Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy.

Chemotherapy is one of the conventional treatments for cancer in clinical practice. However, poor delivery efficiency, systemic toxicity, and the lack of pharmacokinetic monitoring during treatment are the critical limitations of current chemotherapy. Herein, we reported a brand-new antitumor drug delivery strategy that harnesses an optical fiber endoscopically therapeutic probe. The fiber probe carries photosensitizers in the fiber core and antitumor agents on the fiber surface mediated by a temperature-responsive hydrogel film, giving rise to an activable photothermal-chemotherapy that orchestrates the localized hyperthermia and thermal-stimuli drug release to the tumor lesion. Furthermore, the dynamical drug release and in-situ temperature can be real-time supervised through the built-in fiber sensors, including the reflective Mach-Zehnder interferometer and fiber Bragg grating, to visualize the therapy process and thus improve the safety of treatment. Compared with conventional methods, the fiber-optic drug delivery can adequately take advantage of the chemotherapeutics through collaboratively recruiting the photoheating-mediated enhanced permeability and the hydrogel particle-assisted high drug retention, shedding new light on a "central-to-peripheral" drug pervasion and retention mechanism to destroy tumors completely. The fiber-optic chemotherapy strategy incorporates precise drug delivery, accurate controllability of drug release, high drug permeability and retention in tumor, low off-target rate, and real-time drug release and temperature feedback, performing a straightforward and precise photothermal-chemotherapy pathway. More than that, the proposed strategy holds tremendous promise to provide a revolutionized on-demand drug delivery platform for the highly efficient evaluation and screening of antitumor pharmaceuticals.

Glycyrrhiza Extract and Curcumin Alleviates the Toxicity of Cadmium via Improving the Antioxidant and Immune Functions of Black Goats.

To investigate the mitigative effects of glycyrrhiza extract (GE) and curcumin (CUR) on the antioxidant and immune functions of the Guizhou black goat exposed to cadmium (Cd), 50 healthy Guizhou black goats (11.08 ± 0.22 kg, male, six months old) were used in a 60-day trial and were randomly assigned to five groups with 10 replicates per group, one goat per replicate. All goats were fed a basal diet, with drinking water and additives varying slightly between groups. Control group: tap water (0.56 µg·L-1 Cd); Cd group: drinking water containing Cd (20 mg Cd·kg-1·body weight, CdCl2·2.5H2O); GE group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 GE; CUR group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 CUR; combined group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 GE and CUR. Compared with the Cd group, GE and CUR significantly increased the levels of hemoglobin and red blood cell count in the blood, and the activities of serum antioxidant enzyme activity and immune function in the Guizhou black goat (p < 0.05). The treatment effect in the combined group was better than that in the GE and CUR groups. The results showed that GE and CUR improved the antioxidant and immune functions of the serum and livers of the Guizhou black goat and alleviated the toxicity damage of Cd contamination. This research has positive implications for both livestock management and human health.

Magnetic microspheres enhanced peanut structure cascaded lasso shaped fiber laser biosensor for cancer marker-CEACAM5 detection in serum.

The detection of trace cancer markers in body fluids such as blood/serum is crucial for cancer diseases screening and treatment, which requires high sensitivity and specificity of biosensors. In this study, a peanut structure cascaded lasso (PSCL) shaped fiber sensing probe based on fiber laser demodulation method was proposed to specifically detect the carcinoembryonic antigen related cell adhesion molecules 5 (CEACAM5) protein in serum. Thanks for the narrow linewidth and high signal-to-noise ratio (SNR) of the laser spectrum, it is easier to distinguish small spectral changes than interference spectrum. Adding the antibody modified magnetic microspheres (MMS) to form the sandwich structure of "antibody-antigen-antibody-MMS", and amplified the response caused by biomolecular binding. The limit of detection (LOD) for CEACAM5 in buffer could reach 0.11 ng/mL. Considering the common threshold of 5 ng/mL for CEA during medical screening and the cut off limit of 2.5 ng/mL for some kits, the LOD of proposed biosensor meets the actual needs. Human serum samples from a hospital were used to validate the real sensing capability of proposed biosensor. The deviation between the measured value in various serum samples and the clinical value ranged from 1.9 to 9.8 %. This sensing scheme holds great potential to serve as a point of care testing (POCT) device and extend to more biosensing applications.

