Plant growth promoting rhizobacteria offer an effective and eco-sustainable solution to protect crops against phytopathogens. In the present study,
Bacillus safensis
STJP (NAIMCC-B-02323) from the ...rhizospheric soil of
Stevia rebaudiana
showed strong biocontrol activity against phytopathogen,
Alternaria alternata
.
B. safensis
STJP produced antifungal volatile organic compounds (AVOC). In the presence of AVOC, there was no conidia germination, mycelium growth was inhibited, and hyphae ruptured as observed by scanning electron microscopy. When mycelium of the fungus from bacterial treated plate was transferred into fresh potato dextrose agar plate,
A. alternata
could not grow. Extracted AVOC from
B. safensis
STJP were identified by thin-layer chromatography (TLC), Fourier-transform-infrared (FTIR) spectroscopy and gas-chromatography–mass spectrometry (GC–MS). In total 25 bacterial metabolites were identified by GC–MS analysis having alcohol, alkane, phenol, alkyl halide and aromatic compounds. Five of these (phenol, 2,4-bis (1,1-dimethylethyl)-, 3-hexadecanol, pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)-, 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo(1,2-a:1′,2′-d)pyrazine and hexadecanoic acid) inhibited the mycelium growth, controlling spore formation and conidia germination of
A. alternata
. This study concluded that AVOC producing
B. safensis
can be used as a green-fungicide against
A. alternata
. Bacterial metabolites could pave the way for the development of next generation biopesticides. This can be a reliable technology to enhance the quality and reliability of biopesticides.
Wound healing is a complex process, which ultimately leads to fibrosis if not repaired well. Pathologically very similar to fibrosis is the tumor stroma, found in several solid tumors which are ...regarded as wounds that do not heal. Integrins are heterodimeric surface receptors which control various physiological cellular functions. Additionally, integrins also sense ECM-induced extracellular changes during pathological events, leading to cellular responses, which influence ECM remodeling. The purpose and scope of this review is to introduce integrins as key targets for therapeutics and drug delivery within the scope of wound healing, fibrosis and the tumor stroma. This review provides a general introduction to the biology of integrins including their types, ligands, means of signaling and interaction with growth factor receptors. Furthermore, we highlight integrins as key targets for therapeutics and drug delivery, based on their biological role, expression pattern within human tissues and at cellular level. Next, therapeutic approaches targeting integrins, with a focus on clinical studies, and targeted drug delivery strategies based on ligands are described.
Existing integrin drug targeting ligands, applied for the modification of drug molecules, drug carriers and CAR-T cells (CAR-T), in the context of wound healing, fibrosis or tumor stroma and their respective integrin targets. Dashed lines show potential integrin targets for existing ligands (PHSCNK, PR_b, RGD, RKK12, quinolonic, echistatin) that have not yet been used for targeting the respective cell line. In addition to already targeted integrins, integrins that have not yet been targeted but play a role in the pathology of wound healing, fibrosis or tumor stroma are presented. Display omitted
Myofibroblasts are the key players in extracellular matrix remodeling, a core phenomenon in numerous devastating fibrotic diseases. Not only in organ fibrosis, but also the pivotal role of ...myofibroblasts in tumor progression, invasion and metastasis has recently been highlighted. Myofibroblast targeting has gained tremendous attention in order to inhibit the progression of incurable fibrotic diseases, or to limit the myofibroblast-induced tumor progression and metastasis. In this review, we outline the origin of myofibroblasts, their general characteristics and functions during fibrosis progression in three major organs: liver, kidneys and lungs as well as in cancer. We will then discuss the state-of-the art drug targeting technologies to myofibroblasts in context of the above-mentioned organs and tumor microenvironment. The overall objective of this review is therefore to advance our understanding in drug targeting to myofibroblasts, and concurrently identify opportunities and challenges for designing new strategies to develop novel diagnostics and therapeutics against fibrosis and cancer.
