Does intraoperative reduction result in better outcomes in low-grade lumbar spondylolisthesis after transforaminal lumbar interbody fusion? A systematic review and meta-analysis

ObjectiveThis study aimed to compare the clinical efficacy and safety of reduction vs. arthrodesis in situ with transforaminal lumbar interbody fusion (TLIF) for low-grade lumbar spondylolisthesis.Study designSystematic review and meta-analysis.MethodsA comprehensive literature search was implemented in PubMed, Embase, and Cochrane Library databases. Randomized or non-randomized controlled trials that were published until July 2023 that compared reduction vs. arthrodesis in situ techniques with minimally invasive or open-TLIF for low-grade spondylolisthesis were selected. The quality of the included studies was evaluated by the Newcastle–Ottawa Scale (NOS). Data were extracted according to the predefined outcome measures, including operation time and intraoperative blood loss; short- and long-time follow-up of visual analog scale (VAS) back pain (VAS-BP) and Oswestry Disability Index (ODI); slippage and segmental lordosis; and the complication and fusion rate.ResultsFive studies (n = 495 patients) were finally included. All of them were retrospective cohort studies with Evidence Level II. The pooled data revealed that both techniques had similar patient-reported outcomes (VAS, ODI, and good and excellent rate) during short- and long-term follow-up. In addition, no significant differences were observed in the fusion and complication rates. However, although the reduction group did achieve better slippage correction, it was associated with increased operation time and intraoperative blood loss compared with the in situ arthrodesis group.ConclusionsBased on the available evidence, intraoperative reduction does not result in better clinical outcomes in low-grade spondylolisthesis after minimally invasive or open-TLIF, and the in situ arthrodesis technique could be an alternative

Raman Spectroscopy Characterization Extracellular Vesicles from Bovine Placenta and Peripheral Blood Mononuclear Cells

Placenta-derived extracellular vesicles (EVs) are involved in communication between the placenta and maternal immune cells possibly leading to a modulation of maternal T-cell signaling components. The ability to identify EVs in maternal blood may lead to the development of diagnostic and treatment tools for pregnancy complications. The objective of this work was to differentiate EVs from bovine placenta (trophoblast) and peripheral blood mononuclear cells (PBMC) by a label-free, non-invasive Raman spectroscopy technique. Extracellular vesicles were isolated by ultracentrifugation. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) were applied to verify the presence and the size distribution of EVs. Raman peaks at 728 cm-1 (collagen) and 1573 cm-1 (protein) were observed only in PBMC-derived EVs, while the peaks 702 cm-1 (cholesterol) and 1553 cm-1 (amide) appeared only in trophoblast-derived EVs. The discrimination of the Raman spectral fingerprints for both types of EVs from different animals was performed by principal component analysis (PCA) and linear discriminant analysis (LDA). The PCA and LDA results clearly segregated the spectral clusters between the two types of EVs. Moreover, the PBMC-derived EVs from different animals were indistinguishable, while the trophoblast-derived EVs from three placental samples of different gestational ages showed separate clusters. This study reports for the first time the Raman characteristic peaks for identification of PBMC and trophoblast-derived EVs. The development of this method also provides a potential tool for further studies investigating the causes and potential treatments for pregnancy complications

Use of Surface-Enhanced Raman Scattering (SERS) Probes to Detect Fatty Acid Receptor Activity in a Microfluidic Device

In this study, 4-mercaptobenzoic acid (MBA)-Au nanorods conjugated with a GPR120 antibody were developed as a highly sensitive surface-enhanced Raman spectroscopy (SERS) probe, and were applied to detect the interaction of fatty acids (FA) and their cognate receptor, GPR120, on the surface of human embryonic kidney cells (HEK293-GPRR120) cultured in a polydimethylsiloxane (PDMS) microfluidic device. Importantly, the two dominant characteristic SERS peaks of the Raman reporter molecule MBA, 1078 cm−1 and 1581 cm−1, do not overlap with the main Raman peaks from the PDMS substrate when the appropriate spectral scanning range is selected, which effectively avoided the interference from the PDMS background signals. The proposed microfluidic device consisted of two parts, that is, the concentration gradient generator (CGG) and the cell culture well array. The CGG part was fabricated to deliver five concentrations of FA simultaneously. A high aspect ratio well structure was designed to address the problem of HEK cells vulnerable to shear flow. The results showed a positive correlation between the SERS peak intensity and the FA concentrations. This work, for the first time, achieved the simultaneous monitoring of the Raman spectra of cells and the responses of the receptor in the cells upon the addition of fatty acid. The development of this method also provides a platform for the monitoring of cell membrane receptors on single-cell analysis using SERS in a PDMS-based microfluidic device