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.

Fiber Laser-Based Lasso-Shaped Biosensor for High Precision Detection of Cancer Biomarker-CEACAM5 in Serum.

Detection of trace tumor markers in blood/serum is essential for the early screening and prognosis of cancer diseases, which requires high sensitivity and specificity of the assays and biosensors. A variety of label-free optical fiber-based biosensors has been developed and yielded great opportunities for Point-of-Care Testing (POCT) of cancer biomarkers. The fiber biosensor, however, suffers from a compromise between the responsivity and stability of the sensing signal, which would deteriorate the sensing performance. In addition, the sophistication of sensor preparation hinders the reproduction and scale-up fabrication. To address these issues, in this study, a straightforward lasso-shaped fiber laser biosensor was proposed for the specific determination of carcinoembryonic antigen (CEA)-related cell adhesion molecules 5 (CEACAM5) protein in serum. Due to the ultra-narrow linewidth of the laser, a very small variation of lasing signal caused by biomolecular bonding can be clearly distinguished via high-resolution spectral analysis. The limit of detection (LOD) of the proposed biosensor could reach 9.6 ng/mL according to the buffer test. The sensing capability was further validated by a human serum-based cancer diagnosis trial, enabling great potential for clinical use. The high reproduction of fabrication allowed the mass production of the sensor and extended its utility to a broader biosensing field.

TET3 as a non-invasive screening tool for the detection of fibrosis in patients with chronic liver disease.

Ten-eleven translocation protein 3 (TET3) is one of the key enzymes in DNA demethylation which can be expressed in liver tissues. However, the clinical value of TET3 for diagnosis and treatment of chronic liver disease have not been reported previously. We investigated the diagnostic accuracy of serum TET3 as a non-invasive screening tool for liver fibrosis. 212 patients with chronic liver disease from were enrolled in this study. Enzyme-linked immunosorbent assay was used to measure the serum levels of TET3. Receiver operating characteristics (ROC) were determined to examine the diagnostic accuracy of TET3 and combination model for diagnosis fibrosis. Serum TET3 level in fibrosis cases was significantly higher than that in non-fibrosis and controls, respectively. The areas under the ROC curve of the TET3 and fibrosis-4 index for liver fibrosis were 0.863 and 0.813, and 0.916 and 0.957 for liver cirrhosis. The combination of TET3 and fibrosis-4 index had a highly promising positive predictive value for detecting liver fibrosis and cirrhosis different stages of (93.5% and 100%) as compared with each diagnostic tool alone. TET3 is related to the development of liver fibrosis and cirrhosis. The TET3-fibrosis-4 model enhances discriminatory power and represents a promising non-invasive tool for the diagnosis and screening of liver fibrosis.

Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) have a higher prevalence of hypertension and diabetes. However, the causal effects of these vascular risk factors on iNPH remain unclear. This study aimed to explore the causal relationship between vascular risk factors (VRFs) and iNPH. METHODS: We conducted the Mendelian randomization (MR) analysis of iNPH. We included nineteen vascular risk factors related to hypertension, diabetes, lipids, obesity, smoking, alcohol consumption, exercise, sleep, and cardiovascular events as exposure factors. We used the inverse-variance weighted method for causal effect estimation and weighted median, maximum likelihood, and MR Egger regression methods for sensitivity analyses. RESULTS: We found that genetically predicting essential hypertension (OR = 1.608 (1.330-1.944), p = 0.013) and increased sleep duration (OR = 16.395 (5.624-47.799), p = 0.009) were associated with higher odds of iNPH. Type 1 diabetes (OR = 0.869 (0.828-0.913), p = 0.004) was associated with lower odds of iNPH. For the other 16 VRFs, there was no evidence that they were significantly associated with iNPH. Sensitivity analyses showed that essential hypertension and type 1 diabetes were significantly associated with iNPH. CONCLUSION: In our MR study on VRFs and iNPH, we found essential hypertension to be a causal risk factor for iNPH. This suggests that hypertension may be involved in the pathophysiological mechanism of iNPH.

