Nanoscale Extracellular Vesicle-Enabled Liquid Biopsy: Advances and Challenges for Lung Cancer Detection.

Lung cancer is responsible for the death of over a million people worldwide every year. With its high mortality rate and exponentially growing number of new cases, lung cancer is a major threat to public health. The high mortality and poor survival rates of lung cancer patients can be attributed to its stealth progression and late diagnosis. For a long time, intrusive tissue biopsy has been considered the gold standard for lung cancer diagnosis and subtyping; however, the intrinsic limitations of tissue biopsy cannot be overlooked. In addition to being invasive and costly, it also suffers from limitations in sensitivity and specificity, is not suitable for repeated sampling, provides restricted information about the tumor and its molecular landscape, and is inaccessible in several cases. To cope with this, advancements in diagnostic technologies, such as liquid biopsy, have shown great prospects. Liquid biopsy is an innovative non-invasive approach in which cancer-related components called biomarkers are detected in body fluids, such as blood, urine, saliva and others. It offers a less invasive alternative with the potential for applications such as routine screening, predicting treatment outcomes, evaluating treatment effectiveness, detecting residual disease, or disease recurrence. A large number of research articles have indicated extracellular vesicles (EVs) as ideal biomarkers for liquid biopsy. EVs are a heterogeneous collection of membranous nanoparticles with diverse sizes, contents, and surface markers. EVs play a critical role in pathophysiological states and have gained prominence as diagnostic and prognostic biomarkers for multiple diseases, including lung cancer. In this review, we provide a detailed overview of the potential of EV-based liquid biopsy for lung cancer. Moreover, it highlights the strengths and weaknesses of various contemporary techniques for EV isolation and analysis in addition to the challenges that need to be addressed to ensure the widespread clinical application of EV-based liquid biopsies for lung cancer. In summary, EV-based liquid biopsies present interesting opportunities for the development of novel diagnostic and prognostic platforms for lung cancer, one of the most abundant cancers responsible for millions of cancer-related deaths worldwide.

Matrine-loaded Nano-liposome Induces Apoptosis in Human Esophageal-squamous Carcinoma KYSE-150 Cells.

INTRODUCTION: Esophageal-squamous Cell Carcinoma (ESCC) is often diagnosed at the middle or late stage, thus requiring more effective therapeutic strategies. Pharmacologically, the anti-tumor activity of the principal active constituent of Sophora flavescens, matrine (MA), has been explored widely. Notwithstanding, it is significant to nanotechnologically enhance the anti-tumor activity of MA in view of its potential to distribute non-tumor cells. METHODS: Herein, MA-loaded Nano-Liposomes (MNLs) were prepared to enhance the effect of anti-ESCC. The MNL showed a smaller sized particle (25.95 ± 1.02 nm) with a low polydispersed index (PDI = 0.130 ± 0.054), uniform spherical morphology, good solution stability, and encapsulated efficiency (65.55% ± 2.47). Furthermore, we determined the characteristics of KYSE-150 cells by cell viability assay, IC50, Mitochondrial Membrane Potential (MMP), Western blot, and apoptotic analysis, which indicated that MNLs down-regulated the cell viability and IC50 in a concentration-dependent manner and induced a significant change in JC-1 fluorescence from red to green. RESULTS: The above observations resulted in increased Bax and Caspase-3 levels, coupled with a substantial decrease in Bcl-2 and apoptotic promotion at the advanced stage compared with MA. CONCLUSION: Based on these results, MNLs may serve as a more effective and promising therapeutic option for ESCC.

Biomimetic gold nanocages incorporating copper-human serum albumin for tumor immunotherapy via cuproptosis-lactate regulation.

