Direct Killing Research Articles

131I-αPD-L1 immobilized by bacterial cellulose for enhanced radio-immunotherapy of cancer.

Radioisotope therapy (RIT) of cancer is restrained by the nonspecific distribution of radioisotope and ineptitude for metastatic tumors. Meanwhile, the clinical application of immune checkpoint blockade (ICB) confronts problems such as low responsive rate, multiple administration requirements and immune-related adverse events (irAE). To address these challenges, we prepared an injectable suspension by immobilizing 131I-labeled anti-programmed cell death-ligand 1 antibody (αPD-L1) in bacterial cellulose for precise and durable radio-immunotherapy of cancer. The crisscross network structure of bacterial cellulose nanofibers would contribute to the long-term retention of 131I-labeled αPD-L1 within tumors, which could reduce the side effect stemmed from the nonspecific 131I distribution in normal tissues. The potent long-term RIT of 131I, combined with ICB by αPD-L1, could effectively restrain the growth of primary tumor in mice. In addition to the direct killing effect, 131I-αPD-L1 immobilized by bacterial cellulose could enhance the immunogenic cell death (ICD) of cancer cells, activating the maturation of multiple immune cells to induce a systemic anti-tumor immune effect. Our therapeutic strategy could suppress spontaneous cancer metastasis and prolong the survival time of tumor-bearing mice. This study proposed a new approach for combined radio-immunotherapy and a novel solution for tumor metastasis in advanced-stage cancers.

Development of Novel CD47-Specific ADCs Possessing High Potency Against Non-Small Cell Lung Cancer in vitro and in vivo.

Targeted therapies hold promise for efficiently and accurately delivering cytotoxic drugs directly to tumor tissue to exert anticancer effects. CD47 is a membrane protein expressed in a variety of malignant tumors and hematopoietic cells, which plays a key role in immune escape and tumor progression. Although CD47 immunocheckpoint therapy has been developed in recent years, many patients cannot benefit from it because of its low efficiency. To strengthen and extend the therapeutic efficacy of anti-CD47 monoclonal antibody (mAb), we used the newly developed 7DC2 and 7DC4 mAbs as the targeting payload adaptor and VCMMAE as the toxin payload to construct novel CD47-specific immunotoxin (7DC-VCMMAE) by engineering cysteine residues. These CD47-specific ADCs have the better cell penetration, excellent DAR, similar payload distribution and good antigen-binding affinity. In vitro, 7DC-VCMMAE treatment induced death of non-small cell lung cancer (NSCLC) cell lines 95D and SPC-A1, but not A549 that express low levels of CD47 on the cell membrane. This finding suggests that 7DC-VCMMAE may possess greater therapeutic effect on NSCLC tumors expressing a high level of CD47 antigen; however, 7DC-VCMMAE treatment also promoted phagocytosis of A549 cells by macrophages. In vivo, 7DC-VCMMAE treatment had remarkable antitumor effects in a NSCLC cell line-derived xenograft (CDX) mouse model based on nonobese diabetic/severe combined immunodeficient (NOD/SCID). In summary, this study combined VCMMAE with anti-CD47 mAbs, emphasizing a novel and promising immunotherapy method for direct killing of NSCLC, which provides a valuable new way to meet the needs of the cancer therapy field.

Two distinct receptor-binding domains of human glycyl-tRNA synthetase 1 displayed on extracellular vesicles activate M1 polarization and phagocytic bridging of macrophages to cancer cells

Macrophages play important roles in cancer microenvironment. Human cytosolic glycyl-tRNA synthetase (GARS1) was previously shown to be secreted via extracellular vesicles (EVs) from macrophages to trigger cancer cell death. However, the effects of GARS1-containing EVs (GARS1-EVs) on macrophages as well as on cancer cells and the working mechanisms of GARS1 in cancer microenvironment are not yet understood. Here we show that GARS1-EVs induce M1 polarization and facilitate phagocytosis of macrophages. GARS1-EVs triggers M1 polarization of macrophage via the specific interaction of the extracellular cadherin subdomains 1–4 of the cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2) with the N-terminal WHEP domain containing peptide region of GARS1, and activates the RAF-MEK-ERK pathway for M1 type cytokine production and phagocytosis. Besides, GARS1 interacted with cadherin 6 (CDH6) of cancer cells via its C-terminal tRNA-binding domain to induce cancer cell death. In vivo model, GARS1-EVs showed potent suppressive activity against tumor initiation via M1 type macrophages. GARS1 displayed on macrophage-secreted extracellular vesicles suppressed tumor growth in dual mode, namely through pro-apoptotic effect on cancer cells and M1 polarization effect on macrophages. Collectively, these results elucidate the unique tumor suppressive activity and mechanism of GARS1-EVs by activating M1 macrophage via CELSR2 as well as by direct killing of cancer cells via CDH6.

