Application of fluorocarbon nanoparticles of 131I-fulvestrant as a targeted radiation drug for endocrine therapy on human breast cancer.

BACKGROUND: Breast cancer is the most prevalent malignant tumor among women, with hormone receptor-positive cases constituting 70%. Fulvestrant, an antagonist for these receptors, is utilized for advanced metastatic hormone receptor-positive breast cancer. Yet, its inhibitory effect on tumor cells is not strong, and it lacks direct cytotoxicity. Consequently, there's a significant challenge in preventing recurrence and metastasis once cancer cells develop resistance to fulvestrant. METHOD: To address these challenges, we engineered tumor-targeting nanoparticles termed 131I-fulvestrant-ALA-PFP-FA-NPs. This involved labeling fulvestrant with 131I to create 131I-fulvestrant. Subsequently, we incorporated the 131I-fulvestrant and 5-aminolevulinic acid (ALA) into fluorocarbon nanoparticles with folate as the targeting agent. This design facilitates a tri-modal therapeutic approach-endocrine therapy, radiotherapy, and PDT for estrogen receptor-positive breast cancer. RESULTS: Our in vivo and in vitro tests showed that the drug-laden nanoparticles effectively zeroed in on tumors. This targeting efficiency was corroborated using SPECT-CT imaging, confocal microscopy, and small animal fluorescence imaging. The 131I-fulvestrant-ALA-PFP-FA-NPs maintained stability and showcased potent antitumor capabilities due to the synergism of endocrine therapy, radiotherapy, and CR-PDT. Throughout the treatment duration, we detected no notable irregularities in hematological, biochemical, or histological evaluations. CONCLUSION: We've pioneered a nanoparticle system loaded with radioactive isotope 131I, endocrine therapeutic agents, and a photosensitizer precursor. This system offers a combined modality of radiotherapy, endocrine treatment, and PDT for breast cancer.

Spatial optimization mode of China's rural settlements based on quality-of-life theory.

This paper studies the optimization mode of the spatial organization of rural settlements based on the two-way interactive mechanism between the space of rural settlements and quality-of-life theory. It examines three main aspects: the integration of spatial function, the optimization of spatial structure, and the regulation of spatial scale. In this paper, we built an optimization mode and framework of spatial organization, called the road-oriented mode of rural settlements, based on quality-of-life theory. We systematically analyzed the mode's conceptual connotation, construction principles, frame, type, and spatial scale. At the same time, this paper realized the reasonable proportion and optimized combination of internal spatial type in settlements and focused on a reasonably sized scale of a single settlement and the distance scale between settlements. Our findings can be used as insight into the theoretical development of the spatial structure of rural areas. Results also provide a scientific basis for future spatial optimization and integration of rural settlements to improve quality of life.

Vincristine-cyclophosphamide combination therapy positively affects T-cell subset distribution in systemic lupus erythematosus patients.

BACKGROUND: This study aimed to analyze the T-cell subset distribution in systemic lupus erythematosus (SLE) patients and determine whether vincristine-cyclophosphamide combination therapy can positively affect their T-cell subset distribution to keep the disease in remission. MATERIAL AND METHODS: Thirteen SLE patients with 'low activity' (SLE Disease Activity Index (SLEDAI)≤9), 17 SLE patients with 'high activity' (SLEDAI>9), and 15 healthy controls were recruited. SLE patients were treated with vincristine-cyclophosphamide combination therapy. CD3+, CD4+, and CD8+ T-cell percentages were analyzed by flow cytometry at baseline, 3 months, 6 months, 12-24 months, and >24 months. RESULTS: Significantly negative correlations were observed between the CD3+ and CD4+ T-cell percentages and SLEDAI scores at baseline (r=-0.471, P=0.015; r=-0.473, P=0.015, respectively). A significantly positive correlation was observed between CD4+ T-cell percentage and the complement component C3 at baseline (r=0.612, P=0.002). After 3 months of combination therapy, the CD3+ and CD4+ T-cell percentages were significantly higher than the high activity baseline (P<0.01, P<0.05, respectively). After 6 months, the CD3+, CD4+, and CD8+ T-cell percentages were all significantly higher than the high activity baseline (P<0.01, P<0.05, P<0.05, respectively). CONCLUSIONS: T-cell subset distributions vary across different levels of SLE disease activity with higher CD3+ T-cell and CD4+ Th cell percentages favoring lower SLE activity. As CD3+ T-cell and CD4+ Th cell percentages negatively correlate with SLEDAI, vincristine-cyclophosphamide combination therapy appears to positively affect the T-cell subset distribution in SLE patients to keep the disease in remission by increasing their CD3+ T-cell and CD4+ Th cell percentages.

