Motile bacteria are able to penetrate in the distal areas of blood vessel, which makes bacteria attractive to researchers as a drug delivery vehicle carrying anti-cancer drugs to tumors. Not only ...therapeutic bacteria show wide anti-tumor effect but also the combination of therapeutic bacteria and conventional chemotherapy leads to dramatically large synergetic effect. We provide a mechanistic understanding of enhanced drug delivery in tumors by co-administration of chemotherapeutic agents and therapeutic bacteria. In this work, simultaneous delivery of C. novyi-NT and chemotherapeutic agents in tumors is mathematically modeled. Simulated doxorubicin concentration in tumors after Doxil administration with or without bacteria agreed reasonably well with experimental literature. Simulated doxorubicin concentration in tumors by the combination of Doxil and C. novyi-NT is over twice higher than that of Doxil alone. This enhanced doxorubicin concentration in tumors is due to the degradation of extracellular matrix of collagen by bacterial proteolytic activity, which increases hydraulic conductivity of interstitium, reduces interstitial fluid pressure, and thus increases convection through vessel walls. Additionally, it alleviates solid stress, which decompresses blood vessels, and thus increases vessel density. On the other hand, simulated doxorubicin concentration in tumors for non-liposomal free-doxorubicin is not enhanced by C. novyi-NT because vascular permeability of free-doxorubicin is larger than Doxil, and thus increased but relatively small convection across vessel walls is offset by the efflux due to increased interstitial flow. A strategy to further enhance this combination therapy is discussed along with sensitivity analysis.
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•Delivery of anti-cancer agents and therapeutic bacteria in tumors is mathematically modeled.•Predicetd drug concentraiton in tumors for both Doxil and doxorubicin compared well•Degradation of ECM of collagen by bacterial proteolysis reduces interstitial fluid pressure.•Reduced interstitial fluid pressure increases convection through vessel walls
As oral or intestinal bacteria have been found in pancreatic cystic fluid and tumors, understanding bacterial migration from the duodenum into the pancreas via hepato-pancreatic duct is critical. ...Mathematical models of migration of aerobic bacteria from the duodenum to the pancreas with tumors were developed. Additionally, the bacterial distributions under the pH gradient and those under flow were measured in double-layer flow based microfluidic device and T-shaped cylinders. Migration of aerobic bacteria from the duodenum into pancreas is counteracted by bile and pancreatic juice flow but facilitated by pH-taxis from acidic duodenum fluid toward more favorable slightly alkaline pH in pancreatic juice. Additionally, the reduced flow velocity in cancer patients, due to compressed pancreatic duct by solid tumor, facilitates migration. Moreover, measured distribution of GFP E. coli under the pH gradient in a microfluidic device validated pH-tactic behaviors. Furthermore, Pseudomonas fluorescens in hydrochloride solution, but not in bicarbonate solution, migrated upstream against bicarbonate flow of > 20 μm/s, with an advancement at approximately 50 μm/s.
Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates ...that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC (migDC) populations, specifically increasing and activating the Lang
and CD11b
Lang
subsets in skin, and that the Ab responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave NIR laser adjuvant showed limited effects on the migDC subsets. Our vaccination study demonstrated that the efficacy of the CW NIR laser is significantly better than that of the pulsed wave laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migDCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migDC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by an NIR laser-adjuvanted vaccine.
Oxygen molecules are essential for producing energy in living organisms, meaning that oxygen measurement is required not only in the medical field, but also in research experiments. Porphyrin dyes in ...polystyrene microparticles were loaded and embedded in dimethylpolysiloxane to create oxygen sensing film. The lifetime of phosphorescence emitted from the film by laser excitation varied depending on the oxygen concentration, and the oxygen partial pressure was quantified from the lifetime. We revealed that the smaller the microparticle size and film thickness, the shorter the response time to the change in oxygen concentration. Next, the film was placed in cell culture microfluidic devices that can form oxygen gradients in the culture layer, and changes of the gradients due to oxygen metabolism of cells and implanted tumor tissues on the sensing film. From this, we demonstrated the effectiveness of the developed oxygen sensing film for medical and biological applications.
Early detection of various diseases is expected using surface-enhanced Raman scattering (SERS). For example, a method of labeling an antibody of a disease-related molecule on metal nanoparticles and ...detecting the SERS signals of the particles bound to the antigen is a promising approach. However, the problems of a slow antigen–antibody reaction and low sensitivity remain unsolved. In this study, we fabricated nanoparticles that can be freely moved using an external magnetic field for rapid antigen–antibody reaction and also nanoengineered the substrate to increase the density of hotspots required for SERS. Gold-coated magnetic nanoparticles (Au-MNPs) with a core–shell structure were prepared by applying multiple coatings of gold onto magnetic iron(II,III) oxide nanoparticles, which were used as the core. A neodymium magnet easily moved and converged the Au-MNPs in the solution within a few seconds. In addition, a silver nanoparticle substrate (Ag-NS) with a hexagonal close-packed structure fixed on a polydimethylsiloxane thin film was prepared, and the stable generation of SERS was confirmed over the entire substrate. Upon aggregation of the Au-MNPs onto Ag-NS using a neodymium magnet, the total SERS strength per unit area drastically increased, suggesting that the combination of Au-MNPs and Ag-NS increased the density of the generated hotspots. In future work, with the labeling of antibodies onto Au-MNPs, we expect the proposed method to be applied in the sensitive measurement of biomarkers associated with diseases.
