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Mesenchymal stem cell-derived exosomes (MSCs-exo) can be used for treating Alzheimer’s disease (AD) by promoting amyloid-β (Aβ) degradation, modulating immune responses, protecting neurology, promoting axonal growth, and improving cognitive impairment. Increasing evidence suggests that the alteration of gut microbiota is closely related to the occurrence and development of Alzheimer's disease. In this study, we hypothesized that dysbiosis of gut microbiota might limit the effectiveness of MSCs-exo, whereas regulating the gut microbiota would improve the therapy of MSCs-exo. Methods: In this original research study, we used MSCs-exo to treat 5×FAD mice and fed them antibiotic cocktails for 1 week to detect cognitive ability and neuropathy. The mice’s feces were collected to investigate alterations in the microbiota and metabolites. Results: The results revealed that the AD gut microbiota eliminated the therapeutic effect of MSCs-exo, whereas antibiotic modulation of disordered gut microbiota and associated metabolites enhanced the therapeutic effect of MSCs-exo. Conclusions: These results encourage the research of novel therapeutics to enhance MSCs-exo treatment for AD, which could benefit a broader range of patients with AD.

Prostate cancer (PCa) is the most common new cancer case and the second most fatal malignancy in men. Surgery, endocrine therapy, radiotherapy and chemotherapy are the main clinical treatment options for PCa. However, most prostate cancers can develop into castration-resistant prostate cancer (CRPC), and due to the invasiveness of prostate cancer cells, they become resistant to different treatments and activate tumor-promoting signaling pathways, thereby inducing chemoresistance, radioresistance, ADT resistance, and immune resistance. Nanotechnology, which can combine treatment with diagnostic imaging tools, is emerging as a promising treatment modality in prostate cancer therapy. Nanoparticles can not only promote their accumulation at the pathological site through passive targeting techniques for enhanced permeability and retention (EPR), but also provide additional advantages for active targeting using different ligands. This property results in a reduced drug dose to achieve the desired effect, a longer duration of action within the tumor and fewer side effects on healthy tissues. In addition, nanotechnology can create good synergy with radiotherapy, chemotherapy, thermotherapy, photodynamic therapy and gene therapy to enhance their therapeutic effects with greater scope, and reduce the resistance of prostate cancer. In this article, we intend to review and discuss the latest technologies regarding the use of nanomaterials as therapeutic and diagnostic tools for prostate cancer.

Purpose Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Methods We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. Results Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. Conclusion PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA-DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA-DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA-DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.

Cell therapies for intervertebral disc degeneration (IDD) are intended to replace lost intervertebral disc (IVD) cells. The key to this treatment is to promote the migration of transplanted cells to the lesion site. The purpose of this study was to evaluate the repair effect of umbilical cord mesenchymal stem cells (UCMSCs) labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) on rat caudal vertebra disc degeneration. We characterized UCMSCs labeled with Fe3O4@PDA NPs, analyzed the effects of nanoparticles on UCMSCs and evaluated UCMSCs labeled with Fe3O4@PDA NPs to repair IDD in vivo. We found that UCMSC Fe3O4@PDA NPs could enhanced the migration of UCMSCs by up-regulating the expression of CXC chemokine receptor type 4 (CXCR4) without effecting UCMSC functionality and the Fe3O4@PDA NPs-labeled UCMSC group had better disc height, better tissue morphology performance and a higher number of transplanted cells and induced notably better regeneration of IVD, evidenced by the higher expression of aggrecan, type II collagen, and Sox-9 and lower expression of Mmp-13, Tnf-α and Il-1β at both mRNA and protein levels than the unlabeled group. We demonstrated systemic delivery of UCMSCs labeled with Fe3O4@PDA NPs could be an appropriate protocol for accelerating and optimizing clinically applicable UCMSC treatment for IDD.

Purpose Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. Methods We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. Results Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. Conclusion PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.

