembly. It was found th...

Objective : Liuwei Dihuang (LW) decoction are classical traditional Chinese medicinal prescription for anti‐aging. Senescence‐accelerated mouse (SAM) is a good model to study mechanisms of aging. To better understand the mechanisms of actions of LW on antiaging, systematic techniques, including proteomic and metabonomic methods, were employed in th...

Lycium barbarum L., known as wolfberry, is an important Chinese herbal medicine. In the research, we purified water-soluble polysaccharide-protein complex (LBPF4) and polysaccharide (LBPF4-OL) from the fruiting bodies of Lycium barbarum L. The monosaccharide and amino acid composition of LBPF4 and LBPF4-OL was elucidated with fractional acid hydrol...

β-site amyloid-β protein precursor cleaving enzyme 1 (BACE1) is the first protease and the rate limiting enzyme in the genesis of amyloid-β (Aβ). This protein remains an important potential disease-modifying target for the development of drugs to treat Alzheimer's disease (AD). We are pursuing potent BACE1 inhibitors in an effort to identify suitab...

The relationship between learning/memory performance and long-term potentiation (LTP) induction is ambiguous. Although a large body of data supports a strong correspondence between learning/memory performance and LTP, many studies have also provided evidence to the contrary. In this study, we found that 2-month-old senescence-accelerated mice/prone...

Introduction Naturally occurring CD4+CD25+ regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune disease...

Liuwei Dihuang decoction (LW) is a typical traditional Chinese medicine (TCM) prescription and consists of six herbs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea opposite Thunb. (family: Dioscoreaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae), Poria co...

(2)-Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. A number of studies have demonstrated EGCG has the possibility for delaying the onset or retarding the progression of Alzheimer's disease (AD) and indicated EGCG possess inhibition of β-secretase activity. We utilized homogeneous time-resolved fluorescence assay w...

The senescence accelerated mouse prone 8 (SAMP8), an animal model of Alzheimer's disease, has amyloid-β deposition in the brain. This study showed that β-secretase activity increased age-dependently in cerebral cortex of SAMP8 and SAMP8's control, SAM resistant/1 (SAMR1), and was higher in the hippocampus of SAMP8 than that of age-matched SAMR1. Ca...

Hemiasterlin is a tripeptide with highly alkylated unnatural amino acids. It acts as a potent tumor cell growth inhibitor. From the comparison of the N-terminal between hemiasterlin and its analogues, a further modification was conducted on this position for a SAR study. Some unnatural amino acids with aryl or ureido groups were introduced into the...

PEGylation is an effective way to improve the pharmacokinetic profiles of pharmaceutical proteins or peptides. But the relatively large and long PEG chains would be likely to shelter the active site of a small peptide because of its small size, compared with a protein. Therefore, the positions and numbers of PEGylation are crucial for the bioactivi...

In this work, metabonomic methods utilizing (1)H NMR spectroscopy and multivariate statistical technique have been applied to investigate the metabolic profiles of SAM. The serum metabolome of senescence-prone 8 (SAMP8), a murine model of age-related learning and memory deficits and Alzheimer's disease (AD), was compared with that of control, senes...

Senescence-accelerated mouse (SAM) prone/8 (SAMP8) is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits such as Alzheimer's disease (AD) at the gene and protein levels, and SAM resistant/1 (SAMR1) is its normal control. Calcium/calmodulin-dependent protein kinase II-alpha (CaMKIIalpha) is one...

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (T alpha 1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide g...

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (Tα1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide greatly...

LXT-101 is a newly developed GnRH (gonadotropin-releasing hormone) analogue. In this study, the in vivo pharmacological profile in intact male rats and binding characters of LXT-101 were illustrated, and regulation of mRNA of hormone receptors related to the pituitary-gonadal axis during and after administration was observed to reveal its molecular...

The effect of Liuwei Dihuang decoction (LW), a traditional Chinese medicine (TCM) prescription, on voltage-dependent currents and synaptic transmission were investigated in cultured hippocampal neurons of rat by whole-cell patch clamp recording technique. After application with serum from LW-treated rats, termed LW-containing serum (LWCS) for 48 h,...

Whole‐cell currents in cultured hippocampal neurons were recorded to investigate the effects of SO‐3, a new O‐superfamily conopeptide derived from Conus striatus , on voltage‐sensitive channels. SO‐3 had no effect on voltage‐sensitive sodium currents, delayed rectifier potassium currents, and transient outward potassium currents. Similar to the sel...

The molecular and cellular mechanisms underlying the cognitive deficiency of senescence-accelerated mouse prone/8 (SAMP8) have been attributed to many pathological changes in neurons. Recently, increasing evidence has shown that astrocytes, by mean of d-serine, involve in the process of synaptic transmission. Here we reported that the long-term pot...

Estrogen receptor (ER) has two subtypes, ERα and ERβ. In this study, age-related changes of hippocampal gene expressions of ERα and ERβ were examined in senescence-accelerated mouse (SAM) with real-time reverse transcription-polymerase chain reaction (RT-PCR) technique, in an attempt to explore the relationship between estrogen receptor expression...

Senescence-accelerated mouse (SAM) have been used as animal models in the studies of senescence and age-associated disorders for many years. The typical feature of SAM-prone8 (SAMP8), a substrain of SAM, is the development of early onset of learning and memory deficit during its aging process, while SAM-resistant1 (SAMR1) shows normal aging process...

Liuwei Dihuang decoction (LW) is a classical traditional Chinese medicinal prescription used clinically in the treatment of the diseases manifesting “Kidney-Yin” deficiency syndrome such as cancer, diabetes, autoimmune diseases, and the diseases related to the disorder of endocrine function including climacteric syndrome, sexual inadequacy, sterili...

Selective blockers of the N-type voltage-sensitive calcium (Ca V) channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type Ca V channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-...