The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts

Heterogeneous nuclear ribonucleoprotein （hnRNP） C plays a key role in RNA processing but also exerts a dominant negative effect on responses to 1,25-dihydroxyvitamin D （1,25（OH）2D） by functioning as a vitamin D response element-binding protein （VDRE-BP）. hnRNPC acts a tetramer of hnRNPC1 （huC1） and hnRNPC2 （huC2）, and organization of these subunits is critical to in vivo nucleic acid-binding. Overexpression of either huC1 or huC2 in human osteoblasts is sufficient to confer VDRE-BP suppression of 1,25（OH）2D-mediated transcription. However, huC1 or huC2 alone did not suppress 1,25（OH）2D-induced transcription in mouse osteoblastic cells. By contrast, overexpression of huC1 and huC2 in combination or transfection with a bone-specific polycistronic vector using a ＂self-cleaving＂ 2A peptide to co-express huC1/C2 suppressed 1,25D-mediated induction of osteoblast target gene expression. Structural diversity of hnRNPC between human/NWPs and mouse/rat/rabbit/dog was investigated by analysis of sequence variations within the hnRNP CLZ domain. The predicted loss of distal helical function in hnRNPC from lower species provides an explanation for the altered interaction between huC1/C2 and their mouse counterparts. These data provide new evidence of a role for hnRNPC1/C2 in 1,25（OH）2D-driven gene expression, and further suggest that species-specific tetramerization is a crucial determinant of its actions as a regulator of VDR-directed transactivation.

Synthesis and properties of Au-Fe_3O_4 and Ag-Fe_3O_4 heterodimeric nanoparticles

Monodisperse Au-Fe3O4 heterodimeric nanoparticles （NPs） were prepared by injecting precursors into a hot reaction solution. The size of Au and Fe3O4 particles can be controlled by changing the injection temperature. UVis spectra show that the surface plasma resonance band of Au-Fe3O4 heterodimeric NPs was evidently red-shifted compared with the resonance band of Au NPs of similar size. The as-prepared heterodimeric Au-Fe3O4 NPs exhibited superparamagnetic properties at room temperature. The Ag-Fe3O4 heterodimeric NPs were also prepared by this synthetic method simply using AgNO3 as precursor instead of HAuCl4. It is indicated that the reported method can be readily extended to the synthesis of other noble metal conjugated heterodimeric NPs.

Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

Src heterodimerically activates Lyn or Fyn to serve as targets for the diagnosis and treatment of esophageal squamous cell carcinoma

Although Src is one of the oldest and most investigated oncoproteins,its function in tumor malignancy remains to be defined further.In this study,we demonstrated that the inhibition of Src activity by ponatinib effectively suppressed several malignant phenotypes of esophageal squamous cell carcinoma(ESCC)both in vitro and in vivo,whereas it did not produce growthinhibitory effects on normal esophageal epithelial cells(NEECs).Importantly,we combined phosphoproteomics and several cellular and molecular biologic strategies to identify that Src interacted with the members of Src-family kinases(SFKs),such as Fyn or Lyn,to form heterodimers.Src interactions with Fyn and Lyn phosphorylated the tyrosine sites in SH2(Fyn Tyr^(185)or Lyn Tyr^(183))and kinase domains(Fyn Tyr^(420) or Lyn Tyr^(397)),which critically contributed to ESCC development.By contrast,Src could not form heterodimers with Fyn or Lyn in NEECs.We used RNA sequencing to comprehensively demonstrate that the inhibition of Src activity effectively blocked several critical tumor-promoting pathways,such as JAK/STAT,mTOR,stemness-related,and metabolism-related pathways.Results of the real-time polymerase chain reaction(RT-PCR)assay confirmed that Lyn and Fyn were critical effectors for the Src-mediated expression of tumor growth or metastasis-related molecules.Furthermore,results of the clinical ESCC samples showed that the hyperactivation of pSrc Tyr^(419),Fyn Tyr^(185) or Tyr^(420),and Lyn Tyr^(183)or Tyr^(397)could be biomarkers of ESCC prognosis.This study illustrates that Src/Fyn and Src/Lyn heterodimers serve as targets for the treatment of ESCC.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers

In our recent studies, we found that LMP1 encoded by Epstein-Barr virus could accelerate the formation of active c-Jun/Jun B heterodimer. We studied the regulation of cyclinD1 by c-Jun/Jun B heterodimers by laser scanning confocal influorescence microscopy, Western blot, luciferase activity assay, super-EMSA and flow cytometry in the Tet-on-LMP1 HNE2 cell line, in which LMP1 expression was regulated by Tet-on system. c-Jun/Jun B heterodimers induced by LMP1 could up regulate cyclin D1 promoter activity and expression. Overexpression of cy-clinD1 accelerated the progression of cell cycle.

Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1

Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.

A Novel Ratiometric Oxygen Sensor Based On a Sextuple Hydrogen-Bonding Self-Assembly Molecular Heterodimer

A novel sextuple hydrogen-bonding （HB） self-assembly molecular heterodimer bearing an iridium complex as the indicator dye and two carbazoles as the reference dye, namely 6HB-Irbt-Cz, was synthesized, and its molecular structure was confirmed by ^1H NMR, ^13CNMR, TOF-MS and 2D NMR. Because of the inefficient energy transfer process between the carbazole and iridium complex units, 6HB-Irbt-Cz exhibits distinct fluorescence/ phosphorescence dual emission in neat film state. More importantly, the neat film sample of 6HB-Irbt-Cz could display linear ratiometric optical response toward oxygen in the full oxygen concentration range from 0 to 100 vol%, together with good stability, reversibility and rapid response-recovery times. Note that this represents the first discovery of neat-film-based oxygen sensor capable of showing strictly linear ratiometric Stem-Volmer behavior in the oxygen concentration of 0- 100 vol%.

Recyclable magnetite-silver heterodimer nanocomposites with durable antibacterial performance

There is a significant need for magnetite-silver nanocomposites that exhibit durable and recyclable antimicrobial activity.In this study,magnetic iron oxide nanoparticles(Fe3O4 NPs)coated with ethylenediamine-modified chitosan/polyacrylic acid copolymeric layer(Fe3O4@ECS/PAA)were fabricated.Subsequently,directly deposited silver(Ag)NPs procedure was carried out to form the antibacterial heterodimers of Fe3O4@ECS/PAA-Ag NPs.The composition and morphology of the resultant nanostructures were confirmed by FT-IR,XRD,TEM and TGA.The overall length of the heterodimers was approximately 45 nm,in which the mean diameter of Fe3O4@ECS/PAA NPs reached up to 35 nm,and that of Ag NPs was around 15 nm.The mass fraction of silver NPs in the nanocomposites was about 63.1%.The obtained Fe3O4@ECS/PAA NPs exhibited good colloidal stability,and excellent response to additional magnetic field,making the NPs easy to recover after antibacterial tests.In particular,the Fe3O4@ECS/PAAAg NPs retained nearly 100%biocidal efficiency(106e107 CFU/mg nanoparticles)for both Gram-negative bacteria E.coli and Gram-positive bacteria S.aureus throughout ten cycles without washing with any solvents or water,exhibiting potent and durable antibacterial activity.

Ergochaeglobosins A—E, Unprecedented Heterodimers of Cytochalasan and Ergosterol from Chaeglobosin globosum P2-2-2

Five novel heterodimers of cytochalasan and ergosterol,ergochaeglobosins A—E,were isolated from an endophytic fungus Chaetomium globosum P2-2-2.Ergochaeglobosin A(1) possesses an unprecedented 5/6/13/6/5/6/6/6 fused octacyclic ring system,and ergochaeglobosins B(2) and C(3) form a unique 5/6/13/6/6/6/6/5 fused octacyclic ring system,whereas ergochaeglobosins D(4) and F(5) are the first cytochalasan heterodimers formed via a N-1′/C-3′′single bond.Their structures with absolute configurations were established by extensive spectroscopic analyses,single-crystal X-ray diffraction,and ECD calculations.The plausible biogenetic pathway of 1—5 was postulated.Compound 1 exhibited inhibitory effects against ConA-induced T cells and LPS-induced B cells proliferation with IC50 values of 19.2 and 14.1μmol/L,respectively.Co-treatment of 3(20μmol/L)with TRAIL(150 ng/mL)could significantly decrease the cell viability of A549 by 24.9%comparing with monotherapy of 3(20μmol/L).