Modification of ultrafiltration membrane with antibacterial agent intercalated layered nanosheets: Toward superior antibiofouling performance for water treatment

Membrane fouling, especially biofouling induced by biofilm formation on membranes, can result in frequent cleaning or even replacement of membranes. Fabrication of membrane with excellent antibiofouling property is quite attractive due to its effectiveness and low-impact on the operation of membrane-based process. Herein, a cationic antibacterial agent, quaternary ammonium compound (QAC), was intercalated into the interlayer spaces of the MgAl layered double hydroxide (QAC/LDH) by self-assembly. The QAC/LDH composite was incorporated into polyethersulfone (PES) ultrafiltration (UF) membrane (PES-QLDH). The QAC/LDH enhanced the hydrophilicity, water flux, and resistance to organic fouling for the PES-QLDH membrane. The PES-QLDH membrane exhibited superior antibiofouling performance than the control PES membrane, with deposition of a thinner biofilm layer consisted of almost dead cells. The superior antibacterial activity inhibits the adhesion and growth of bacteria on the membrane surface, effectively retarding the formation of biofilms. Importantly, the synergistic effect of QAC and LDH in the PES-QLDH membrane resulted in a high biocidal activity based on both direct and indirect killing mechanisms. The PES-QLDH membrane maintained a stable and high antibacterial activity after several fouling-cleaning cycles. These results imply that the PES-QLDH membrane provides an effective and promising strategy for its long-term application in wastewater treatment.

Complex Dynamics of a Three-Species Food Chain Model with Fear and Allee Effect

In ecology, predator–prey interactions are very complex in nature. Apart from direct killing, predator induces fear among their prey which affects the life-history, behavioral changes, and reproduction potential of the prey population. On the other hand, the Allee effect has a great impact on regulating the population size, community structure and population dynamics. In the present investigation, we modify the Hastings–Powell (HP) [1991] model by considering the cost of fear in middle predator and the Allee effect in top predator. The stability conditions for the biologically feasible equilibria are derived using linear stability analysis. Considering the cost of fear and the Allee effect as key parameters, the Hopf bifurcation analysis is carried out around the interior equilibrium. The direction of Hopf bifurcation and the stability of the bifurcating periodic solution are determined by applying the normal form theory and center manifold theorem. Our numerical results suggest that the fear effect can stabilize the system. It is observed that high levels of fear among middle predator decrease the population density of top predator. We also observe that if the Allee parameter is increased, then the system becomes stable from chaotic oscillations. However, further increase in the Allee parameter leads to population extinction. We have also drawn several one- and two-parameter bifurcation diagrams which explore rich dynamical behaviors.

Glycolipid-loaded nanoparticle immunotherapy cooperates with checkpoint inhibitors to harness iNKT cells for tumor control

