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Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound P6. A total of 33 compounds were designed and synthesized. In the enzyme inhibitory assay, several molecules S18, S26, S27 and T5 showed potent SIRT3 inhibitory activity with IC50 value of 0.53, 1.86, 5.06, and 2.88 μM, respectively. Moreover, the tested compounds exhibited SIRT3 inhibitory selectivity over SIRT1 and SIRT2. Compounds S27 and T5 were potent in inhibition the growth of MM1.S and RPMI‐8226 cells in the in vitro antiproliferative test. Significantly, representative compounds, especially S27 and T5, promoted differentiation of tested MM cells in the cellular morphological evaluation, accompanied by increasing the expression of differentiation antigen CD49e and human immunoglobulin light chain lambda and kappa. Additionally, molecule S18 without antiproliferative potency itself, showed significant inhibitory activity against growth factor IL‐6 induced RPMI‐8226 cell proliferation. Collectively, potent SIRT3 selective inhibitors with MM cell differentiation potency were developed for further discovery of anticancer drugs. [ABSTRACT FROM AUTHOR]

Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy. In vivo manipulation of the dynamics of nanoparticles' is essential for disease-specific imaging and therapy, but tends to involve complex design processes. Here, the authors report a strategy for manipulating the assembly of nanoparticles in vivo through a self-catalysis-instructed dimerization of tyrosine, offering convenient fabrication, high reaction specificity and biocompatibility. [ABSTRACT FROM AUTHOR]

Background: BICRA, a transcript regulator, was identified as the genetic factor of Coffin–Siris syndrome 12 (CSS12) recently, which was characterized by diverse neurodevelopmental delays. Up to now, limited studies of BICRA in neurodevelopmental delay have been reported. Methods: Clinical data such as EEGs, MRIs, routine blood, and physical examination were collected. Trio whole exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated by Sanger sequencing. The BICRA‐related literature was reviewed and the clinical characteristics were summarized. Results: We reported a CSS12 proband with a narrow and slightly clinical phenotype who only exhibited language developmental delay, hypotonia, and slight gastrointestinal features. WES revealed a de novo variant in exon 6 of BICRA [NM_015711.3: c.1666C>T, p.Gln556*]. This variant resulted in an early translation termination at 556th of BICRA, not collected in the public population database (gnomAD), and classified as pathogenic according to the ACMG guideline. Conclusion: Our results expanded the pathogenic genetic and clinical spectrum of BICRA‐related diseases. [ABSTRACT FROM AUTHOR]

Platinum (Pt) resistance in cancer almost inevitably occurs during clinical Pt-based chemotherapy. The spontaneous nucleotide-excision repair of cancer cells is a representative process that leads to Pt resistance, which involves the local DNA bending to facilitate the recruitment of nucleotide-excision repair proteins and subsequent elimination of Pt-DNA adducts. By exploiting the structural vulnerability of this process, we herein report a nuclease-mimetic Pt nanozyme that can target cancer cell nuclei and induce concurrent DNA platination and oxidative cleavage to overcome Pt drug resistance. We show that the Pt nanozyme, unlike cisplatin and conventional Pt nanoparticles, specifically induces the nanozyme-catalyzed cleavage of the formed Pt-DNA adducts by generating in situ reactive oxygen species, which impairs the damage recognition factors-induced DNA bending prerequisite for nucleotide-excision repair. The recruitment of downstream effectors of nucleotide-excision repair to DNA lesion sites, including xeroderma pigmentosum groups A and F, is disrupted by the Pt nanozyme in cisplatin-resistant cancer cells, allowing excessive accumulation of the Pt-DNA adducts for highly efficient cancer therapy. Our study highlights the potential benefits of applying enzymatic activities to the use of the Pt nanomedicines, providing a paradigm shift in DNA damaging chemotherapy. One of the mechanisms underlying platinum (Pt) resistance is the spontaneous nucleotide-excision repair of cancer cells. Here, nuclease-mimetic Pt nanozymes are targeted to the cancer cell nucleus and induce concurrent DNA platination and oxidative cleavage to overcome Pt resistance. [ABSTRACT FROM AUTHOR]

