Research on the roles of the bacteria in tumor development and progression is a rapidly emerging field. Increasing evidence links bacteria with the modification of the tumor immune microenvironment, ...which greatly influences the antitumor response. In view of the individual immune effects of various bacteria in various tumors, developing personalized bacteria-modulating therapy may be a key to successful antitumor treatment. This review emphasizes the critical role of the bacteria in immune regulation, including both the tumor bacteria and gut bacteria. Aiming at tumor-related bacteria, we focus on various precise modulation strategies and discuss their impact and potential for tumor suppression. Finally, engineered bacteria with tumor-targeting ability could achieve precise delivery of various payloads into tumors, acting as a precision tool. Therefore, a precise tumor-related bacteria therapy may be a promising approach to suppress the development of tumors, as well as an adjuvant therapy to improve the antitumor efficacy of other approaches.
Key points
•
The mini-review updates the knowledge on complex effect of bacteria in TME
.
•
Insight into the interaction and adjustment of bacteria in gut for TME
.
•
Prospects and limitations of bacteria-related personalized therapy in the clinical anticancer therapy
.
With rapidly aging populations, family care functions can become weakened, and community health services often lack unified standards. A standardized and professional community home-based long-term ...care model (CHLCM) for the elderly is urgently needed in many regions of China and in other countries. Here, we explored the indicators of the need for a CHLCM among elderly individuals, and we constructed a CHLCM. We created and distributed a questionnaire regarding the requirement of long-term care services, based on a literature review. The two-rounds Delphi method was used, involving 20 experts who were randomly selected from among the medical universities, community health service centers, and nursing homes in Nanning, Guangxi, China. The experts' enthusiasm rates in the questionnaire's two rounds were 95% and 100%, respectively. The authentic coefficient of the experts' consulting was 0.857, and that of the experts' academic level was 0.835; the judgement coefficient was 0.880 and the familiar coefficient was 0.855. The CHLCM includes service content and an evaluation. The coordination coefficients for the two primary, eight secondary, and 29 tertiary indicators were 0.200, 0.386, and 0.184, respectively (p<0.05). The experts' enthusiasm and authority were high. The coordination of the experts' agreement was sufficient, and the analysis results were reliable. The CHLCM includes 29 items that provide a foundation and references for the formulation of concrete indicators and subsequent research.
•SLC plasmid enables engineered SSE strain to repeat delivery of tumor-localized sialidase.•SSE@ZIF-90/Oxa biohybrid promotes the co-delivery of sialidase and oxaliplatin in melanoma model.•The ...SSE@ZIF-90/Oxa biohybrid reverses the tumor immunosuppression mediated by sialoglycan.•The SSE@ZIF-90/Oxa biohybrid exhibits the strongest anti-tumor efficacy in vivo.
Sialic acid, as the new immunosuppressive molecule, is positively correlated with tumor progression, metastasis, and drug resistance. Although targeting desialylation strategy has promising implications for regulating immunosuppressive environment and sensitizing chemotherapy, delivery strategies that integrate the amplifying effects of desialylation and immunogenic chemotherapy are still unexplored. Here, we engineered an Escherichia coli Nissle 1917 hybrid (SSE@ZIF-90/Oxa) to integrate the co-delivery of sialidase and immunogenic cell death inducers which were expected to boost strong antitumor response. In the tumor-hypoxic environment, engineered SSE bacteria exert hypoxia-responsive sialidase expression and periodic lysis to release sialidase, disrupting the sialoglycan-mediated immune suppression. ZIF-90/Oxa was hybridized on the surface of SSE to further induce ICD effect to recruit more infiltration of immune cells. In melanoma models in male mice, this SSE@ZIF-90/Oxa facilitated the co-delivery of sialidase and Oxa both deeply penetrated into and across tumor, suppressed the tumor, and prolonged the survival time of mice, by markedly increasing mature DCs, TNF-α+ CD8+ T cells, and M1 macrophages, while reducing PD-1+CD8+ T cells and Tregs, indicating effective activation of anti-tumor immune cells. Thus, our study provides an intelligent biohybrid therapeutic platform for boosting the combined effect of desialylation-based immunotherapy and immunogenic chemotherapy.