Abstract Invariant natural killer T cells (iNKT) have a well-documented role in direct and indirect killing of tumor cells through their release of proinflammatory cytokines and cytotoxic compounds. To improve outcomes in poorly immunogenic cancers while avoiding NKT cell anergy, we induced anti-tumor responses by activating NKT cells with polymeric nanoparticles containing a low dose of a glycolipid adjuvant, α-Galactosyl-Ceramide (aGalCer), and a model tumor neoantigen, ovalbumin (OVA). Prophylactic vaccination of mice with aGalCer-OVA nanoP before inoculation with B16F10-OVA melanoma cells reduced tumor growth rate and increased overall survival compared to mice immunized with control nanoparticles. In mice with an established B16 tumor, therapeutic administration of aGalCer-OVA nanoP provided significantly greater anti-tumor effects, reduced tumor growth rate and increased survival, compared to control nanoparticles. Therapeutic treatment with aGalCer-OVA nanoP, but not control nanoPs, also induced significant infiltration of iNKT, NK, and antigen-specific CD8 T cells in the tumor, and enhanced production of granzyme B and perforin by CD8 T cells. Furthermore, immune checkpoint blockade treatment (anti-CTLA-4 + anti-PD-1) enhanced the effectiveness of aGalCer-OVA nanoP, leading to clearance of established tumors nearly 50% of the time. These results provide strong evidence that activation of iNKT cells via nanoparticles containing a glycolipid adjuvant and tumor antigen is a viable anti-cancer strategy that partners well with other clinically used immunotherapies. Supported by grants from NIH (T32 AI138944) and the CTSA (TL1 TR002467)

Nanomedicines Targeting Heat Shock Protein 90 Gene Expression in the Therapy of Breast Cancer

AbstractBreast cancer is the second leading cause of death all over the globe among women. Nanotechnology has emerged recently to overcome the limitations of the traditional drug delivery system. Conventional chemotherapies have several side effects that damage the immune system and other organs. Several other cancer treatments cause the proliferation of normal cells, making them cancerous due to nonspecific targeting, inability to enter the core of the tumor, and poor solubility. To overcome the problems of chemotherapies, nanotechnology has come up with the direct killing of a tumor cell with fewer side effects. Nanoparticles are designed to recognize the cancer cells and provide accurate drug delivery without interacting with the healthy cells. The use of nanoparticles with anticancer drug therapies has shown promising effects in the killing of cancer cells. The major objective of this review is to discuss the role of Heat Shock Protein 90 (Hsp90) in breast cancer and its treatment by targeted therapy via nanotechnology. This review covers research published since 2001 describing the nanotechnology mediated Hsp90 targeted breast cancer therapy.

Gold nanocluster & indocyanine green based triple-effective therapy for MRSA infected central nervous system

For the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections occur in the central nervous system, the commonly used vancomycin (Van) is highly nephrotoxic, hard to cross the blood-brain barrier (BBB), and prone to induce bacterial resistance during long-term usage. Herein, QAI, the quaternary ammonium salt modified gold nanocluster (QA) combined with indocyanine green (ICG), was synthesized. With the help of the near-infrared laser, QAI could effectively cross the BBB and treat intracranial MRSA infection at low doses through a triple-combination synergistic therapy of direct-killing (DK), photothermal therapy (PTT), and photodynamic therapy (PDT). Another attractive feature of QAI was the difficulty to produce drug resistance, which was attributed to its physical antibacterial mechanism. Compared with traditional Van therapy, QAI therapy was significantly less toxic to the liver and kidney and thus would be a healthier strategy for intracranial MRSA-infection therapy.

‘All Fishing Is Wildlife Poaching:’ Nonhuman Animal Imagery and Mutual Avowal in Racing Extinction and Seaspiracy

Images of nonhuman animals may be effective tools in producing climate concern and empathy for animals, particularly if animals are shown in natural habitats. Visual and narrative analysis of the documentary Racing Extinction identifies a practice of selectively recognizing the individuality of certain animals. Despite emphasizing the intrinsic worth of often-marginalized animals, Racing Extinction reproduces the marginalization of domesticated animals raised for consumption and less charismatic marine life. A close reading of the film’s animal imagery also reveals a spatialized bias—visualizing violence against marine life overwhelmingly in China and Indonesia and by comparison associating the U.S. with indirect climate harm rather than the direct killing of animals. Intertwining a decolonial ethic with a critical animal studies perspective, this paper reveals how disjointed imagery of nonhuman animal suffering facilitates racial scapegoating, masks the exploitation of marine life by the U.S. and partitions uneven ethical responsibilities towards nonhuman animals. This is contrasted to the documentary Seaspiracy, which advances a universal, non-speciesist ethic of “mutual avowal”, contextualizing images of violence against marine life in a global frame.

Predation risk can modify the foraging behaviour of frugivorous carnivores: Implications of rewilding apex predators for plant-animal mutualisms.