Aminopeptidase N (APN, CD13) is closely associated with the development and progression of cancer. Previous studies suggested APN as a biomarker for cancer stem cells. APN inhibitors have been intensively evaluated as chemosensitizers for cancer treatments. In the present study, tetrahydro- β -carboline scaffold was introduced to the structure of APN inhibitors. The synthesized compounds showed potent enzyme inhibitory activities compared with Bestatin, an approved APN inhibitor, in cell-based enzymatic assay. In combination with chemotherapeutic drugs, representative APN inhibitor molecules D12 , D14 and D16 significantly improved the antiproliferative potency of anticancer drugs in the in vitro tests. Further mechanistic studies revealed that the anticancer effects of these drug combinations are correlated with decreased APN expression, increased ROS level, and induction of cell apoptosis. The spheroid-formation assay and colony-formation assay results showed effectiveness of Paclitaxel-APN inhibitor combination against breast cancer stem cell growth. The combined drug treatment led to reduced mRNA expression of OCT-4, SOX-2 and Nanog in the cancer stem cells tested, suggesting the reduced stemness of the cells. In the in vivo study, the selected APN inhibitors, especially D12 , exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies. [ABSTRACT FROM AUTHOR]

Optineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders. Optineurin (OPTN) has been implicated in various biological processes, but its function in dendritic cells (DC) maturation is still unclear. Here the authors show, by characterizing Optn-conditional knockout mice, that the loss of OPTN induces Jak2/Stat3 activation and IL-10 production to suppress DC maturation and function, thereby ameliorating autoimmune responses in mice. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a prevalent and lethal adverse event that severely affects cancer patients receiving chemotherapy. It is correlated with the collateral damage to renal cells caused by reactive oxygen species (ROS). Currently, ROS management is a practical strategy that can reduce the risk of chemotherapy-related AKI, but at the cost of chemotherapeutic efficacy. Herein, we report catalytic activity tunable ceria nanoparticles (CNPs) that can prevent chemotherapy-induced AKI without interference with chemotherapeutic agents. Specifically, in the renal cortex, CNPs exhibit catalytic activity that decomposes hydrogen peroxide, and subsequently regulate the ROS-involved genes by activating the Nrf2/Keap1 signaling pathway. These restore the redox homeostasis for the protection of kidney tubules. Under an acidic tumor microenvironment, CNPs become inert due to the excessive H+ that disrupts the re-exposure of active catalytic sites, allowing a buildup of chemotherapy-mediated ROS generation to kill cancer cells. As ROS-modulating agents, CNPs incorporated with context-dependent catalytic activity, hold a great potential for clinical prevention and treatment of AKI in cancer patients. Reactive oxygen species management is a practical strategy that can reduce the risk of chemotherapy-induced acute kidney injury, but at the cost of chemotherapeutic efficacy. Here the authors report catalytic activity tunable ceria nanoparticles as context-dependent reactive oxygen species scavengers, which can prevent chemotherapy-induced acute kidney injury without interfering with chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Breast cancer is a common type of cancer in females. Our previous studies indicated that leucine aminopeptidase 3 (LAP3) promotes migration and invasion of breast cancer cells. Vimentin is a mesenchymal marker, and its upregulation represents the promotion of epithelial–mesenchymal transition. In this study, we found that LAP3 and vimentin were highly expressed in breast cancer tissues, and the overexpression of LAP3 in breast cancer cells promoted the expression of vimentin. Western blot analysis indicated that the overexpression of LAP3 upregulated the phosphorylation of Erk1/2. MEK inhibitor PD98059 downregulated the expression of vimentin, matrix metalloproteinase-2/9 (MMP-2/9), and fascin through the inhibition of Erk1/2 activity. We hypothesized that LAP3 promoted tumor migration and invasion by upregulating vimentin. The knockdown of vimentin resulted in the inhibited migration and invasion of MDA-MB-231 and MDA-MB-468 cells. The expression of MMP-2/9 and fascin could also be downregulated. In conclusion, vimentin might play an important role in the promotion of breast cancer metastasis by LAP3. [ABSTRACT FROM AUTHOR]

