Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy.

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

[Bioactive secondary metabolites from an endophytic fungus Aspergillus sp. CCH-1E from Catharanthus roseus].

This study focused on the bioactive secondary metabolites of an endophytic fungus Aspergillus sp. CCH-1E from Catharanthus roseus. The secondary metabolites from Aspergillus sp. CCH-1E were isolated by using various chromatographic methods [such as normal-phase and reversed-phase chromatography and high-performance liquid chromatography(HPLC)], and their structures were identified by various spectroscopic methods [e.g., ultraviolet(UV) spectroscopy, infrared(IR) spectroscopy, nuclear magnetic resonance(NMR) spectroscopy, and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)]. Twelve compounds were yielded and identified from Aspergillus sp. CCH-1E, which are chermesinone H(1), chermesinone I(2), chermesinone B(3), 8,11-didehydrochermesinone B(4), chermesinone C(5), chermesinone A(6), chevalone B(7), barbacenic acid(8), 3,6,8-trihydroxy-3,5,7-trimethyl-3,4-dihydroisocoumarin(9), 5-hydroxy-2-methoxy-7-methyl-1,4-naphthoquinone(10), 1-hydroxy-6,8-dimethoxy-3-methylanthracene-9,10-dione(11), and 7-drimen-9α,11,12-triol(12). Among them, compounds 1 and 2 are new compounds. The growth inhibition effects of all compounds were evaluated against non-small cell lung cancer cell lines A549 and NCI-H1650, as well as human cervical cancer cell line HeLa by using methylthiazolyldiphenyl-tetrazolium bromide(MTT). Compound 7 significantly inhibited the growth of three tumor cells with the IC_(50) values of 1.22-2.43 µmol·L~(-1), respectively. Compounds 1-6 showed moderate cell growth inhibition with the IC_(50) values of 16.24-35.28 µmol·L~(-1).

Comparison of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for the diagnosis of neonatal sepsis: a systematic review and meta-analysis.

PURPOSE: To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS). METHODS: PubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured. RESULTS: Thirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61-0.87), 0.82 (95%CI: 0.68-0.91), and 0.86 (95%CI: 0.83-0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63-0.92), 0.80 (95%CI: 0.24-0.98), and 0.87 (95%CI: 0.83-0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p = 0.01 for SEN), gold standard (p = 0.03 for SPE), and pre-set threshold (p<0.05 for SPE) might be the sources of heterogeneity for NLR, whereas the pre-set threshold (p<0.05 for SPE) might be the source of heterogeneity for PLR. CONCLUSIONS: NLR and PLR would be of great accuracy for the diagnosis of NS, and the two indicators have similar diagnostic performance. However, the overall risk of bias was high, and significant heterogeneity was identified among the included studies. The results of this study should be interpreted prudently, and the normal or cut-off values and the type of sepsis should be considered. More prospective studies are needed to further support the clinical application of these findings.

Large, Anionic Liposomes Enable Targeted Intraperitoneal Delivery of a TLR 7/8 Agonist To Repolarize Ovarian Tumors' Microenvironment.

Ovarian cancer is the most lethal gynecological malignancy in the United States. Current standard of treatment includes surgical debulking and chemotherapy, such as cisplatin and paclitaxel. However, the patients' response rate for chemotherapy in ovarian cancer is not optimal, and they often develop chemoresistance and suffer from side effects. Current clinical trials make extensive use of immune checkpoint blockade (ICB) as a novel cancer immunotherapeutic strategy against ovarian tumors. However, the response rates for ICB antibodies remain limited to 10-20% of treated ovarian cancer patients despite the success of this approach in melanoma, renal, head and neck, and nonsmall cell lung cancers. This lack of efficacy is often attributed to the "cold" immune status of ovarian tumors, as these tumors often have a low number of tumor-infiltrating lymphocytes (TILs) but a high number of suppressive immune cells, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), or regulatory T cells (Tregs). Repolarizing TAMs could be a promising strategy to reshape the tumor immune microenvironment and promote antitumor activity when combined with ICBs. Toll-like receptor (TLR) 7 and 8 agonists, such as imiquimod and resiquimod, are potent immunostimulatory molecules with potential to repolarize macrophages. However, these small molecules have poor pharmacokinetic profiles and can induce severe side effects when administered systemically. Previously, our group demonstrated that various large, anionic nanomaterials (silica, PLGA, and polystyrene) specifically target TAMs when administered intraperitoneally (IP) to ovarian tumor-bearing mice. In the present study, we demonstrate that large, anionic liposomes administered IP also efficiently localize to TAMs and can be used to target the delivery of resiquimod. Resiquimod delivered in this targeted fashion promoted activation of M1 macrophages and T cell infiltration, while reducing the percentage of Tregs in the tumor microenvironment. Finally, liposome-formulated resiquimod significantly enhanced the efficacy of PD1 blockade against syngeneic ovarian tumors. We anticipate that further optimization of our liposomal delivery strategy can generate a clinically relevant strategy for more effective and safer immunotherapy for ovarian cancer patients.

