Hypoxia exosome derived CEACAM5 promotes tumor-associated macrophages M2 polarization to accelerate pancreatic neuroendocrine tumors metastasis via MMP9.

Exosomes play significant roles in the communications between tumor cells and tumor microenvironment. However, the specific mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic neuroendocrine tumors (pNETs) are not well understood. This study aims to investigate these mechanisms and made several important discoveries. We found that hypoxic exosomes derived from pNETs cells can activate tumor-associated macrophages (TAM) to the M2 phenotype, in turn, the M2-polarized TAM, facilitate the migration and invasion of pNETs cells. Further investigation revealed that CEACAM5, a protein highly expressed in hypoxic pNETs cells, is enriched in hypoxic pNETs cell-derived exosomes. Hypoxic exosomal CEACAM5 was observed to induce M2 polarization of TAM through activation of the MAPK signaling pathway. Coculturing pNETs cells with TAM or treated with hypoxic exosomes enhanced the metastatic capacity of pNETs cells. In conclusion, these findings suggest that pNETs cells generate CEACAM5-rich exosomes in a hypoxic microenvironment, which in turn polarize TAM promote malignant invasion of pNETs cells. Targeting exosomal CEACAM5 could potentially serve as a diagnostic and therapeutic strategy for pNETs.

Direction-switchable transverse optical torque on a dipolar phase-change nanoparticle.

We propose that a transition from positive optical torque (OT) to negative OT occurs in a dipolar nanoparticle subjected to a simple optical field composed of two circularly polarized plane waves. This phenomenon can be observed in a phase-change nanoparticle comprising insulating and metallic phases. The analytical expression based on the multipole expansion theory reveals that the positive OT in the metallic phase originates from the electric response during light-matter interaction. However, in the insulating phase, the magnetic response is excited, leading to a significant negative OT due to the contribution of the magnetic field-magnetic dipole interaction. It is noted that the phenomenon of reversible transverse OT is robust to the angle between two constituent plane waves, ensuring its practical application.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Comparing the interactions of nitrendipine with lysozyme or human serum albumin and the effects of vitamin C and naringin on these interactions by spectroscopy and molecular docking methods.

The interactions between drugs and proteins play a pivotal role in determining the pharmacological effects and disposition of drugs within the human body. This study focuses on exploring the interaction between nitrendipine and lysozyme/human serum albumin. Spectroscopic analysis indicated a compound static quenching, indicative of the formation of stable complexes between the drug and proteins. The addition of vitamin C or naringin resulted in a decrease of the binding constant between nitrendipine and lysozyme/human serum albumin. The presence of these compounds may disrupt the interactions between the drug and proteins, potentially leading to an increased concentration of free nitrendipine in the bloodstream. Nitrendipine binds more easily to human serum albumin at 310 K, and human serum albumin has an average binding site ratio with nitrendipine approximately 0.1 higher than that with lysozyme. Vitamin C has a greater impact on the binding constant of nitrendipine to human serum albumin and lysozyme. Compared to the binary system of proteins with the drug, the ternary system with the addition of vitamin C at 310 K reduces the binding constants of lysozyme and human serum albumin by 85%. In conclusion, this study explores the significance of considering drug-protein interactions in understanding drug behavior and potential drug-food interactions.

Enhanced transverse optical gradient force on Rayleigh particles in two plane waves.

Based on the full wave simulation and the Maxwell stress tensor theory, we demonstrate an enhanced transverse optical gradient force acting on Rayleigh particles immersed in a simple optical field formed by two linearly polarized plane waves. The optical gradient force acting on a conventional dielectric particle can be enhanced by two orders of magnitude via coating an extremely thin silver shell, whose thickness is only about one-tenth of the dielectric core. The analytical results based on the multipole expansion theory reveal that the enhanced optical gradient force comes mostly from the interaction between the incident field and the electric quadrupole excited in the core-shell particle. It is worth noting that the force expression within the dipole approximation commonly used for Rayleigh particles is invalid in our situation, even the particle is within the Rayleigh regime. In addition, both the optical potential energy and the optical trapping stiffness for the core-shell particle exhibit a great enhancement by two orders of magnitude stronger than a conventional dielectric particle and thus is favorable to a stable optical trapping. These results may extend the application range of optical tweezers and enrich optical manipulation techniques.

