Search

Cancer immunotherapy is a promising approach that has recently gained its importance in treating cancer. Despite various approaches of immunotherapies being used to target cancer cells, they are either not effective against all types of cancer or for all patients. Although efforts are being made to improve the cancer immunotherapy in all possible ways, one important hindrance that lowers the immune response to kill cancer cells is the infiltration of Regulatory T (Treg) cells into the tumor cells, favoring tumor progression, on one hand, and inhibiting the activation of T cells to respond to cancer cells, on the other hand. Therefore, new anti-cancer drugs and vaccines fail to show promising results against cancer. This is due to the infiltration of Treg cells into the tumor region and suppression of anti-cancer activity. Thus, regardless of various types of immunotherapies being practiced, understanding the mechanisms of how Treg cells favor tumor progression and inhibition of anti-cancer activity is worthwhile. Therefore, the review highlights the importance of Tregs cells and how depletion of Treg cells can pave the way to an effective immunotherapy by activating the immune responses against cancer.

Arabinogalactan proteins (AGPs) are essential members of hyperglycosylated glycoproteins and are critical for the sexual reproduction of plants. To our knowledge, currently Arabodopsis FLA3 and Brassica BcMF8 are the only two members of AGPs reported concerning pollen intine formation. Previously, the orthologue of AtAGP6 in B. campestris, BcMF18, was isolated and proved to affect microspore development. In this study, western blot assay and subcellular localization showed that BcMF18 encoded an approximately 19.5 kDa secretory AGP protein which anchored to extracellular matrices. Ectopic overexpression of BcMF18 (OE) in Arabodopsis caused reduced male fertility and resulted in short siliques with low seed set. Approximately 46% of OE pollen grains were aborted and lacked viability, without all cytoplasmic materials and nuclei. Pollen abortion which led to defective microspore production with no cellulose was observed to start at the bicellular stage. At this point, intine layer displayed abnormalities and degraded from the bicellular stage, which led to the failure in keeping the internal environment stability and resulted in hollow remnants of microspores. However, the basic structure and patterning of the exine layer of collapsed pollen grains seemed unaffected, completed with intact nexine, baculum, and tectum to constitute a pronounced reticulate structure filled with typhine. Based on these results presented here, it is proposed that BcMF18 functions in Arabodopsis and is associated with pollen intine formation, possibly through participating in the formation of proteoglycan structures, which provide strong evidence for subfunctionalization from AtAGP6 to BcMF18.

Cancer remains a daunting and cureless disease, which is responsible for one-sixth of human deaths worldwide. These mortality rates have been expected to rise in the future due to the side effects of conventional treatments (chemotherapy, radiotherapy, and surgery), which can be addressed by applying nanomedicine. In order to escape from biological barriers, such nanomedicine should be mimicked and designed to be stealthy while navigating in the bloodstream. To achieve this, scientists take advantage of erythrocytes (red blood cells; RBCs) as drug carriers and develop RBC membrane (RBCm) coating nanotechnology. Thanks to the significant advances in nanoengineering, various facile surface functionalization methods can be applied to arm RBCm with not only targeting moieties, but also imaging agents, therapeutic agents, and nanoparticles, which are useful for theranostic nanomedicine. This review focuses on refunctionalization of erythrocyte-based nanomedicine for enhancing cancer-targeted drug delivery.

Cytoplasmic male sterility (CMS) is a widely used trait in angiosperms caused by perturbations in nucleus-mitochondrion interactions that suppress the production of functional pollen. MicroRNAs (miRNAs) are small non-coding RNAs that act as regulatory molecules of transcriptional or post-transcriptional gene silencing in plants. The discovery of miRNAs and their possible implications in CMS induction provides clues for the intricacies and complexity of this phenomenon. Previously, we characterized an Ogura-CMS line of turnip (Brassica rapa ssp. rapifera) that displays distinct impaired anther development with defective microspore production and premature tapetum degeneration. In the present study, high-throughput sequencing was employed for a genome-wide investigation of miRNAs. Six small RNA libraries of inflorescences collected from the Ogura-CMS line and its maintainer fertile (MF) line of turnip were constructed. A total of 120 pre-miRNAs corresponding to 89 mature miRNAs were identified, including 87 conversed miRNAs and 33 novel miRNAs. Among these miRNAs, the expression of 10 differentially expressed mature miRNAs originating from 12 pre-miRNAs was shown to have changed by more than two-fold between inflorescences of the Ogura-CMS line and inflorescences of the MF line, including 8 down- and 2 up-regulated miRNAs. The expression profiles of the differentially expressed miRNAs were confirmed by stem-loop quantitative real-time PCR. In addition, to identify the targets of the identified miRNAs, a degradome analysis was performed. A total of 22 targets of 25 miRNAs and 17 targets of 28 miRNAs were identified as being involved in the reproductive development for Ogura-CMS and MF lines of turnip, respectively. Negative correlations of expression patterns between partial miRNAs and their targets were detected. Some of these identified targets, such as squamosa promoter-binding-like transcription factor family proteins, auxin response factors and pentatricopeptide repeat-containing proteins, were previously reported to be involved in reproductive development in plants. Taken together, our results can help improve the understanding of miRNA-mediated regulatory pathways that might be involved in CMS occurrence in turnip.

Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.

Our data present H 2 S in a new role, serving as a multi-faceted transducer to different response mechanisms during NO-induced acquisition of tolerance to flooding-induced hypoxia in maize seedling roots. Nitric oxide (NO), serving as a secondary messenger, modulates physiological processes in plants. Recently, hydrogen sulfide (H2S) has been demonstrated to have similar signaling functions. This study focused on the effects of treatment with H2S on NO-induced hypoxia tolerance in maize seedlings. The results showed that treatment with the NO donor sodium nitroprusside (SNP) enhanced survival rate of submerged maize roots through induced accumulation of endogenous H2S. The induced H2S then enhanced endogenous Ca2+ levels as well as the Ca2+-dependent activity of alcohol dehydrogenase (ADH), improving the capacity for antioxidant defense and, ultimately, the hypoxia tolerance in maize seedlings. In addition, NO induced the activities of key enzymes in H2S biosynthesis, such as l-cysteine desulfhydrases (l-CDs), O-acetyl-l-serine (thiol)lyase (OAS-TL), and β-Cyanoalanine Synthase (CAS). SNP-induced hypoxia tolerance was enhanced by the application of NaHS, but was eliminated by the H2S-synthesis inhibitor hydroxylamine (HA) and the H2S-scavenger hypotaurine (HT). H2S concurrently enhanced the transcriptional levels of relative hypoxia-induced genes. Together, our findings indicated that H2S serves as a multi-faceted transducer that enhances the nitric oxide-induced hypoxia tolerance in maize (Zea mays L.)

Growth factors (GFs) act as important active molecules for the treatment of skin wounds. However, their clinical translation is seriously restrained due to single function and short half-life. Besides, the underlying GFs-mediated wound healing mechanism remains elusive. Therefore, we aimed to develop a thermo-sensitive chitosan hydrogel embedding with poly lactic-co-glycolic acid (PLGA) microspheres which can deliver platelet-derived growth factor receptor (PDGF) for wound healing. The generated PDGF-PLGA hydrogel was systematically evaluated for its wound healing efficiency by the in vivo experiments, including biocompatibility testing, cell proliferation and migration, wound closure rate, granulation tissue formation and collagen deposition. Further, the expression levels of autophagy-related proteins were detected. The results showed that the PDGF-PLGA hydrogel exhibited excellent cell compatibility, cell proliferation and migration. The PDGF-PLGA hydrogel was superior to PDGF alone and control groups in promoting wound closure, granulation tissue formation and collagen synthesis. In addition, the autophagy levels were significantly decreased by PDGF hydrogel in wound tissue of treated mice as compared with PDGF alone and control groups. We also found that the autophagy activator rapamycin delayed PDGF hydrogel-mediated wound healing. This study provides a novel mechanism for the beneficial effects of PDGF-PLGA hydrogel on the wound repair.

Flooding of soils often results in hypoxic conditions surrounding plant roots, which is a harmful abiotic stress to crops. Hydrogen sulfide (H2S) is a highly diffusible, gaseous molecule that modulates cell signaling and is involved in hypoxia signaling in animal cells. However, there have been no previous studies of H2S in plant cells in response to hypoxia. The effects of H2S on hypoxia-induced root tip death were studied in pea (Pisum sativum) via analysis of endogenous H2S and reactive oxygen species (ROS) levels. The activities of key enzymes involved in antioxidative and H2S metabolic pathways were determined using spectrophotometric assays. Ethylene was measured by gas chromatography. We found that exogenous H2S pretreatment dramatically alleviated hypoxia-induced root tip death by protecting root tip cell membranes from ROS damage induced by hypoxia and by stimulating a quiescence strategy through inhibiting ethylene production. Conversely, root tip death induced by hypoxia was strongly enhanced by inhibition of the key enzymes responsible for endogenous H2S biosynthesis. Our results demonstrated that exogenous H2S pretreatment significantly alleviates hypoxia-induced root tip death in pea seedlings and, therefore, enhances the tolerance of the plant to hypoxic stress.