Biomimetic cell membrane coated nanoparticles (NPs) with desirable features have been extensively applied for various personalized biomedicine. However, there have not been relative explorations by employing the membrane nanocomplexes for small interfering RNA (siRNA) delivery. Herein, Fe3O4@PDA NPs with good photothermal capability were applied for efficient siRNA loading and delivery, which were then coated by mesenchymal stem cells (MSCs) to form a membrane. The data showed that MSCs membrane coated Fe3O4@PDA–siRNA NPs (Fe3O4@PDA–siRNA@MSCs) maintained the photothermal functionality and the capability of magnetic resonance imaging inherited from Fe3O4@PDA. The synthesized nanocomplexes exhibited excellent abilities in the delivery of siRNA into DU145 cells. Furthermore, Fe3O4@PDA–siRNA@MSCs NPs delivering siRNA against Plk1 gene could inhibit the expression of endogenous Plk1 gene and cause obvious apoptosis in DU145 cells. The synergistic combination of photothermal treatment and gene silencing showed...

Gold nanorods (GNRs) have become an attractive candidate in photothermal ablation against cancer cells for their excellent photothermal transduction effect. However, the applications of GNRs in nan...

The present study aimed to explore whether culture method had an influence on DNA methylation in colorectal cancer (CRC). In the present study, CRC cells were cultured in two-dimensional (2D), three-dimensional (3D) and mouse orthotopic transplantation (Tis) cultures. Principal component analysis (PCA) was used for global visualization of the three samples. A Venn diagram was applied for intersection and union analysis for different comparisons. The methylation condition of 5'-C-phosphate-G-3' (CpG) location was determined using unsupervised clustering analysis. Scatter plots and histograms of the mean β values between 3D vs. 2D, 3D vs. Tis and Tis vs. 2D were constructed. In order to explore the biological function of the genes, gene ontology and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analyses were utilized. To explore the influence of culture condition on genes, quantitative methylation specific polymerase chain reaction (QMSP) was performed. The three samples connected with each other closely, as demonstrated by PCA. Venn diagram analysis indicated that some differential methylation positions were commonly shared in the three groups of samples and 16 CpG positions appeared hypermethylated in the three samples. The methylation patterns between the 3D and 2D cultures were more similar than those of 3D and Tis, and Tis and 2D. Results of gene ontology demonstrated that differentially expressed genes were involved in molecular function, cellular components and biological function. KEGG analysis indicated that genes were enriched in 13 pathways, of which four pathways were the most evident. These pathways were pathways in cancer, mitogen-activated protein kinase signaling, axon guidance and insulin signaling. Furthermore, QMSP demonstrated that methylation of mutL homolog, phosphatase and tensin homolog, runt-related transcription factor, Ras association family member, cadherin-1, O-6-methylguanine-DNA-methyltransferase and P16 genes had no obvious difference in 2D, 3D and Tis culture conditions. In conclusion, the culture method had no influence on DNA methylation in CRC cells.

Au nanorods (AuNRs) have attracted extensive attention in diagnosis and therapy, because of their excellent photothermal effects. Although many of attempts have been employed to prepare AuNRs with a good-size monodispersity, facile and feasible preparation methods are still welcomed in consideration of theranostics-related photothermal applications. In this work, AuNRs are prepared through a seedless method using hydroquinone as the reductant. The longitudinal located surface plasmon resonance peak of the as-prepared AuNRs can be tuned from 650 to 840 nm and the AuNRs indicate a good photothermal conversion efficiency. To lower the toxicity, natural red blood cell membranes are employed to coat the AuNRs. In the primary experiment in vitro, red blood cell membrane-coated AuNRs exhibit good biocompatibility and photothermal treatment effect.

Gene silencing using small interfering RNA (siRNA) has shown significant potential in the treatment of cancer. Herein, we developed the lipid-polymer hybrid nanoparticles (PEG-LP/siRNA NPs) for siRNA delivery. The cell viability assay indicated that PEG-LP/siRNA NPs had negligible cell cytotoxicity. The cellular uptake efficiency of PEG-LP/siRNA NPs measured by flow cytometry was up to 94.4%. Importantly, in vitro gene knockdown experiments demonstrated that PEG-LP/siJnk-1 NPs could significantly downregulate the expression of Jnk-1 at both the mRNA and protein levels in DU145 cells. Gene knockdown of Jnk-1 could activate apoptosis in part by the mitochondrial pathway in DU145 cells. Moreover, the PEG-LP/siJnk-1 NPs could inhibit tumor growth in a DU145 xenograft murine model, suggesting its therapeutic promise in cancer therapy.

Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR) antibody-directed polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@ PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability) because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy.