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Present work investigates the application of electro-catalytic oxidation (EO) technique using dimensionally stable anode, titanium coated with ruthenium dioxide (Ti/RuO2), for abatement of ...amoxicillin trihydrate (AMT), a much commonly prescribed antibiotic detected in water and wastewater. AMT removal efficiency (%ARE) and TOC (Total organic carbon) removal efficiency (%TRE) were measured by varying process parameters such as initial pH, current density (i), initial AMT concentration (C0) and supporting electrolyte (NaCl) concentration (S0). Mineralization current efficiency (%MCE) and specific energy consumption (SEC) values were evaluated and compared for different values of i and S0. Furthermore, decay kinetics of AMT was studied by varying i and C0. Moreover, AMT degradation and mineralization mechanism was explored in detail. Additionally, a possible pathway of AMT degradation/mineralization was proposed by identifying the intermediates formed during EO reactions using UPLC-Q-TOF-MS. Besides, economic feasibility of EO treatment method was analysed by calculating the operating cost. The optimum current density and initial pH were found to be 5.88 mA cm−2 and 7.0, at which, 60% ARE and 48% TRE were achieved in 60 and 240 min of electrolysis, respectively. Mineralization current efficiency was observed decreasing from 11.77% to 7.67% with increasing i value.
In the present study, phosphate solubilizing rhizobacterial isolate STJP from the rhizosphere of
Stevia rebaudiana
was identified as a
Bacillus
sp. on the basis of phenotypic, biochemical, and 16S ...rRNA gene sequencing. In addition to phosphate solubilization ability, isolate
Bacillus
sp. STJP produced a significant quantity of siderophore (16.06 µg/ml) and indole 3-acetic acid (30.59 µg/ml). In the greenhouse experiment, treatment with STJP along with tricalcium phosphate (TCP
200
) showed significant increase in the plant growth parameters, oil yield and P uptake in
M. arvensis
as compared to the control plants. Amongst all the treatments, highest oil yield and menthol content were observed when treated with
Bacillus
sp. STJP + TCP
200
. Hence, an integrated approach of using
Bacillus
sp. STJP along with TCP can be used to increase the production of menthol and oil yield of
M. arvensis
. This approach of using fertilizer along with phosphate solubilizing
Bacillus
sp. worked very well and was more effective in comparison with individual treatment of fertilizer or plant growth promoting rhizobacteria. A combined use of efficient phosphate solubilising bacteria loaded with plant growth promoting characters along with TCP can thus be far effective way for enhancing the yield of crops in a sustainable manner.
The application of chemical fertilizers to enhance crop production is a major concern due to associated environmental pollution and health hazards. Hence, there is an urgent need to develop an ...eco-friendly solution to improve crop production and promote sustainable agriculture simultaneously.
Stevia rebaudiana
is an important medicinal crop being substitute for sugar, superior flavor outline, extensive medicinal properties, and also of agronomic interest. In the present study, bacterium STJP isolated from the rhizospheric soil of
S. rebaudiana
and identified as
Bacillus safensis
on the basis of 16S rRNA gene sequencing, showed good amount of zinc (4.4 mg/L) and potassium (5.4 mg/L) solubilization. Paneer-whey (a dairy waste) based bioformulation (P-WBF) was developed utilizing isolate
B. safensis
STJP (accession number NAIMCC TB-2833) and inspected for the quality and ability to enhance the growth, nutrients uptake, and stevioside content in
S. rebaudiana
. The application of P-WBF displayed a significantly higher concentration (153.12%) of stevioside in
S. rebaudiana
as compared to control. P-WBF treated Stevia plants showed significantly higher fresh and dry weight as well (as compared to control). Further, enhancement of phosphorous, nitrogen, potassium, and zinc uptake in plant tissue was also recorded by application of P-WBF. This study suggests the use of P-WBF based biofertilizer using
B. safensis
STJP to increase stevioside content in Stevia plant by a nutrient(s) linked mechanism. This novel approach can also be beneficial for utilization of a dairy waste in preparation of bioformulation and, for enhancement of crop yield by an ecofriendly manner leading to sustainable agriculture.