Synthesis and photophysical properties of porphyrin-phthalocyanine heterodimer linked by piperazine

A porphyrin-phthalocyanine heterodimer linked by piperazine has been synthesized and characterized by spectroscopic methods. UV-visible absorption spectra indicated the presence of weak intramolecular interaction between the two chromophores. Selective excitation of the porphyrin moiety leads to energy transfer process to the phthalocyanine subunit. Furthermore, on the bases of the solvent-dependent fluorescence data, a competing electron transfer reaction is shown to occur in this heterodimer. The efficiency of both photophysical processes depends strongly on solvent polarity and is related to the separation distance of the two chromophores and their relative orientation. The value of ΔG obtained using the Rehm-Weller equation clearly indicates that the heterodimer exists preferably in the “boat form” upon excitation in good agreement with the experimental results of co-occurence of energy and electron transfer process observed for the heterodimer.

TLR4 signaling and the inhibition of liver hepcidin expression by alcohol

AIM:To understand the role of toll-like receptor 4(TLR4)signaling in the regulation of iron-regulatory hormone,hepcidin by chronic alcohol consumption.METHODS:For chronic alcohol intake studies,TLR4mutant mice on C3H/HeJ background and wildtype counterpart on C3H/HeOuJ background were pair-fed with regular(control)and ethanol-containing Lieber De Carli liquids diets.Gene expression was determined by real-time quantitative PCR.Protein-protein interactions and protein expression were determined by co-immunoprecipitation and western blotting.The occupancy of hepcidin gene promoter was determined by chromatin immunoprecipitation assays.RESULTS:Chronic alcohol intake suppressed hepcidin mRNA expression in the livers of wildtype,but not TLR4 mutant,mice.The phosphorylation and nuclear translocation of nuclear factor(NF)-κB p65 subunit protein was observed in alcohol-fed wildtype,but not in alcohol-fed TLR4 mutant,mice.Similarly,alcohol induced the binding of NF-κB p50 subunit protein to hepcidin gene promoter in wildtype,but not in TLR4mutant,mice.In contrast,the phosphorylation of Stat3in the liver was stronger in alcohol-treated TLR4 mutant mice compared to alcohol-treated wildtype mice.The occupancy of hepcidin gene promoter by Stat3was observed in alcohol-fed mutant,but not in wildtype,mice.An interaction between NF-κB p65 subunit protein and small heterodimer partner protein(SHP)was observed in the livers of both wildtype and TLR4mutant mice fed with the control diet,as shown by coimmunoprecipitation studies.Alcohol intake elevated cytosolic SHP expression but attenuated its interaction with NF-κB in the liver,which was more prominent in the livers of wildtype compared to TLR4 mutant mice.CONCLUSION:Activation of TLR4 signaling and NF-кB are involved in the suppression of hepcidin gene transcription by alcohol in the presence of inflammation in the liver.

Abnormal DNA-PKcs and Ku 70/80 expression may promote malignant pathological processes in gastric carcinoma

AIM:To determine the expression of the catalytic subunit of DNA-dependent protein kinase(DNA-PKcs)and the Ku70/Ku80 heterodimer(Ku 70/80)in gastric carcinoma.METHODS:Gastric biopsies were obtained from 146gastric carcinoma patients[Helicobacter pylori(H.pylori)-negative:89 and H.pylori-positive:57]and 34from normal subjects(H.pylori-negative:16 and H.pylori-positive:18)via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University.Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system.An‘‘in-house’’rapid urease test and modified Giemsa staining were employed to detect H.pylori infection.The expression of DNA-PKcs and the Ku 70/80protein was detected by immunohistochemistry.RESULTS:Overall,the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer(χ2=133.04,P<0.001 for DNA-PKcs andχ2=13.06,P<0.01 for Ku)compared with normal gastric mucosa.There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa,and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0%(0/34),whereas the rate in gastric cancer(GC)was 93.8%(137/146).The difference between the two groups was statistically significant.Additionally,the positive rate of Ku 70/80 was79.4%(27/34)in normal gastric mucosa and 96.6%(141/146)in gastric cancer.The DNA-PKcs protein level was significantly increased in gastric cancer(MannWhitney U=39.00,P<0.001),compared with normal gastric mucosa.In addition,there was a significant difference in the expression of Ku 70/80(Mann-Whitney U=1117.00,P<0.001)between gastric cancer and normal gastric mucosa.There was also a significant difference in Ku70/80 protein expression between GC patients with and without H.pylori infection(P<0.05).Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression(r=-0.447,P<0.05).Moreover,Ku70/80 expression was negatively correlated with both clinical stage(r=-0.189,P<0.05)and H.pylori colonization(r=-0.168,P<0.05).CONCLUSION:Overall,this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.