Visualizing nitroreductase activity in living cells and tissues under hypoxia and hepatic inflammation.

Detecting nitroreductase (NTR) activity in hypoxic cells and tissues in situ represents an important step toward accurate delineation of hypoxic disease loci. However, it remains challenging to develop fluorescent probes with the necessary attributes of selectivity, sensitivity, precise targeting and aqueous solubility. Herein, two kinds of fluorescent probes (NNP and cRGD-NNP) built on a 2-nitroimidazole sensing platform were synthesized for the detection of NTR activity in cell and in vivo models of hypoxia. In the presence of NADH, NNP displayed high selectivity for NTR, a strong fluorescence enhancement (108 fold), and a low detection limit (3.6 ng mL-1). Benefiting from the hydrophilic structure and tumor-targeting properties of the cRGD cyclopeptide group, the probe cRGD-NNP efficiently detected NTR activity in MCF cancer cells under hypoxia. In addition, the liposome-encapsulated probe was successfully applied to visualize NTR during liver inflammation in mice.

Fiber-Optic Theranostics (FOT): Interstitial Fiber-Optic Needles for Cancer Sensing and Therapy.

Photonics has spurred a myriad of diagnostic and therapeutic applications for defeating cancer owing to its superiority in spatiotemporal maneuverability and minimal harm. The limits of light penetration depth and elusiveness of photosensitizer utilization, however, impede the implementation of the photodiagnostic and -therapy for determining and annihilating the deep-situated tumor. Herein, a promising strategy that harnesses functional optical fibers is developed and demonstrated to realize an in vivo endoscopic cancer sensing and therapy ensemble. Tumor detection is investigated using hypoxia-sensitive fluorescent fibers to realize fast and accurate tumor recognition and diagnosis. The tumor treatment is further performed by exploiting the endogenous photothermal effect of rare-earth-doped optical fibers. The eradication of orthotopic and subcutaneous xenografts significantly validates the availability of tumoricidal fibers. The strategy opens horizons to inspire the design of optical fiber-mediated "plug and play" precise tumor theranostics with high safety, which may intrigue broader fields, such as fiber optics, materials, chemistry, medicine, and clinics.

Development of an optical microfiber immunosensor for prostate specific antigen analysis using a high-order-diffraction long period grating.

Fiber-optic biosensors are of great interest to many bio/chemical sensing applications. In this study, we demonstrate a high-order-diffraction long period grating (HOD-LPG) for the detection of prostate specific antigen (PSA). A HOD-LPG with a period number of less than ten and an elongated grating pitch could realize a temperature-insensitive and bending-independent biosensor. The bio-functionalized HOD-LPG was capable of detecting PSA in phosphate buffered saline with concentrations ranging from 5 to 500 ng/ml and exhibited excellent specificity. A limit of detection of 9.9 ng/ml was achieved, which is promising for analysis of the prostate specific antigen.

Inverse Molecular Sentinel-Integrated Fiberoptic Sensor for Direct and in Situ Detection of miRNA Targets.

Molecular advances have been made in analysis systems for a wide variety of applications ranging from biodiagnostics, biosafety, bioengineering, and biofuel research applications. There are, however, limited practical tools necessary for in situ and accurate detection of nucleic acid targets during field work. New technology is needed to translate these molecular advances from laboratory settings into the real-life practical monitoring realm. The exquisite characteristics (e.g., sensitivity and adaptability) of plasmonic nanosensors have made them attractive candidates for field-ready sensing applications. Herein, we have developed a fiber-based plasmonic sensor capable of direct detection (i.e., no washing steps required) of nucleic acid targets, which can be detected simply by immerging the sensor in the sample solution. This sensor is composed of an optical fiber that is decorated with plasmonic nanoprobes based on silver-coated gold nanostars (AuNS@Ag) to detect target nucleic acids using the surface-enhanced Raman scattering (SERS) sensing mechanism of nanoprobes referred to as inverse molecular sentinels (iMS). These fiber-optrodes can be reused for several detection-regeneration cycles (>6). The usefulness and applicability of the iMS fiber-sensors was tested by detecting target miRNA in extracts from leaves of plants that were induced to have different expression levels of miRNA targets. These fiber-optrodes enable direct detection of miRNA in plant tissue extract without the need for complex assays by simply immersing the fiber in the sample solution. The results indicate the fiber-based sensors developed herein have the potential to be a powerful tool for field and in situ analysis of nucleic acid samples.

