Gonadal hormones and metabolic syndrome in middle-aged and elderly males: results from a prospective cohort study in China.

Background: Research has shown that gonadal hormones are involved in metabolic pathways relevant to metabolic syndrome (MetS). Nevertheless, no longitudinal study has been conducted on the association between SHBG and MetS in Chinese. The objective of our study was to determine whether there is any association between middle-aged and elderly males in China. Methods: A total of 531 eligible male subjects, aged above 40 years or older, without MetS at baseline, were recruited. Sex hormone binding globulin (SHBG), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. A harmonized definition and recommended thresholds for the Chinese population were used to determine metabolic syndrome. Results: During 3.2 years of follow-up, 20.7% of subjects had developed MetS. Compared with the non-MetS group, subjects in the new-onset MetS group had significantly lower SHBG (43.5 nmol/L [28.8, 74.9] vs 53.7nmol/L [33.8, 115.0], P=0.0018), TT (18.1nmol/L [13.6-21.7] vs 19.5nmol/L[15.0-23.6], P=0.0204), and LH (5.13mIU/L [3.63-7.29] vs 5.87mIU/L [4.05-8.36]) at baseline. The incidence of MetS was decreased according to elevated SHBG quartiles (Q1:26.9%, Q2:22.7%, Q3:21.1%, Q4:12.1%, P for trend =0.0035), TT (Q1: 25.2%, Q2:23.7%, Q3: 17.3%, Q4: 16.7%, P for trend=0.0425), and LH (Q1:25.0%, Q2:21.8%, Q3: 21.8%, Q4: 14.3%, P for trend=0.0411). Compared with those in quartile 4, the OR[CI] of incident MetS for participants in Quartile 1 was 2.33[1.13-4.79] after multiple adjustments. But associations between incident MetS and different quartiles of LH, TT, and FSH were not observed after multiple adjustments. In the subgroup analyses, the significant association between SHBG level and Mets was detected in subjects over 60 years or older, with normal BMI, without insulin resistance, and with eGFR ≥90 mL/min per 1.73m2. Conclusion: Compared with TT, LH, and FSH, a lower level of SHBG is significantly related to the incidence of MetS among middle-aged and elderly males in China.

Molecular breast cancer subtype identification using photoacoustic spectral analysis and machine learning at the biomacromolecular level.

Breast cancer threatens the health of women worldwide, and its molecular subtypes largely determine the therapy and prognosis of patients. However, an uncomplicated and accurate method to identify subtypes is currently lacking. This study utilized photoacoustic spectral analysis (PASA) based on the partial least squares discriminant algorithm (PLS-DA) to identify molecular breast cancer subtypes at the biomacromolecular level in vivo. The area of power spectrum density (APSD) was extracted to semi-quantify the biomacromolecule content. The feature wavelengths were obtained via the variable importance in projection (VIP) score and the selectivity ratio (Sratio), to identify the biomarkers. The PASA achieved an accuracy of 84%. Most of the feature wavelengths fell into the collagen-dominated absorption waveband, which was consistent with the histopathological results. This paper proposes a successful method for identifying molecular breast cancer subtypes and proves that collagen can be treated as a biomarker for molecular breast cancer subtyping.

CaCO3 powder-mediated biomineralization of antigen nanosponges synergize with PD-1 blockade to potentiate anti-tumor immunity.

Antigen self-assembly nanovaccines advance the minimalist design of therapeutic cancer vaccines, but the issue of inefficient cross-presentation has not yet been fully addressed. Herein, we report a unique approach by combining the concepts of "antigen multi-copy display" and "calcium carbonate (CaCO3) biomineralization" to increase cross-presentation. Based on this strategy, we successfully construct sub-100 nm biomineralized antigen nanosponges (BANSs) with high CaCO3 loading (38.13 wt%) and antigen density (61.87%). BANSs can be effectively uptaken by immature antigen-presenting cells (APCs) in the lymph node upon subcutaneous injection. Achieving efficient spatiotemporal coordination of antigen cross-presentation and immune effects, BANSs induce the production of CD4+ T helper cells and cytotoxic T lymphocytes, resulting in effective tumor growth inhibition. BANSs combined with anti-PD-1 antibodies synergistically enhance anti-tumor immunity and reverse the tumor immunosuppressive microenvironment. Overall, this CaCO3 powder-mediated biomineralization of antigen nanosponges offer a robust and safe strategy for cancer immunotherapy.

The Mechanism of Alisol B23 Acetate Inhibiting Lung Cancer: Targeted Regulation of CD11b/CD18 to Influence Macrophage Polarization.

Background: Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure. Methods: After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1ß, IL-10 and TGF-ß. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins. Results: AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis. Conclusion: AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.