Graphic abstract
Tumor‐associated macrophages (TAMs) are the key effector cells in the tumor microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis while suppressing the tumor immune system. ...These protumoral macrophages display an M2 phenotype induced by IL‐4 and IL‐13 cytokines. In this study, we hypothesized that the inhibition of the signal transducer and activator of transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL‐4 and IL‐13, may be an interesting strategy by which to inhibit TAM differentiation and, thus, their protumorigenic activities. In vitro inhibition of the Stat6 pathway by using small interfering RNA or the pharmacologic inhibitor, AS1517499, inhibited the differentiation of mouse RAW264.7 macrophages into the M2 phenotype, as demonstrated by the reduction of Arg‐1 (arginase‐1) and Mrc‐1 (mannose receptor 1) expression and arginase activity. In vivo, AS1517499 significantly attenuated tumor growth and early liver metastasis in an orthotopic 4T1 mammary carcinoma mouse model. Furthermore, in another experiment, we observed an increase in the intrahepatic mRNA expression of F4/80 (EGF‐like module‐containing mucin‐like hormone receptor‐like 1; total macrophages) and M2 macrophage markers Ym‐1 (chitinase 3–like protein 3) and Mrc‐1 and metastatic niche markers Mmp‐2 (matrix metalloproteinase‐2), Postn (periostin), and Cd34 in mice with increasing growth of primary tumors. Of interest, these markers were found to be reduced after treatment with AS1517499. In summary, inhibition of the Stat6 pathway in TAMs is a vital therapeutic approach to attenuate tumor growth and metastasis by inhibiting TAM‐induced protumorigenic and prometastatic activities.—Binnemars‐Postma, K., Bansal, R., Storm, G., Prakash, J. Targeting the Stat6 pathway in tumor‐associated macrophages reduces tumor growth and metastatic niche formation in breast cancer. FASEB J. 32, 969–978 (2018). www.fasebj.org
Glioblastoma‐associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells ...is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D‐bioprinted mini‐brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction. It is demonstrated that in the mini‐brains, glioblastoma cells actively recruit macrophages and polarize them into a GAM‐specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, it is shown that macrophages induce glioblastoma cell progression and invasiveness in the mini‐brains. Finally, it is demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and more sensitivity to chemotherapy. It is envisioned that this 3D‐bioprinted tumor model is used to improve the understanding of tumor biology and for evaluating novel cancer therapeutics.
A novel 3D bioprinted model recapitulating the microenvironment of glioblastoma multiforme is presented. The interaction between glioblastoma cells and glioma‐associated macrophages is investigated, demonstrating clinically relevant cell phenotypes, polarization and invasion of cancer cells and macrophages. Moreover, this model is able to mimic the responsiveness to chemotherapy and immunotherapy similar to the clinical situation.
The whole world is struggling with current coronavirus pandemic that shows urgent need to develop novel technologies, medical innovations or innovative materials for controlling SARS-CoV-2 infection. ...The mode of infection of SARS-CoV-2 is still not well known and seems to spread through surface, air, and water. Therefore, the whole surrounding environment needs to be disinfected with continuous function. For that purpose, materials with excellent antiviral properties, cost effective, environmental friendly and practically applicable should be researched. Titanium dioxide (TiO2) under ultraviolet light produces strong oxidative effect and is utilized as photocatalytic disinfectant in biomedical field. TiO2 based photocatalysts are effective antimicrobial/antiviral agents under ambient conditions with potential to be used even in indoor environment for inactivation of bacteria/viruses. Interestingly, recent studies highlight the effective disinfection of SARS-CoV-2 using TiO2 photocatalysts. Here, scope of TiO2 photocatalysts as emerging disinfectant against SARS-CoV-2 infection has been discussed in view of their excellent antibacterial and antiviral activities against various bacteria and viruses (e.g. H1N1, MNV, HSV, NDV, HCoV etc.). The current state of development of TiO2 based nano-photocatalysts as disinfectant shows their potential to combat with SARS-CoV-2 viral infection and are promising for any other such variants or viruses, bacteria in future studies.
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•Development of TiO2 based photocatalysts with excellent anti-bacterial/viral activities.•Emerging application of TiO2 based photocatalysts in fighting against SARS-CoV-2.•TiO2 based photocatalyst nanomaterials are effective for ambient and dark conditions.•TiO2 photocatalysts based nano-coating can be applied to the surface of objects and common places.•TiO2 photocatalysts nano coating could stop the spreading/transmission of SARS-CoV-2 and other viruses.
In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different ...subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.
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