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1.
Gene ; 921: 148499, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38718970

RESUMO

Cell wall invertase (CIN) is a vital member of plant invertase (INV) and plays a key role in the breakdown of sucrose. This enzyme facilitates the hydrolysis of sucrose into glucose and fructose, which is crucial for various aspects of plant growth and development. However, the function of CIN genes in foxtail millet (Setaria italica) is less studied. In this research, we used the blast-p of NCBI and TBtools for bidirectional comparison, and a total of 13 CIN genes (named SiCINs) were identified from foxtail millet by using Arabidopsis and rice CIN sequences as reference sequences. The phylogenetic tree analysis revealed that the CIN genes can be categorized into three subfamilies: group 1, group 2, and group 3. Furthermore, upon conducting chromosomal localization analysis, it was observed that the 13 SiCINs were distributed unevenly across five chromosomes. Cis-acting elements of SiCIN genes can be classified into three categories: plant growth and development, stress response, and hormone response. The largest number of cis-acting elements were those related to light response (G-box) and the cis-acting elements related to seed-specific regulation (RY-element). qRT-PCR analysis further confirmed that the expression of SiCIN7 and SiCIN8 in the grain was higher than that in any other tissues. The overexpression of SiCIN7 in Arabidopsis improved the grain size and thousand-grain weight, suggesting that SiCIN7 could positively regulate grain development. Our findings will help to further understand the grain-filling mechanism of SiCIN and elucidate the biological mechanism underlying the grain development of SiCIN.

2.
Acta Pharmacol Sin ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605180

RESUMO

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

3.
Biomed Pharmacother ; 174: 116565, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603888

RESUMO

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.


Assuntos
Anticorpos Biespecíficos , Molécula L1 de Adesão de Célula Nervosa , Linfócitos T , Animais , Feminino , Humanos , Camundongos , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Antineoplásicos Imunológicos/farmacologia , Complexo CD3/imunologia , Linhagem Celular Tumoral , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Molécula L1 de Adesão de Célula Nervosa/imunologia , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Plant Biotechnol J ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363812

RESUMO

High-quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi-C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein-coding genes and 1265 non-coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship with Salvia splendens and Salvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole-genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi-omics (integrated transcriptome and metabolome) analysis showed the tissue-specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up-regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments.

5.
Int J Mol Sci ; 25(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38338870

RESUMO

Amyloidosis involves the deposition of misfolded proteins. Even though it is caused by different pathogenic mechanisms, in aggregate, it shares similar features. Here, we tested and confirmed a hypothesis that an amyloid antibody can be engineered by a few mutations to target a different species. Amyloid light chain (AL) and ß-amyloid peptide (Aß) are two therapeutic targets that are implicated in amyloid light chain amyloidosis and Alzheimer's disease, respectively. Though crenezumab, an anti-Aß antibody, is currently unsuccessful, we chose it as a model to computationally design and prepare crenezumab variants, aiming to discover a novel antibody with high affinity to AL fibrils and to establish a technology platform for repurposing amyloid monoclonal antibodies. We successfully re-engineered crenezumab to bind both Aß42 oligomers and AL fibrils with high binding affinities. It is capable of reversing Aß42-oligomers-induced cytotoxicity, decreasing the formation of AL fibrils, and alleviating AL-fibrils-induced cytotoxicity in vitro. Our research demonstrated that an amyloid antibody could be engineered by a few mutations to bind new amyloid sequences, providing an efficient way to reposition a therapeutic antibody to target different amyloid diseases.


Assuntos
Doença de Alzheimer , Amiloidose , Anticorpos Monoclonais Humanizados , Humanos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Amiloide/metabolismo , Peptídeos beta-Amiloides/imunologia , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/uso terapêutico , Amiloidose/terapia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico
6.
Physiol Plant ; 176(1): e14207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38383826

RESUMO

Root phenes are associated with the absorptive efficiency of water and fertilizers. However, there are few reports on the genetic variation and stability of peanut (Arachis hypogaea L.) root architecture under different environments. In this study, the diversity, variance and stability of root phenes of 89 peanut varieties were investigated with shovelomics (high throughput phenotyping of root system architecture) for two years in both field and laboratory experiments. The root phenes of these peanut genotypes presented rich diversity; for example, the value of total root length (TRL) ranged from 347.84 cm to 1013.80 cm in the field in 2018, and from 55.14 cm to 206.22 cm in the laboratory tests. The root phenes of different genotypes varied differently; for example, the coefficient of variation (CV) of TRL ranged from 24.0 to 83.5 across the two-year field test. Field and laboratory evaluations were highly correlated, especially on lateral root density (LRD) and root angle (RA), and the quadrant graph analysis of LRD and RA implied that 69.7% of the roots belong to the same type. These not only further reflect root phenes stability through different environment but also demonstrate that some root phenes identified at early stage can indicate their status at later growth stage. In addition, root phenes showed a strong correlation with shoot growth, especially root dry weight (RDW), TRL and(nodule number)NN. Thus, laboratory tests in combination with field shovelomics can efficiently screen and select genotypes with contrasting root phenes to optimize water and nutrient management.


