Production of cowpea (Vigna unguiculata (L.) Walp.), a staple legume crop in Sub-Saharan Africa, faces challenges due to biotic and abiotic constraints. Induced mutagenesis was deployed to create genetic variation in ...Production of cowpea (Vigna unguiculata (L.) Walp.), a staple legume crop in Sub-Saharan Africa, faces challenges due to biotic and abiotic constraints. Induced mutagenesis was deployed to create genetic variation in two cowpea varieties (KVX396-4-5-2D and Moussa local). The radio-sensitivity tests led to determe the lethal dose 50 (LD50) corresponding to 230 Gy and 220 Gy for KVX396-4-5-2D and Moussa local varieties, respectively. Dried seeds (M0) of each variety were gamma-ray irradiated with LD50 − 50, LD50 and LD50 + 50. M1 seeds were advanced to generate M2, M3 and M4 mutants using the single-seed-descent method. M4 mutant lines were evaluated in rain-fed conditions using a randomized complete block design to assess phenotypic differences. Data on seven qualitative and eleven quantitative traits were collected. The results indicated that the mutation induced variability in three qualitative traits: in KVX 396-4-5-2D mutant lines, with flower and seed color frequencies at 2.61% and 0.56% respectively, and pod dehiscence at a frequency of 0.24%. While in Moussa local mutants, a pod color changed at a frequency of 17%. ANOVA results revealed significant differences between mutants of both varieties for all quantitative traits, including photosynthetic parameters. Positive correlations were observed between leaf diameter and 100-seed weight, and between branch number and 100-seed weight. Hierarchical clustering revealed three clusters among KVX 396-4-5-2D mutants and six clusters among Moussa local mutants. Early maturity and high foliage were induced traits in Cluster 3 of KVX 396-4-5-2D mutants while high hundred-seed weight was induced in Cluster 6 of Moussa local mutants.展开更多
Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal organization.Protein phosphatase 2A(PP2A)is highly conserved and is the predominant serine/th...Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal organization.Protein phosphatase 2A(PP2A)is highly conserved and is the predominant serine/threonine phosphatase in the nervous system,constituting more than 70%of all neuronal phosphatases.PP2A is involved in diverse regulatory functions,including cell cycle progression,apoptosis,and DNA repair.Although PP2A has historically been identified as a tumor suppressor,inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various cancers.LB100,a water-soluble,small-molecule competitive inhibitor of PP2A,has shown particular promise as a chemo-and radio-sensitizing agent.Preclinical success has led to a profusion of clinical trials on LB100 adjuvant therapies,including a phase I trial in extensive-stage small-cell lung cancer,a phase I/II trial in myelodysplastic syndrome,a phase II trial in recurrent glioblastoma,and a completed phase I trial assessing the safety of LB100 and docetaxel in various relapsed solid tumors.Herein,we review the development of LB100,the role of PP2A in cancer biology,and recent advances in targeting PP2A inhibition in immunotherapy.展开更多
Objective To investigate the radiosensitizing effect of nitric oxide(NO) combined with radiation on esophageal cancer cell line TE-1.Methods Methyl thiazolyl tetrazolium(MTT) assay was used to assess the effects of NO...Objective To investigate the radiosensitizing effect of nitric oxide(NO) combined with radiation on esophageal cancer cell line TE-1.Methods Methyl thiazolyl tetrazolium(MTT) assay was used to assess the effects of NO and radiation on TE-1 cells regarding inhibition of cell proliferation.Flow cytometry was used to examine the effect of NO and radiation on cell apoptosis and cycle.Reverse transcription polymerase chine reaction and Western blot were used to evaluete the effect of NO on mRNA and protein expression of manganese superoxide dismutase(MnSOD).Results NO inhibited the proliferation of TE-1 cells while significantly enhancing their radiosensitivity.The application of NO combined with radiation significantly increased the apoptosis rate and G2/M phase proportion of TE-1 cells,with substantial decreases in the MnSOD mRNA and protein expression levels.Conclusions NO reduces the MnSOD mRNA and protein expression levels by affecting TE-1 cell cycle,further inhibiting the apoptosis of esophageal cancer cells and enhancing the killing effect of radiation on esophageal cancer cells.展开更多
