Disturbed Yin-Yang balance: stress increases the susceptibility to herpes simplex virus type 1 primary and recurrent infections
Publication date: Available online 22 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Chang Yan, Zhuo Luo, Wen Li, Xue Li, Robert Dallmann, Hiroshi Kurihara, Yi-Fang Li, Rong-Rong HeAbstractHerpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues via nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the...
Source: Acta Pharmaceutica Sinica B - June 25, 2019 Category: Cancer & Oncology Source Type: research

Development and Application of Hyaluronic Acid in Tumor Targeting Drug Delivery
Publication date: Available online 20 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Zhijian Luo, Yan Dai, Huile GaoAbstractHyaluronic acid (HA) is a natural polysaccharide that has gained much attention due to its biocompatibility, enzyme degradation capacity and active tumor targeting capacity. Its receptor, CD44, is overexpressed in many kinds of cancers and is associated with tumor progress, infiltration and metastasis. Therefore, many researchers have developed various HA-based drug delivery systems for CD44-mediated tumor targeting. In this review, we systemically overview the basic theory of HA, its receptor...
Source: Acta Pharmaceutica Sinica B - June 22, 2019 Category: Cancer & Oncology Source Type: research

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care
Publication date: Available online 19 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jian Li, Olajide E. Olaleye, Xuan Yu, Weiwei Jia, Junling Yang, Chuang Lu, Songqiao Liu, Jingjing Yu, Xiaona Duan, Yaya Wang, Kai Dong, Rongrong He, Chen Cheng, Chuan LiAbstractManaging the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality via modulating the host response, pharmacokinetic herb‒drug interaction is a widely recogniz...
Source: Acta Pharmaceutica Sinica B - June 20, 2019 Category: Cancer & Oncology Source Type: research

New Era of Drug Innovation in China
Publication date: Available online 18 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xuan Ye, Qingli Wang, Haixue Wang (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - June 20, 2019 Category: Cancer & Oncology Source Type: research

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma
Publication date: Available online 14 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xiyue Zhao, Xiaoyu Liu, Pengcheng Zhang, Yiran Liu, Wei Ran, Ying Cai, Junyang Wang, Yihui Zhai, Guanru Wang, Yaping Ding, Yaping LiAbstractChemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide...
Source: Acta Pharmaceutica Sinica B - June 16, 2019 Category: Cancer & Oncology Source Type: research

A one-step specific assay for continuous detecting the activity of Sirtuin 2
In this study, we designed a series of fluorescent nonapeptide probes derived from substrates of SIRT1–SIRT3. Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore, which makes this system free of lysine-recognizing protease. Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1–SIRT3 and SIRT6, it was confirmed that this assessment system was the most suitable for SIRT2 activity detection. Thus, SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide. Finally, two specific and effici...
Source: Acta Pharmaceutica Sinica B - June 8, 2019 Category: Cancer & Oncology Source Type: research

Targeting peptide‒decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor
Publication date: Available online 5 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Tao Tan, Yuqi Wang, Jing Wang, Zhiwan Wang, Hong Wang, Haiqiang Cao, Jie Li, Yaping Li, Zhiwen Zhang, Siling WangAbstractThe limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy...
Source: Acta Pharmaceutica Sinica B - June 6, 2019 Category: Cancer & Oncology Source Type: research

Insulin-like Growth Factor 1 Modulates the Phosphorylation, Expression, and Activity of Organic Anion Transporter 3 through Protein Kinase A Signaling Pathway
In conclusion, our study demonstrated that IGF-1 regulates OAT3 expression and transport activity through PKA signaling pathway, possibly by phosphorylating the transporter.Graphical abstractIGF-1/PKA signaling pathway regulates OAT3 phosphorylation, expression and transport activity. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - June 6, 2019 Category: Cancer & Oncology Source Type: research