Cancer immunotherapy remains a significant challenge due to insufficient proliferation of immune cells and the sturdy immunosuppressive tumor microenvironment. Herein, we proposed the hypothesis of cuproptosis-lactate regulation to provoke cuproptosis and enhance anti-tumor immunity. For this purpose, copper-human serum albumin nanocomplex loaded gold nanocages with bacterial membrane coating (BAu-CuNCs) were developed. The targeted delivery and disassembly of BAu-CuNCs in tumor cells initiated a cascade of reactions. Under near infrared (NIR) laser irradiation, the release of copper-human serum albumin (Cu-HSA) was enhanced that reacted with intratumoral glutathione (GSH) via a disulfide exchange reaction to liberate Cu2+ ions and exert cuproptosis. Subsequently, the cuproptosis effect triggered immunogenic cell death (ICD) in tumor by the release of damage associated molecular patterns (DAMPs) to realize anti-tumor immunity via robust production of cytotoxic T cells (CD8+) and helper T cells (CD4+). Meanwhile, under NIR irradiation, gold nanocages (AuNCs) promoted excessive reactive oxygen species (ROS) generation that played a primary role in inhibiting glycolysis, reducing the lactate and ATP level. The combine action of lower lactate level, ATP reduction and GSH depletion further sensitized the tumor cells to cuproptosis. Also, the lower lactate production led to the significant blockage of immunosuppressive T regulatory cells (Tregs) and boosted the anti-tumor immunity. Additionally, the effective inhibition of breast cancer metastasis to the lungs enhanced the anti-tumor therapeutic impact of BAu-CuNCs + NIR treatment. Hence, BAu-CuNCs + NIR concurrently induced cuproptosis, ICD and hindered lactate production, leading to the inhibition of tumor growth, remodeling of the immunosuppressive tumor microenvironment and suppression of lung metastasis. Therefore, leveraging cuproptosis-lactate regulation, this approach presents a novel strategy for enhanced tumor immunotherapy.

Maximizing arsenic trioxide's anticancer potential: Targeted nanocarriers for solid tumor therapy.

Arsenic trioxide (ATO) has gained significant attention due to its promising therapeutic effects in treating different diseases, particularly acute promyelocytic leukemia (APL). Its potent anticancer mechanisms have been extensively studied. Despite the great efficacy ATO shows in fighting cancers, drawbacks in the clinical use are obvious, especially for solid tumors, which include rapid renal clearance and short half-life, severe adverse effects, and high toxicity to normal cells. Recently, the emergence of nanomedicine offers a potential solution to these limitations. The enhanced biocompatibility, excellent targeting capability, and desirable effectiveness have attracted much interest. Therefore, we summarized various nanocarriers for targeted delivery of ATO to solid tumors. We also provided detailed anticancer mechanisms of ATO in treating cancers, its clinical trials and shortcomings as well as the combination therapy of ATO and other chemotherapeutic agents for reduced drug resistance and synergistic effects. Finally, the future study direction and prospects were also presented.

The Protective Effects of Ecdysterone on Cognitive Impairment through Regulating Akt/GSK-3ß/Nrf2 Signaling Pathway and Oxidative Stress in Cognitive Mice Model and Aß-Induced Cell Neurotoxicity.

BACKGROUND: Severe neurological condition like Alzheimer's disease (AD) has a significantly negative impact on families and society, wherein there is no proven cure. As one of the principal active constituents of Achyranthes bidentata Blume, ecdysterone (ECR) has demonstrated antioxidant and cognitive dysfunction improvement effects. Nonetheless, the mechanism underlying the improvement of cognitive dysfunction by ECR remains unclear. This study sought to ascertain whether ECR may allebviate cognitive impairment by reducing oxidative stress via activation of the nuclear factor erythroid-2-related factor-2 (Nrf2) antioxidant system through Akt/GSK3ß pathway. METHODS: In terms of the experimental procedure, we determined the neuroprotective benefits of ECR in vivo via a cognitive impairment model of senescence-accelerated mouse prone 8 (SAMP8), we performed procedures such as behavioral testing, biochemical assaying, Nissl and TUNEL stainings, as well as flow cytometry, immunohistochemistry and western blotting. Furthermore, we investigated the underlying mechanistic action of ECR by activating PC12 cells with ß-amyloid peptide fragment 25-35 (Aß25-35). RESULTS: In vivo studies showed that ECR effectively improved cognitive impairment in SAMP8 via enhancement of learning and memory capabilities, but decreased oxidative stress, apoptosis and neuronal damage in the hippocampus. During the in vitro study, we observed that ECR dose-dependently reduced the oxidative stress and apoptosis that were induced in PC12 cells by Aß25-35. Additionally, the use of Akt inhibitors further established the potential of ECR to control Nrf2 through activation of the Akt/GSK3ß pathway and protect the PC12 cells from Aß25-35 induced damage. CONCLUSIONS: These findings offer proof that ECR reduces cognitive impairment by triggering the Nrf2 antioxidant system via the Akt/GSK3ß pathway and offer fresh information on ECR's potential as a promising therapeutic development candidate for AD.