Bacteria and their derivatives (membrane vesicles, MVs) exhibit great advantages for targeting hypoxic tumor cores, strong penetration ability and activating immune responses, holding great potential ...as auspicious candidates for therapeutic and drug-delivery applications. However, the safety issues and low therapeutic efficiency by single administration still need to be solved. To further optimize their performance and to utilize their natural abilities, scientists have strived to modify bacteria with new moieties on their surface while preserving their advantages. The aim of this review is to give a comprehensive overview of a non-genetic engineering modification strategy that can be used to optimize the bacteria with nanomaterials and the design strategy that can be used to optimize MVs for better targeted therapy. Here, the advantages and disadvantages of these processes and their applicability for the development of bacteria-related delivery system as antitumor therapeutic agents are discussed. The prospect and the challenges of the above targeted delivery system are also proposed.
Parasitic mutual inductance between capacitors is critical for the high-frequency performance of electromagnetic interference filter. In this article, a new cancelation method is proposed to ...eliminate mutual inductance completely without adding additional components. The principle of the cancelation method is to design the layout of input and output traces, and the mutual coupling of traces can be equivalent to adding a negative inductance on the transfer branch of the filter to cancel the mutual inductance between capacitors. The two cancelation designs of the filters with small and large capacitor spacing are proposed, respectively. Then, the filter model is established in the finite-element method analysis tool, and the mutual inductances under different layout parameters are calculated to explore the recommended layout, which is to make the negative mutual inductance of traces fully offsets the positive mutual inductance between capacitors. Finally, the effectiveness of cancelation method and the accuracy of model are verified by experiments. The method can significantly improve the filter performance without extra costs and is expected to become a filter design that can be widely promoted.
Lithium metal is the most attractive anode material due to its extremely high specific capacity, minimum potential, and low density. However, uncontrollable growth of lithium dendrite results in ...severe safety and cycling stability concerns, which hinders the application in next generation secondary batteries. In this paper, a new and facile method imposing a magnetic field to lithium metal anodes is proposed. That is, the lithium ions suffering Lorentz force due to the electromagnetic fields are put into spiral motion causing magnetohydrodynamics (MHD) effect. This MHD effect can effectively promote mass transfer and uniform distribution of lithium ions to suppress the dendrite growth as well as obtain uniform and compact lithium deposition. The results show that the lithium metal electrodes within the magnetic field exhibit excellent cycling and rate performance in a symmetrical battery. Additionally, full batteries using limited lithium metal as anodes and commercial LiFePO4 as cathodes show improved performance within the magnetic field. In summary, a new and facile strategy of suppressing lithium dendrites using the MHD effect by imposing a magnetic field is proposed, which may be generalized to other advanced alkali metal batteries.
An novel external strategy of imposing a magnetic field to lithium metal anodes is presented. The generated Lorentz force due to the electromagnetic fields is used to promote mass transfer and uniform distribution of lithium ions. This magnetohydrodynamics effect can effectively suppress the dendrite growth as well as obtain uniform and compact lithium deposition with the remarkable performance.
The uniform growth of carbon nanotubes (CNTs) on the surface of carbon fiber cloth (CFC) was carried out using quasi-vacuum chemical vapor deposition (CVD). It was found that the oxidation of CFC by ...H2O2 was critical to the uniform growth of CNTs. A large number of oxygen-containing functional groups were introduced on the surface of the fiber during oxidation, the content of activated carbon had increased by 27.06%, which could improve the wettability of the fiber and the binding property to the catalyst precursor. After prepared into composites, the interlaminar shear strength (ILSS) was increased by 6.28%, as measured by the short beam test. The analysis of the fracture surfaces revealed that the growth of CNTs enhanced the mechanical interlocking and improved the mechanical properties. For the CNTs-grown CFC/epoxy composite, the strength and toughness can be increased and the stress concentration can be reduced due to the long-distance diffusion of destructive cracks from the resin matrix to the carbon fiber. Finally, the mechanism of improvement in composite performance was explained from the perspective of multiscale enhancement.