Carrier frequency of HLA-DQB1*02 allele in patients affected with celiac disease:A systematic review assessing the potential rationale of a targeted allelic genotyping as a first-line screening

BACKGROUND Celiac Disease(CD)is an immune-mediated disorder,in which the HLA immunogenetic background(DQ2 and DQ8 heterodimers)and environmental trigger(gluten)are well established.Indeed,both factors are necessary–but not sufficient–to develop CD.However,it is very likely that CD is underdiagnosed in both developing and developed countries,due to several aspects,including the fact that a lot of patients present mild and/or atypical symptoms,without the presence of any recognized risk factors.Therefore,the possibility and feasibility of widened screening strategies to identify CD patients are debated.AIM To provide further evidence of the main epidemiological importance of HLADQB1*02 allele in the population of CD patients.METHODS We performed a systematic search in PubMed,EMBASE,Cochrane,Web of Science and Scopus databases,in order to produce a systematic review assessing the carrier frequency of HLA-DQB1*02 allele in the celiac population.Following the PRISMA guidelines,we retrieved all the original articles describing CD patients’HLA-DQB1 genotype in such a way that could allow to assess the HLADQB1*02 carrier frequency among CD patients,along with the evidence of the appropriate diagnostic work-up to achieve a correct and final diagnosis of CD.RESULTS The final output of this systematic search in the medical literature consisted of 38 studies providing the appropriate HLA-DQB1 genotype information of the respective CD population.According to this systematic review,including a pool of 4945 HLA-DQ genotyped CD patients,the HLA-DQB1*02 carrier frequency was 94.94%,meaning that only 5.06%of CD patients were completely lacking this allelic variant.Interestingly,if we consider only the studies whereby the prevalence of CD patients affected with type 1 diabetes mellitus was supposed or clearly established to be very low,the frequency of non-HLA-DQB1*02 carriers among CD patients dropped to 3.65%.CONCLUSION Such a high carrier frequency of the HLA-DQB1*02 allelic variant(which is>95%-96%in CD patients without risk factors,like type 1 diabetes mellitus comorbidity)might be exploited to consider a cost-effective and widened screening approach.If a sustainable strategy could be implemented through a low-cost targeted genetic test to detect the individual presence of HLA-DQB1*02 allele,an appropriate algorithm for serological screening in individuals resulting to be genetically predisposed to CD,might be considered.

G蛋白偶联受体异源二聚化在抑郁症中的作用

G蛋白偶联受体(G protein-coupled receptors,GPCRs)在人体中广泛表达,它所介导的信号转导在抑郁症的发生和发展中起到了非常重要的作用,是抗抑郁药物发挥药效的重要靶点。研究表明,GPCRs不仅以单体的形式存在,还可以以二聚体或高阶寡聚体的形式发挥作用。本文主要阐述了与抑郁症相关的GPCRs二聚体,以便更好地理解受体异源二聚体相互作用的分子机制,并为抑郁症的治疗提供更有效的方法。

Expression Characteristics and Putative Functions of KIF3A/KIF3B During Spermiogenesis of Phascolosoma esculenta

The microtubule(MT)-associated proteins KIF3A and KIF3B are ubiquitously expressed in a wide range of taxa.This study investigated the functions of these proteins in spermiogenesis,which involves various MT-dependent processes,in Phasco-losoma esculenta.We cloned the complete cDNA of Pe-KIF3A/3B.Structural predictions showed that Pe-KIF3A/3B are composed of a highly conserved motor domain,a coiled-coil domain,and a tail domain.Real-time quantitative PCR showed that Pe-kif3a/3b are expressed in all tissues evaluated,with the highest levels in sperm masses.Fluorescence in situ hybridization and immunofluo-rescence were employed to analyze the dynamic expression patterns of KIF3A/3B during spermiogenesis.Pe-KIF3A/3B consistently co-localized with MTs at all stages of spermiogenesis,indicating their potential functions in cargo trafficking.Pe-KIF3A/3B co-localized with mitochondria,suggesting that they may mediate mitochondrial movement.In late-stage spermatids and mature sperm,co-localization was detected in the midpiece,suggesting that Pe-KIF3A/3B could facilitate midpiece formation.The co-localization of Pe-KIF3A and Pe-KIF3B at all stages of spermiogenesis suggests their function as the heterodimeric KIF3AB.Basing on the ob-served temporal and spatial expression patterns of Pe-KIF3A/3B,MTs,and mitochondria in our study,we suggest that heterodimer KIF3AB has a potential role in acrosome biogenesis,sperm head remodeling,enflagellation,and mitochondrial migration during spermiogenesis in P.esculenta.In addition,our study on the morphological characteristics of spermatogenic cells provided fundamental data on the reproductive biology of P.esculenta.