A Synergistic Combination of Oleanolic Acid and Apatinib to Enhance Antitumor Effect on Liver Cancer Cells and Protect against Hepatic Injury.

BACKGROUND: As a pentacyclic triterpenoid, OA (oleanolic acid) has exhibited antiinflammatory, immunomodulatory and antitumor effects. VEGFR-2 (vascular endothelial cells receptor-2) tyrosine kinase activity could be inhibited by apatinib, a small-molecule antiangiogenic agent. OBJECTIVE: Thus, this study sought to investigate the mechanism underlying the synergistic antitumor activity of combined OA and apatinib patent. METHODS: Through CCK8 (Cell counting kit 8 assay), flow cytometric and western blotting techniques, we conducted in vitro studies on apatinib and OA effects on cell proliferation and apoptosis in H22 cell line. H22 tumor-burdened mice model was established in vivo, while the related signaling pathways were studied via pathological examination, western blotting and qPCR (quantitative polymerase chain reaction). RESULTS: Growth of H22 cells in vitro and in vivo could be inhibited effectively by apatinib and OA. Thus, OA repaired liver function and inhibited oxidative stress induced by apatinib. CONCLUSION: OA can treat apatinib induced liver injury in H22 Tumor-burdened mice by enhancing the suppresssive effect of apatinib on the growth of tumor.

Tumor-derived microvesicles for cancer therapy.

Extracellular vesicles (EVs) are vesicles with lipid bilayer structures shed from the plasma membrane of cells. Microvesicles (MVs) are a subset of EVs containing proteins, lipids, nucleic acids, and other metabolites. MVs can be produced under specific cell stimulation conditions and isolated by modern separation technology. Due to their tumor homing and large volume, tumor cell-derived microvesicles (TMVs) have attracted interest recently and become excellent delivery carriers for therapeutic vaccines, imaging agents or antitumor drugs. However, preparing sufficient and high-purity TMVs and conducting clinical transformation has become a challenge in this field. In this review, the recent research achievements in the generation, isolation, characterization, modification, and application of TMVs in cancer therapy are reviewed, and the challenges facing therapeutic applications are also highlighted.