Anomalously enhanced transverse optical torque on a dipolar plasmonic nanoparticle in two-wave interference.

Based on the multipole expansion theory, we show that a transverse optical torque acting on a dipolar plasmonic spherical nanoparticle can be anomalously enhanced in two plane waves with linear polarization. Compared with a homogeneous Au nanoparticle, the transverse optical torque acting on an Au-Ag core-shell nanoparticle with an ultra-thin shell thickness can be dramatically enhanced by more than two orders of magnitude. Such enhanced transverse optical torque is dominated by the interaction between the incident optical field and the electric quadrupole excited in the dipolar core-shell nanoparticle. It is thus noted that the torque expression based on the dipole approximation usually used for dipolar particles is not available even in our dipolar case. These findings deepen the physical understanding of the optical torque (OT) and may have applications in optically driven rotation of plasmonic microparticles.

Quantitative study of conservative gradient force and non-conservative scattering force exerted on a spherical particle in optical tweezers.

We rigorously calculate the conservative gradient force (GF) and the non-conservative scattering force (SF) associated with the optical tweezers (the single beam optical trap). A wide range of parameters are considered, with particle size ranging from the Rayleigh to Mie regime (radius ∼3 µm), dielectric constant ranging from metallic (large and negative) to high dielectrics (large and positive), numerical aperture (NA) ranging from 0.5 to 1.33, and different polarizations. The trap depth associated with GF can reach 123 and 168 kBT per mW for a 0.5 µm-radius polystyrene particle illuminated by a 1064 nm Gaussian beam with NA = 0.9 and 1.3, respectively. This indicates that unless at a low beam power or with a small NA, the Brownian fluctuations do not play a role in the stability. The transverse GF orthogonal to beam propagation always dominates over the transverse SF. While the longitudinal SF can be larger than the longitudinal GF when the scattering is strong, the NA is small, or when absorption is present, optical trapping under these conditions is difficult. Generally speaking, absorption reduces GF and enhances SF, while increasing a dielectric constant enhances GF slightly but boosts SF significantly owing to stronger scattering. These results verify previous experimental observations and explain why optical tweezers are so robust across such a wide range of conditions. Our quantitative calculations will also provide a guide to future studies.

Tailoring the gradient and scattering forces for longitudinal sorting of generic-size chiral particles.

Based on the concepts of conservative and non-conservative optical forces (COF and NCOF), we analyze the physical mechanism of longitudinal chirality sorting along the direction of light propagation in some simple optical fields. It is demonstrated, both numerically and analytically for particle of arbitrary size, that the sorting relies solely on the NCOF, which switches its direction when particle chirality is reversed. For particles larger than half of the optical wavelength λ, the NCOF far surpasses its counterpart COF, enabling the longitudinal chirality sorting. When the particle is much smaller than λ, however, the COF outweighs the NCOF, destroying the sorting mechanism. A scenario is thus proposed that totally eliminates the COF while leaving the sorting NCOF unchanged, extending the applicability of longitudinal chirality sorting to small particles.

Lateral Optical Force due to the Breaking of Electric-Magnetic Symmetry.

Lateral optical forces in a direction perpendicular to light propagation have attracted increasing interest in recent years. Up to now, all lateral forces can be attributed to the symmetry breaking in the lateral directions caused by either the morphology of the scatterer geometry or the optical fields impinging on the scatterer. Here we demonstrate, both numerically and analytically, that when an isotropic scatterer breaks the electric-magnetic symmetry, a new type of anomalous lateral force can be induced along the direction of translational invariance where the illumination striking the scatterer has no propagation, field gradient, or spin density vortex (Belinfante's spin momentum). Our analytical results are rigorous for an arbitrary size scatterer, ensuring the universality of our conclusion. Furthermore, the electric-magnetic symmetry-breaking-induced lateral force is comparable in magnitude to other components of the optical force and reversible in direction for different polarizations of the illuminating light, rendering it capable of practical optical manipulation as well as enriching the understanding of light-matter interaction.

Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice.

Radix Paeoniae Alba (RPA) is widely used in clinical treatment for gynecological diseases, particularly abnormal menstruation, menstrual pain, and breast tenderness; however, no scientific evidence base links RPA to estrogen replacement therapy. In this study, we characterize estrogenic activity of RPA using immature and ovariectomized (OVX) mice together with in vitro studies focus on estrogen receptor (ER) pathway for molecular mechanism. RPA treatments demonstrated significant estrogenic activity, as indicated by promoting the development of uterus and vagina in immature mice, reversing the atrophy of uterus and vagina in OVX mice, up-regulating the expressions of ERα and ERß at protein and mRNA level in reproductive tissues. Meanwhile, RPA significantly increased serum estradiol and clearly decreased serum luteinizing hormone and follicle-stimulating hormone of immature/OVX mice. Moreover, RPA could induce ER positive MCF-7 cell from S-phase to G2 stage and induce proliferation and no influence on ER negative MDA-MB-231 cell. RPA could bind with ERα and ERß and significantly stimulate ERα/ß-estrogen response element (ERE) luciferase reporter gene expression. All activities were inhibited by the ER antagonist ICI 182,780. This study illustrates RPA exerts estrogenic effects by stimulating biosynthesis of estrogen in circulation, up-regulating ERs in target tissues, and mimicking the estrogen through ER-ERE-dependent pathway.

Involvement of nerve growth factor in mouse hippocampal neuronal cell line (HT22) differentiation and underlying role of DNA methyltransferases.

DNA methylation is an epigenetic event involved in regulation of gene transcription during cell differentiation. DNA methyltransferases (DNMT) play a role in differentiation of neural stem cells into neurons. The aim of this study was to determine whether nerve growth factor (NGF) was involved in differentiation of mouse hippocampal neuronal cell line (HT22) as assessed by IncuCyte. Quantitative PCR and western blot were used to measure gene and protein expression of DNMT as well as the activity of DNMTs. Treatment with NGF was found to upregulate both gene and protein expressions as well as total activity of DNMTs in differentiating HT22 cells. Compared to undifferentiating cells, the percentage of differentiating cells at S phase increased significantly when incubated with NGF. In undifferentiated cells, NGF failed to induce gene and protein expressions and activity of DNMTs. Data demonstrate that differentiation of HT22 cells by exposure to NGF involve the activation of DNMTs pathway.

The influence of Schisandrin B on a model of Alzheimer's disease using ß-amyloid protein Aß1-42-mediated damage in SH-SY5Y neuronal cell line and underlying mechanisms.

Schisandrin B, an active substance, is derived from Chinese herb fruit Wuweizi, which exerts various pharmacological activities and has displayed significant beneficial effects in ameliorating Alzheimer's disease (AD). The aim of this study was to further extend our examination for the use of schisandrin B extract in the potential treatment of AD effects by investigating DNA methylation (DNMT), known to be modified in this disease using SH-SY5Y neuronal cell line exposed to ß-amyloid protein (Aß1-42). In particular, the purpose of this investigation was to examine alterations in mRNA and protein expression of DNMT. Data demonstrated that schisandrin B blocked Aß1-42-mediated injury in SH-SY5Y neuronal cell line as evidenced by a restoration of cellular morphology and cell viability to approximate control levels at the highest 10 µg/ml Schisandrin B. Incubation with Aß1-42 significantly decreased mRNA and protein expression of DNMT3A and DNMT1 in SH-SY5Y neuronal cell line. Incubation with Aß1-42 followed by 24 treatment with schisandrin B significantly inhibited the Aß1-42 -induced changes in mRNA and protein expression of DNMT3A and DNMT3B in a concentration-dependent manner. It is of interest that the mRNA expression of DNMT3A and DNMT1 were significantly higher than control. Data thus indicate schisandrin B was effective in inhibiting the actions of Aß1-42 on cell survival and morphology and that DNA methylation may be associated with the beneficial findings.