Mutagenesis is used for creating new genetic variability in cultivar improvement. Optimal mutagenic treatment is required for effective mutation induction in crop species. Therefore, radio-sensitivity of cowpea access...Mutagenesis is used for creating new genetic variability in cultivar improvement. Optimal mutagenic treatment is required for effective mutation induction in crop species. Therefore, radio-sensitivity of cowpea accessions to gamma irradiation was investigated. Seeds of eight cowpea accessions were irradiated with <sup>60</sup>Co gamma radiation doses of 100, 200, 300, 400 and 500 Gy. The seeds were sown in pots to evaluate the treatment effects on seed germination (SG), seedling survival (SS) and growth habits of M1 generation. Data were analyzed using descriptive statistics. Low rates of SG (10% - 45%) were recorded at higher doses (500 - 400 Gy) in Ife Brown (IB) and its derivatives, whereas high SG rates (74% - 94%) were observed in IT90K-284-2 across all treatments. Percentage SS was inversely related to gamma dosage. A wide range of LD<sub>50</sub> for SG (329 - 1054 Gy) and SS (149 - 620 Gy) were observed across the cowpea accessions. Low LD<sub>50</sub> scores for SG (329 - 516 Gy) and SS (149 - 357 Gy) were observed among cowpea with rough seed coat, whereas cowpea with smooth seed coat recorded higher LD<sub>50</sub> for SG (521 and 1054 Gy) and SS (449 and 620 Gy). Seed germination LD<sub>50</sub> and SS LD<sub>50</sub> were highly correlated with mean coat thickness (0.899 and 0.937) than mean seed weight (0.621 and 0.678). Gamma irradiation of cowpea seed at low dosage (100 Gy) increased the vigor of M<sub>1</sub> seedlings with respect to primary leaf area, terminal leaflet area, seedling height and plant height at six weeks. Doses of 200 Gy and above resulted in a progressive reduction in vigor of plant and seed setting of cowpea. Radio-sensitivity varied with cowpea genotype and was associated with seed testa texture, thickness and seed weight. Low gamma irradiation treatment (100 Gy) may be used to enhance seedling vigor, vegetative growth and yield of cowpea at M<sub>1</sub> generation.展开更多
This study was concentrated on the biosynthesis of silver nanoparticles from Penicillium aurantiogresium (IMI 89372) with a focus on its cytotoxicity in MCF-7 and MCT cancer cell lines as well as Vero (normal) cell li...This study was concentrated on the biosynthesis of silver nanoparticles from Penicillium aurantiogresium (IMI 89372) with a focus on its cytotoxicity in MCF-7 and MCT cancer cell lines as well as Vero (normal) cell line that was assessed by crystal violet assay after treatment with various concentrations (0.44 – 145 μg/ml) for 24 h. The cell morphology was examined by inverted light microscopy. Further, the radiosensitizing effect of silver nanoparticles (AgNPs) on MCF-7 was also demonstrated by assessing cell morphology, cell proliferation of MTT assay, LDH activity and induction of apoptosis through checking of some apoptotic genes that altered during carcinogenesis, including caspase-3, Bax and Bcl-2. Caspase-3 activity was also estimated. Synthesis of AgNPs was determined by UV-Visible spectrum and it was further characterized by TEM, FT-IR and X-Ray analysis (EDX, XRD). The biosynthesized AgNPs were spherical and of 12.7 nm in size as recorded by direct electron microscopy visualization. The biosynthesized AgNPs showed variation in cytotoxicity against MCF-7, MCT and Vero cell lines in a concentration dependant response with a varied degree of alteration in cell morphology. The result showed that AgNPs were highly toxic towards MCF-7 with IC50 value of 10.5 μg/ml. Treatment of MCF-7 (10.5 μg/ml) prior to irradiation improved the effect of irradiation dose (6 Gy) via increasing alteration of cell morphology, inhibition of cell proliferation, activation of the lactate dehydrogenase (LDH) and caspase-3 leading to induction of apoptosis which was further confirmed through increasing nuclear DNA damage and up regulation of caspase 3 and Bax genes and downrgulation of Bcl-2 genes. In conclusion, the present findings clearly indicated that AgNPs showed dose dependant cytotoxicity and verified that AgNPs acted as a potent radiosensitizer and could enhance gamma irradiation induced killing of MCF-7 breast cancer cells.展开更多
Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics.It has made significant progress in breaking the limitat...Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics.It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors,especially when combined with traditional therapy,such as radiotherapy.According to their different biological characteristics,bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues.Moreover,genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy.In this review,we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years,expounding that the bacteria,bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment(TME)and immune effects.Furthermore,some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory,anti-oxidation and apoptosis inhibition.In conclusion,the prospect of bacteria in radiotherapy will be very extensive,but its biological safety and mechanism need to be further evaluated and studied.展开更多
Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth sign...Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance.Thence,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication.The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,respectively.Further,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy.Hereto,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy.Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.展开更多
文摘Production of cowpea (Vigna unguiculata (L.) Walp.), a staple legume crop in Sub-Saharan Africa, faces challenges due to biotic and abiotic constraints. Induced mutagenesis was deployed to create genetic variation in two cowpea varieties (KVX396-4-5-2D and Moussa local). The radio-sensitivity tests led to determe the lethal dose 50 (LD50) corresponding to 230 Gy and 220 Gy for KVX396-4-5-2D and Moussa local varieties, respectively. Dried seeds (M0) of each variety were gamma-ray irradiated with LD50 − 50, LD50 and LD50 + 50. M1 seeds were advanced to generate M2, M3 and M4 mutants using the single-seed-descent method. M4 mutant lines were evaluated in rain-fed conditions using a randomized complete block design to assess phenotypic differences. Data on seven qualitative and eleven quantitative traits were collected. The results indicated that the mutation induced variability in three qualitative traits: in KVX 396-4-5-2D mutant lines, with flower and seed color frequencies at 2.61% and 0.56% respectively, and pod dehiscence at a frequency of 0.24%. While in Moussa local mutants, a pod color changed at a frequency of 17%. ANOVA results revealed significant differences between mutants of both varieties for all quantitative traits, including photosynthetic parameters. Positive correlations were observed between leaf diameter and 100-seed weight, and between branch number and 100-seed weight. Hierarchical clustering revealed three clusters among KVX 396-4-5-2D mutants and six clusters among Moussa local mutants. Early maturity and high foliage were induced traits in Cluster 3 of KVX 396-4-5-2D mutants while high hundred-seed weight was induced in Cluster 6 of Moussa local mutants.
基金the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundationthe American Association for Dental Research+2 种基金the Colgate-Palmolive Companyprivate donorssupported partly by the Intramural Research Program at the National Cancer Institute at the NIH
文摘Protein phosphatases play essential roles as negative regulators of kinases and signaling cascades involved in cytoskeletal organization.Protein phosphatase 2A(PP2A)is highly conserved and is the predominant serine/threonine phosphatase in the nervous system,constituting more than 70%of all neuronal phosphatases.PP2A is involved in diverse regulatory functions,including cell cycle progression,apoptosis,and DNA repair.Although PP2A has historically been identified as a tumor suppressor,inhibition of PP2A has paradoxically demonstrated potential as a therapeutic target for various cancers.LB100,a water-soluble,small-molecule competitive inhibitor of PP2A,has shown particular promise as a chemo-and radio-sensitizing agent.Preclinical success has led to a profusion of clinical trials on LB100 adjuvant therapies,including a phase I trial in extensive-stage small-cell lung cancer,a phase I/II trial in myelodysplastic syndrome,a phase II trial in recurrent glioblastoma,and a completed phase I trial assessing the safety of LB100 and docetaxel in various relapsed solid tumors.Herein,we review the development of LB100,the role of PP2A in cancer biology,and recent advances in targeting PP2A inhibition in immunotherapy.
文摘Objective To investigate the radiosensitizing effect of nitric oxide(NO) combined with radiation on esophageal cancer cell line TE-1.Methods Methyl thiazolyl tetrazolium(MTT) assay was used to assess the effects of NO and radiation on TE-1 cells regarding inhibition of cell proliferation.Flow cytometry was used to examine the effect of NO and radiation on cell apoptosis and cycle.Reverse transcription polymerase chine reaction and Western blot were used to evaluete the effect of NO on mRNA and protein expression of manganese superoxide dismutase(MnSOD).Results NO inhibited the proliferation of TE-1 cells while significantly enhancing their radiosensitivity.The application of NO combined with radiation significantly increased the apoptosis rate and G2/M phase proportion of TE-1 cells,with substantial decreases in the MnSOD mRNA and protein expression levels.Conclusions NO reduces the MnSOD mRNA and protein expression levels by affecting TE-1 cell cycle,further inhibiting the apoptosis of esophageal cancer cells and enhancing the killing effect of radiation on esophageal cancer cells.