SIRT6 Reduces Rheumatoid Arthritis Injury by Inhibiting MyD88-ERK Signaling Pathway.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by destruction of synovial joints, abnormal immune responses and chronic inflammatory manifestations, which seriously affects patients' well-being. We explored this study to ascertain the effect and mechanism of silent information regulator 6 (SIRT6) on RA. METHODS: Genes of RA patients and normal volunteers were analyzed using Gene Expression Omnibus (GEO), Kyoto-Encyclopedia of Genes and Genomes (KEGG) and Disconet databases. Serum samples of RA patients and normal subjects were collected before detection of myeloid differentiation factor-88 (MyD88)-extracellular signal-regulated kinase (ERK) pathway proteins expression with Western blot. In vitro RA fibroblast-like synoviocytes (FLS) cell model (RA-FLS) was established by treating RSC-364 with recombinant rat IL-1ß (10 ng/mL) after which SIRT6 and MyD88 adenoviruses treatment was carried out. The enzyme linked immunoassay (ELISA), real time polymerase chain reaction (RT-PCR) and Western blot were respectively used to measure inflammatory factors, related messenger ribonucleic acid (mRNA) and protein expressions. Also, we constructed RA rat model with bovine type II collagen (BIIC) and complete Freund's adjuvant, before treatment with SIRT6 and MyD88 adenoviruses. RESULTS: Low expression of SIRT6 gene were detected in RA patients. Also, levels of MyD88, ERK and phosphorylated extracellular signal-regulated protein kinase (p-ERK) protein expressions in RA patients were increased, whilst that of SIRT6 protein decreased. Compared to FLS cells in Control group, inflammatory factors levels of rats in Model batch increased significantly. SIRT6 adenovirus treatment potentially and significantly inhibited inflammation including suppression of increased inflammatory factors induced by MyD88. In comparison with FLS cells in Control group, Model batch cells' MyD88, interleukin (IL)-1ß, IL-21, IL-22, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) mRNA expressions increased but SIRT6 gene treatment could reduce mRNA expression of the aforesaid factors, even after MyD88 adenovirus treatment. Besides, overpressed SIRT6 negatively regulated levels of MyD88, ERK and p-ERK proteins expressions. SIRT6 demonstrated anti-RA effect by regulating MyD88-ERK pathway and inhibiting inflammatory response in RA rats. CONCLUSIONS: SIRT6 could potentially inhibit the inflammatory response of RA via a regulatory mechanism mainly relating to MyD88-ERK signal pathway. Thus, SIRT6 and its agonists may serve as new targets for developing drugs that can potentially treat RA.

Engineered tumor microvesicles modified by SP94 peptide for arsenic trioxide targeting drug delivery in liver cancer therapy.

Liver cancer is among the leading cause of cancer related death worldwide. There is growing interest in using traditional Chinese medicines such as arsenic trioxide (ATO) to treat liver cancer. ATO have attracted attention due to its wide range of anti-cancer activities. However, the current ATO formulations are associated with drawbacks such as short half-life, lack of targeting ability towards solid tumors and apparent toxic side effects. Tumor microvesicles (TMVs) has shown encouraging results for the delivery of drugs to solid tumor. In this work, we designed ATO loaded TMVs further modified by SP94 peptide as liver cancer specific ligand (ATO@SP94-TMVs). This drug delivery system utilized SP94 peptide that selectively targets liver cancer cells while TMVs increase the accumulation of ATO at tumor site and activate immune response owing to the associated antigens. ATO@SP94-TMVs exhibited high encapsulation efficiency and tumor microenvironment triggered enhanced release of ATO in vitro. Cytotoxicity and uptake studies revealed remarkable inhibition and specific targeting of H22 cells. In addition, excellent immune response was detected in vitro, enhancing anti-tumor efficacy. Furthermore, a tumor inhibition rate of about 53.23 % was observed in H22 bearing tumor model. Overall, these results confirm that ATO@SP94-TMVs can be a promising nano drug delivery system for the future liver cancer therapy and improve its clinical applications.

Progress of cell membrane-derived biomimetic nanovesicles for cancer phototherapy.

In recent years, considerable attention has been given to phototherapy, including photothermal and photodynamic therapy to kill tumor cells by producing heat or reactive oxygen species (ROS). It has the high merits of noninvasiveness and limited drug resistance. To fully utilize this therapy, an extraordinary nanovehicle is required to target phototherapeutic agents in the tumor cells. Nanovesicles embody an ideal strategy for drug delivery applications. Cell membrane-derived biomimetic nanovesicles represent a developing type of nanocarrier. Combining this technique with cancer phototherapy could enable a novel strategy. Herein, efforts are made to describe a comprehensive overview of cell membrane-derived biomimetic nanovesicles for cancer phototherapy. The description in this review is mainly based on representative examples of exosome-derived biomimetic nanomedicine research, ranging from their comparison with traditional nanocarriers to extensive applications in cancer phototherapy. Additionally, the challenges and future prospectives for translating these for clinical application are discussed.