Germline Deletion of the Expression of a Human Bispecific Mucosal Immunoglobulin: Genetic Predisposition to Cancer and Communicable Diseases Predominantly among African-Americans

In a previous report we had reported on the discovery of a novel bispecific immunoglobulin expressed by colonic epithelial cells as they transform into immunomimetic cells during exfoliation (Albaugh et al. (2020) Open Journal of Preventive Medicine, 10, 126-150). Colonic cells isolated from 0.5 gm aliquots of fresh stools (SCSR-10, Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD) preserved at room temperature for up to one week, with viability of >85% were used to determine the number of cells expressing this novel bispecific immunoglobulin. Over the course of this period (18 years) we recognized that these cells opened the opportunity to investigate the expression of cell membrane biomarkers. As the applications grew, we introduced a new terminology, termed COPROCYTOBIOLOGY*. In this study, we surveyed a cohort of 58 free-living adults for the expression of the newly discovered bi-specific chimeric antibody. Almost all of the subjects showed a strong signal during flow-cytometric evaluation of their stool samples;averaging around 65%. However, two subjects exhibited a total loss of this signal and both these individuals were of African-American lineage (one male and one female). These cells upon culturing in vitro remained defective in contrast to the rest of the group where their progeny continued to generate the antibody. We propose that this signals the existence of a germ-line deletion of the gene for which a novel test (MEDISHIELD†) is suggested. This syndrome may be associated with a lack of response to prophylactic vaccines involving m-RNA.

具荧光活性的节旋藻藻蓝蛋白α亚基在大肠杆菌中的重组表达

为探索节旋藻藻蓝蛋白的生物合成机理,以钝顶节旋藻(Arthrospira platensisFACHB314)基因组DNA为模板克隆了藻蓝蛋白α亚基基因cpcA、催化脱辅基蛋白与色基结合的裂合酶基因cpcE和cpcF,以及催化色基合成的铁氧蛋白氧化还原酶基因pcyA;以Synechocystissp.PCC6803基因组DNA为模板克隆了亚铁血红素氧化酶基因hox1。然后分别将cpcA、cpcE和cpcF基因构建到质粒pACYCDuet-1中,将hox1和pcyA基因构建到质粒pET-24a(+)中,用电击法将二者共同转化E.coliBL21(DE3),经诱导表达得到具有荧光活性的节旋藻藻蓝蛋白α亚基。在590 nm激发波长下,荧光发射峰为637.8 nm,证实了节旋藻自身的裂合酶CpcE和CpcF能够催化色基PCB与藻蓝蛋白脱辅基结合产生有荧光活性的藻蓝蛋白α亚基,为表达有荧光活性的藻蓝蛋白提供理论和实验基础。

G蛋白偶联受体研究进展

G蛋白偶联受体(G protein coupled receptors,GPCRs)是一类广泛存在于细胞表面具有7个跨膜螺旋的膜蛋白,是人体中种类和数量最多的膜受体蛋白家族.由于GPCR参与了生物体内的众多细胞信号转导和生理反应过程,所以GPCR已成为治疗多种疾病的重要药物靶点,其立体结构的解析对于相关药物设计具有非常重要的意义.通过查询相关学术期刊网上与GPCR相关文献并进行解析,简要综述了GPCR的结构、磷酸化、异源二聚化,GPCR与疾病及其靶向药物,然后对GPCR未来的相关研究进行展望.

Self-assembled nanoformulations of paclitaxel for enhanced cancer theranostics

Chemotherapy has occupied the critical position in cancer therapy,especially towards the post-operative,advanced,recurrent,and metastatic tumors.Paclitaxel(PTX)-based formulations have been widely used in clinical practice,while the therapeutic effect is far from satisfied due to off-target toxicity and drug resistance.The caseless multi-components make the preparation technology complicated and aggravate the concerns with the excipients-associated toxicity.The self-assembled PTX nanoparticles possess a high drug content and could incorporate various functional molecules for enhancing the therapeutic index.In this work,we summarize the self-assembly strategy for diverse nanodrugs of PTX.Then,the advancement of nanodrugs for tumor therapy,especially emphasis on monochemotherapy,combinational therapy,and theranostics,have been outlined.Finally,the challenges and potential improvements have been briefly spotlighted.