Assuntos
Arachis , Fabaceae , Arachis/genética , Raízes de Plantas/genética , Genótipo , Água
8.
Plant Commun ; 5(2): 100728, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-37803827

RESUMO

Cotton (Gossypium) stands as a crucial economic crop, serving as the primary source of natural fiber for the textile sector. However, the evolutionary mechanisms driving speciation within the Gossypium genus remain unresolved. In this investigation, we leveraged 25 Gossypium genomes and introduced four novel assemblies-G. harknessii, G. gossypioides, G. trilobum, and G. klotzschianum (Gklo)-to delve into the speciation history of this genus. Notably, we encountered intricate phylogenies potentially stemming from introgression. These complexities are further compounded by incomplete lineage sorting (ILS), a factor likely to have been instrumental in shaping the swift diversification of cotton. Our focus subsequently shifted to the rapid radiation episode during a concise period in Gossypium evolution. For a recently diverged lineage comprising G. davidsonii, Gklo, and G. raimondii, we constructed a finely detailed ILS map. Intriguingly, this analysis revealed the non-random distribution of ILS regions across the reference Gklo genome. Moreover, we identified signs of robust natural selection influencing specific ILS regions. Noteworthy variations pertaining to speciation emerged between the closely related sister species Gklo and G. davidsonii. Approximately 15.74% of speciation structural variation genes and 12.04% of speciation-associated genes were estimated to intersect with ILS signatures. These findings enrich our understanding of the role of ILS in adaptive radiation, shedding fresh light on the intricate speciation history of the Gossypium genus.


Assuntos
Gossypium , Gossypium/genética , Gossypium/química
9.
Plant J ; 117(2): 573-589, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897092

RESUMO

The characterization of cis-regulatory DNA elements (CREs) is essential for deciphering the regulation of gene expression in eukaryotes. Although there have been endeavors to identify CREs in plants, the properties of CREs in polyploid genomes are still largely unknown. Here, we conducted the genome-wide identification of DNase I-hypersensitive sites (DHSs) in leaf and stem tissues of the auto-octoploid species Saccharum officinarum. We revealed that DHSs showed highly similar distributions in the genomes of these two S. officinarum tissues. Notably, we observed that approximately 74% of DHSs were located in distal intergenic regions, suggesting considerable differences in the abundance of distal CREs between S. officinarum and other plants. Leaf- and stem-dependent transcriptional regulatory networks were also developed by mining the binding motifs of transcription factors (TFs) from tissue-specific DHSs. Four TEOSINTE BRANCHED 1, CYCLOIDEA, and PCF1 (TCP) TFs (TCP2, TCP4, TCP7, and TCP14) and two ethylene-responsive factors (ERFs) (ERF109 and ERF03) showed strong causal connections with short binding distances from each other, pointing to their possible roles in the regulatory networks of leaf and stem development. Through functional validation in transiently transgenic protoplasts, we isolate a set of tissue-specific promoters. Overall, the DHS maps presented here offer a global view of the potential transcriptional regulatory elements in polyploid sugarcane and can be expected to serve as a valuable resource for both transcriptional network elucidation and genome editing in sugarcane breeding.


Assuntos
Cromatina , Saccharum , Succinatos , Saccharum/genética , Saccharum/metabolismo , Desoxirribonuclease I/genética , Desoxirribonuclease I/metabolismo , Melhoramento Vegetal , Genômica , Poliploidia
10.
Plant Sci ; 340: 111937, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043729

RESUMO

Due to the increasing demand for high-quality and high fiber-yielding cotton (Gossypium spp.), research into the development of stress-resilient cotton cultivars has acquired greater significance. Various biotic and abiotic stressors greatly affect cotton production and productivity, posing challenges to the future of the textile industry. Moreover, the content and quality of cottonseed oil can also potentially be influenced by future environmental conditions. Apart from conventional methods, genetic engineering has emerged as a potential tool to improve cotton fiber quality and productivity. Identification and modification of genome sequences and the expression levels of yield-related genes using genetic engineering approaches have enabled to increase both the quality and yields of cotton fiber and cottonseed oil. Herein, we evaluate the significance and molecular mechanisms associated with the regulation of cotton agronomic traits under both normal and stressful environmental conditions. In addition, the importance of gossypol, a toxic phenolic compound in cottonseed that can limit consumption by animals and humans, is reviewed and discussed.