TruScreen detection of cervical tissues for high-risk human papillomavirus-infected women during the COVID-19 pandemic.

Aims: To evaluate the efficacy of TruScreen (TS01) for high-risk human papillomavirus (HR-HPV) women compared with other methods in reducing colposcopy referral rates in hospitals. Methods: A single-center, prospective, case-control study was conducted from December 2019 to June 2020. Results: Among 139 (46.2%) HR-HPV-positive patients, 58 were CIN1, 52 were CIN2-3 and 29 had cervical cancer (n = 29). The sensitivity and specificity of detecting CIN2+ by TS01, colposcopy and HPV16/18 testing were 96.3% and 46.4%, 85.2% and 40.5% and 59.3% and 74.1%, respectively. The highest sensitivity was 96.3% at HPV16/18 and TS01 (each positive results), and the highest specificity was 83.6% at HPV16/18 and TS01 (both positive) for CIN2+ compared with the other methods. Conclusion: TS01 is a noninvasive screening method and can be used to diagnose cervical lesions quickly. It is especially suitable as triage tool for HR-HPV-positive women facing SARS-CoV-2 exposure and infection risks in hospital.

X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples.

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.

Efficacy of a New Therapeutic Option for Vulvar Intraepithelial Neoplasia: Superficial Shaving Combined With Photodynamic Therapy.

BACKGROUND AND OBJECTIVE: Vulvar intraepithelial neoplasia (VIN), a precancerous lesion, is difficult to treat by excision or ablation due to high recurrence rates. Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure and is now widely used to treat non-melanoma skin diseases. However, the clinical response rates of VIN to single PDT are unstable. The reason may be the limited light penetration into deep tissues. OBJECTIVE: To retrospectively evaluate the clinical response and recurrence of VIN after combined treatment with superficial shaving and PDT. STUDY DESIGN/MATERIALS AND METHODS: Seventeen patients with VIN were enrolled. All patients had multifocal high-grade VIN that had failed to respond to various therapies. Superficial shaving was performed only once and prior to the first 5-aminolaevulinic acid (5-ALA)-PDT cycle. Generally, the procedure of 5-ALA PDT for each patient was performed in three sessions. Clinical response, recurrence, cosmetic outcomes, adverse events, patient satisfaction, quality of life, and mental health were assessed. The expression of p16 and Ki-67 in pre- and post-treatment tissue was detected. RESULTS: A clinical response of 94% was observed in 17 patients, who were administered combination therapy, over an observation period of 12 months. Approximately, 71% of patients had excellent cosmetic outcomes. All patients had satisfactory therapeutic effects and significant improvements in quality of life and mental health. Downregulation of p16 and Ki-67 may have been correlated with recurrence after 5-ALA-PDT. CONCLUSION: Combined treatment with superficial shaving and 5-ALA-PDT is a safe and effective option for VIN. In particular, combination therapy is recommended for patients with large, multifocal, high-grade lesions; repeated recurrence; and strong willingness to maintain vulvar configuration and function. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Silica Coated Paclitaxel Nanocrystals Enable Neural Stem Cell Loading For Treatment of Ovarian Cancer.

Ovarian cancer is commonly diagnosed only after it has metastasized to the abdominal cavity (stage III). While the current standard of care of intraperitoneal (IP) administration of cisplatin and paclitaxel (PTX) combination chemotherapy has benefit, patient 5-year survival rates are low and have not significantly improved in the past decade. The ability to target chemotherapy selectively to ovarian tumors while sparing normal tissue would improve efficacy and decrease toxicities. We have previously shown that cisplatin-loaded nanoparticles (NPs) loaded within neural stem cells (NSCs) are selectively delivered to ovarian tumors in the abdominal cavity following IP injection, with no evidence of localization to normal tissue. Here we extended the capabilities of this system to also include PTX delivery. NPs that will be loaded into NSCs must contain a high amount of drug by weight but constrain the release of the drug such that the NSCs are viable after loading and can successfully migrate to tumors. We developed silica coated PTX nanocrystals (Si[PTX-NC]) meeting these requirements. Si[PTX-NC] were more effective than uncoated PTX-NC or Abraxane for loading NSCs with PTX. NSCs loaded with Si[PTX-NC] maintained their migratory ability and, for low dose PTX, were more effective than free PTX-NC or Si[PTX-NC] at killing ovarian tumors in vivo. This work demonstrates that NSC/NP delivery is a platform technology amenable to delivering different therapeutics and enables the pursuit of NSC/NP targeted delivery of the entire preferred chemotherapy regimen for ovarian cancer. It also describes efficient silica coating chemistry for PTX nanocrystals that may have applications beyond our focus on NSC transport.