Structural simplification: an efficient strategy in lead optimization
Publication date: Available online 6 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Shengzheng Wang, Guoqiang Dong, Chunquan ShengAbstractThe trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding “molecular obesity”. The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility...
Source: Acta Pharmaceutica Sinica B - June 6, 2019 Category: Cancer & Oncology Source Type: research

Novel C-17 spirost protostane-type triterpenoids from Alisma plantago-aquatica with anti-inflammatory activity in Caco-2 cells
Publication date: Available online 7 May 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qinghao Jin, Jianqing Zhang, Jinjun Hou, Min Lei, Chen Liu, Xia Wang, Yong Huang, Shuai Yao, Bang Yeon Hwang, Wanying Wu, Dean GuoAbstractTwenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (1–9), were isolated from the of Alisma plantago-aquatica Linn. Structurally, alisolides A‒F (1–6), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H (8) is a novel triterpenoid with an unreported endoperoxid...
Source: Acta Pharmaceutica Sinica B - June 5, 2019 Category: Cancer & Oncology Source Type: research

Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injuryIssued by China Food and Drug Administration
Publication date: May 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 3Author(s): Xiaohe Xiao, Jianyuan Tang, Yimin Mao, Xiuhui Li, Jiabo Wang, Chenghai Liu, Kewei Sun, Yong'an Ye, Zhengsheng Zou, Cheng Peng, Ling Yang, Yuming Guo, Zhaofang Bai, Tingting He, Jing Jing, Fengyi Li, Na An (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - May 29, 2019 Category: Cancer & Oncology Source Type: research

Table of Contents
Publication date: May 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 3Author(s): (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - May 29, 2019 Category: Cancer & Oncology Source Type: research

Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus
In this study, the authors demonstrated that hypericin, as a sarA inhibitor, had synergistic activity with β-lactams both in vitro and in a murine bacteremia model due to MRSA. The mechanisms may be related to significantly reduced biofilm formation, fibronectin binding and expression of virulence genes (e.g., fnbA and hla) (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - May 29, 2019 Category: Cancer & Oncology Source Type: research

Pulmonary immunization: Deposition site is of minor relevance for Influenza vaccination but deep lung deposition is crucial for Hepatitis B vaccination
Publication date: Available online 28 May 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jasmine Tomar, Wouter F. Tonnis, Harshad P. Patil, Anne H. de boer, Paul Hagedoorn, Rita Vanbever, Henderik W. Frijlink, Wouter L.J. HinrichsAbstractVaccination via the pulmonary route could be an attractive alternative to parenteral administration. Research towards the best site of antigen deposition within the lungs to induce optimal immune responses has conflicting results which might be dependent on the type of vaccine and/or its physical state. Therefore, in this study, we explored whether deep lung deposition is crucial for tw...
Source: Acta Pharmaceutica Sinica B - May 29, 2019 Category: Cancer & Oncology Source Type: research

Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis via synergistic upregulation of ALAS1 expression
Publication date: Available online 23 May 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Cai-Ping Chen, Kun Chen, Zhiqi Feng, Xiaoan Wen, Hongbin SunAbstractArtemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. In vitro stu...
Source: Acta Pharmaceutica Sinica B - May 24, 2019 Category: Cancer & Oncology Source Type: research

Predicting Complexation Performance between Cyclodextrins and Guest Molecules by Integrated Machine learning and Molecular Modeling Techniques
In conclusion, the developed predictive models were able to quickly and accurately predict the solubilizing capacity of CD systems. Current research has taken an important step toward the application of machine learning in pharmaceutical formulation design.Graphical abstractCurrent research presented an alternative to traditionally trial-and-error experimentation for drug–CD formulation development. It revealed that the integration of experimental determinations, molecular modeling calculation and data-driven machine learning techniques could provide a new solution for highly efficient and accurate formulation develo...
Source: Acta Pharmaceutica Sinica B - May 9, 2019 Category: Cancer & Oncology Source Type: research

