Unveiling the Potential of Rhizospheric Bacillus subtilis to Enhance Nitrogen Metabolism, Soil Microbiota, and Nutrient Uptake Under Cadmium Stress in Maize

Article

作者: Zheng, Xi ; Zhou, Xun Bo ; Khan, Kashif ; Ahmad, Haseeb ; Ali, Shahid ; Khan, Rayyan ; Shah, Muhammad Ali

ABSTRACT:

Cadmium (Cd) contamination in agricultural soils poses a major threat to soil health and crop productivity. This study aimed to evaluate the potential of Bacillus subtilis (BSS) in alleviating Cd‐induced stress in maize by improving soil nutrients, modulating microbial communities, reducing Cd accumulation, and enhancing plant growth and nutrient uptake. It is hypothesized that rhizospheric B. subtilis will enhance nitrogen metabolism, restore soil nutrients, improve microbes, and reduce Cd uptake in maize. A pot experiment was conducted comprising six treatments, including control, BSS ( B. subtilis ), Cd25 (25 mg kg −1 ), Cd25BSS, Cd50 (50 mg kg −1 ), and Cd50BSS. Soil properties, enzymatic activities, Cd accumulation, microbial diversity, and ionomic profiles in various maize tissues were analyzed. Application of B. subtilis significantly improved soil nutrient availability, particularly nitrogen (N), phosphorus (P), and potassium (K) under Cd stress. B. subtilis reduced Cd accumulation in maize roots by 58.0% and limited translocation to shoots and grains by 66% and 54.2%, respectively. The health risk index declined by 53.7%. B. subtilis enhanced microbial diversity, increasing the abundance of beneficial phyla such as Pseudomonadota , Bacillati , Chloroflexota , and Myxococcota . Plant biomass and enzymatic activities (nitrate reductase, urease, and glutamine synthetase) improved significantly. Ionome analysis showed significant increases in grain N, P, and K contents by 90.3%, 9.4%, and 8.0%, respectively. Additionally, Acidobacteriota , Actinomycetota , and Bacillati were positively correlated with soil nutrients. B. subtilis effectively mitigates Cd toxicity in maize by enhancing soil health, modulating microbial communities, improving nutrient cycling, and reducing Cd bioaccumulation. These findings support its application as a sustainable biotechnological strategy for remediating Cd‐contaminated soils and improving crop productivity.

2014-12-01·JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS

Synthesis, physiochemical characterization, and biocompatibility of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention

Article

作者: Hanton, Lyall R. ; Robinson, Simon ; Liu, Liqi ; Williams, Gail ; Evans, Natasha ; Shi, Zheng ; Cabral, Jaydee D. ; Robinson, Brian H. ; McConnell, Michelle ; Simpson, Jim ; Wormald, Peter J. ; Roxburgh, Marina ; Moratti, Stephen C.

An amine-functionalized succinyl chitosan and an oxidized dextran were synthesized and mixed in aqueous solution to form an in situ chitosan/dextran injectable, surgical hydrogel for adhesion prevention. Rheological characterization showed that the rate of gelation and moduli were tunable based on amine and aldehyde levels, as well as polymer concentrations. The CD hydrogels have been shown to be effective post-operative aids in prevention of adhesions in ear, nose, and throat surgeries and abdominal surgeries in vivo. In vitro biocompatibility testing was performed on CD hydrogels containing one of two oxidized dextrans, an 80 % oxidized (CD-100) or 25 % (CD-25) oxidized dextran. However, the CD-100 hydrogel showed moderate cytotoxicity in vitro to Vero cells. SC component of the CD hydrogel, however, showed no cytotoxic effect. In order to increase the biocompatibility of the hydrogel, a lower aldehyde level hydrogel was developed. CD-25 was found to be non-cytotoxic to L929 fibroblasts. The in vivo pro-inflammatory response of the CD-25 hydrogel, after intraperitoneal injection in BALB/c mice, was also determined by measuring serum TNF-α levels and by histological analysis of tissues. TNF-α levels were similar in mice injected with CD-25 hydrogel as compared to the negative saline injected control; and were significantly different (P < 0.05) as compared to the positive, lipopolysaccharide, injected control. Histological examination revealed no inflammation seen in CD hydrogel injected mice. The results of these in vitro and in vivo studies demonstrate the biocompatibility of the CD hydrogel as a post-operative aid for adhesion prevention.

2014-06-01·Zhongguo shi yan xue ye xue za zhi

[Clinical observation of haploidentical-hematopoietic stem cell transplantation combined with human umbilical cord-derived mesenchymal stem cells for severe aplastic anemia-II].

