Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice.

OBJECTIVE: Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice. DESIGN: A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T>C mouse models). RESULTS: The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process. CONCLUSION: One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

Effect of LRRC15 on autophagy in A549 cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and irreversible interstitial lung disease with unknown cause. To explore the role and regulatory mechanism of leucine-rich repeat-containing protein 15 (LRRC15) in IPF, bleomycin (BLM)-induced pulmonary fibrosis in mouse and A549 cells were constructed, and the expression of LRRC15 were detected. Then, MTT, GFP-RFP-LC3 dual fluorescent labeling system and Western blotting were used to investigate the effects of LRRC15 on cell activity and autophagy after transfection of siLRRC15, respectively. The results indicated that the expression of LRRC15 was significantly increased after the BLM treatment in mouse lung tissue and A549 cells. The designed and synthesized siLRRC15 followed by transfection into A549 cells resulted in a dramatic reduction in LRRC15 expression and partially restored the cell damage induced by BLM. Moreover, the expression of LC3-II and P62 were up-regulated, the amount of autophagosome were increased by GFP-RFP-LC3 dual fluorescent labeling assay after BLM treatment. Meanwhile, this study also showed that the key autophagy proteins LC3-II, ATG5 and ATG7 were up-regulated, P62 was down-regulated and autophagic flux were enhanced after further treatment of A549 cells with siLRRC15. The above findings suggest that LRRC15 is an indicator of epithelial cell damage and may participate in the regulation of fibrosis through autophagy mechanism in IPF. This study provides necessary theoretical basis for further elucidating the mechanism of IPF.

Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional alveolar type II epithelial cells into alveolar type I epithelial cells and inhibiting fibroblast activation and extracellular matrix production potentially by regulation of Nr2f2. In addition, T3 regulated the crosstalk of macrophages with fibroblasts, and the Pros1-Axl signaling axis significantly facilitated the attenuation of fibrosis. The findings demonstrate that administration of a thyroid hormone promotes alveolar regeneration and resolves fibrosis mainly by regulation of the cellular state and cell-cell communication of alveolar epithelial cells, macrophages, and fibroblasts in mouse lungs in comprehensive ways.

Programmable Biomolecule-Mediated Processors.

Programmable biomolecule-mediated computing is a new computing paradigm as compared to contemporary electronic computing. It employs nucleic acids and analogous biomolecular structures as information-storing and -processing substrates to tackle computational problems. It is of great significance to investigate the various issues of programmable biomolecule-mediated processors that are capable of automatically processing, storing, and displaying information. This Perspective provides several conceptual designs of programmable biomolecule-mediated processors and provides some insights into potential future research directions for programmable biomolecule-mediated processors.

Tuftelin1 drives experimental pulmonary fibrosis progression by facilitating stress fiber assembly.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive. METHODS: To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis. RESULTS: Our results demonstrated a significant upregulation of TUFT1 in IPF and the bleomycin (BLM)-induced fibrosis model. Disruption of TUFT1 exerted inhibitory effects on pulmonary fibrosis in both in vivo and in vitro. TUFT1 facilitated the assembly of microfilaments in A549 and MRC-5 cells, with a pronounced association between TUFT1 and Neuronal Wiskott-Aldrich syndrome protein (N-WASP) observed during microfilament formation. TUFT1 can promote the phosphorylation of tyrosine residue 256 (Y256) of the N-WASP (pY256N-WASP). Furthermore, TUFT1 promoted transforming growth factor-ß1 (TGF-ß1) induced fibroblast activation by increasing nuclear translocation of pY256N-WASP in fibroblasts, while wiskostatin (Wis), an N-WASP inhibitor, suppressed these processes. CONCLUSIONS: Our findings suggested that TUFT1 plays a critical role in pulmonary fibrosis via its influence on stress fiber, and blockade of TUFT1 effectively reduces pro-fibrotic phenotypes. Pharmacological targeting of the TUFT1-N-WASP axis may represent a promising therapeutic approach for pulmonary fibrosis.