Novel C-17 spirost protostane-type triterpenoids from Alisma plantago-aquatica with anti-inflammatory activity in Caco-2 cells
Publication date: Available online 7 May 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qinghao Jin, Jianqing Zhang, Jinjun Hou, Min Lei, Chen Liu, Xia Wang, Yong Huang, Shuai Yao, Bang Yeon Hwang, Wanying Wu, Dean GuoAbstractTwenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (1‒9), were isolated from the of Alisma plantago-aquatica Linn. Thunb. Structurally, Alisolides A‒F (1‒6), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H (8) is a novel triterpenoid with an unreported endoperoxide...
Source: Acta Pharmaceutica Sinica B - May 8, 2019 Category: Cancer & Oncology Source Type: research

Emodin alleviates cardiac fibrosis by suppressing activation of cardiac fibroblasts via upregulating metastasis associated protein 3
The objective of this study is to determine the effects of emodin on cardiac fibrosis and the underlying molecular mechanisms. Intragastric administration of emodin markedly decreased left ventricular wall thickness in a mouse model of pathological cardiac hypertrophy with excess fibrosis induced by transaortic constriction (TAC) and suppressed activation of cardiac fibroblasts induced by angiotensin II (AngII). Emodin upregulated expression of metastasis associated protein 3 (MTA3) and restored the MTA3 expression in the setting of cardiac fibrosis. Moreover, overexpression of MTA3 promoted cardiac fibrosis; in contrast, ...
Source: Acta Pharmaceutica Sinica B - April 23, 2019 Category: Cancer & Oncology Source Type: research

Direct interaction of DNMT inhibitors to PrPC suppresses pathogenic process of prion
Publication date: Available online 18 April 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Dae-Hwan Kim, Chunyan Ren, Chongsuk Ryou, Jiaojie LiAbstractThe conversion of the normal cellular prion protein (PrPC) to the misfolded pathogenic scrapie prion protein (PrPSc) is the biochemical hallmark of prion replication. So far, various chemical compounds that inhibit this conformational conversion have been identified. Here, we report the novel anti-prion activity of SGI-1027 and its meta/meta analog (M/M), previously known only as potent inhibitors of DNA methyltransferases (DNMTs). These compounds effectively decreased th...
Source: Acta Pharmaceutica Sinica B - April 18, 2019 Category: Cancer & Oncology Source Type: research

Recent advances of microneedles for biomedical applications: drug delivery and beyond
Publication date: Available online 4 April 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jian Yang, Xinli Liu, Yunzhi Fu, Yujun SongAbstractThe microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summa...
Source: Acta Pharmaceutica Sinica B - April 6, 2019 Category: Cancer & Oncology Source Type: research

Role of vitamin D receptor in the regulation of CYP3A gene expression
Publication date: Available online 4 April 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xuan Qin, Xin WangAbstractVitamin D3 (VD3) is a multifunctional nutrient which can be either synthesized or absorbed from the diet. It plays a pivotal role in systemic calcium and phosphate homeostasis, as well as in various physiological and pathological processes. VD3 is converted to the active form, 1α,25-dihydroxyvitamin D3 (1,25-D3), by cytochrome P450 2R1 (CYP2R1)/CYP27A1 and CYP27B1 sequentially, and deactivated by multiple enzymes including CYP3A4. On the other hand, 1,25-D3 is capable of activating the transcription ...
Source: Acta Pharmaceutica Sinica B - April 6, 2019 Category: Cancer & Oncology Source Type: research

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer
This study demonstrates the improved therapeutic efficacy and its mechanism of transferrin receptor-targeted nanomedicine against breast tumor. Through ligand-receptor mediated active targeting and inducing massive accumulation of autophagic vesicles, combination chemotherapy that acted on both autophagic cell death (ACD) and apoptosis provided enhanced efficacy and reduced toxicity. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - April 6, 2019 Category: Cancer & Oncology Source Type: research

Regulation of microbiotaGLP1 axis by sennoside A in diet-induced obese mice
In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial...
Source: Acta Pharmaceutica Sinica B - March 30, 2019 Category: Cancer & Oncology Source Type: research