Hollow Mesoporous Silica Nanoparticles for Dual Chemo-starvation Therapy of Hepatocellular Carcinoma.

PURPOSE: This study aims at chemotherapy and starvation therapy of HCC via starvation and apoptosis. METHODS: Hollow mesoporous organosilica nanoparticles (HMONs) with the thioether-hybrid structure were developed using an organic/inorganic co-templating assembly approach. Hydrofluoric acid was used to remove the internal MSN core for yielding large radial mesopores for loading drug cargos. The morphology and structure of NPs were determined using TEM and SEM. HMONs were stepwise surface modified with glucose oxidase (GOx), oxygen (O2) and Doxorubicin (DOX), and cancer cell membrane (CCM) for yielding CCM-coated HMONs (targeted stealth biorobots; TSBRs) for starvation, apoptotic, and enhanced cell uptake properties, respectively. The surface area and pore size distribution were determined via BET and BJH assays. The catalytic ability of GOx-modified NPs was measured using in vitro glucose conversion approach authenticated by H2O2 and pH determination assays. MTT assay was used to determine the cytotoxicities of NPs. Cell uptake and apoptotic assay were used for the NPs internalization and apoptosis mechanisms. The subcutaneous HepG2 tumor model was established in mice. The long-term in vivo toxicity was determined using blood assays. RESULTS: The prepared NPs were spherical, hollow and mesoporous with excellent surface area and pore size distribution. The GOx-modified NPs exhibited excellent catalytic activity. The TSBRs showed better cytotoxicity and reduce the tumor size and weight. The NPs showed long-term safety in vivo. CONCLUSION: TSBRs destroyed cancer cells by starvation and chemotherapy in both in-vitro and in-vivo settings which demonstrates its anti-cancer potential.

PEG-grafted arsenic trioxide-loaded mesoporous silica nanoparticles endowed with pH-triggered delivery for liver cancer therapy.

Liver cancer (LC), one of the most common malignant primary tumors, presents a poor prognosis, high morbidity rate, and poor clinical outcomes. Despite conventional treatments have been applied prior to the deterioration, their clinical benefits were still limited. Arsenic trioxide (ATO), a toxic Chinese medicine, has been proven to efficiently inhibit the growth of LC both in vitro and in vivo. However, its therapeutic effects are hindered by poor pharmacokinetics and dose-limited toxicity. In this study, we developed a pH-responsive nanoplatform (PEG-MSN@ATO) consisting of mesoporous silica nanoparticles (MSN) that were modified with amino groups, loaded with ATO, and grafted with PEG to achieve the pH-triggered release and regulate CD8+ T cells and Treg cells in the tumor microenvironment (TME). PEG-MSN@ATO were characterized by uniform size, good loading efficiency, pH-responsive release features, decreased macrophage uptake, and enhanced dendritic cell activation in vitro. Furthermore, in vivo studies demonstrated that PEG-MSN@ATO enhanced the antitumor efficacy by inducing apoptosis and ROS production, inhibiting tumor cell proliferation and metastasis, and activating antitumor immunity within the TME. PEG-MSN@ATO also reduced the system toxicity of ATO by controlling the pH-trigger release in the tumor site. These results indicate that the PEG-MSN@ATO represents a promising drug delivery platform for reducing toxicity and enhancing the therapeutic efficacy of ATO against LC.

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing.