Electrochemical Detection of Metal Ions in Water Using a Six-Electrode Microfluidic Device

To be able to monitor concentration of hazardous metal ions in the environment using a simple, quick, and cost effective method is of great importance. Current standard methods such as, inductively coupled plasma and atomic absorption spectroscopy, are highly expensive and not convenient for field applications. A new device is proposed that has the potential of determining the presence of trace metals simultaneously in water using 6 gold electrodes deposited on a glass substrate in combination with an electrochemical method known as differential pulse stripping voltammetry. Microfluidic channels are incorporated into the device allowing solutions individual access to each electrode, while maintaining the option for testing bulk solutions on all electrodes at once. The device has proven effective at determining lead and cadmium ions simultaneously at sub parts per million concentrations, and has the capability to reach parts per billion. The ability to detect other metal ions such as zinc, chromium, nickel, and copper will be incorporated and tested using modifications to the surface of the gold electrodes. Thus providing a new method for quick and cost effective monitoring of water samples for multiple hazardous metal ions simultaneously

Microfluidic Chip for Non-Invasive Analysis of Tumor Cells Interaction with Anti-Cancer Drug Doxorubicin by AFM and Raman Spectroscopy

Raman spectroscopy has been playing an increasingly significant role for cell classification. Here, we introduce a novel microfluidic chip for non-invasive Raman cell natural fingerprint collection. Traditional Raman spectroscopy measurement of the cells grown in a Polydimethylsiloxane (PDMS) based microfluidic device suffers from the background noise from the substrate materials of PDMS when intended to apply as an in vitro cell assay. To overcome this disadvantage, the current device is designed with a middle layer of PDMS layer sandwiched by two MgF2slides which minimize the PDMS background signal in Raman measurement. Three cancer cell lines, including a human lung cancer cell A549, and human breast cancer cell lines MDA-MB-231 and MDA-MB-231/BRMS1, were cultured in this microdevice separately for a period of three days to evaluate the biocompatibility of the microfluidic system. In addition, atomic force microscopy (AFM) was used to measure the Young\u27s modulus and adhesion force of cancer cells at single cell level. The AFM results indicated that our microchannel environment did not seem to alter the cell biomechanical properties. The biochemical responses of cancer cells exposed to anti-cancer drug doxorubicin (DOX) up to 24 h were assessed by Raman spectroscopy. Principal component analysis over the Raman spectra indicated that cancer cells untreated and treated with DOX can be distinguished. This PDMS microfluidic device offers a non-invasive and reusable tool for in vitro Raman measurement of living cells, and can be potentially applied for anti-cancer drug screening

A Multi-Scale Approach to Study Biochemical and Biophysical Aspects of Resveratrol on Diesel Exhaust Particle-Human Primary Lung Cell Interaction

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm−1) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young’s modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs)

Delivery of therapeutic oligonucleotides in nanoscale

Therapeutic oligonucleotides (TOs) represent one of the most promising drug candidates in the targeted cancer treatment due to their high specificity and capability of modulating cellular pathways that are not readily druggable. However, efficiently delivering of TOs to cancer cellular targets is still the biggest challenge in promoting their clinical translations. Emerging as a significant drug delivery vector, nanoparticles (NPs) can not only protect TOs from nuclease degradation and enhance their tumor accumulation, but also can improve the cell uptake efficiency of TOs as well as the following endosomal escape to increase the therapeutic index. Furthermore, targeted and on-demand drug release of TOs can also be approached to minimize the risk of toxicity towards normal tissues using stimuli-responsive NPs. In the past decades, remarkable progresses have been made on the TOs delivery based on various NPs with specific purposes. In this review, we will first give a brief introduction on the basis of TOs as well as the action mechanisms of several typical TOs, and then describe the obstacles that prevent the clinical translation of TOs, followed by a comprehensive overview of the recent progresses on TOs delivery based on several various types of nanocarriers containing lipid-based nanoparticles, polymeric nanoparticles, gold nanoparticles, porous nanoparticles, DNA/RNA nanoassembly, extracellular vesicles, and imaging-guided drug delivery nanoparticles