[Research progress in phytoestrogens of traditional Chinese medicine].

Phytoestrogens are plant-derived compounds, which have a similarity in structure with human endogenous estrogen 17-ß-estradiol. Structural likeness enables phytoestrogens to interact with estrogen receptors, not simply mimicking the effects of human steroidal estrogen but also exhibiting similar and divergent actions. The global literature relating to phytoestrogen in recent years was systematically summarized in this paper. Chemical compositions of phytoestrogens were mainly flavonoids, coumarins, lignans, terpenoids, steroids, etc., with a character of prevention and treatment of perimenopausal syndrome, osteoporosis, cardiovascular disease, metabolic diseases, cancer, regulation of brain function and other pharmacological effects. The mechanisms of action mainly included classical estrogen receptor pathway, epigenetic effect, activation of 5'-adenosyl-phospho-activated protein kinase, inhibition of kinase, activation of peroxisome proliferator-activated receptor, regulation of apoptosis-related proteins, inhibition of nuclear factor κB signaling pathway and so on. According to their efficacy classification, phytoestrogens were mainly distributed in the tonifying medicines, blood-activating and stasis-resolving medicines and heat-clearing medicines. The classical prescriptions with estrogen activity included tonifying formula, Qi-regulating formula and harmonizing formula, etc. This review was aimed at providing a certain reference for the further study of phytoestrogens by researchers and clinicians.

[Effect of Coixenolide on Foxp3+ CD4+ CD25+ Regulatory T Cells in Collagen-induced Arthritis Mice].

OBJECTIVE: To study the effect of coixenolide on Foxp3+ CD4+ CD25+ regulatory T cells (Treg) in collagen induced arthritis (CIA) mice, and to explore its possible mechanism for treating rheumatiol arthritis. METHODS: Five mice were recruited as a normal control group from 25 mice, and the rest 20 were used in CIA modeling. After successful modeling they were randomly divided in the model control group and the coixenolide group, 10 in each group. Coixenolide injection at 25 mL/kg was intraperitoneally injected to mice in the coixenolide group, while normal saline at 25 mL/kg was intraperitoneally injected to mice in the normal control group and the model control group. The injection lasted for 21 days. Scoring for CIA was performed after injection and arthritis index was calculated. The peripheral blood Foxp3+ CD4+ CD25+ Treg ratio was determined by flow cytometry (FCM). RESULTS: Compared with the normal control group, the arthritis index obviously increased in the model control group (P < 0.01). The arthritis index obviously decreased more in the coixenolide group than in the model control group (P < 0.01). Foxp3+ CD4+ CD25+ Treg levels obviously decreased more in the model control group than in the normal control group (P < 0.01 ). Foxp3+ CD4+ CD25+ Treg levels obviously increased more in the coixenolide control group than in the model control group (P < 0.01). CONCLUSION: Coixenolide could up-regulate Foxp3+ CD4+ CD25+ Treg ratios in CIA mice, which might play certain immunoregulation roles in the incidence of CIA.

Rice false smut pathogen: implications for mycotoxin contamination, current status, and future perspectives.

Rice serves as a staple food across various continents worldwide. The rice plant faces significant threats from a range of fungal, bacterial, and viral pathogens. Among these, rice false smut disease (RFS) caused by Villosiclava virens is one of the devastating diseases in rice fields. This disease is widespread in major rice-growing regions such as China, Pakistan, Bangladesh, India, and others, leading to significant losses in rice plantations. Various toxins are produced during the infection of this disease in rice plants, impacting the fertilization process as well. This review paper lightens the disease cycle, plant immunity, and infection process during RFS. Mycotoxin production in RFS affects rice plants in multiple ways, although the exact phenomena are still unknown.