A new modified animal model of myosin-induced experimental autoimmune myositis enhanced by defibrase.

INTRODUCTION: We investigated the effect of defibrase (a proteolytic enzyme extraction of Agkistrodon halys venom) on experimental autoimmune myositis (EAM) in guinea pigs and explored the option of using a modified pig model of EAM to enhance the study of this disease. MATERIAL AND METHODS: Guinea pigs were divided into 3 groups: group A (control group) was immunized with complete Freund adjuvant (CFA), then received 6 injections of saline weekly; group B (EAM group) was immunized with partially purified rabbit myosin emulsified with CFA, then received an injection of saline; group C (EAM + defibrase group) was immunized with purified rabbit myosin emulsified with CFA, then received an injection of defibrase. The animals were observed for their general health condition and the body weight was measured daily. Plasma levels of fibrinogen and creatine kinase (CK) were determined. Muscle tissues were examined histologically. RESULTS: After immunizations for 6 weeks, incidence of EAM in groups A, B and C was 0 (0/7), 83.3% (10/12) and 100% (15/15), respectively. Guinea pigs with EAM presented angeitis symptoms of muscle weakness. Histological analysis revealed a significant difference. Muscles with EAM had scattered or diffuse inflammatory manifestations, which are also common pathological features of human idiopathic polymyositis (IPM). Defibrase-treated animals displayed extensive inflammation and fiber necrosis compared with the EAM group (histological score: 2.80 ±1.15 vs. 1.88 ±1.32, p < 0.05). Severity of inflammation of group B was mainly mild to moderate; 16.7% (2/12) of animals developed severe inflammation. Incidence of severe inflammation with a score up to 4 in group C was 40% (6/15). CONCLUSIONS: Defibrase can exacerbate myosin-induced EAM; thus a new modified model was generated.

Probabilistic MRI brain anatomical atlases based on 1,000 Chinese subjects.

Brain atlases are designed to provide a standard reference coordinate system of the brain for neuroscience research. Existing human brain atlases are widely used to provide anatomical references and information regarding structural characteristics of the brain. The majority of them, however, are derived from one paticipant or small samples of the Western population. This poses a limitation for scientific studies on Eastern subjects. In this study, 10 new Chinese brain atlases for different ages and genders were constructed using MR anatomical images based on HAMMER (Hierarchical Attribute Matching Mechanism for Elastic Registration). A total of 1,000 Chinese volunteers ranging from 18 to 70 years old participated in this study. These population-specific brain atlases represent the basic structural characteristics of the Chinese population. They may be utilized for basic neuroscience studies and clinical diagnosis, including evaluation of neurological and neuropsychiatric disorders, in Chinese patients and those from other Eastern countries.

BoLA-DRB3 gene polymorphism and FMD resistance or susceptibility in Wanbei cattle.