Apex predators play key roles in food webs and their recovery can trigger trophic cascades in some ecosystems. Intra‐guild competition can reduce the abundances of smaller predators and perceived predation risk can alter their foraging behaviour thereby limiting seed dispersal by frugivorous carnivores. However, little is known about how plant–frugivore mutualisms could be disturbed in the presence of larger predators.We evaluated the top‐down effect of the regional superpredator, the Iberian lynx Lynx pardinus, on the number of visits and fruits consumed by medium‐sized frugivorous carnivores, as well as the foraging behaviour of identified individuals, by examining the consumption likelihood and the foraging time.We carried out a field experiment in which we placed Iberian pear Pyrus bourgaeana fruits beneath fruiting trees and monitored pear removal by frugivorous carnivores, both inside and outside lynx ranges. Using camera traps, we recorded the presence of the red fox Vulpes vulpes, the Eurasian badger Meles meles and the stone marten Martes foina, as well as the number of fruits they consumed and their time spent foraging.Red fox was the most frequent fruit consumer carnivore. We found there were fewer visits and less fruit consumed by foxes inside lynx ranges, but lynx presence did not seem to affect badgers. We did not observe any stone marten visits inside lynx territories. The foraging behaviour of red foxes was also altered inside lynx ranges whereby foxes were less efficient, consuming less fruit per unit of time and having shorter visits. Local availability of fruit resources, forest coverage and individual personality also were important variables to understand visitation and foraging in a landscape of fear.Our results show a potential trophic cascade from apex predators to primary producers. The presence of lynx can reduce frugivorous carnivore numbers and induce shifts in their feeding behaviour that may modify the seed dispersal patterns with likely consequences for the demography of many fleshy‐fruited plant species. We conclude that knowledge of the ecological interactions making up trophic webs is an asset to design effective conservation strategies, particularly in rewilding programs.

BTK Inhibitors Impair Platelet-Mediated Antifungal Activity.

In recent years, the introduction of new drugs targeting Bruton’s tyrosine kinase (BTK) has allowed dramatic improvement in the prognosis of patients with chronic lymphocytic leukemia (CLL) and other B-cell neoplasms. Although these small molecules were initially considered less immunosuppressive than chemoimmunotherapy, an increasing number of reports have described the occurrence of unexpected opportunistic fungal infections, in particular invasive aspergillosis (IA). BTK represents a crucial molecule in several signaling pathways depending on different immune receptors. Based on a variety of specific off-target effects on innate immunity, namely on neutrophils, monocytes, pulmonary macrophages, and nurse-like cells, ibrutinib has been proposed as a new host factor for the definition of probable invasive pulmonary mold disease. The role of platelets in the control of fungal growth, through granule-dependent mechanisms, was described in vitro almost two decades ago and is, so far, neglected by experts in the field of clinical management of IA. In the present study, we confirm the antifungal role of platelets, and we show, for the first time, that the exposure to BTK inhibitors impairs several immune functions of platelets in response to Aspergillus fumigatus, i.e., the ability to adhere to conidia, activation (as indicated by reduced expression of P-selectin), and direct killing activity. In conclusion, our experimental data suggest that antiplatelet effects of BTK inhibitors may contribute to an increased risk for IA in CLL patients.

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models.

Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.

Elotuzumab, a potential therapeutic humanized anti-SLAMF7 monoclonal antibody, enhances natural killer cell-mediated killing of primary effusion lymphoma cells.

Primary effusion lymphoma (PEL) is a rare aggressive B-cell non-Hodgkin's lymphoma with no optimal treatment. Signaling lymphocytic activation molecule-F7 (SLAMF7, CD319), a type I transmembrane glycoprotein highly expressed in multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. SLAMF7 also expresses on several hematopoietic lineages including NK cells. Elotuzumab (Elo), a humanized antibody targeting SLAMF7, is approved by FDA for MM treatment. In this study, we analyzed the expression of SLAMF7 on seven PEL cell lines. All PEL cells and NK cells showed high expression of SLAMF7. NK cells were enriched from PBMCs of healthy donors by MACS and expanded by co-culturing with MHC-class I negative K562 cells in the presence of IL-2 and IL-15. Expanded NK cells showed direct killing, and Elo demonstrated potent ADCC against PEL in an Effector:Target (E:T) dependent manner. Surface expression of CD107a on NK cells also increased in the process of ADCC. We also examined SLAMF7 expression of NK subpopulations and found that the CD56+CD16+ NK subpopulation demonstrated the highest SLAMF7 expression. Full-length-Elo but not F(ab')2-Elo exerts direct engagement to the expressing SLAMF7 on NK cells, promotes CD107a expression, and further augments NK cytotoxicity toward PEL. Elo enhanced survival of PEL-bearing immunodeficient mice with adoptive transfer of human NK cells. Taken together, our results show that NK cells play roles in PEL killing, and Elo causes ADCC/SLAMF7 ligation to boost NK cytotoxicity against PEL, offering promising preclinical evidence of Elo as a therapeutic monoclonal antibody treatment for PEL.