Probing energy losses from dye desorption in cobalt complex-based dye-sensitized solar cells.

Self-assembly of organic sensitizer layers in cobalt complex-based DSCs was studied to elucidate its role in reducing the loss of charge recombination. DSCs with various dye loadings were fabricated by dye desorption without the aid of basic solvent. The FT-IR and UV results indicate the deprotonation of the anchoring organic sensitizers, which influences the conduction band of TiO2 remarkably by changing the surface potential. Positive band edge shifts and a decrease of the recombination rate constant are demonstrated to be the main factors affecting energy loss at open circuit. In contrast, absorbed photon conversion efficiency (APCE) analyses illuminate the crucial role of the packing of the anchoring sensitizer in reducing recombination loss at short circuit. This is further supported by numerical simulations, which show that APCE is primarily dependent on the recombination rate constant rather than the band edge shift at short circuit. These results highlight the importance of self-assembly of sensitizers with insulating groups in retarding charge recombination by forming overlapping molecular layers.

Synthesis and Biological Evaluation of Novel Alkyl Amine Substituted Icariside II Derivatives as Potential Anticancer Agents.

A series of novel alkyl amine-substituted icariside II (ICA II) derivatives were synthesized by Mannich reactions at the 6-C position (compounds 4a⁻d) and changing the carbon chain length at the 7-OH position (compounds 7a⁻h), and their in vitro antitumor activity towards human breast cancer lines (MCF-7 and MDA-MB-231) and human hepatoma cell lines (HepG2 and HCCLM3-LUC) were evaluated by the MTT assay. Compared with ICA II, most of the twelve derivatives showed good micromole level activity and a preliminary structure-activity relationship (SAR) for the anticancer activity was obtained. Compound 7g showed the most potent inhibitory activity for the four cancer cell lines (13.28 µM for HCCLM3-LUC, 3.96 µM for HepG2, 2.44 µM for MCF-7 and 4.21 µM for MDA-MB-231), which was 2.94, 5.54, 12.56 and 7.72-fold stronger than that of ICA II. The preliminary SAR showed that the introduction of a alkyl amine substituent at 6-C was not favorable for the anticancer activity, while most of the 7-O-alkylamino derivatives exhibited good antitumor activity and the anticancer activity 7-O-alkylamino derivatives were influenced by the alkyl chain length and the different terminal amine substituents. Furthermore, the effects of compound 7g on apoptosis and cell cycle of MCF-7 cells were further investigated, which showed that compound 7g triggered apoptosis and arrested the cell cycle at the G0/G1 phase in MCF-7 cells. Our findings indicate that compound 7g may be a promising anticancer drug candidate lead.

An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma.

Background: To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. Methods: The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. Results: We found that Valyl-Glutamate, N, N'-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. Conclusions: This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.

Development and validation of Social Support Needs Questionnaire (SSNQ) for the left-behind older adults in rural China.

Objectives: This study compiled a Social Support Needs Questionnaire (SSNQ) for the left-behind older adults in rural China and assessed its psychometric properties. Methods: The formation of the SSNQ included three stages. First, item pool was established based on literature analysis. Second, through expert consultation, the 1-version questionnaire items were determined. Third, pre-survey with 901 cases of rural left-behind older adults was used to develop and test final-version of the Social Support Needs Questionnaire (SSNQ). Results: The Cronbach's α of the SSNQ was 0.914, ranging from 0.815 to 0.886 for each factor. The item-content validity index ranged from 0.875 to 1.00, and the scale-content validity index was 0.969. Conclusions: The SSNQ prepared by this study can be used as an evaluation tool for the social support needs of left-behind older adults in rural China, providing a basis for further establishment of the social support system.

PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy.

OBJECTIVE: The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1m) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB). METHODS: Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1m, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot. RESULTS: Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131-37.700), cytology (OR, 24.978; 95% CI, 3.085-540.236), and PAX1 methylation levels by grade (PAX1m grade) (OR, 7.801; 95% CI, 1.548-44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901-0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model's strong agreement between predicted and observed probabilities. CONCLUSION: The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.

Association between chronic illness resources and health behaviors in hypertensive stroke patients at 6 months after discharge: a cross-sectional study.