Many insects spin cocoons to protect the pupae from unfavorable environments and predators. After emerging from the pupa, the moths must escape from the sealed cocoons. Previous works identified cocoonase as the active enzyme loosening the cocoon to form an escape-hatch. Here, using bioinformatics tools, we show that cocoonase is specific to Lepidoptera and that it probably existed before the occurrence of lepidopteran insects spinning cocoons. Despite differences in cocooning behavior, we further show that cocoonase evolved by purification selection in Lepidoptera and that the selection is more intense in lepidopteran insects spinning sealed cocoons. Experimentally, we applied gene editing techniques to the silkworm Bombyx mori, which spins a dense and sealed cocoon, as a model of lepidopteran insects spinning sealed cocoons. We knocked out cocoonase using the CRISPR/Cas9 system. The adults of homozygous knock-out mutants were completely formed and viable but stayed trapped and died naturally in the cocoon. This is the first experimental and phenotypic evidence that cocoonase is the determining factor for breaking the cocoon. This work led to a novel silkworm strain yielding permanently intact cocoons and provides a new strategy for controlling the pests that form cocoons. Author summary: Spinning and cocooning are the instincts of many insects, providing a shelter to the residing pupae to resist adverse factors. After the metamorphosis of pupa into adult, the adult must break open the cocoon to emerge, which is called decocooning. We have bioinformatically identified that cocoonase is specific to Lepidoptera, and demonstrated that it is the determining factor for breaking the sealed cocoon experimentally for the first time. This work led to a novel silkworm strain yielding permanently intact cocoons and provides a new strategy for controlling the pests that form cocoons and for breeding. [ABSTRACT FROM AUTHOR]

Cyanogramide (1) from the marine actinomycete Actinoalloteichus cyanogriseus WH1‐2216‐6 features a unique spirooxindole skeleton and exhibits significant bioactivity to efficiently reverse drug resistance in tumor cells. The biosynthetic gene cluster of 1 in A. cyanogriseus WH1‐2216‐6 was identified and refactored by promoter engineering for heterologous expression in Streptomyces coelicolor YF11, thereby enabling the production of 1 and five new derivatives. Interesting, four of them, including 1, were identified as enantiomeric mixtures in different ratios. The functions of tailoring enzymes, including two methyltransferases (CyaEF), and three cytochrome P450 monooxygenases (CyaGHI) were confirmed by gene inactivation and feeding experiments, leading to the elucidation of a concise biosynthetic pathway for 1. Notably, CyaH was biochemically verified to catalyze the formation of the spirooxindole skeleton in 1 through an unusual carbocation‐mediated semipinacol‐type rearrangement reaction. [ABSTRACT FROM AUTHOR]

Cyanogramide (1) from the marine actinomycete Actinoalloteichus cyanogriseus WH1‐2216‐6 features a unique spirooxindole skeleton and exhibits significant bioactivity to efficiently reverse drug resistance in tumor cells. The biosynthetic gene cluster of 1 in A. cyanogriseus WH1‐2216‐6 was identified and refactored by promoter engineering for heterologous expression in Streptomyces coelicolor YF11, thereby enabling the production of 1 and five new derivatives. Interesting, four of them, including 1, were identified as enantiomeric mixtures in different ratios. The functions of tailoring enzymes, including two methyltransferases (CyaEF), and three cytochrome P450 monooxygenases (CyaGHI) were confirmed by gene inactivation and feeding experiments, leading to the elucidation of a concise biosynthetic pathway for 1. Notably, CyaH was biochemically verified to catalyze the formation of the spirooxindole skeleton in 1 through an unusual carbocation‐mediated semipinacol‐type rearrangement reaction. [ABSTRACT FROM AUTHOR]