Biophysical Assessment of Single Cell Cytotoxicity: Diesel Exhaust Particle-Treated Human Aortic Endothelial Cells

Exposure to diesel exhaust particles (DEPs), a major source of traffic-related air pollution, has become a serious health concern due to its adverse influences on human health including cardiovascular and respiratory disorders. To elucidate the relationship between biophysical properties (cell topography, cytoskeleton organizations, and cell mechanics) and functions of endothelial cells exposed to DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of DEPs on a model cell line from human aortic endothelial cells (HAECs). Fluorescence microscopy and flow cytometry were also applied to further explore DEP-induced cytotoxicity in HAECs. Results revealed that DEPs could negatively impair cell viability and alter membrane nanostructures and cytoskeleton components in a dosage- and a time-dependent manner; and analyses suggested that DEPs-induced hyperpolarization in HAECs appeared in a time-dependent manner, implying DEP treatment would lead to vasodilation, which could be supported by down-regulation of cell biophysical properties (e.g., cell elasticity). These findings are consistent with the conclusion that DEP exposure triggers important biochemical and biophysical changes that would negatively impact the pathological development of cardiovascular diseases. For example, DEP intervention would be one cause of vasodilation, which will expand understanding of biophysical aspects associated with DEP cytotoxicity in HAECs

In-vitro fluorescence imaging, surface-enhanced Raman spectroscopy and photothermal therapy of human lung adenocarcinoma epithelial cells by CaMoO4:Eu@Au hybrid nanoparticles

Multifunctional Eu3+-doped CaMoO4@Au-nanorods (GNR) core/shell nanoparticles (NPs) were synthesized for fluorescence imaging, SERS detection and PTT applications. Anti-epidermal growth factor receptor (EGFR) antibodies were conjugated with the synthesized NPs to enhance the specificity because EGFR, as a biomarker of cancer, was overexpressed on human lung adenocarcinoma epithelial cells (A549). The red fluorescence of the synthesized NPs coms from the Europium ion (Eu3+). The GNR component serves both as a SERS-active and PTT substrates. By conjugating with a Raman reporter molecule, 4-mercaptobenzoic acid (MBA), it generates SERS signals. Meantime, heat can be rapidly generated by 808 nm near-infrared (NIR) laser irradiation of the prepared NPs. Fluorescence microscopy exhibited that these particles largely located around cellular cytoplasm. Meantime, Raman mapping confirmed the distribution of these NPs by SERS characteristic peak selection. In addition, these NPs effectively suppressed A549 cells viability upon 808 nm laser irradiation. Thus, this study shows the potential of CaMoO4:Eu@GNR NPs with fluorescence imaging, SERS detection and PTT functionalities

In vitro biomechanical properties, fluorescence imaging, surface-enhanced Raman spectroscopy, and photothermal therapy evaluation of luminescent functionalized CaMoO4:Eu@Au hybrid nanorods on human lung adenocarcinoma epithelial cells

Highly dispersible Eu3+-doped CaMoO4@Au-nanorod hybrid nanoparticles (HNPs) exhibit optical properties, such as plasmon resonances in the near-infrared region at 790 nm and luminescence at 615 nm, offering multimodal capabilities: fluorescence imaging, surface-enhanced Raman spectroscopy (SERS) detection and photothermal therapy (PTT). HNPs were conjugated with a Raman reporter (4-mercaptobenzoic acid), showing a desired SERS signal (enhancement factor 5.0 × 105). The HNPs have a heat conversion efficiency of 25.6%, and a hyperthermia temperature of 42°C could be achieved by adjusting either concentration of HNPs, or laser power, or irradiation time. HNPs were modified with antibody specific to cancer biomarker epidermal growth factor receptor, then applied to human lung cancer (A549) and mouse hepatocyte cells (AML12), and in vitro PTT effect was studied. In addition, the biomechanical properties of A549 cells were quantified using atomic force microscopy. This study shows the potential applications of these HNPs in fluorescence imaging, SERS detection, and PTT with good photostability and biocompatibility