Colon mucosal inflammation attracts a plethora of immune cells with overexpressed surface receptors. Colon drug targeting can be aided by exploiting overexpressed cell surface receptors which improve drug site retention for an extended period. We developed Tofacitinib citrate (Tofa) loaded transferrin anchored PLGA nanocarriers (Tofa-P/tfr NCs) via the quality by design (QbD) approach for specific binding to the transferrin receptor (TFR-1/CD71) overexpressed on macrophages and colon epithelial cells. Nanocarriers were produced using a modified emulsion-evaporation method with a protein adsorption technique. The QbD-risk assessment method was adopted to screen the variables impacting the quality of nanocarriers, which were then optimized using the 33 Box-Behnken design of experiment (DOE). The obtained nanocarriers have the desired physicochemical properties, drug entrapment, tfr adsorption, stability, mucoadhesion, and sustained drug release pattern at pH 7.4 (colon pH). In vitro cell-based studies confirmed the cellular biocompatibility and considerable uptake of nanocarriers by colon and macrophage cells; the uptake was diminished by anti-CD71/TFR1 antibodies. Tofa-P/tfr NCs demonstrated good colon targeting potential in the dextran sulfate sodium (DSS) induced ulcerative colitis (UC) model. In vivo therapeutic efficacy against UC was established through restored morphological and histopathological scores, vascular integrity, antioxidant levels, hematological parameters, pro-inflammatory cytokine/marker levels, and microbial indices. Tofa-P/tfr NCs shut down the elevated STAT-1 and TFR-1 levels, demonstrating the enhanced efficacy of the encapsulated drug. Thus, the QbD-driven approach successfully developed Tofa-P/tfr NCs with good potential to mitigate mucosal inflammation by targeting colon and macrophage surface receptors.

Liposome-based diagnostic and therapeutic applications for pancreatic cancer.

Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.

Research progress and challenges of TRPV1 channel modulators as a prospective therapy for diabetic neuropathic pain.

Diabetic neuropathic pain (DNP) is a common, complex, and severe complication of diabetes. It can lead to increased mortality, lower-limb amputations, and distressing neuropathic symptoms. Available therapies for DNP are broad-spectrum analgesics, related to various side effects. Transient receptor potential vanilloid-1 (TRPV1) is widely expressed within the peripheral and central nervous systems and plays an essential role in pain perception and regulation. Both TRPV1 agonists and antagonists could reduce the sensitivity to nociception. Some exhibit blood glucose homeostasis regulates function by influencing insulin secretion and receptor sensitivity. Since TRPV1 has exhibited the unique advantages of simultaneously managing blood sugar and pain, developing new TRPV1 channel modulators for diabetes-related pain syndrome is a promising alternative to conventional therapy. In this review, the role of TRPV1 in the pathogenesis of DNP has been described and challenges of TRPV1 modulators have been explored to be a new therapy for DNP.

Co-treatment of Astragaloside IV with Vitamin D in Diabetic Peripheral Neuropathic Rats: Protective Effects and Potential Mechanisms.

OBJECTIVE: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. METHODS: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. RESULTS: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin-angiotensin-aldosterone system, and promotion of ß-cell sensitivity to insulin. CONCLUSION: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Lung Cancer Nodules Detection via an Adaptive Boosting Algorithm Based on Self-Normalized Multiview Convolutional Neural Network.

Lung cancer is the deadliest cancer killing almost 1.8 million people in 2020. The new cases are expanding alarmingly. Early lung cancer manifests itself in the form of nodules in the lungs. One of the most widely used techniques for both lung cancer early and noninvasive diagnosis is computed tomography (CT). However, the intensive workload of radiologists to read a large number of scans for nodules detection gives rise to issues like false detection and missed detection. To overcome these issues, we proposed an innovative strategy titled adaptive boosting self-normalized multiview convolution neural network (AdaBoost-SNMV-CNN) for lung cancer nodules detection across CT scans. In AdaBoost-SNMV-CNN, MV-CNN function as a baseline learner while the scaled exponential linear unit (SELU) activation function normalizes the layers by considering their neighbors' information and a special drop-out technique (α-dropout). The proposed method was trained and tested using the widely Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) and Early Lung Cancer Action Program (ELCAP) datasets. AdaBoost-SNMV-CNN achieved an accuracy of 92%, sensitivity of 93%, and specificity of 92% for lung nodules detection on the LIDC-IDRI dataset. Meanwhile, on the ELCAP dataset, the accuracy for detecting lung nodules was 99%, sensitivity 100%, and specificity 98%. AdaBoost-SNMV-CNN outperformed the majority of the model in accuracy, sensitivity, and specificity. The multiviews confer the model's good generalization and learning ability for diverse features of lung nodules, the model architecture is simple, and has a minimal computational time of around 102 minutes. We believe that AdaBoost-SNMV-CNN has good accuracy for the detection of lung nodules and anticipate its potential application in the noninvasive clinical diagnosis of lung cancer. This model can be of good assistance to the radiologist and will be of interest to researchers involved in the designing and development of advanced systems for the detection of lung nodules to accomplish the goal of noninvasive diagnosis of lung cancer.