Develop a 3D neurological disease model of human cortical glutamatergic neurons using micropillar-based scaffolds
This study provided an in vitro disease-like model of traumatic brain injury, which would facilitate mechanistic studies and drug screening for neurotrauma or other neurological diseases. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - March 23, 2019 Category: Cancer & Oncology Source Type: research

Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via maintaining AMPKα/UCP2 pathway
Publication date: Available online 16 March 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Can Hu, Xin Zhang, Wenying Wei, Ning Zhang, Haiming Wu, Zhenguo Ma, Lingli Li, Wei Deng, Qizhu TangAbstractOxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as ...
Source: Acta Pharmaceutica Sinica B - March 17, 2019 Category: Cancer & Oncology Source Type: research

Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy
Publication date: March 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 2Author(s): Lu Zhong, Lu Xu, Yanying Liu, Qingsong Li, Dongyang Zhao, Zhenbao Li, Huicong Zhang, Haotian Zhang, Qiming Kan, Yongjun Wang, Jin Sun, Zhonggui HeAbstractHyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunat...
Source: Acta Pharmaceutica Sinica B - March 14, 2019 Category: Cancer & Oncology Source Type: research

Table of Contents
Publication date: March 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 2Author(s): (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - March 14, 2019 Category: Cancer & Oncology Source Type: research

Targeting the untargetable KRAS in cancer therapy
Publication date: Available online 6 March 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Pingyu Liu, Yijun Wang, Xin LiAbstractRAS is one of the most well-known proto-oncogenes. Its gain-of-function mutations occur in approximately 30% of all human cancers. As the most frequently mutated RAS isoform, KRAS is intensively studied in the past years. Despite its well-recognized importance in cancer malignancy, continuous efforts in the past three decades failed to develop approved therapies for KRAS mutant cancer. KRAS has thus long been considered to be undruggable. Encouragingly, recent studies have aroused renewed inter...
Source: Acta Pharmaceutica Sinica B - March 7, 2019 Category: Cancer & Oncology Source Type: research

Bioactive A-ring rearranged limonoids from the root barks of Walsura robusta
Publication date: Available online 1 March 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Faliang An, Xiaobing Wang, Minghua Yang, Jun Luo, Lingyi KongAbstractScreening active natural products, rapid identification, and accurate isolation are of great important for modern natural lead compounds discovery1. We herely reported the isolation of seven new neotecleanin-type liminoids (1‒7), seven new limonoids with 5-oxatricyclo[5.4.0.11, 4]hendecane ring system (8‒14), and two new precursors (15‒16) together with four known limonoids (17‒20) from the root barks of Walsura robusta. Their structures, including their a...
Source: Acta Pharmaceutica Sinica B - March 4, 2019 Category: Cancer & Oncology Source Type: research

Targeting slug-mediated non-canonical activation of c-Met to overcome chemo-resistance in metastatic ovarian cancer cells
In this study, SKOV3/T4, a metastatic subpopulation of ovarian cancer SKOV3 cells, was enriched to explore potential interventions against metastatic-associated drug resistance. Quantitative genomic and functional analyses were performed and found that slug was significantly increased in the SKOV3/T4 subpopulation and contributed to the high resistance of SKOV3/T4. Further studies showed that slug activated c-Met in a ligand-independent manner due to elevated levels of fibronectin and provoked integrin α V function, which was confirmed by the significant correlation of slug and p-Met levels in 121 ovarian cancer pati...
Source: Acta Pharmaceutica Sinica B - March 4, 2019 Category: Cancer & Oncology Source Type: research

Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect
In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with mod...
Source: Acta Pharmaceutica Sinica B - March 4, 2019 Category: Cancer & Oncology Source Type: research

Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3 inflammasome activation in LPS-induced vascular injury
Publication date: Available online 28 February 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xing Zhou, Yanjiao Wu, Lifeng Ye, Yunting Wang, Kaiming Zhang, Lingjun Wang, Yi Huang, Lei Wang, Shaoxiang Xian, Yang Zhang, Yang ChenAbstractThe loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation...
Source: Acta Pharmaceutica Sinica B - March 1, 2019 Category: Cancer & Oncology Source Type: research

Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes
The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to ch...
Source: Acta Pharmaceutica Sinica B - February 27, 2019 Category: Cancer & Oncology Source Type: research

Improvement in affinity and thermostability of a fully human antibody against interleukin-17A by yeast-display technology and CDR grafting
Publication date: Available online 22 February 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Wei Sun, Zhaona Yang, Heng Lin, Ming Liu, Chenxi Zhao, Xueying Hou, Zhuowei Hu, Bing CuiAbstractMonoclonal antibodies (mAbs) are widely used in many fields due to their high specificity and ability to recognize a broad range of antigens. IL-17A can induce a rapid inflammatory response both alone and synergistically with other proinflammatory cytokines. Accumulating evidence suggests that therapeutic intervention of IL-17A signaling offers an attractive treatment option for autoimmune diseases and cancer. Here, we present a comb...
Source: Acta Pharmaceutica Sinica B - February 23, 2019 Category: Cancer & Oncology Source Type: research

Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway
This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro. The in vivo study was performed using male C57BL/6 mice fed with methionine– choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative...
Source: Acta Pharmaceutica Sinica B - February 22, 2019 Category: Cancer & Oncology Source Type: research

Cilastatin protects against imipenem-induced nephrotoxicity via inhibition of renal organic anion transporters (OATs)
Publication date: Available online 18 February 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xiaokui Huo, Qiang Meng, Changyuan Wang, Yanna Zhu, Zhihao Liu, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Huijun Sun, Kexin LiuAbstractImipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated in vitro and in rabbits. Our results i...
Source: Acta Pharmaceutica Sinica B - February 19, 2019 Category: Cancer & Oncology Source Type: research

Ablation of gut microbiota alleviates obesity-induced hepatic steatosis and glucose intolerance by modulating bile acid metabolism in hamsters
This study is of potential translational significance in determining the role of gut microbiota-mediated bile acid metabolism in modulating diet-induced glucose intolerance and hepatic steatosis in the hamster.Graphical abstractIn the antibiotic-treated hamsters, hepatic CYP7B1-mediated alternative bile acid synthesis was activated. In hamsters, intestinal TβMCA accumulated and secondary bile acid levels were downregulated after gut microbiota depletion. Gut microbiota depletion-derived bile acid modulation results in intestinal FXR suppression and improvements of metabolic disorders in HFD-fed hamsters. (Source: Acta...
Source: Acta Pharmaceutica Sinica B - February 17, 2019 Category: Cancer & Oncology Source Type: research

Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome
In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.Graphical abstractCardamonin is a broad-spectrum inhibitor of NLRP3 inflammasome triggered by multiple stimuli. Moreover, the suppression of cardamonin on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Importantly, cardamonin improves the survival of mice suffering from LPS-induced lethal endotoxic shock, which is shown to be NLRP3 dependent. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - February 15, 2019 Category: Cancer & Oncology Source Type: research

Updated developments on molecular imaging and therapeutic strategies directed against necrosis
Publication date: Available online 13 February 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Dongjian Zhang, Meng Gao, Qiaomei Jin, Yicheng Ni, Jian ZhangAbstractCell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosi...
Source: Acta Pharmaceutica Sinica B - February 14, 2019 Category: Cancer & Oncology Source Type: research

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate
We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cell...
Source: Acta Pharmaceutica Sinica B - February 11, 2019 Category: Cancer & Oncology Source Type: research

Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer
Publication date: Available online 31 January 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jiaojie Wei, Yang Long, Rong Guo, Xinlei Liu, Xian Tang, Jingdong Rao, Sheng Yin, Zhirong Zhang, Man Li, Qin HeAbstractImmunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-D-α-tocopheryl succinate (TOS) micelles (LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hy...
Source: Acta Pharmaceutica Sinica B - February 1, 2019 Category: Cancer & Oncology Source Type: research