CAR T CELL THERAPY. A NEW MILESTONE IN THE TREATMENT OF B CELL LYMPHOMAS

The outcome of patients with malignant lymphoma has significantly improved over the last decades. Major contributions have come from an increased knowledge of the disease, from its better classification, and from relevant advances in treatment. Novel important therapies have been added to the existing approach, making it possible to improve direct cancer cell killing. … Continued

Biological traits interact with human threats to drive extinctions: A modelling study

How a particular threat influences extinction risk may depend on biological traits. Empirical studies relating threats and traits are needed, but data are scarce, making simulations useful. We implemented an eco-evolutionary model to analyse how five threat types influence the extinction risk of virtual organisms differing in body size, maturity age, fecundity, and dispersal ability. The model consisted of observing the evolutionary shift in the mean trait values of an assemblage of organisms when a threat was added into the virtual world where they lived. If a positive shift was found in trait values, we considered that the threat negatively influenced organisms with lower values for that trait. Direct killing mostly affected organisms with slow life cycles (slower-living) and poorly dispersive organisms. Habitat loss caused a reduction in the average dispersal ability of organisms. Habitat fragmentation caused an increase of average dispersal ability, and had a negative effect on larger, less fecund organisms. Habitat degradation and the introduction of invasive competitors had similar effects, mostly affecting large and fast-living organisms, with habitat degradation also affecting highly fecund and poorly dispersive organisms. These results agree with previous empirical studies in which larger, slower-lived, and less fecund organisms are more vulnerable to a greater range of threats. On the other hand, our results challenge two commonly seen hypotheses in the literature: that organisms with high dispersal ability fare well under any high habitat loss scenarios, and that fast-living, highly fecund organisms always do well during environmental change. Our study shows that highly dispersive organisms may be the losers when habitat loss removes large continuous areas of habitat, and fast-living and highly reproductive organisms may be the losers when resources or energy availability dwindle to very low levels. Most importantly, our study underpins the importance of considering the type of threat when analysing the relation between traits and extinction. Even in simple scenarios such as the ones modelled here, different threats lead to different, sometimes opposite, extinction probabilities according to the biological traits of organisms.

Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages.

Malaria is still the most widespread parasitic disease and causes the most infections globally. Owing to improvements in sanitary conditions and various intervention measures, including the use of antimalarial drugs, the malaria epidemic in many regions of the world has improved significantly in the past 10 years. However, people living in certain underdeveloped areas are still under threat. Even in some well-controlled areas, the decline in malaria infection rates has stagnated or the rates have rebounded because of the emergence and spread of drug-resistant malaria parasites. Thus, new malaria control methods must be developed. As the spread of the Plasmodium parasite is dependent on the part of its life cycle that occurs in mosquitoes, to eliminate the possibility of malaria infections, transmission-blocking strategies against the mosquito stage should be the first choice. In fact, after the gametocyte enters the mosquito body, it undergoes a series of transformation processes over a short period, thus providing numerous potential blocking targets. Many research groups have carried out studies based on targeting the blocking of transmission during the mosquito phase and have achieved excellent results. Meanwhile, the direct killing of mosquitoes could also significantly reduce the probability of malaria infections. Microorganisms that display complex interactions with Plasmodium, such as Wolbachia and gut flora, have shown observable transmission-blocking potential. These could be used as a biological control strategy and play an important part in blocking the transmission of malaria.