An evaluation of aging measures: from biomarkers to clocks.

With the increasing number of aged population and growing burden of healthy aging demands, a rational standard for evaluation aging is in urgent need. The advancement of medical testing technology and the prospering of artificial intelligence make it possible to evaluate the biological status of aging from a more comprehensive view. In this review, we introduced common aging biomarkers and concluded several famous aging clocks. Aging biomarkers reflect changes in the organism at a molecular or cellular level over time while aging clocks tend to be more of a generalization of the overall state of the organism. We expect to construct a framework for aging evaluation measurement from both micro and macro perspectives. Especially, population-specific aging clocks and multi-omics aging clocks may better fit the demands to evaluate aging in a comprehensive and multidimensional manner and make a detailed classification to represent different aging rates at tissue/organ levels. This framework will promisingly provide a crucial basis for disease diagnosis and intervention assessment in geroscience.

Pilot study of relationship between prenatal stress during the COVID-19 pandemic and social-emotional development of 12-month-old children: the mediation effects of home environment.

There is increasing evidence that prenatal stress elevates the risk of children's social-emotional development, but the mechanisms underlying this association are unclear. Home environment provides learning opportunities and stimulation required for children's early development and can be influenced by prenatal maternal stress. This study aimed to examine whether home environment can mediate the association between prenatal stress during the pandemic of coronavirus disease 2019 (COVID-19) and their offspring's social-emotional problems thereafter. A pilot sample was derived from 2020 to 2021 Maternal and Child Health Cohort study (N = 82) with the pregnant women recruited during the COVID-19 lockdown period in 2020. Prenatal stress was assessed using the Perceived Stress Scale. Home environment was measured using the Child Home Nurture Environment Scales. Mother-reported toddler social-emotional problems were assessed at 12 months of age. The mediation model was used for data analysis. The mean scores of social-emotional problems, which include externalizing, internalizing, dysregulation, and competence, were 10.98 (5.08), 14.72 (6.49), 15.15 (6.31), and 36.73 (10.26), respectively. Prenatal stress, home environment, and social-emotional problems were significantly related (P < 0.05). Home environment significantly mediated the association between prenatal stress and social-emotional problems with the indirect effect [95% CI] of 0.06 [0.01, 0.14] for externalizing behaviors, 0.10 [0.00, 0.24] for internalizing behaviors, - 0.15 [- 0.31, - 0.01] for competence, 0.08 [0.01, 0.17] and 0.08 [0.01, 0.21] for dysregulation. These findings suggest that prenatal stress may affect offspring's social-emotional problems through the home environment. Screening for prenatal stress and promoting supportive home environment may be potential strategies for social-emotional problems interventions in children.

AutoBar: Automatic Barrier Coverage Formation for Danger Keep Out Applications in Smart City.

Barrier coverage is a fundamental application in wireless sensor networks, which are widely used for smart cities. In applications, the sensors form a barrier for the intruders and protect an area through intrusion detection. In this paper, we study a new branch of barrier coverage, namely warning barrier coverage (WBC). Different from the classic barrier coverage, WBC has the inverse protect direction, which moves the sensors surrounding a dangerous region and protects any unexpected visitors by warning them away from the dangers. WBC holds a promising prospect in many danger keep out applications for smart cities. For example, a WBC can enclose the debris area in the sea and alarm any approaching ships in order to avoid their damaging propellers. One special feature of WBC is that the target region is usually dangerous and its boundary is previously unknown. Hence, the scattered mobile nodes need to detect the boundary and form the barrier coverage themselves. It is challenging to form these distributed sensor nodes into a barrier because a node can sense only the local information and there is no global information of the unknown region or other nodes. To this end, in response to the newly proposed issue of the formation of barrier cover, we propose a novel solution AutoBar for mobile sensor nodes to automatically form a WBC for smart cities. Notably, this is the first work to trigger the coverage problem of the alarm barrier, wherein the regional information is not pre-known. To pursue the high coverage quality, we theoretically derive the optimal distribution pattern of sensor nodes using convex theory. Based on the analysis, we design a fully distributed algorithm that enables nodes to collaboratively move toward the optimal distribution pattern. In addition, AutoBar is able to reorganize the barrier even if any node is broken. To validate the feasibility of AutoBar, we develop the prototype of the specialized mobile node, which consists of two kinds of sensors: one for boundary detection and another for visitor detection. Based on the prototype, we conduct extensive real trace-driven simulations in various smart city scenarios. Performance results demonstrate that AutoBar outperforms the existing barrier coverage strategies in terms of coverage quality, formation duration, and communication overhead.