Genomic and Epigenomic Features of Glioblastoma Multiforme and its Biomarkers.

Glioblastoma multiforme is a serious and life-threatening tumor of central nervous system, characterized by aggressive behavior, poor prognosis, and low survival rate. Despite of the availability of aggressive antitumor therapeutic regimen for glioblastoma (radiotherapy followed by chemotherapeutic dose), recovery rate, and patients' survival ratio is attributed to the lack of selectivity of therapeutic drugs and less advancement in cancer therapeutics over last decade. Moreover, tools employed in conventional diagnosis of glioblastoma are more invasive and painful, making the process excruciating for the patients. These challenges urge for the need of novel biomarkers for diagnosis, prognosis, and prediction purpose with less invasiveness and more patient compliance. This article will explore the genetic biomarkers isocitrate dehydrogenase mutation, MGMT mutations, and EGFR that can be deployed as an analytical tool in diagnosis of disease and prognosis of a therapeutic course. The review also highlights the importance of employing novel microRNAs as prognostic biomarkers. Recent clinical advancements to treat GBM and to prevent relapse of the disease are also discussed in this article in the hope of finding a robust and effective method to treat GBM.

Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy.

Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a GSH-sensitive material, ATRA-SS-HA, was developed and self-assembled with curcumin, a natural polyphenol antitumor drug, into nanomicelles Cur@ATRA-SS-HA. The micelles had a suitable particle size, excellent drug loading, encapsulation rate, stability, biocompatibility, and stable release behaviour. In the tumor microenvironment, GSH induced disulfide bond rupture in Cur@ATRA-SS-HA and promoted the release of curcumin, improving tumor targeting. Following GSH-induced release, the curcumin IC50 value was significantly lower than that of free curcumin and better than that of 5-FU. In vivo pharmacokinetic experiments showed that the drug-loaded nanomicelles exhibited better metabolic behaviour than free drugs, which greatly increased the blood concentration of curcumin and increased the half-life of the drug. The design of the nanomicelle provides a novel clinical treatment for oesophageal cancer.

Stem cell membrane-coated abiotic nanomaterials for biomedical applications.

Nanoscale materials have been extensively employed for diagnostic and therapeutic purposes. However, the developed nanosystems still suffer from some limitations, namely the rapid elimination by the immune system, lack of targeting to specific cells, and insufficient biocompatibility. Therefore, novel strategies based upon a biomimetic approach have received attention to improving the pharmacokinetics and safety profile of nanosystems. One promising strategy is the application of a biomimetic coating consisting of cell membranes derived from different cell types onto nanoparticle cores. Stem cells have been investigated to develop targeted nanodevices owing to their excellent intrinsic tissue-specific homing features, protecting them from the immune system to reach the sites of inflammation. This targeting ability is conferred by a surface repertoire of stem cell-associated biomolecules. Such nanoscopical materials offer sustained circulation and boosted drug accumulation at target sites, augmenting therapeutic efficacy and safety. Additionally, the coating of nanoparticles with cell membranes acts as a camouflage mechanism to increase their circulation time. The current review explores the particular features of stem cell membrane coating as multifunctional biomimetic surface functionalization agents to camouflage nanoparticle cores. Biomedical applications of engineered stem cell membrane-coated nanoparticles, challenges in clinical translation, and their future prospects are addressed.