In vitro and in vivo activity of D-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus
In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies.Graphical abstractIn this study, the authors found that D-Ser had synergistic activity with β-lactams (represented by oxacillin and meropenem) against MRSA strains both in vitro and in vivo, demonstrated by results in MIC determination/Checkerboard assay, Time–kill curve analysis, murine systemic infection model and neut...
Source: Acta Pharmaceutica Sinica B - February 1, 2019 Category: Cancer & Oncology Source Type: research

Aurone derivatives as Vps34 inhibitors that modulate autophagy
We report in this study the identification of a natural product-like antagonist (1a) of Vps34 as a potent autophagy modulator via structure-based virtual screening. Aurone derivative 1a strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, 1a prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. In silico modeling and kinetic data revealed that 1a could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy in vivo and without inducing heart or liver damage in mice. 1a could be utilized as a new motif for more selective and effic...
Source: Acta Pharmaceutica Sinica B - January 31, 2019 Category: Cancer & Oncology Source Type: research

Table of Contents
Publication date: January 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 1Author(s): (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - January 30, 2019 Category: Cancer & Oncology Source Type: research

Editor Profiles: Guest Editors of Special Issue on Enhancement of Dissolution and Oral Bioavailability of Poorly Water-soluble Drugs
Publication date: January 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 1Author(s): Wei Wu, Yi Lu, Jianping Qi (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - January 30, 2019 Category: Cancer & Oncology Source Type: research

Editorial: Persistent endeavors for the enhancement of dissolution and oral bioavailability
Publication date: January 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 1Author(s): Wei Wu, Yi Lu, Jianping Qi (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - January 30, 2019 Category: Cancer & Oncology Source Type: research

Regulation of microbiota-GLP1 axis by Sennoside A (SA) in diet-induced obese mice
In this study, SA impact on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial str...
Source: Acta Pharmaceutica Sinica B - January 30, 2019 Category: Cancer & Oncology Source Type: research

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication
Publication date: Available online 29 January 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Menghao Huang, Hu Li, Rong Xue, Jianrui Li, Lihua Wang, Junjun Cheng, Zhouyi Wu, Wenjing Li, Jinhua Chen, Xiaoqin Lv, Qiang Li, Pei Lan, Limin Zhao, Yongfeng Yang, Zonggen Peng, Jiandong JiangAbstractBicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe,...
Source: Acta Pharmaceutica Sinica B - January 30, 2019 Category: Cancer & Oncology Source Type: research

GLUT1-mediated effective anti-miRNA21 pompon for cancer therapy
Publication date: Available online 28 January 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qin Guo, Chao Li, Wenxi Zhou, Xinli Chen, Yu Zhang, Yifei Lu, Yujie Zhang, Qinjun Chen, Donghui Liang, Tao Sun, Chen JiangAbstractOncogenic microRNAs are essential components in regulating the gene expression of cancer cells. Especially miR21, which is a major player involved of tumor initiation, progression, invasion and metastasis in several cancers. The delivery of anti-miR21 sequences has significant potential for cancer treatment. Nevertheless, since anti-miR21 sequences are extremely unstable and they need to obtain certai...
Source: Acta Pharmaceutica Sinica B - January 29, 2019 Category: Cancer & Oncology Source Type: research

Red blood cell membrane-camouflaged nanoparticles: A novel drug delivery system for antitumor application
Publication date: Available online 24 January 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qing Xia, Yongtai Zhang, Zhe Li, Xuefeng Hou, Nianping FengAbstractErythrocytes (red blood cells, RBCs) are the most abundant circulating cells in the blood and have been widely used in drug delivery systems (DDS) because of their features of biocompatibility, biodegradability, and long circulating half-life. Accordingly, a “camouflage” comprised of erythrocyte membranes renders nanoparticles as a platform that combines the advantages of native erythrocyte membranes with those of nanomaterials. Following injection in...
Source: Acta Pharmaceutica Sinica B - January 25, 2019 Category: Cancer & Oncology Source Type: research