Mitochondrial Dysfunction and Chronic Liver Disease.

Mitochondria are generally considered the powerhouse of the cell, a small subcellular organelle that produces most of the cellular energy in the form of adenosine triphosphate (ATP). In addition, mitochondria are involved in various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested in different aspects, like increased mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, adenosine triphosphate (ATP) synthesis disorder, abnormal mitophagy, as well as changes in mitochondrial morphology and structure. Mitochondrial dysfunction is related to the occurrence and development of various chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic fatty liver (AFL), and non-alcoholic fatty liver (NAFL). In this review, we summarize and discuss the role and mechanisms of mitochondrial dysfunction in chronic liver disease, focusing on and discussing some of the latest studies on mitochondria and chronic liver disease.

Mechanistic investigations of hirsutene biosynthesis catalyzed by a chimeric sesquiterpene synthase from Steccherinum ochraceum.

The high efficiency and elegance of terpene synthases is fascinating in constructing the molecular skeleton of complicated terpenoids with multiple chiral centers. Although the rapid development of sequencing technology has led to the discovery of an increasing number of terpene synthases, the cyclization mechanisms of some terpene synthases remains elusive. Here, we report that a chimeric sesquiterpene synthase from Steccherinum ochraceum is responsible for the biosynthesis of (+)-hirsutene, a linear triquinane sesquiterpene. Structural validation, and isotope labeling experiments demonstrate that the biosynthesis of (+)-hirsutene employs an unusual cyclization mode, involving three different cyclization processes (C1-C11, C2-C9, C3-C6), one intramolecular 1,2-hydride shift (C9-C10) and three successive 1,2-alkyl shifts to construct the 5-5-5 fused ring skeleton of (+)-hirsutene.

Prognostic significance of preoperative prognostic immune and nutritional index in patients with stage I-III colorectal cancer.

BACKGROUND: To explore the value of preoperative prognostic immune and nutritional index (PINI) in predicting postoperative complications and long-term outcomes in patients with stage I-III colorectal cancer (CRC). METHODS: Restricted cubic splines were used to assess the relationship between PINI and survival in patients with CRC. The Kaplan-Meier method and log-rank test were used to plot the survival curves. The Cox proportional hazards model was used to evaluate independent prognostic predictors in patients with CRC. A logistic regression analysis was performed to identify independent predictors of postoperative complications. The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used for feature screening. RESULTS: An evident positive dose-response relationship between PINI and survival in patients with CRC was identified. Compared with patients with a high PINI, those with a low PINI had worse disease-free survival (DFS) (47.9% vs. 66.9%, p < 0.001) and overall survival (OS) (49.7% vs. 70.2%, p < 0.001). The Cox proportional hazards model revealed that PINI was independently associated with DFS (hazard ratio [HR], 0.823; 95% confidence interval [CI], 0.754-0.898; p < 0.001) and OS (HR, 0.833; 95% CI, 0.761-0.912; p < 0.001) in patients with CRC. In the logistic regression analysis, PINI was an independent factor affecting postoperative complications in patients with CRC (odds ratio, 0.710; 95%CI: 0.610-0.810, p < 0.001). The LASSO logistic regression algorithm was used to screen for effective prognostic variables. Finally, we constructed PINI-based nomograms to predict postoperative 1-5-year PFS, and OS in patients with CRC. CONCLUSION: PINI is an effective biomarker for predicting postoperative complications, DFS, and OS in patients with stage I-III CRC.