Proteolysis targeting chimeras (PROTACs) are hetero-bifunctional molecules that could simultaneously bind to the target protein and the E3 ubiquitin ligase, thereby leading to selective degradation of the target protein. Polo-like kinase 1 (PLK1) and bromodomain 4 (BRD4) are both attractive therapeutic targets in acute myeloid leukemia (AML). Here, we developed a small-molecule BRD4 and PLK1 degrader HBL-4 based on PROTAC technology, which leads to fast, efficient, and prolonged degradation of BRD4 and PLK1 in MV4-11 cells tested in vitro and vivo, and potent anti-proliferation and BRD4 and PLK1 degradation ability in human acute leukemia MOLM-13 and KG1 cells. Meanwhile, HBL-4 more effectively suppresses c-Myc levels than inhibitor BI2536, resulting in more effective inducing apoptosis activity in MV4-11 cells. At the same time, HBL-4 induced dramatically improved efficacy in the MV4-11 tumor xenograft model as compared with BI2536. This study is, to our knowledge, the first reports about dual PLK1 and BRD4 degraders, which potentially represents an important therapeutic advance in the treatment of cancer.

A series of novel pyrimidin-4(3H)-one hydroxamate derivatives was designed, synthesized and studied for their activities against histone deacetylases(HDACs). The results indicate that all the compounds show HDACs inhibitiory activity. The antiproliferative activities of the compounds against HeLa and A549 cells were also investigated. The pharmacological results show compound 9g has potent activity in the enzymatic inhibition assay and cell-based assay.

Prostate carcinoma is a global health problem and is estimated to be diagnosed in 1.1 million men/year, making this malignancy the second most frequently diagnosed cancer in males worldwide. micro RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. miRNAs contribute to cancer development and progression, and are expressed differently in normal tissues and cancers. In the present study, the biological function of miR-106a in the human prostate carcinoma and the associated regulatory mechanisms were investigated. miR-106a was significantly upregulated in human prostate cancer tissues when compared with normal tissues (P

Prostate cancer is the second most common cancer in men worldwide. This study focused to clarify the roles of Metadherin (MTDH) and miR-342-3p in prostate cancer. We identified that MTDH was up-regulated and miR-342-3p was down-regulated in the prostate tissues, and there is an inverse correlation between MTDH and miR-342-3p. Functional studies revealed that miR-342-3p directly targets MTDH via binding to the 3′ untranslated regions (UTRs) in the prostate cancer cells. Moreover, we also found MTDH overexpression in DU145 and PC3 cells inhibited apoptosis. Subsequently, miR-342-3p has been revealed to reverse the MTDH effect on the cellular apoptosis in the further studies. Our results indicate that MTDH repress apoptosis of prostate cancer in vitro and provides a new strategy for human prostate cancer therapy in the future. Keywords: MTDH, miR-342-3p, Apoptosis

Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming.

Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR) antibody-directed polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@ PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability) because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy.

Type 1 diabetes mellitus (T1DM) is mainly caused by reduction of the endogenous insulin secretion due to autoimmune destruction of pancreatic β cells, and a promising therapeutic approach for T1DM is pancreas and islet cell replacement. The major obstacle is the limited source of insulin-producing cells. Here, we report an efficient approach to induce human adipose-derived stromal cells (hADSCs) to differentiate into insulin-producing cells, with glucagon-like peptide-1 (GLP-1). hADSCs were successfully isolated from the adipose tissue, with adipogenic and osteogenic differentiation potency. Islet-like cell clusters formed in the culture, which was enhanced with the treatment of GLP-1. Reverse transcription polymerase chain reaction analysis showed the expression of the pancreas-related genes in the differentiated cells, such as pdx-1, ngn3, insulin, glucagon, somatostatin, glucokinase n and glut2. Immunocytochemical analysis showed that the induced cells co-expressed insulin, C-peptide and PDX-1. The GLP-1 receptor was present in the differentiated cells. In addition, flow cytometry analysis and ELISA showed that, in the presence of GLP-1, the percentage of insulin-producing cells was increased from 5.9% to 28.0% and the release of insulin increased from 9.53±0.7 pmol/106 cells to 15.86±1.3 pmol/106 cells. Insulin was released in response to glucose stimulation in a manner comparable to that of adult human islets. These results indicated that hADSCs isolated from adipose tissues can be induced to differentiate into insulin-producing cells, which is further enhanced with the treatment of GLP-1. These findings confirm that the differentiation of hADSCs to insulin-producing cells is indeed possible and indicate that the differentiated insulin-producing cells can be used as a potential source for transplantation into patients with T1DM.