Except for histological study, there are currently no suitable techniques available for the detection and identification of primordial follicles in ovary of primary ovarian insufficiency patients who ...have undetectable AMH levels. Also, the ability to locate and quantify follicles on ovarian cortex strips, without fixation, is valuable for patients who could undergo subsequent successful ovarian tissue transplantation. Although optical coherence tomography (OCT) is a well-established high resolution imaging technique without fixation commonly applied in biomedicine, few reports are available on ovarian tissue imaging. In present study, we established standard OCT follicle images at each developmental stage, including the primordial follicle, and demonstrated the efficacy of OCT to estimate IVF outcome in transplanted mice ovary like ovarian reserve tests. Unfortunately, the current commercial OCT could not be used to accurate follicle count the number of follicles for whole ovary, because the maximum depth of examination was 100 μm. And we demonstrated the safety of OCT examination, it did not affect IVF outcome and birth defect rate, and reproductive ability. Although there is room for improvement, these findings will be first step to bring OCT examination a step closer to clinical application for measuring true ovarian reserve and localizing follicles.
Purpose
A treatment device without a stent is needed for peripheral stenotic artery treatment. We have proposed short-term heating balloon angioplasty, photo-thermo dynamic balloon angioplasty ...(PTDBA). Though smooth muscle cells (SMCs) after PTDBA are fixed in a stretched formation in a porcine model, influences of this stimulus on SMCs have not been investigated. SMC migration after vascular dilatation would be related to chronic restenosis. The aim of this study was to examine respiratory activity and recovery ability of SMCs after short-term heating/stretch-fixing
in vitro
for chronic phase treatment effect discussion.
Methods
SMCs on a stretch chamber were heated for 15 s with stretching and fixed in a stretched formation. SMC migration is correlated with the cell respiratory activity. The amount of ATP production was measured using a WST-8 assay for respiratory activity evaluation. The intracellular expression of heat shock protein 70 was measured by an ELISA for recovery ability evaluation.
Results
In the case of 60 °C heating, SMC respiratory activity after short-term heating/stretch-fixing decreased drastically in all stretching rates. In the case of 50 °C heating, SMC respiratory activity decreased and then increased. Alternatively, the recovery ability at 60 °C was greater than that at 50 °C.
Conclusions
SMCs heated at 60 °C with stretching would have high recovery ability and low respiratory activity related to SMC migration. These results may be important evidence in determining the treatment condition in PTDBA.
Minimally invasive medical operations, especially endoscope operations, have attracted much attention and play a major role in modern medicine. Endoscope operations are superior to decrease ...incisions, enabling good post-operation progress. However, during its implementation, blood adheres to the lens of the endoscope, resulting in obstructed vision. This prolongs the operation time and causes the patient to gain weight. Hence, we developed a blood-repelling and transparent material for coating the surface of an endoscope lens. The coating material was produced from plant oil and a rough material for trapping the oil. Edible plant oil was particularly used to enable application to medical devices. A fine surface asperity was achieved by a one-dip treatment, which also enhanced the capillary force and durability of the oil under a water shower. The application of the developed coating material to an endoscope lens in an animal experiment enabled the effective repulsion of blood and other body fluids, the maintenance of a clear vision, and high transmittance. The developed coating material promises to contribute to the achievement of antifouling surfaces in medical devices.
The treatment of skin with a low-power continuous-wave (CW) near-infrared (NIR) laser prior to vaccination is an emerging strategy to augment the immune response to intradermal vaccine, potentially ...substituting for chemical adjuvant, which has been linked to adverse effects of vaccines. This approach proved to be low cost, simple, small, and readily translatable compared with the previously explored pulsed-wave medical lasers. However, little is known on the mode of laser-tissue interaction eliciting the adjuvant effect. In this study, we sought to identify the pathways leading to the immunological events by examining the alteration of responses resulting from genetic ablation of innate subsets including mast cells and specific dendritic cell populations in an established model of intradermal vaccination and analyzing functional changes of skin microcirculation upon the CW NIR laser treatment in mice. We found that a CW NIR laser transiently stimulates mast cells via generation of reactive oxygen species, establishes an immunostimulatory milieu in the exposed tissue, and provides migration cues for dermal CD103
dendritic cells without inducing prolonged inflammation, ultimately augmenting the adaptive immune response. These results indicate that use of an NIR laser with distinct wavelength and power is a safe and effective tool to reproducibly modulate innate programs in skin. These mechanistic findings would accelerate the clinical translation of this technology and warrant further explorations into the broader application of NIR lasers to the treatment of immune-related skin diseases.
Tiny amount of bacteria are found in the pancreas in pancreatitis and cancer, which seemed involved in inflammation and carcinogenesis. However, bacterial infiltration from the duodenum is inhibited ...by the physical defense mechanisms such as bile flow and the sphincter of Oddi. To understand how the bacteria possibly infiltrate the pancreas through a deformable pancreatic duct, influenced by the periodic contractions of the sphincter of Oddi, a mathematical model of bacterial infiltration is developed that considered large deformation, fluid flow, and bacterial transport in a deformable pancreatic duct. In addition, the sphincter's contraction wave is modeled by including its propagation from the pancreas toward the duodenum. Simulated structure of the deformed duct with the relaxed sphincter and simulated bile distribution agreed reasonably well with the literature, validating the model. Bacterial infiltration from the duodenum in a deformable pancreatic duct, following the sphincter's contraction, is counteracted by a gradual peristalsis-like deformation of the pancreatic duct, due to an antegrade contraction wave propagation from the pancreas to the duodenum, Parametric sensitivity analysis demonstrated that bacterial infiltration is increased with lower bile and pancreatic juice flow rate, greater contraction amplitude and frequency, thinner wall thickness, and retrograde contraction wave propagation. Since contraction waves following retrograde propagation are increased in patients with common bile duct stones and pancreatitis, they may possibly be factors for continuum inflammation of pancreas. (224 words).
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