To explore the relationship between the moisture content of withered tea leaves and their physical properties (i.e., elasticity, plasticity, flexibility, and texture) during withering, texture analyzer was employed to test the elasticity and flexibility of withered tea leaves with different moisture contents. The texture was evaluated by computer vision technology. The withered tea leaves with different moisture contents were used to process congou black tea, which was then subjected to sensory evaluation. Results showed that good elasticity, optimal flexibility, and plasticity were achieved when the moisture content of the withered tea leaves of Fudingdabai comprising two leaves and one bud varied arranging from 65.51 to 61.48%. The sensory evaluation of congou black tea revealed that moderate withering was better than long‐term withering and that both moderate and long‐term withering were better than no withering during processing. The moisture content was significantly correlated with the flexibility and plasticity of the withered tea leaves. Fresh tea leaves undergoing moderate withering with moisture content of 65.51–61.48% to process congou black tea, good tea shape and liquor color were achieved. This study provided new evidence that the moisture content of withered tea leaves significantly affected the quality of black tea. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the effects and the molecular mechanisms of ARK5 in ovarian cancer cell invasion. The plasmid pGCsilencerU6/GFP/Neo-RNAi-ARK5 and the control vector with a scramble sequence were transfected into SKOV3 cells to establish ARK5-deficient SKOV3 cells (siARK5/SKOV3) and a control cell line (Scr/SKOV3), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were used to determine the mRNA and protein expression levels of ARK5. Migration and invasion abilities of SKOV3 cells were determined in chemotaxis and invasion assays, respectively. The epidermal growth factor-1 (EGF-1)-induced expression of matrix metallopeptidase (MMP)-2 and MMP-9, epithelial-mesenchymal transition (EMT) and phosphorylation of mechanistic target of rapamycin kinase (mTOR) in siARK5/SKOV3 and Scr/SKOV3 cells were detected by western blot. RT-PCR and western blot analyses demonstrated that the expression of ARK5 was significantly downregulated in siARK5/SKOV3 cells at the mRNA and protein levels (P<0.01). The migration and invasion abilities of siARK5/SKOV3 cells were markedly decreased compared with Scr/SKOV3 cells (P<0.01). In addition, the results demonstrated that EGF-1-induced expression of MMP-2 and MMP-9, EMT and phosphorylation of mTOR were suppressed in siARK5/SKOV3 cells as compared with Scr/SKOV3 cells (P<0.01). The current study demonstrated that ARK5 is a critical factor involved in SKOV3 cell invasion and ARK5 increases invasive potential by promoting EMT and activating the Akt-mTOR-MMPs pathway. [ABSTRACT FROM AUTHOR]

In vitro mutagenesis via isolated microspore culture provides an efficient way to produce numerous double haploid (DH) lines with mutation introduction and homozygosity stabilization, which can be used for screening directly. In this study, 356 DH lines were produced from the malt barley (Hordeum vulgare L.) cultivar Hua-30 via microspore mutagenic treatment with ethyl methane sulfonate or pingyangmycin during in vitro culture. The lines were subjected to field screening under high nitrogen (HN) and low nitrogen (LN) conditions, and the number of productive tillers was used as the main screening index. Five mutant lines (A1-28, A1-84, A1-226, A16-11, and A9-29) with high numbers of productive tillers were obtained over three consecutive years of screening. In the fifth year, components related to N-use efficiency (NUE), including N accumulation, utilization, and translocation, were characterized for these lines based on N uptake efficiency (NUpE), N utilization efficiency (NUtE), and N translocation efficiency (NTE). The results show that the NUpE of four mutant lines (A1-84, A1-226, A9-29, and A16-11) improved significantly under HN, whereas that of two lines (A1-84 and A9-29) improved under LN. As a result, their NUE improved greatly. No improvement in NUtE was observed in any of the five mutant lines. A1-84 and A9-29 were selected as an enhanced genotype in N uptake, and A1-28 showed improved NTE at the grain-filling stage. Our results imply that high-NUpE mutants can be produced through microspore mutagenesis and field screening, and that improvement of NUE in barley depends on enhancement of N uptake. [ABSTRACT FROM AUTHOR]

In this paper, a novel method of QuEChERS-based extraction coupled with high-performance liquid chromatography has been developed for the simultaneous determination of ursolic acid (UA) and oleanolic acid (OA) in guava leaves. The QuEChERS-based extraction parameters, including the amount of added salt, vortex-assisted extraction time, and absorbent amount, and the chromatographic conditions were investigated for the analysis of UA and OA in guava leaves. Under the optimized conditions, the method showed good linearity over a range of 1–320 μg mL−1, with correlation coefficients above 0.999. The limits of detection of UA and OA were 0.18 and 0.36 μg mL−1, respectively. The intraday and interday precision were below 1.95 and 2.55%, respectively. The accuracies of the UA and OA determinations ranged from 97.4 to 111.4%. The contents of UA and OA in the guava leaf samples were 2.50 and 0.73 mg g−1, respectively. These results demonstrate that the developed method is applicable to the simultaneous determination of UA and OA in guava leaves. [ABSTRACT FROM AUTHOR]