Moisture-resistant and green cyclodextrin metal-organic framework nanozyme based on cross-linkage for visible detection of cellular hydrogen peroxide.

A moisture-resistant and green cyclodextrin metal-organic framework (CD-MOF) nanosheet has been prepared via an one-pot antisolvent synthesis procedure. After the treatment of in situ chemical cross-linkage, the two-dimensional (2D) cross-linked CD-MOF exhibited both peroxidase (POD) and oxidase (OXD) enzymatic activities, as well as hydrolytic stability. On the basis of its POD mimics function, the proof-of-concept biosensors were constructed to realize the colorimetric detection for H2O2 and glucose, respectively. In vitro cytotoxicity experiments showed that the 2D cross-linked CD-MOF nanozymes still maintained excellent biocompatibility even at a concentration reaching up to several mg/mL. The in situ colorimetric detection of H2O2 secreted by HepG2 cells further confirmed its promising biocompatibility, showing its great promises as label-free colorimetric probe in early cancer detection and pathological process monitoring.

Overexpression of miR-125a-5p Inhibits Hepatocyte Proliferation through the STAT3 Regulation In Vivo and In Vitro.

microRNAs (miRNAs) are critically involved in liver regeneration (LR). miR-125a-5p (miR-125a) is a tumor-suppressing miRNA, but its role in LR has not been studied. Our previous studies have proved that miR-125a was related to LR at the initiation phase, while the mechanism hepatocyte proliferation triggered by miR-125a in LR has been rarely evaluated. Herein, we mainly studied the molecular mechanism of miR-125a in triggering hepatocyte proliferation and the proliferation stage of LR. Firstly, a striking reduction of miR-125a was found at 24 h as well as 30 h following partial hepatectomy (PH) in rat liver tissue by miRNAs expression profiles as well as qRT-PCR analysis. Furthermore, in vitro, upregulation of miR-125a decreased proliferation as well as G1/S conversion, which promoted hepatocytes apoptosis. STAT3 was the target of miR-125a. In vivo, upregulation of miR-125a by tail vein injection of agomir inhibited LR index. Upregulation of miR-125a inhibited LR index and hepatocytes proliferation by STAT3/p-STAT3/JUN/BCL2 axis. In summary, these current discoveries indicated that miR-125a inhibited hepatocytes proliferation as well as LR by targeting STAT3 and via acting on the STAT3/p-STAT3/JUN/BCL2 axis.

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021.

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) about 22 nucleotides in size, which play an important role in gene regulation and are involved in almost all major cellular physiological processes. In recent years, the abnormal expression of miRNAs has been shown to be associated with human diseases including cancer. In the past ten years, the link between miRNAs and various cancers has been extensively studied, and the abnormal expression of miRNAs has been reported in various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, and prostate cancer. Due to the high malignancy grade of these cancers, it is more necessary to develop the related diagnostic and prognostic methods. According to the study of miRNAs, many potential cancer biomarkers have been proposed for the diagnosis and prognosis of diseases, especially cancer, thus providing a new theoretical basis and perspective for cancer screening. The use of miRNAs as biomarkers for diagnosis or prognosis of cancer has the advantages of being less invasive to patients, with better accuracy and lower price. In view of the important clinical significance of miRNAs in human cancer research, this article reviewed the research status of miRNAs in the above-mentioned cancers in 2021, especially in terms of diagnosis and prognosis, and provided some new perspectives and theoretical basis for the diagnosis and treatment of cancers.

A collaborative robot for COVID-19 oropharyngeal swabbing.