The human peptide rhA beta(1-42) was effectively produced through a novel expression system and purification procedure. The peptide rhA beta(1-42) was successfully expressed in Pichia pastoris, the methylotrophic yeast that has never been used as host. The cDNA encoding full-length hA beta(1-42) was synthesized with yeast bias codons and cloned into the pPICZ alpha A vector in frame with the yeast alpha-factor secretion signal under the transcriptional control of the AOX1 promoter and integrated into the secreting expression organism P. pastoris strain X33. Production of rhA beta(1-42) through fermentation was further optimized and scaled up in an 80 L fermentor. Secreted rhA beta(1-42) was purified using a two-step purification scheme: SP Sepharose ion exchange chromatography and source 30 RPC. The purification procedure is fast and efficient and reached a recovery of >93% without loss of activity. The purified rhA beta(1-42) was confirmed by Western blotting analysis and N-terminals amino sequencing analysis. This efficient and cost-effective expression system facilitates large-scale production and purification for recombinant rhA beta(1-42).

Oncostatin M (OSM) is a multifunctional cellular regulator that belongs to the IL-6 subfamily and can act on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. In order to achieve the higher level yield of recombinant human Oncostatin M (rhOSM), we determined the optimal pH condition of rhOSM expressed in the methylotrophic yeast Pichia pastoris X-33 and carried out the fermentation culture of rhOSM in 80 L fermentor in a fed-batch mode. SDS–PAGE and Western blotting assays demonstrated that rhOSM was successfully expressed and secreted into the culture medium with an apparent molecular weight of 28 kDa. N-terminals were correctly processed through amino-terminal sequencing. The maximum yield of rhOSM was 280 mg/L. rhOSM was purified by phenyl Sepharose hydrophobic interaction chromatography and SP Sepharose Fast Flow cation exchange chromatography, which resulted in a final yield of purified rhOSM of 6.94 g with a recovery of 62% and a purity of 95%. The purified rhOSM had a specific growth inhibition activity of 6.26 × 10 4 RU/μg, which was commensurate with typical values (6.2 × 10 4 RU/μg) obtained with standard hOSM.

Basic fibroblast growth factor [basic FGF (bFGF); FGF-2] is an important member of the FGF family, bFGF is a potent angiogenic molecule in vivo and in vitro stimulate smooth muscle cell growth, wound healing, and tissue repair. The full-length hbFGF coding sequence, gained by RT-PCR, was cloned into the pPICZalphaA vector in frame with the yeast alpha-factor secretion signal under the transcriptional control of the AOX promoter and integrated into Pichia pastoris strain X33, and the high level expression of rhbFGF has been achieved. SDS-PAGE and Western blotting assays of culture broth from a methanol-induced expression strain demonstrated that rhbFGF, an 18 kDa protein, was secreted into the culture medium. The growth conditions of the transformant strain were optimized in 50 ml conical tubes including methanol concentration, pH and inducing time. Under the optimal conditions, stable production of rhbFGF around 150 mg/l was achieved. The expressed rhbFGF was purified more than 94% purity using SP Sepharose ion exchange chromatography and source 30RPC. A preliminary biochemical characterization of purified rhbFGF was performed by biological activity analysis which was used by NIH/3T3 cell cultures, and the results demonstrated that the purified rhbFGF stimulated the growth of NIH/3T3 cells similarly to standard material.

The highly conserved extracellular domain of M2 protein (M2e) of influenza A viruses has limited immunogenicity on its own. Hence, aiming to enhance immunogenicity of M2e protein, optimal approaches remain to be established. In this study, we created recombinant fusion protein vaccines by linking M2e consensus sequence of influenza A viruses with C-terminal domain of human serum albumin (HSA). Then HSA/M2e recombinant fusion protein was studied. Our results showed that HSA/M2e could induce strong anti-M2e specific humoral immune responses in the established mice model. Administration of HSA/M2e with Freund's adjuvant resulted in a higher number of IFN-γ-producing cells compared to HSA/M2e or M2e peptide emulsified in Freund's adjuvant. Furthermore, HSA/M2e was able to reduce viral load in the mice lungs and provide significant protection against lethal challenge with an H1N1 or an H3N2 virus compared to controls. In conclusion, this study has demonstrated a potential vaccine that could provide protection in preventing the threat of influenza outbreak because of rapid variation of the influenza virus.