Synthesis of Aryl-methylene Ethers through Pd(0)-Catalyzed Coupling between Hydrobenzoxazoles and Dichloromethane.

Using dichloromethane (DCM) as the C1 feedstock, the first Pd(0)-catalyzed synthesis of aryl-methylene ether motifs from hydrobenzoxazoles (hydrothiazoles) has been reported. This protocol has exhibited an ample substrate scope (38 examples) and wide functional group tolerance. Aryl-methylene ether adducts have been successfully engaged in coupling with isocyanate to provide bis-iminoisoindolinones. In this reaction, DCM has served as a twofold electrophile for reaction with hydrobenzoxazoles via double C-Cl bond cleavage.

Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease.

Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood-brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6-RES-OPC-HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6-RES-OPC-HA nanoparticles have the potential to prevent and alleviate early AD.

Reshifting Na+ from Shoots into Long Roots Is Associated with Salt Tolerance in Two Contrasting Inbred Maize (Zea mays L.) Lines.

Maize, as a glycophyte, is hypersensitive to salinity, but the salt response mechanism of maize remains unclear. In this study, the physiological, biochemical, and molecular responses of two contrasting inbred lines, the salt-tolerant QXH0121 and salt-sensitive QXN233 lines, were investigated in response to salt stress. Under salt stress, the tolerant QXH0121 line exhibited good performance, while in the sensitive QXN233 line, there were negative effects on the growth of the leaves and roots. The most important finding was that QXH0121 could reshift Na+ from shoots into long roots, migrate excess Na+ in shoots to alleviate salt damage to shoots, and also improve K+ retention in shoots, which were closely associated with the enhanced expression levels of ZmHAK1 and ZmNHX1 in QXH0121 compared to those in QXN233 under salt stress. Additionally, QXH0121 leaves accumulated more proline, soluble protein, and sugar contents and had higher SOD activity levels than those observed in QXN233, which correlated with the upregulation of ZmP5CR, ZmBADH, ZmTPS1, and ZmSOD4 in QXH0121 leaves. These were the main causes of the higher salt tolerance of QXH0121 in contrast to QXN233. These results broaden our knowledge about the underlying mechanism of salt tolerance in different maize varieties, providing novel insights into breeding maize with a high level of salt resistance.

Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation.

BACKGROUND: In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1), which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control. METHODS: Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay. RESULTS: We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5' flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen) and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation. CONCLUSIONS: Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.

Structural characterization of hydrogel-oleogel biphasic systems as affected by oleogelators.

This work developed novel bi-phasic gel systems containing a hydrogel (κ-carrageenan) and an oleogel, and investigated the roles of different oleogelators (glycerol monostearate-GMS and beeswax-BW) on the structures of the bigels. Stable bigels were obtained via a facile blending approach by carefully controlling the mixing temperature. Microstructural observation indicated that GMS-based bigels were of oil-in-water type, and BW-based bigels were of water-in-oil type. In GMS-based bigels, both water holding capacity and oil holding capacity after freeze-thawing were enhanced with the increase in GMS content. The bigel with 8% (w/w) GMS had water holding capacity and oil holding capacity of 94.81% and 93.13%, respectively. In BW-based bigels, oil holding capacity was also increased (from 36.98% to 88.39%), but separation of oleogel and hydrogel was detected after centrifugation. Textural and rheological analysis revealed that gel strength of the bigels were gradually increased with the increase in oleogelator content, and BW-based bigels were much stronger than GMS-based ones. Moreover, BW-based bigels had higher relaxation degree. DSC analysis found that thermodynamic stability of the bigels were increased with the increase in oleogelator content. Temperature sweep rheological analysis indicated that GMS-based bigels were not able to fully recover their original structure and gel strength after heating-cooling cycle due to the nature of the crystals formed in bigels. This study offered profound structural information about the bigels as affected by different oleogelators, which was also useful for the development of novel functional products.