Assuntos
Gossypium , Gossipol , Humanos , Gossypium/metabolismo , Óleo de Sementes de Algodão/metabolismo , Fibra de Algodão , Gossipol/metabolismo , Genômica
11.
Biomaterials ; 305: 122455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160626

RESUMO

The therapeutic efficacy of cuproptosis combined with phototheranostics is still hindered by easy copper efflux, nonspecific accumulation and limited light penetration depth. Here, a high-performance NIR-II semiconductor polymer was first synthesized through dual-donor engineering. Then a biomimetic cuproptosis amplifier (PCD@CM) was prepared by Cu(II)-mediated coordinative self-assembly of NIR-II ultrasmall polymer dots and the chemotherapeutic drug DOX, followed by camouflaging of tumor cell membranes. After homologous targeting delivery to tumor cells, overexpressed GSH in the tumor microenvironment (TME) triggers the disassembly of the amplifier and the release of therapeutic components through the reduction of Cu(II) to Cu(I), which enable NIR-II fluorescence/photoacoustic imaging-guided NIR-II photothermal therapy (PTT) and chemotherapy. The released Cu(I) induces the aggregation of lipoylated mitochondrial proteins accompanied by the loss of iron-sulfur proteins, leading to severe proteotoxic stress and eventually cuproptosis. NIR-II PTT and GSH depletion render tumor cells more sensitive to cuproptosis. The amplified cuproptosis sensitization provokes significant immune surveillance, triggering the immunogenic cell death (ICD) to promote cytotoxic T lymphocyte infiltration together with aPD-L1-mediated immune checkpoint blockade. This work proposes a new strategy to develop cuproptosis sensitization systems enhanced by NIR-II phototheranostics with homologous targeting and anti-tumor immune response capabilities.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Fototerapia , Cobre/uso terapêutico , Biomimética , Polímeros/uso terapêutico , Neoplasias/terapia , Imunoterapia , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente Tumoral
12.
Acta Pharm Sin B ; 13(12): 4856-4874, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045049

RESUMO

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

13.
BMC Genomics ; 24(1): 726, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041011

RESUMO

BACKGROUND: Pre-exposing plants to abiotic stresses can induce stress memory, which is crucial for adapting to subsequent stress exposure. Although numerous genes involved in salt stress response have been identified, the understanding of memory responses to salt stress remains limited. RESULTS: In this study, we conducted physiological and transcriptional assays on maize plants subjected to recurrent salt stress to characterize salt stress memory. During the second exposure to salt stress, the plants exhibited enhanced salt resistance, as evidenced by increased proline content and higher POD and SOD activity, along with decreased MDA content, indicative of physiological memory behavior. Transcriptional analysis revealed fewer differentially expressed genes and variations in response processes during the second exposure compared to the first, indicative of transcriptional memory behavior. A total of 2,213 salt stress memory genes (SMGs) were identified and categorized into four response patterns. The most prominent group of SMGs consisted of genes with elevated expression during the first exposure to salt stress but reduced expression after recurrent exposure to salt stress, or vice versa ([+ / -] or [- / +]), indicating that a revised response is a crucial process in plant stress memory. Furthermore, nine transcription factors (TFs) (WRKY40, WRKY46, WRKY53, WRKY18, WRKY33, WRKY70, MYB15, KNAT7, and WRKY54) were identified as crucial factors related to salt stress memory. These TFs regulate over 53% of SMGs, underscoring their potential significance in salt stress memory. CONCLUSIONS: Our study demonstrates that maize can develop salt stress memory, and the genes identified here will aid in the genetic improvement of maize and other crops.


Assuntos
Transcriptoma , Zea mays , Zea mays/genética , Zea mays/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
14.
Int J Mol Sci ; 24(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38139459