Combining multiscale niche modeling, landscape connectivity, and gap analysis to prioritize habitats for conservation of striped hyaena (Hyaena hyaena).

Identifying spatial gaps in conservation networks requires information on species-environment relationships, and prioritization of habitats and corridors. We combined multi-extent niche modeling, landscape connectivity, and gap analysis to investigate scale-dependent environmental relationships, and identify core habitats and corridors for a little-known carnivore in Iran, the striped hyaena (Hyaena hyaena). This species is threatened in Iran by road vehicle collisions and direct killing. Therefore, understanding the factors that affect its habitat suitability, spatial pattern of distribution, and connectivity among them are prerequisite steps to delineate strategies aiming at human-striped hyaena co-existence. The results showed that the highest predictive power and extent of habitats was obtained at the extent sizes of 4 and 2 km, respectively. Also, connectivity analysis revealed that the extent and number of core habitats and corridors changed with increasing dispersal distance, and approximately 21% of the landscape was found to support corridors. The results of gap analysis showed that 15–17% of the core habitats overlapped with conservation areas. Given the body size of the species, its mobility, and lack of significant habitat specialization we conclude that this species would be more strongly influenced by changes in habitat amount rather than landscape configuration. Our approach showed that the scale of variables and dispersal ability must be accounted for in conservation efforts to prioritize habitats and corridors, and designing conservation areas. Our results could facilitate the conservation of striped hyaena through the identification and prioritization of habitats, establishment of conservation areas, and mitigating conflicts in corridors.

Bovine Natural Antibody Relationships to Specific Antibodies and Fasciola hepatica Burdens after Experimental Infection and Vaccination with Glutathione S-Transferase.

Fasciola hepatica is the causative agent of fasciolosis, a significant parasitic disease occurring worldwide. Despite ongoing efforts, there is still no vaccine to control liver fluke infections in livestock. Recently, it has been suggested that natural antibodies (NAbs) can amplify specific antibodies (SpAb) and have a direct killing effect, but it is unknown if this phenomenon occurs during parasitic helminth infection or targeted vaccination. NAbs are antibodies produced by the innate immune system, capable of binding antigens without prior exposure. This study explores the role of bovine NAbs, using the exogenous glycoprotein keyhole limpet hemocyanin (KLH), in response to F. hepatica infection and SpAb production after infection and vaccination. The cattle’s NAbs were differently influenced by parasite infection and vaccination, with an increase in KLH-binding IgG and IgM levels after infection and reduced KLH-binding IgM levels following vaccination. Underlying NAbs reacting to KLH showed no correlations to the final fluke burdens after experimental infection or vaccination. However, NAbs reacting to whole-worm extract (WWE) prior to infection were positively correlated to increased fluke burdens within the infected bovine host. Furthermore, after infection, the specific IgG reacting to WWE was positively reflected by the underlying NAb IgG response. Following subcutaneous vaccination with F. hepatica native glutathione S-transferase (GST), there was a non-significant 33% reduction in fluke burden. Vaccinated animals with higher underlying NAbs had a higher induction of vaccine-induced SpAbs, with trends observed between KLH-binding IgM and anti-GST IgG and IgM. Our findings provide a platform to allow further investigation to determine if NAb levels could mirror fluke-SpAb production for exploitation in a combined selective breeding and vaccination program. Additionally, this work suggests that liver fluke could possibly evade the host’s immune system by utilising surface-bound IgM NAbs.

The Role of Graphene Oxide Nanocarriers in Treating Gliomas.

Gliomas are the most common primary malignant tumors of the central nervous system, and their conventional treatment involves maximal safe surgical resection combined with radiotherapy and temozolomide chemotherapy; however, this treatment does not meet the requirements of patients in terms of survival and quality of life. Graphene oxide (GO) has excellent physical and chemical properties and plays an important role in the treatment of gliomas mainly through four applications, viz. direct killing, drug delivery, immunotherapy, and phototherapy. This article reviews research on GO nanocarriers in the treatment of gliomas in recent years and also highlights new ideas for the treatment of these tumors.

Realistic and critical review of the state of systemic antimicrobial peptides.

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility of adding new candidates to the list of the existing peptide antibiotics to more effectively combat antibiotic-resistant bacteria, fungi, and parasites.