Myocardial infarct border demarcation by dual-wavelength photoacoustic spectral analysis.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Modern therapeutic strategies targeting the infarct border area have been shown to benefit overall cardiac function after MI. However, there is no non-invasive diagnostic technique to precisely demarcate the MI boundary till to now. In this study, the feasibility of demarcating the MI border using dual-wavelength photoacoustic spectral analysis (DWPASA) was investigated. To quantify specific molecular characteristics before and after MI, "the ratio of the areas of the power spectral densities (R APSD)" was computed from the DWPASA results. Compared to the normal tissue, MI tissue was shown to contain more collagen, resulting in higher R APSD values (p < 0.001). Cross-sectional MI lengths and the MI area border demarcated in two dimensions by DWPASA were in substantial agreement with Masson staining (ICC = 0.76, p < 0.001, IoU = 0.72). R APSD has been proved that can be used as an indicator of disease evolution to distinguish normal and pathological tissues. These findings indicate that the DWPASA method may offer a new diagnostic solution for determining MI borders.

Multimodal Imaging-Guided Spatiotemporal Tracking of Photosensitive Stem Cells for Breast Cancer Treatment.

Stem cell therapy has shown great potential in treating a wide range of diseases including cancer. The real-time tracking of stem cells with high spatiotemporal resolution and stable imaging signals remains the bottleneck to evaluate and monitor therapeutic outcomes once transplanted into patients. Here, we developed a photosensitive mesenchymal stem cell (MSC) loaded with mesoporous silica-coated gold nanostars (MGNSs) integrated with indocyanine green for spatiotemporal tracking and imaging-guided photothermal therapy (PTT) in treating breast cancers. The MGNS served as a stable imaging probe with multifunctional properties for photoacoustic imaging (PAI), fluorescence imaging, and PT imaging. Owing to the excellent PT stability of MGNSs, long-term three-dimensional (3D) PAI was achieved to monitor stem cells in real time at the tumor site, while the tumor structure was imaged using 3D B-mode ultrasound imaging. PAI revealed that the photosensitive stem cells reached the widest distribution area at the tumor site post 24 h of intratumoral injection, which was further confirmed via two-dimensional (2D) PT and fluorescence imaging. With this optimal cell distribution window, in vivo studies showed that the photosensitive stem cells via both intratumoral and intravenous injections successfully inhibited breast cancer cell growth and decreased the tumor recurrence rate post PTT. Our results support that this photo-integrated platform with stable optical properties is promising to achieve real-time tracking and measure the cell distribution quantitatively with high spatiotemporal resolution for stem cell therapy.

Quick identification of prostate cancer by wavelet transform-based photoacoustic power spectrum analysis.

Pathology is currently the gold standard for grading prostate cancer (PCa). However, pathology takes considerable time to provide a final result and is significantly dependent on subjective judgment. In this study, wavelet transform-based photoacoustic power spectrum analysis (WT-PASA) was used for grading PCa with different Gleason scores (GSs). The tumor region was accurately identified via wavelet transform time-frequency analysis. Then, a linear fitting was conducted on the photoacoustic power spectrum curve of the tumor region to obtain the quantified spectral parameter slope. The results showed that high GSs have small glandular cavity structures and higher heterogeneity, and consequently, the slopes at both 1210 nm and 1310 nm were high (p < 0.01). The classification accuracy of the PA time frequency spectrum (PA-TFS) of tumor region using ResNet-18 was 89% at 1210 nm and 92.7% at 1310 nm. Further, the testing time was less than 7 mins. The results demonstrated that identification of PCa can be rapidly and objectively realized using WT-PASA.

Characterization of multi-biomarkers for bone health assessment based on photoacoustic physicochemical analysis method.

Photoacoustic (PA) techniques are potential alternatives to histopathology. The physicochemical spectrogram (PCS) generated by the PA measurement at multiple wavelengths can presents the morphology and chemical composition target at multi-biomarkers simultaneously. In this work, via multi-wavelength PA measurements performed on rabbit bone models, we investigated the feasibility of using PCSs for bone health assessment. A comprehensive analysis of the PCSs, termed PA physicochemical analysis (PAPCA), was conducted. The "slope" and "relative content" were used as the PAPCA-quantified parameters to characterize the changes in the physical and chemical properties of bone tissue, respectively. The findings are consistent well with the gold-standard imaging results. It demonstrated that the PAPCA can be used to characterize both the microstructure and content of multi-biomarkers which highly related with bone health. Considering the PA technique is noninvasive and radiation-free, it has great potential in the implementation and monitoring of bone diseases progression.