Article

作者: Liu, Zhou-Yang ; Xu, Li-Xin ; Yang, Xue-Liang ; Wu, Ya-Mei ; DA, Wan-Ming ; Li, Xiao-Hong ; Wu, Xiao-Xiong ; Cao, Yong-Bin ; Yan, Bei

This study was purposed to investigate the efficacy and safety of haploidentical hematopoietic stem cells (allo-HSCT) transplantation combined with human umbilical cord-derived mesenchymal stem cell infusion (hUC-MSC) for severe aplastic anemia-II (SAA-II). Eight SAA-II patients received haploidentical allo-HSCT, the G-CSF mobilized peripheral hematopoietic stem cells and bone marrow haploidentical hematopoietic stem cells were selected as graft, the human umbilical cord-derived mesenchymal stem cells (hUC-MSC) were infused as the third party. Conditioning regimen consisted of rabbit anti-thymic lymphocytes protein(ATG), cyclophosphamide(CTX) and fludarabine(Flu). For two patients out of 8 SAA-II patients the conditioning regimen was combined with busulfan(BU). The graft versus host disease(GVHD) was prevented with CSA, MTX, ATG, CD25 and mycophenolate mofetil. The results showed that the average number of nucleated cells were 9.13×10(8)/kg, and number of CD34(+)cells were 3.76×10(6)/ kg. All the 8 SAA-II patients achieved hematopoietic reconstitution. The average time of neutrophils count>0.5×10(9)/L was 11.9 days, and average time of Plt level >20×10(9)/L was 14.6 days. The incidence of acute GVHD of I-II grade was 25%, and that of III-IVgrade was 12.5%, the transplantation-related mortality was 25%. It is concluded that haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA.

项与 AST-202 (Aptamer Sciences) 相关的新闻（医药）

2024-03-26

·PRNewswire

Aptamer Sciences Inc. Files IND Application for Innovative Liver Cancer Treatment AST-201: A Promising Approach to Address Under Medical Needs

SEONGNAM, South Korea, March 25, 2024 /PRNewswire/ -- Aptamer Sciences Inc. (KOSDAQ, 291650) announced the filing of an Investigational New Drug (IND) application for the phase 1 clinical trial of AST-201 with the Korean Ministry of Food and Drug Safety on March 12th, 2024. Continue Reading AST-201 structure & mechanism of action AST-201, the company's pioneering candidate in its pipeline, is an ApDCTM (Aptamer-Drug Conjugate) designed to target GPC3 protein, which exhibits high expression levels in specific cancer cells, notably liver cancer. It comprises gemcitabine as the payload and an aptamer that selectively binds to GPC3 protein. Gemcitabine, a proven systemic anticancer agent, is widely utilized in treating various cancers, including ovarian, breast, non-small cell lung, and pancreatic cancer. The choice of gemcitabine as the payload was deliberate, owing to its moderate toxicity profile, particularly suitable for liver targeting, given the organ's susceptibility to drug toxicity. Additionally, gemcitabine's nature as a DNA analogue facilitates its synthesis within the aptamer DNA sequence. The company's strategic focus on liver cancer addresses significant unmet medical needs, as evidenced by AST-201's superior efficacy over sorafenib in animal models and its synergistic effect when co-administered with anti-PD-1 therapy. Liver cancer poses a significant health challenge, particularly in East Asia, with a dismal survival rate. While combination therapies such as atezolizumab and bevacizumab have emerged as standard treatments for advanced liver cancer, recent findings published in Nature Medicine suggest their limited efficacy in certain liver cancer populations with high GPC3 expression levels, highlighting substantial unmet medical needs. In this context, AST-201 offers a promising therapeutic approach by specifically targeting GPC3. The planned phase 1 trial seeks to evaluate the safety, pharmacokinetic profile, and preliminary efficacy of AST-201 in patients with GPC3-positive advanced solid tumors. Notably, Dr. Hong Jae Chon from CHA Bundang Medical Center, a prominent medical oncologist in South Korea, will serve as the coordinating investigator. The trial will be conducted across four hospitals, including CHA Bundang Medical Center, Samsung Medical Center, Severance Hospital, and the National Cancer Center in South Korea. Dr. Chon remarked, "GPC3 has garnered considerable attention in liver cancer therapeutic development among biopharmaceutical companies," expressing optimism that "AST-201 may emerge as a novel treatment option for liver cancer patients." Aptamer Sciences Inc. aims to showcase the clinical benefits of AST-201 and the technological value of its ApDCTM platform through this trial. Moreover, the company anticipates that this milestone will propel its research and development efforts, enhancing the competitiveness of its subsequent hemato-oncology pipeline products, including AST-202 targeting CD25, ApRC (Aptamer Radioligand Conjugate), ApIS (Aptamer Immune Stimulator Conjugate), and so on. Dr. Dong-il Han, CEO of Aptamer Sciences Inc., emphasized, "Since the second aptamer drug Izervay approved by FDA last year, aptamer technology has garnered significant attention in the pharmaceutical market," highlighting, "The AST-201 clinical trial will showcase the technological capabilities of the ApDCTM platform and expedite ongoing technology transfer discussion with multiple partners. This milestone underscores Aptamer Sciences Inc.'s commitment to advancing innovative therapies and addressing critical unmet needs in oncology." Fig 1. AST-201 structure (Among the sequence of GPC3 aptamer, the payload of gemcitabine is conjugated as the part of sequence.) Fig 2. AST-201 mechanism of action 1. AST-201 targets and binds to the GPC3 protein located on the surface of cancer cells. 2. The drug undergoes internalization into the cancer cell by endocytosis. 3. After the lysosomal degradation, gemcitabine monophosphate (dFdCMP), the active form of gemcitabine, is released within the cell leading to programmed cell death of the tumor cell (apoptosis). About Aptamer Sciences, Inc. Aptamer Sciences Inc., listed on KOSDAQ in South Korea, is a global leading company in aptamer field. The company has established an integrated aptamer technology platform, called ApDCTM (Aptamer Drug Conjugate) and focused on developing oncology pipelines. For more information, please visit the website, or contact [email protected]. SOURCE Aptamer Sciences Inc.