For the further characterization of foot-and-mouth disease virus (FMDV)-induced foot-and-mouth disease, we investigated the association between polymorphism of BoLA-DRB3 gene and FMD resistance/susceptibility of Wanbei cattle challenged with FMDV. One hundred cattle were challenged with FMDV and exon 2 of BoLA-DRB3 genes was amplified by hemi-nested polymerase chain reaction from asymptomatic animals and from animals with FMD. PCR products were characterized by the RFLP technique using restriction enzymes Hae III. The results revealed extensive polymorphisms, 6 RFLP patterns were identified. By analyzing alleles and genotypic frequencies between healthy and infection with FMD cattle, we found that allele Hae III A was associated with susceptibility to FMD in Wanbei cattle (P < 0.05), whereas Hae III C was associated with resistance to FMD (P < 0.01) and may have a strong protective effect against FMD. Hae IIICC and Hae III BC genotype were associated with resistance to FMD (P < 0.01). By contrast, Hae III AA genotype was associated with susceptibility to FMD (P < 0.01). Sequence analysis show that 89 amino acids were translated in exon 2 of BoLA-DRB3 and 13.70 % of nucleotide mutated, which resulted in 14.61 % of amino acid change. One PKC, one Tyr and one CAMP phosphorylation were increased; the hydrophobicity and secondary structure of proteins produced change after amino acid substitution. These results revealed that Wanbei cattle had the ability of resistance to disease by mutation which result changes of the protein structure to perform the regulation of the cell using different signaling pathways in the long process of choice evolution.

Self-assembly and emulsification of poly{[styrene-alt-maleic acid]-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]}.

Self-assembled polymeric micelles can be used as efficient particulate emulsifiers. To explore the relationship between the structure and the oil-water interfacial behavior of the micelle emulsifiers, a new type of amphiphilic random copolymer, poly{(styrene-alt-maleic acid)-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]} (SMA-Dopa), was synthesized, self-assembled into micelles, and used as emulsifiers. SMA-Dopa was synthesized via an aminolysis reaction between dopamine and commercial alternating copolymer poly(styrene-alt-maleic anhydride) (SMA). Dopamine moiety facilitated the self-assembly of the SMA-Dopa in selective-solvent into stable micelles, and increased the adsorption of the SMA-Dopa at the oil-water interface. Additionally, the structural transition of the self-assembled SMA-Dopa52 micelles in response to pH and salinity changes were confirmed by means of TEM, AFM, DLS, aqueous electrophoresis techniques, potentiometric titration, and pyrene fluorescence probe methods. Micelles shrunk with increasing salinity, and flocculation of the shrunken primary micelles occurred at salt concentration exceeding 0.1 M. The micelles swelled with increasing pH, and the disassociation of the SMA-Dopa52 micelles occurred at pH above approximately 6.5. The structure of the micelles plays a crucial role in the oil-water interfacial performance. Micelles with various structures were used as emulsifiers to adsorb at the styrene-water and toluene-water interfaces. The emulsifying characteristics demonstrated that self-assembled SMA-Dopa52 micelles with moderately swollen structure (at 2 < pH < 6) combine the advantages of the solid particulate emulsifiers and polymeric surfactants, possessing excellent emulsifying efficiency and good emulsion stability. Moreover, the emulsifying performance of the SMA-Dopa52 micelles could be enhanced by the addition of salt.

Does Powerlessness Explain Elevated HIV Risk Amongst Tajik Labor Migrants? An Ethnographic Study.

To investigate the role of powerlessness in elevated HIV risk among labor migrants, we compared internal verses external male migrant workers from Tajikistan using minimally structured interviews and focused field observations. The sample included 30 male labor migrants who traveled to work in Regar, Tajikistan (internal labor migrants), and 30 who traveled to work in Moscow, Russia (external labor migrants). Though powerlessness did not appear to account for whether labor migrants engaged in more HIV risk behaviors, the harsh living and working conditions of external labor migration impacted how the migrants manifested these HIV risks by amplifying group masculine norms and behaviors. Progress in preventing HIV infection amid the difficult social conditions of labor migration is contingent upon adequate conceptualization of how such conditions impact HIV risk behaviors.

Is endometrial polyp formation associated with increased expression of vascular endothelial growth factor and transforming growth factor-beta1?