Photostability enhancement of silica-coated gold nanostars for photoacoustic imaging guided photothermal therapy.

Gold nanostars (GNSs) are promising contrast agents for simultaneous photothermal therapy and photoacoustic imaging (PAI) owing to their excellent photothermal conversion efficiency. However, GNSs are easily reshaped under transient high-intensity laser pulses, which can cause a rapid shift in the light absorption peak, resulting in a decrease in both therapeutic and monitoring effects. In this work, we synthesized GNSs without toxic surfactants and coated them with a silica shell to retain their shape, thus maintaining their photostability. The excellent performance of these silica-coated GNSs was verified through both in vitro and in vivo PAI experiments. The silica-coated GNSs exhibited a threefold improvement in photoacoustic stability, as compared with the non-coated GNSs. The proposed silica coating method for GNSs was found to improve the photostability of GNSs, making them efficient, safe, and reliable nanoparticles for PAI.

Prostate cancer identification via photoacoustic spectroscopy and machine learning.

Photoacoustic spectroscopy can generate abundant chemical and physical information about biological tissues. However, this abundance of information makes it difficult to compare these tissues directly. Data mining methods can circumvent this problem. We describe the application of machine-learning methods (including unsupervised hierarchical clustering and supervised classification) to the diagnosis of prostate cancer by photoacoustic spectrum analysis. We focus on the content and distribution of hemoglobin, collagen, and lipids, because these molecules change during the development of prostate cancer. A higher correlation among the ultrasonic power spectra of these chemical components is observed in cancerous than in normal tissues, indicating that the microstructural distributions in cancerous tissues are more consistent. Different classifiers applied in cancer-tissue diagnoses achieved an accuracy of 82 % (better than that of standard clinical methods). The technique thus exhibits great potential for painless early diagnosis of aggressive prostate cancer.

Photoacoustic power azimuth spectrum for microvascular evaluation.

The tubular structures and dendritic distributions of blood vessels emit anisotropic photoacoustic (PA) signals with different intensities and frequency components at different angles. Therefore, spectral analysis of PA signals from a single angle cannot accurately determine the physical characteristics of microvessels. This study investigated the feasibility of using the PA power azimuth spectrum (PA-PAS) method to evaluate microvessel structures. We mapped the acoustic power spectrum of the PA signals along the azimuth direction. Based on a frequency-domain analysis of the broadband PA signal, we calculated the spectral parameter power-weighted mean frequency (PWMF). The results demonstrate that the PA signal information of the microvessel is mainly concentrated in the direction of its width. In addition, the PWMF decreases linearly with the microvascular size. The experimental findings exhibit good agreement with the simulation results, thus demonstrating that this approach can effectively differentiate the sizes of microvessels.

An abundant porous biochar material derived from wakame (Undaria pinnatifida) with high adsorption performance for three organic dyes.

In this study, an activated wakame biochar material (AWBM) was prepared by a one-step calcination and activation method, whose adsorption performances for methylene blue (MB), Rhodamine B (RB) and malachite green (MG) were also analyzed. The results showed AWBM was a mesoporous fluffy structure material with a higher specific surface (1156.25 m2/g), exhibiting superior adsorption capacities for MB (841.64 mg/g), RB (533.77 mg/g) and MG (4066.96 mg/g), respectively. In addition, FT-IR analysis showed that AWBM possessed abundant active groups (such as -OH, -CO and -CH), further enhancing the adsorption efficiencies. The Langmuir model could better fit the three dyes adsorption isotherms process using AWBM, and the Pseudo-second-order model could better describe the adsorption kinetic experimental data. The thermodynamic analysis showed that the three dyes adsorption using AWBM was spontaneous endothermic reaction. This study suggests AWBM has enormous potential in the application of removing organic dyes from wastewater.