Cellular therapies with polyclonal regulatory T-cells (Tregs) in transplantation and autoimmune diseases have been carried out in both animal models and clinical trials. However, The use of large ...numbers of polyclonal Tregs with unknown antigen specificities has led to unwanted effects, such as systemic immunosuppression, which can be avoided via utilization of antigen-specific Tregs. Antigen-specific Tregs are also more potent in suppression than polyclonal ones. Although antigen-specific Tregs can be induced
, these iTregs are usually contaminated with effector T cells during
expansion. Fortunately, Tregs can be efficiently engineered with a predetermined antigen-specificity via transfection of viral vectors encoding specific T cell receptors (TCRs) or chimeric antigen receptors (CARs). Compared to Tregs engineered with TCRs (TCR-Tregs), CAR-modified Tregs (CAR-Tregs) engineered in a non-MHC restricted manner have the advantage of widespread applications, especially in transplantation and autoimmunity. CAR-Tregs also are less dependent on IL-2 than are TCR-Tregs. CAR-Tregs are promising given that they maintain stable phenotypes and functions, preferentially migrate to target sites, and exert more potent and specific immunosuppression than do polyclonal Tregs. However, there are some major hurdles that must be overcome before CAR-Tregs can be used in clinic. It is known that treatments with anti-tumor CAR-T cells cause side effects due to cytokine "storm" and neuronal cytotoxicity. It is unclear whether CAR-Tregs would also induce these adverse reactions. Moreover, antibodies specific for self- or allo-antigens must be characterized to construct antigen-specific CAR-Tregs. Selection of antigens targeted by CARs and development of specific antibodies are difficult in some disease models. Finally, CAR-Treg exhaustion may limit their efficacy in immunosuppression. Recently, innovative CAR-Treg therapies in animal models of transplantation and autoimmune diseases have been reported. In this mini-review, we have summarized recent progress of CAR-Tregs and discussed their potential applications for induction of immunological tolerance.
ObjectiveInvestigative studies report contradictory results of the relationship between serum lipid levels and the risk of colorectal cancer (CRC). We conducted a meta-analysis of prospective ...published studies to clarify the relationship between serum lipid and CRC risk.DesignSystematic review and meta-analysis.Data SourcesPubMed and Embase from inception until December 2020.Eligibility criteriaWe considered prospective cohort and case–control studies that evaluated differences in serum lipid levels with the risk of developing CRC.Data extraction and synthesisTwo independent reviewers screened and included the studies using standardised electronic data extraction forms. The relative risks of the studies were combined with random-effect and fixed-effect models and were analysed for heterogeneity, publication bias and sensitivity.ResultsTwenty-four prospective studies, including 4 224 317 individuals with 29 499 CRC cases, were included in the meta-analysis. The total pooled risk ratio (RR) for high vs low concentrations of triglyceride (TG) concentrations was reported at 1.21 (95% CI 1.09 to 1.34; I2=46.8%), total cholesterol (TC) was at 1.15 (95% CI 1.08 to 1.22; I2=36.8%), high-density lipoprotein cholesterol (HDL-C) was 0.86 (95% CI 0.77 to 0.97; I2=28.8%) and low-density lipoprotein cholesterol (LDL-C) was observed at 1.03 (95% CI 0.75 to 1.41; I2=69.4%).ConclusionsThis meta-analysis shows that high levels of serum TG and TC are positively correlated with the incidence rate of CRC, while high levels of serum HDL-C are negatively correlated with CRC incidence rate. Furthermore, no association was found between LDL-C and the risk of developing CRC. Nevertheless, the heterogeneity brought about by comparative methods, demographic differences and pathological differences between the research subjects limits the effectiveness of the overall pooled results.
Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, ...anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment.
Display omitted
•Quercetin exhibits appreciable anti-psoriasis effects in IMQ-induced mice.•Quercetin displays anti-psoriatic effects through the improvement of antioxidant and anti-inflammatory status.•Quercetin exhibits anti-psoriatic effects by inhibiting the NF-κB pathway.
PDF