RESUMO

Antibody-drug conjugates (ADCs) have greatly improved the outcomes of advanced breast tumors. However, the treatment of breast tumors with existing ADCs is still hindered by many issues, such as tumor antigen heterogeneity and drug resistance. Therefore, ADCs against new targets would provide options for the treatment of these challenges. Sortilin-1 (SORT1) may be a promising target for ADC as it is upregulated in breast cancer. To evaluate the possibility of SORT1 as an ADC target, a humanized antibody_8D302 with high affinity against SORT1 was generated. Additionally, 8D302 was conjugated with MMAE and DXd to generate two ADCs_8D302-MMAE and 8D302-DXd, respectively. Both 8D302-MMAE and 8D302-DXd showed effective cytotoxicity against SORT1 positive breast tumor cell lines and induced bystander killing. Consequently, 8D302-MMAE showed relatively better anti-tumor activity than 8D302-DXd both in vitro and in vivo, but 8D302-DXd had superior safety profile and pharmacokinetics profile over 8D302-MMAE. Furthermore, SORT1 induced faster internalization and lysosomal trafficking of antibodies and had a higher turnover compared with HER2. Also, 8D302-DXd exhibited superior cell cytotoxicity and tumor suppression over trastuzumab-DXd, a HER2-targeted ADC. We hypothesize that the high turnover of SORT1 enables SORT1-targeted ADC to be a powerful agent for the treatment of SORT1-positive breast tumor.


Assuntos
Neoplasias da Mama , Imunoconjugados , Neoplasias Mamárias Animais , Animais , Humanos , Feminino , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacocinética , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias Mamárias Animais/tratamento farmacológico , Receptor ErbB-2/metabolismo
15.
Int J Mol Sci ; 24(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38003245

RESUMO

Human epidermal growth factor receptor 2 (HER2) is considered an ideal antibody-drug conjugate (ADC) target because the gene is overexpressed in many tumors compared to normal tissues. Multiple anti-HER2 ADCs conjugated with different toxic payloads bring benefits to patients with high HER2 expression. However, HER2-targeted ADC technology needs further optimization to improve its effect for the treatment of patients with low HER2 expression. We hypothesized that bispecific antibody-drug conjugate (bsADC) targeting HER2 and Sortilin-1 (SORT1) would overcome this limitation. SORT1 is a suitable target for pairing with HER2 to generate a bispecific antibody (BsAb) since the gene is co-expressed with HER2 in tumors and possesses rapid internalization. We developed a BsAb (bsSORT1×HER2) that exhibited strong binding and internalization activity on HER2-low-expression tumor cells and facilitated higher HER2 degradation. The bsSORT1×HER2 was further conjugated with DXd to generate a bsADC (bsSORT1×HER2-DXd) that showed strong cytotoxicity on HER2-low-expression tumor cells and antitumor efficacy in an MDA-MB-231 xenograft mice model. These results demonstrated that employment of a SORT1×HER2-targeted bsADC may be promising to improve the antitumor efficacy of HER2-targeted ADC for the treatment of tumors with low HER2 expression.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Imunoconjugados , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Receptor ErbB-2/metabolismo , Anticorpos Biespecíficos/farmacologia , Imunoconjugados/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Plant Physiol Biochem ; 204: 108141, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37926000

RESUMO

Cotton (Gossypium spp.) is a globally significant crop that provides natural fibers for the textile industry and also an important oil and biopharmaceutical resources. However, the production of cotton faces substantial challenges due to various biotic and abiotic stress factors that can negatively impact cotton growth, yield, and fiber quality. This review offers a comprehensive overview of the effects of biotic stress factors, such as insect pests, bacterial, fungal, and viral pathogens, and nematodes, as well as abiotic stress factors, including extreme hot and cold temperature, drought, toxicity induced by heavy metal and salinity, on the antioxidant systems in cotton. We discuss the crucial antioxidants, such as glutathione, proline, and phenolics, and highlight major antioxidant enzymes, including ascorbate peroxidase (APX), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR), and their roles in cotton's response to these stress factors. Furthermore, we explore the potential mechanisms and the crosstalk between different stress factors signaling pathways. We also examine the implications of stress-induced changes in antioxidant levels and enzyme activities for cotton productivity and breeding strategies. Additionally, we shed light on the unanswered questions, research gaps, and future perspectives in this field, paving the way for further investigations to enhance our understanding of cotton's antioxidant defenses and develop novel strategies for improving cotton stress tolerance and yield stability.


Assuntos
Antioxidantes , Gossypium , Antioxidantes/metabolismo , Gossypium/metabolismo , Melhoramento Vegetal , Peroxidases , Estresse Fisiológico , Superóxido Dismutase/metabolismo
17.
Sci Rep ; 13(1): 16919, 2023 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-37805649

RESUMO

Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCß, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/ß inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/ß inhibition to T2D and obesity in humans is warranted.