Background: The adoption of appropriate health behaviors can prevent the recurrence of stroke. Previous research found a downward trend in hypertensive stroke patients' health behaviors from 3 to 6 months after discharge. The provision of appropriate support by chronic illness resources has been shown to predict patients' engagement in appropriate health behaviors in other chronic illness populations. This study sought to explore the association between chronic illness resources and health behaviors in hypertensive stroke patients in order to provide a foundation for the secondary prevention of stroke. Methods: Using convenience sampling method, we enrolled 133 hypertensive stroke patients at 6 months after discharge in Guangzhou, China. All the patients completed a demographic and disease-specific questionnaire, the Health Behavior Scale for Stroke Patients (HBS-SP) and the Chronic Illness Resources Survey (CIRS). A multiple stepwise regression analysis was conducted to test the association of chronic illness resources with health behaviors. Results: The total scores of the HBS-SP and CIRS were (2.89±0.38) and (2.94±0.66), respectively. The correlation coefficient for chronic illness resources and health behaviors was 0.517 (P<0.001). The positive association between chronic illness resources and health behaviors remained statistically significant after controlling for gender, education level, and the Barthel Index (unstandardized coefficient: 0.317, P<0.001). Conclusions: The chronic illness resources has positive association with health behaviors in hypertensive stroke patients at 6 months after discharge. A good support provided by chronic illness resources may contribute to promote positive health behaviors, and thus prevent the recurrence of stroke.

Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case-Control Study.

Background: The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods: This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582m) were determined by quantitative methylation-specific polymerase chain reaction (qMSP) and expressed in ΔCp. Receiver operating characteristic curves were used to evaluate predictive accuracy. Results: The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high-grade squamous intraepithelial lesion (HSIL), and 39 (14.08%) were squamous cervical cancer (SCC). PAX1m and ZNF582m increased as lesions progressed from inflammation/LSIL, HSIL, to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared with common screening strategies, whether individually or combined. A 4.33-fold increase in the probability of inflammation/LSIL was observed in patients with lower ZNF582 methylation levels (ΔCpZNF582 ≥ 19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582 < 7.09). Conclusions: DNA methylation would be an alternative screening method to triage and predict the final outcome of conization in CIN3 cases.

Quantitative considerations about the size dependence of cellular entry and excretion of colloidal nanoparticles for different cell types.

Most studies about the interaction of nanoparticles (NPs) with cells have focused on how the physicochemical properties of NPs will influence their uptake by cells. However, much less is known about their potential excretion from cells. However, to control and manipulate the number of NPs in a cell, both cellular uptake and excretion must be studied quantitatively. Monitoring the intracellular and extracellular amount of NPs over time (after residual noninternalized NPs have been removed) enables one to disentangle the influences of cell proliferation and exocytosis, the major pathways for the reduction of NPs per cell. Proliferation depends on the type of cells, while exocytosis depends in addition on properties of the NPs, such as their size. Examples are given herein on the role of these two different processes for different cells and NPs.

Integrated Analysis of Immune Infiltration Features for Cervical Carcinoma and Their Associated Immunotherapeutic Responses.

Cervical cancer is the fourth most prevalent cancer in women, which decreases quality of life of the patients. Traditional interventions have failed to improve the overall survival period of patients due to high tumor recurrence after treatment or late diagnosis. Fortunately, preliminary evidence suggests that anti-angiogenic and immunotherapy can efficiently treat against cervical cancer. However, there is no clear evidence on the efficacy of immunotherapy in cervical cancer. Therefore, in this study, we classified cervical cancers in the TCGA dataset using various algorithms and explored the relationship between the immune profile and corresponding sensitivity of the tumors to immunotherapy. Results showed that patients with tumors had higher expression of immunocytes and longer overall survival time. In addition, we build a scoring system based on the immune landscape of the tumor microenvironment of cervical cancer. Tumors with higher scores exhibited better survival outcomes and were more sensitive to immunotherapy. In this study, the immune landscape of cervical cancer was analyzed, and the subtype of cervical cancer based on that difference was proposed. Besides, the subtype of cervical cancer showed different sensitivity to immunotherapeutic response which further confirmed its relationship with tumor immune landscape.

Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer.

BACKGROUND: Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. METHODS: To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies. RESULTS: Here, we report efficient tumor tropism of HB1.F3.CD 21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. CONCLUSIONS: Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.

X-ray-Based Techniques to Study the Nano-Bio Interface.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery.

INTRODUCTION: A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. MATERIALS AND METHODS: HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. RESULTS: DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100-120 nm), narrow size distribution, and negative zeta potential (-6.7 to -31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 µg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. CONCLUSION: HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.