临床1期临床申请上市批准

2024-03-25

·Pharmaindustrial

Aptamer Sciences Files IND Application for Phase 1 Clinical Trial of AST-201

Aptamer Sciences Inc. has filed for an Investigational New Drug (IND) application for the phase 1 clinical trial of AST-201 with the Korean Ministry of Food and Drug Safety on March 12, 2024. AST-201, the company's pioneering candidate in its pipeline, is an ApDCTM (Aptamer-Drug Conjugate) designed to target GPC3 protein, which exhibits high expression levels in specific cancer cells, notably liver cancer. It comprises gemcitabine as the payload and an aptamer that selectively binds to the GPC3 protein. Gemcitabine, a proven systemic anticancer agent, is widely utilized in treating various cancers, including ovarian, breast, non-small cell lung, and pancreatic cancer. The choice of gemcitabine as the payload was deliberate, owing to its moderate toxicity profile, particularly suitable for liver targeting, given the organ's susceptibility to drug toxicity. Additionally, gemcitabine's nature as a DNA analogue facilitates its synthesis within the aptamer DNA sequence. The company's strategic focus on liver cancer addresses significant unmet medical needs, as evidenced by AST-201's superior efficacy over sorafenib in animal models and its synergistic effect when co-administered with anti-PD-1 therapy. Liver cancer poses a significant health challenge, particularly in East Asia, with a dismal survival rate. While combination therapies such as atezolizumab and bevacizumab have emerged as standard treatments for advanced liver cancer, recent findings published in Nature Medicine suggest their limited efficacy in certain liver cancer populations with high GPC3 expression levels, highlighting substantial unmet medical needs. In this context, AST-201 offers a promising therapeutic approach by specifically targeting GPC3. The planned phase 1 trial seeks to evaluate the safety, pharmacokinetic profile, and preliminary efficacy of AST-201 in patients with GPC3-positive advanced solid tumors. Notably, Dr. Hong Jae Chon from CHA Bundang Medical Center, a prominent medical oncologist in South Korea, will serve as the coordinating investigator. The trial will be conducted across four hospitals, including CHA Bundang Medical Center, Samsung Medical Center, Severance Hospital, and the National Cancer Center in South Korea. Dr. Chon remarked, "GPC3 has garnered considerable attention in liver cancer therapeutic development among biopharmaceutical companies expressing optimism that AST-201 may emerge as a novel treatment option for liver cancer patients." Aptamer Sciences Inc. aims to showcase the clinical benefits of AST-201 and the technological value of its ApDCTM platform through this trial. Moreover, the company anticipates that this milestone will propel its research and development efforts, enhancing the competitiveness of its subsequent hemato-oncology pipeline products, including AST-202 targeting CD25, ApRC (Aptamer Radioligand Conjugate), ApIS (Aptamer Immune Stimulator Conjugate), and so on. Dr. Dong-il Han, CEO of Aptamer Sciences Inc., emphasized, "Since the second aptamer drug Izervay approved by the FDA last year, aptamer technology has garnered significant attention in the pharmaceutical market. The AST-201 clinical trial will showcase the technological capabilities of the ApDCTM platform and expedite ongoing technology transfer discussion with multiple partners. This milestone underscores Aptamer Sciences Inc.'s commitment to advancing innovative therapies and addressing critical unmet needs in oncology."