Fiber Light-Coupled Optofluidic Waveguide (FLOW) Immunosensor for Highly Sensitive Detection of p53 Protein.

Highly sensitive detection of molecular tumor markers is essential for biomarker-based cancer diagnostics. In this work, we showcase the implementation of fiber light-coupled optofluidic waveguide (FLOW) immunosensor for the detection of p53 protein, a typical tumor marker. The FLOW consists of a liquid-core capillary and an accompanying optical fiber, which allows evanescent interaction between light and microfluidic sample. Molecular binding at internal surface of the capillary induces a response in wavelength shift of the transmission spectrum in the optical fiber. To enable highly sensitive molecular detection, the evanescent-wave interaction has been strengthened by enlarging shape factor R via fine geometry control. The proposed FLOW immunosensor works with flowing microfluid, which increases the surface molecular coverage and improves the detection limit. As a result, the FLOW immunosensor presents a log-linear response to the tumor protein at concentrations ranging from 10 fg/mL up to 10 ng/mL. In addition, the nonspecifically adsorbed molecules can be effectively removed by the fluid at an optimal flow rate, which benefits the accuracy of the measurement. Tested in serum samples, the FLOW successfully maintains its sensitivity and specificity on p53 protein, making it suitable for diagnostics applications.

Label-Free Detection of Cancer Biomarkers Using an In-Line Taper Fiber-Optic Interferometer and a Fiber Bragg Grating.

A compact and label-free optical fiber sensor based on a taper interferometer cascaded with a fiber Bragg grating (FBG) is proposed and experimentally demonstrated for detection of a breast cancer biomarker (HER2). The tapered fiber-optic interferometer is extremely sensitive to the ambient refractive index (RI). In addition, being insensitive to the RI variation, the FBG can be applied as a temperature thermometer due to its independent response to the temperature. Surface functionalization to the sensor is carried out to achieve specific targeting of the unlabeled biomarkers. The result shows that the proposed sensor presents a low limit-of-detection (LOD) of 2 ng/mL, enabling its potentials of application in early diagnosis on the breast cancer.

Targeting autophagy in multiple myeloma.

Autophagy plays an important role in plasma cell ontogeny and in the pathophysiology of multiple myeloma. Autophagy is usually considered a pro-survival mechanism, and cooperates with the ubiquitin proteasome system in maintaining the homeostasis of myeloma cells by degrading excessive and misfolded proteins for energy recycling. Therefore, the inhibition of autophagy could effectively induce death in myeloma cells, and could synergize with proteasome inhibitors. However, the excessive activation of autophagy could also lead to the extreme degradation of the organelles that induce autophagic cell death. Hence, the activation of autophagic cell death might also represent a promising approach for treating myeloma. Recent studies have demonstrated that autophagy also mediates drug resistance in myeloma cells and the complications of myeloma, while the inhibition of autophagy may reverse the response to drugs. In this study, we have mainly reviewed recent research on autophagy in relationship to the therapeutic effect, the reversal of drug resistance, and the mediation of complications.

Nasopharyngeal carcinoma segmentation via HMRF-EM with maximum entropy.

This paper presents a novel automatic nasopharyngeal carcinoma segmentation approach used in magnetic resonance images. Adaptive calculation of the nasopharyngeal region location is first performed. The contour of the tumor is determined through distance regularized level set evolution with the initial contour obtained by the nearest neighbor graph model. To further refine the segmentation, a hidden Markov random field model with maximum entropy (HMRF-EM) is introduced to model the spatial information with prior knowledge. The proposed method is tested on magnetic resonance images of 26 nasopharyngeal carcinoma patients, and achieves good results.