Assuntos
Adiposidade , Diabetes Mellitus Tipo 2 , Humanos , Ratos , Animais , Adiposidade/fisiologia , Proteína Quinase C-alfa , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Hiperfagia/complicações , Hiperfagia/tratamento farmacológico , Rim/fisiologia
18.
Autoimmunity ; 56(1): 2250099, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37822112

RESUMO

BACKGROUND: The pathogenesis of pulmonary fibrosis is not fully understood. Previous work has demonstrated the important role of circular RNA (circRNA) in pulmonary fibrosis development. This study aims to analyse the role of circ_0035796 in pulmonary fibrosis and the underlying mechanism. METHODS: Human foetal lung fibroblast 1 (HFL1) cells were treated with transforming growth factor-ß1 (TGF-ß1) to mimic a pulmonary fibrosis cell model. The expression of circ_0035796, microRNA-150-5p (miR-150-5p) and L1 cell adhesion molecule (L1CAM) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of L1CAM, collagen I and fibronectin was detected by Western blot. Cell viability was analysed by CCK-8 assay. Cell proliferation, invasion and migration were investigated by 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell invasion assay and wound-healing assay, respectively. The secretion of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) was analysed by Enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by detecting Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) level using commercial kits. The association of miR-150-5p with circ_0035796 and L1CAM was identified by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0035796 and L1CAM expression were dramatically upregulated, while miR-150-5p expression was downregulated in TGF-ß1-treated HFL1 cells. TGF-ß1 treatment induced cell proliferation, migration, invasion, IL-6 and TNF-α secretion, and oxidative stress, whereas circ_0035796 depletion relieved these effects. In addition, circ_0035796 acted as a sponge of miR-150-5p and miR-150-5p combined with L1CAM. Moreover, miR-150-5p depletion attenuated circ_0035796 knockdown-mediated effects in TGF-ß1-exposed HFL1 cells. The regulation of miR-150-5p on TGF-ß1-induced fibroblast activation involved the downregulation of L1CAM. Further, circ_0035796 modulated L1CAM expression by interacting with miR-150-5p in TGF-ß1-exposed HFL1 cells. CONCLUSION: Circ_0035796 knockdown ameliorates TGF-ß1-induced pulmonary fibrosis through the miR-150-5p/L1CAM axis in vitro.


Assuntos
MicroRNAs , Molécula L1 de Adesão de Célula Nervosa , Fibrose Pulmonar , Humanos , Fator de Crescimento Transformador beta1/genética , Interleucina-6/genética , Fibrose Pulmonar/genética , Fator de Necrose Tumoral alfa , Proliferação de Células/genética , MicroRNAs/genética
19.
Plants (Basel) ; 12(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37836188

RESUMO

The world population's growing demand for food is expected to increase dramatically by 2050. The agronomic productivity for food is severely affected due to biotic and abiotic constraints. At a global level, insect pests alone account for ~20% loss in crop yield every year. Deployment of noxious chemical pesticides to control insect pests always has a threatening effect on human health and environmental sustainability. Consequently, this necessitates for the establishment of innovative, environmentally friendly, cost-effective, and alternative means to mitigate insect pest management strategies. According to a recent study, using chloroplasts engineered with double-strand RNA (dsRNA) is novel successful combinatorial strategy deployed to effectively control the most vexing pest, the western flower thrips (WFT: Frankliniella occidentalis). Such biotechnological avenues allowed us to recapitulate the recent progress of research methods, such as RNAi, CRISPR/Cas, mini chromosomes, and RNA-binding proteins with plastid engineering for a plausible approach to effectively mitigate agronomic insect pests. We further discussed the significance of the maternal inheritance of the chloroplast, which is the major advantage of chloroplast genome engineering.

20.
Chem Biodivers ; 20(9): e202300479, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37667613

RESUMO

Leaves of jamun collected as agro by-produce during the cultivation of jamun is traditionally used as ayurvedic medicine to treat diabetes, gall bladder stones and other ailments. Most of the beneficial effects of jamun leaves are associated with phytochemicals found in jamun leaves such as gallic acid, tannins, mallic acid, flavonoids, essential oils, jambolin, ellagic acid, jambosine, antimellin and betulinic acid. Jamun possess curative activities like anticancer, antidiabetic, antifertility, anti-inflammatory, antidiarrheal, antimicrobial, antinociceptive, antioxidant, antiradiation, chemotherapeutic, and gastroprotective. The main goal of this review article is to provide information on the nutritional content, phytochemical composition and health promoting properties of jamun leaves. The review of literature based on the phytochemical composition and health promoting benefits of the jamun leaves, suggests that leaves can be used as potential constituent in the formulation of pharmacological drugs. From the review literature it is found that clinical, in-vivo, in-vitro studies are still required to check the health promoting effects of jamun leaves extracts on humans.


Assuntos
Syzygium , Humanos , Antioxidantes/farmacologia , Ácido Betulínico , Flavonoides , Ácido Gálico
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