Water extract of ginseng and astragalus regulates macrophage polarization and synergistically enhances DDP's anticancer effect.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, supplementing Qi and strengthening body resistance are an important principle of anticancer treatment. Panax ginseng C.A.Mey. (ginseng) and Astragalus membranaceus Bunge (astragalus) are the representative herbs for this therapeutic principle. AIM OF THE STUDY: This study aims to explore the effect of the water extract of ginseng and astragalus (WEGA) on regulating macrophage polarization and mediating anticancer in the tumor microenvironment. MATERIALS AND METHODS: A549 cells were cultured in tumor-associated macrophage (TAM) supernatant with various concentrations of WEGA (0, 5, 10, 20 mg/mL). A549 cell proliferation was determined through methyl thiazole tetrazolium (MTT) assay and real-time cell analysis (RTCA), respectively. In vivo experiments were performed with a Lewis lung cancer (LLC) xenograft mouse model. Forty-eight mice were divided into six groups and treated with saline, WEGA, or cis-diamine dichloro platinum (DDP) with dosage of WEGA (0, 30, 60, 120 mg/kg body weight/day). The different groups were administered with drugs via oral or intraperitoneal injection once a day for 21 consecutive days. Tumor inhibition rate, spleen index, thymus index, cytokine, protein, and mRNA expression levels were detected in mice. RESULTS: In a co-culture system, WEGA remarkably inhibited A549 cell proliferation, promoted the expression of M1 macrophage markers and inhibited M2 TAMs markers. Therefore, WEGA affected the biological behavior of cancer cells by regulating the expression of some markers relevant to macrophage polarization. In addition, the group of WEGA and DDP chemotherapy effectively inhibited the transplanted tumor growth in mice and improved weight loss and immunosuppressive with the cisplatin inducing. CONCLUSIONS: This study provides mechanistic insights into the anticancer effect of WEGA through the regulation of macrophage polarization and highlights that WEGA could be a novel option for integrative cancer therapies.

A Light-Triggered Mesenchymal Stem Cell Delivery System for Photoacoustic Imaging and Chemo-Photothermal Therapy of Triple Negative Breast Cancer.

Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic-magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))-loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions. In addition, CXCR4 on the MSCs is upregulated by iron oxide nanoparticles in the LDGI. Importantly, the drug release and photothermal therapy can be simultaneously achieved upon light irradiation. The released drug can enter the cell nucleus and promote cell apoptosis. Interestingly, light irradiation can control the secretion of cellular microvehicles carrying LDGI for targeted treatment. A remarkable in vitro anticancer effect is observed in MDA-MB-231 with near-infrared laser irradiation. In vivo studies show that the MSCs-LDGI has the enhanced migration and penetration abilities in the tumor area via both intratumoral and intravenous injection approaches compared with LDGI. Subsequently, MSCs-LDGI shows the best antitumor efficacy via chemo-photothermal therapy compared to other treatment groups in the TNBC model of nude mice. Thus, MSCs-LDGI multifunctional system represents greatly synergistic potential for cancer treatment.

Interstitial assessment of aggressive prostate cancer by physio-chemical photoacoustics: An ex vivo study with intact human prostates.

PURPOSE: Transrectal ultrasound (TRUS)-guided biopsy is the standard procedure for evaluating the presence and aggressiveness of prostate cancer. TRUS biopsy involves tissue removal, and suffers from low core yield as well as high false negative rate. A less invasive and more accurate diagnostic procedure for prostate cancer is therefore highly desired. Combining the optical sensitivity and ultrasonic resolution to resolve the spatial distribution of the major molecular components in tissue, photoacoustic (PA) technology could be an alternative approach for the diagnosis of prostate cancer. The purpose of this study was to examine the feasibility of identifying aggressive prostate cancer using interstitial PA measurements. METHODS: Seventeen patients with prebiopsy magnetic resonance imaging (MRI), TRUS biopsies, and planned prostatectomies were enrolled in this study. The interstitial PA measurements were achieved using our recently developed needle PA probe, which was inserted into the ex vivo prostates in the fashion of a biopsy needle. A total of 70 interstitial PA measurements were acquired. The PA measurements were quantified by a previously established PA physio-chemical analysis (PAPCA) method. The histology has confirmed the nonaggressive and aggressive cancerous conditions at the insertion locations. The diagnostic accuracy was also compared to that provided by the prebiopsy MRI. RESULTS: The quantitative study shows significant differences between the individual parameters of the nonaggressive and the aggressive cancerous regions (P < 0.005). Multivariate analysis of the quantitative features achieved a diagnostic accuracy of 78.6% for differentiating nonaggressive and aggressive prostate cancer tissues. CONCLUSIONS: The proposed procedure has shown promises in the diagnosis of aggressive prostate cancer.

OCF can repress tumor metastasis by inhibiting epithelial-mesenchymal transition involved in PTEN/PI3K/AKT pathway in lung cancer cells.

A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro. Currently, we also have demonstrated the inhibitory effect of OCF on A549 cell migration and invasion in vitro. According to Lewis lung cancer cells (LLC) allograft in C57BL/6 mice and A549 xenograft in nude mice experiment, we found that the anti-tumor and anti-metastasis effects of OCF treatment were related to the inhibition of epithelial-mesenchymal transition (EMT). Further studies showed that the inhibitory effect of OCF on EMT was associated with the PTEN/PI3K/AKT pathway. Therefore, all studies revealed that OCF could prevent cancer progression and tumor metastasis by inhibiting EMT involved PTEN/PI3K/AKT signaling pathway in lung cancer cells.