The coronavirus disease 2019 (COVID-19) outbreak has increased mortality and morbidity world-wide. Oropharyngeal swabbing is a well-known and commonly used sampling technique for COVID-19 diagnose around the world. We developed a robot to assist with COVID-19 oropharyngeal swabbing to prevent frontline clinical staff from being infected. The robot integrates a UR5 manipulator, rigid-flexible coupling (RFC) manipulator, force-sensing and control subsystem, visual subsystem and haptic device. The robot has strength in intrinsically safe and high repeat positioning accuracy. In addition, we also achieve one-dimensional constant force control in the automatic scheme (AS). Compared with the rigid sampling robot, the developed robot can perform the oropharyngeal swabbing procedure more safely and gently, reducing risk. Alternatively, a novel robot control schemes called collaborative manipulation scheme (CMS) which combines a automatic phase and teleoperation phase is proposed. At last, comparative experiments of three schemes were conducted, including CMS, AS, and teleoperation scheme (TS). The experimental results shows that CMS obtained the highest score according to the evaluation equation. CMS has the excellent performance in quality, experience and adaption. Therefore, the proposal of CMS is meaningful which is more suitable for robot-sampling.

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BACKGROUND: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. METHODS: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1-2N-, T1-2N+, T3-4N-, and T3-4N+). RESULTS: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3-4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for T3-4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3-4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups. CONCLUSIONS: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

Poorly differentiated is more significant than signet ring cell component for lymph node metastasis in mixed-type early gastric cancer: a retrospective study from a large-volume hospital.

OBJECTIVE: The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer. METHODS: A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria. RESULTS: LNM was more common in mixed (21.9%) than in PD (7.5%, P < 0.001) or SRC (11.3%, P < 0.001). When analyzed the subgroups of mixed type, LNM was more frequent in MD-P (15.4%) than in PD (7.5%, P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P < 0.001) rather than Poorly-D (22.7%, P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%). CONCLUSION: The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

Photodynamic immunotherapy of cancers based on nanotechnology: recent advances and future challenges.

Photodynamic therapy (PDT) is a non-invasive or minimally-invasive treatment which applies photosensitizers (PSs) to create reactive oxygen species (ROS) exposed to light trigger to destroy cancer cells. PDT can activate host anti-tumor immune responses but not powerful enough to kill metastatic tumors. Because of its carrier advantage, imaging, and therapeutic function together with enhanced permeability and retention (EPR) effect, nano-materials have already been used in photo-immunotherapy. Herein, photodynamic immunotherapy (PDIT) based on nanotechnology seems to be a hopeful new form of cancer therapy. In this article, we firstly summarize the recent development in photodynamic immunotherapy based on nanotechnology.

Myocardial angiogenesis induced by exercise training involves a regulatory mechanism mediated by kinin receptors.

OBJECTIVE: To demonstrate that the kallikrein-kinin system (KKS) is upstream of angiogenic signaling pathway, and to determine the role of the kinin B1 and B2 receptors in myocardial angiogenesis induced by exercise training. METHODS: Forty Wistar rats were randomly assigned to an exercise control (EC) group, a B1 receptor antagonist (B1Ant) group, a B2 receptor antagonist (B2Ant) group, and a double receptor antagonist ((B1+ B2)Ant) group. A myocardial infarction model was employed. Animals in all groups received 30 min of exercise training for 4 weeks. The expression of VEGF and eNOS, capillary supply, and apoptosis rate were evaluated. RESULTS: The mRNA and protein expression of VEGF and eNOS showed similar trends in all groups, and were lowest in the (B1+ B2) Ant group, and highest in the EC group. Levels of VEGF and eNOS mRNA were significantly lower in the B1Ant group than in the B2Ant group (p< .001 and p< .05, respectively). VEGF and eNOS protein in the B1Ant group was also significantly lower (p< .01 and p< .05, respectively) than in the B2Ant group. The capillary numbers in the (B1+ B2) Ant group were significantly lower than in the EC group (395.8 ± 105 vs. 1127.9 ± 192.98, respectively). The apoptosis rate of cardiomyocytes was highest in the (B1+ B2) Ant group. CONCLUSION: KKS may act as an upstream signal transduction pathway for angiogenic factors in myocardial angiogenesis. The B1 and B2 receptors exert additive effects, and the B1 receptor has the most prominent role in mediating KKS-induced myocardial angiogenesis.