Eucalyptol, also known as 1,8-cineol, is a monoterpene and has been shown to exert anti-inflammatory and antioxidant effect. It is traditionally used to treat respiratory disorders due to its secretolytic properties. In the present study, we evaluated the effect of 1,8-cineol on pulmonary inflammation in a mouse model of acute lung injury. We found that 1,8-cineol significantly decreased the level of TNF-α and IL-1β, and increased the level of IL-10 in lung tissues after acute lung injury induced by lipopolysaccharide (LPS). It also reduced the expression of nuclear factor kappa B (NF-κB) p65 and toll-like receptor 4 (TLR4), and myeloperoxidase activity in lung tissues. In addition, 1,8-cineol reduced the amounts of inflammatory cells in bronchoalveolar lavage fluid (BALF), including neutrophils and macrophages, and significantly decreased the protein content in BALF and the lung wet/dry weight ( W/ D) ratio. Its effect on LPS-induced pulmonary inflammation was associated with suppression of TLR4 and NF-κB expressions. Our results provide evidence that 1,8-cineol inhibits acute pulmonary inflammation, indicating its potential for the treatment of acute lung injury. [ABSTRACT FROM AUTHOR]

Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it is not known whether Gab2 has any role in the migration and invasion of gliomas. This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be a useful prognostic marker for gliomas and a novel therapeutic target for glioma invasion intervention. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutics. In this study, we mainly explore the molecular mechanism of ROS-induced CD13 expression using hepatocarcinoma cells as the research object. We show that the drug of fluorouracil (5FU), epirubicin (EPI) and gemcitabine (GEM) can induce ROS generation, activate Ets2 and promote CD13 expression. Meanwhile, CD13 can activate NRF1 and up-regulate ROS scavenging genes transcription, such as SOD1, GPX1, GPX2 and GPX3, leading to down-regulation of intracellular ROS level and reducing the sensitivity of cells to chemotherapy agent. We also detected the anti-tumor effect of the combination therapy, CD13 inhibitor ubenimex and a variety of conventional anti-cancer drugs, such as 5FU, EPI, GEM, pemetrexed (Pem) and paclitaxel (PTX) were employed in combination. Ubenimex enhances the sensitivity of different chemotherapeutic agents and cooperates with chemotherapeutic agents to suppress tumor growth in vitro and in vivo. In general, overexpression of CD13 can lead to chemotherapy resistance, and CD13 inhibitor can reverse this effect. Combination of chemotherapy agent and ubenimex will become a potential treatment strategy for liver cancer resistance. [ABSTRACT FROM AUTHOR]

Stroke is the major cause of death and disability worldwide and ischemic stroke contributes 80% among them. Although limited number of patients display hemorrhagic stroke (HS), the disability and death rate are higher in HS. Several studies have been reported on identification of suitable markers for diagnosis of stroke, but none of them holds true worldwide. These observations direct toward identification of population-specific biomarker of stroke. In this study, we screened various blood biomarkers in a large cohort of well-characterized Chinese stroke patients and healthy controls. A total of 308 stroke patients including 262 acute ischemic stroke (AIS) patients and 42 HS patients were enrolled in the study and blood samples were collected within 6–24 h of stroke onset. In addition, 46 stroke mimic subjects were included for comparison of blood markers with stroke patients. Furthermore, healthy controls (n = 200) and patient controls (n = 125) from similar ethnic group were enrolled in the study. Biomarkers (S100 calcium-binding protein B (S100B), C-reactive protein (CRP), interleukin 6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), matrix metallopeptidase 9 (MMP-9), P-selectin, intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor α (TNF-α), low-density lipoprotein (LDL) cholesterol, interleukin 10 (IL-10), nitric oxide (NO), and glial fibrillary acidic protein (GFAP)) were quantified by ELISA. Blood levels of S100B, CRP, IL-6, PAI-1, MMP-9, P-selectin, ICAM-1, and TNF-α were significantly higher in AIS and HS patients compared to healthy controls, patient controls, and stroke mimic patients. Receiver operating characteristic (ROC) curve analysis revealed CRP, IL-6, PAI-1, P-selectin, and TNF-α as possible biomarkers for AIS patients, and HS patients can be diagnosed based on S100B, IL-6, PAI-1, MMP-9, and TNF-α. Interestingly, significant area under ROC curves were observed for plasma S100B and CRP for differentiating AIS from HS. The results of this study validated certain blood parameters used for diagnosis of AIS or HS in Chinese patients. Furthermore, S100B and CRP are promising biomarkers for differentiation of AIS from HS. [ABSTRACT FROM AUTHOR]