OBJECTIVE: Endometrial polyp is a common cause of abnormal uterine bleeding, but the etiology and pathogenesis remain unclear. Vascular endothelial growth factor (VEGF) is angiogenic, related to thick walled vessels and transforming growth factor-beta1 (TGF-ß1) is related to fibrotic tissue, which are characteristics of endometrial polyps. The primary objective of this study was to find out if endometrial polyp formation is associated with increased expression of VEGF or TGF-ß1, or both. A secondary objective is to determine if the changes are related to steroid receptor expression. STUDY DESIGN: This prospective study compared VEGF and TGF-ß1 expression of endometrial polyps and adjacent endometrial tissue in 70 premenopausal women. The comparison of results was separately made for endometrium specimens obtained in the proliferative and secretory phases. The results were correlated with the steroid receptors (estrogen receptor and progesterone receptor) expression. RESULTS: The score of VEGF in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P<0.001) and the secretory phase (P=0.03); the score of VEGF in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium only in proliferative phase (P=0.006). The score of TGF-ß1 in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium in proliferative phase (P=0.02); whereas the score of TGF-ß1 in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P=0.006) and the secretory phase (P=0.008). There was a significant correlation between the expression of steroid receptors and VEGF and TGF-ß1 (Spearman's correlation P<0.001 and P<0.05, respectively). CONCLUSIONS: There was increased expression of TGF-ß1 and VEGF in polyps compared to adjacent normal endometrial tissue. It suggested that these cytokines might play a role in endometrial polyp formation. In addition, there was a significant correlation between steroid receptor expression and VEGF and TGF-ß1 expression.

Numerical simulation of bubble dynamics in a micro-channel under a nonuniform electric field.

A numerical method is used to simulate the motion and coalescence of air bubbles in a micro-channel under a nonuniform electric field. The channel is equipped with arrays of electrodes embedded in its wall and voltages are applied on the electrodes to generate a specified electric field gradient in the longitudinal direction. In the study, the Navier-Stokes equations are solved by using the level set method handling the deformable/moving interfaces between the bubbles and the ambient liquid. Both the polarization Coulomb force and the dielectrophoresis force are considered as the force source of the Navier-Stokes equations by solving the Maxwell's equations. The flow field equations and the electric field equations are coupled and solved by using the finite element method. The electric field characteristics and the dynamic behavior of a bubble are analyzed by studying the distributions of the electric field and the force, the deformation and the moving velocity of the air bubble. The result suggests that the model of dispersed drops suspended in the immiscible dielectric liquid and driven by a nonuniform electric field is an effective method for the transportation and coalescence of micro-drops.

Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.

A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.

Synthesis and biological evaluation of bicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes.

A series of novel bicyclo[3.3.0]octane derivatives have been synthesized and found to be dipeptidyl peptidase 4 (DPP-4) inhibitors. Compounds 10a and 10b demonstrate good efficacies in oral glucose tolerance tests.

Hepatitis E virus chimeric DNA vaccine elicits immunologic response in mice.

AIM: To construct the plasmid pcHEV23 containing fragments of HEV ORF2 and ORF3 chimeric gene and to assess its ability to elicit specific immunologic response in mice. METHODS: The gene encoding the structural protein of HEV ORF2 fragment and full-length ORF3 was amplified by PCR. The PCR products were cloned into an eucaryotic expression plasmid pcDNA3. The resulting plasmid pcHEV23 was used as a DNA vaccine to inoculate BALB/c mice intramuscularly thrice at a dose of 100 or 200 microg. Mice injected with empty pcDNA3 DNA or saline served as control and then specific immune responses in the mice were detected. RESULTS: After 2-3 times of inoculation, all mice injected with pcHEV23 had anti-HEV IgG seroconversion and specific T lymphocyte proliferation. The lymphocyte stimulation index in the group immunized with pcHEV23 (3.1+/-0.49) was higher than that in the control group (0.787+/-0.12, P<0.01). None in the control group had a detectable level of anti-HEV IgG. CONCLUSION: DNA vaccine containing HEV ORF2 and ORF3 chimeric gene can successfully induce specific humoral and cellular immune response in mice.