文摘Mutagenesis is used for creating new genetic variability in cultivar improvement. Optimal mutagenic treatment is required for effective mutation induction in crop species. Therefore, radio-sensitivity of cowpea accessions to gamma irradiation was investigated. Seeds of eight cowpea accessions were irradiated with <sup>60</sup>Co gamma radiation doses of 100, 200, 300, 400 and 500 Gy. The seeds were sown in pots to evaluate the treatment effects on seed germination (SG), seedling survival (SS) and growth habits of M1 generation. Data were analyzed using descriptive statistics. Low rates of SG (10% - 45%) were recorded at higher doses (500 - 400 Gy) in Ife Brown (IB) and its derivatives, whereas high SG rates (74% - 94%) were observed in IT90K-284-2 across all treatments. Percentage SS was inversely related to gamma dosage. A wide range of LD<sub>50</sub> for SG (329 - 1054 Gy) and SS (149 - 620 Gy) were observed across the cowpea accessions. Low LD<sub>50</sub> scores for SG (329 - 516 Gy) and SS (149 - 357 Gy) were observed among cowpea with rough seed coat, whereas cowpea with smooth seed coat recorded higher LD<sub>50</sub> for SG (521 and 1054 Gy) and SS (449 and 620 Gy). Seed germination LD<sub>50</sub> and SS LD<sub>50</sub> were highly correlated with mean coat thickness (0.899 and 0.937) than mean seed weight (0.621 and 0.678). Gamma irradiation of cowpea seed at low dosage (100 Gy) increased the vigor of M<sub>1</sub> seedlings with respect to primary leaf area, terminal leaflet area, seedling height and plant height at six weeks. Doses of 200 Gy and above resulted in a progressive reduction in vigor of plant and seed setting of cowpea. Radio-sensitivity varied with cowpea genotype and was associated with seed testa texture, thickness and seed weight. Low gamma irradiation treatment (100 Gy) may be used to enhance seedling vigor, vegetative growth and yield of cowpea at M<sub>1</sub> generation.
文摘This study was concentrated on the biosynthesis of silver nanoparticles from Penicillium aurantiogresium (IMI 89372) with a focus on its cytotoxicity in MCF-7 and MCT cancer cell lines as well as Vero (normal) cell line that was assessed by crystal violet assay after treatment with various concentrations (0.44 – 145 μg/ml) for 24 h. The cell morphology was examined by inverted light microscopy. Further, the radiosensitizing effect of silver nanoparticles (AgNPs) on MCF-7 was also demonstrated by assessing cell morphology, cell proliferation of MTT assay, LDH activity and induction of apoptosis through checking of some apoptotic genes that altered during carcinogenesis, including caspase-3, Bax and Bcl-2. Caspase-3 activity was also estimated. Synthesis of AgNPs was determined by UV-Visible spectrum and it was further characterized by TEM, FT-IR and X-Ray analysis (EDX, XRD). The biosynthesized AgNPs were spherical and of 12.7 nm in size as recorded by direct electron microscopy visualization. The biosynthesized AgNPs showed variation in cytotoxicity against MCF-7, MCT and Vero cell lines in a concentration dependant response with a varied degree of alteration in cell morphology. The result showed that AgNPs were highly toxic towards MCF-7 with IC50 value of 10.5 μg/ml. Treatment of MCF-7 (10.5 μg/ml) prior to irradiation improved the effect of irradiation dose (6 Gy) via increasing alteration of cell morphology, inhibition of cell proliferation, activation of the lactate dehydrogenase (LDH) and caspase-3 leading to induction of apoptosis which was further confirmed through increasing nuclear DNA damage and up regulation of caspase 3 and Bax genes and downrgulation of Bcl-2 genes. In conclusion, the present findings clearly indicated that AgNPs showed dose dependant cytotoxicity and verified that AgNPs acted as a potent radiosensitizer and could enhance gamma irradiation induced killing of MCF-7 breast cancer cells.
基金partially supported by the National Natural Science Foundation of China(U1932208,32171382)Key Research and Development Program of Social Development of Jiangsu Province(BE2022725,China)+2 种基金Hui-Chun Chin and Tsung-Dao Lee Chinese Undergraduate Research Endowment(CURE,China)Undergraduate Training Program for Innovation and Entrepreneurship Soochow University(202010285046Z,China)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD,China)。
文摘Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics.It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors,especially when combined with traditional therapy,such as radiotherapy.According to their different biological characteristics,bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues.Moreover,genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy.In this review,we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years,expounding that the bacteria,bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment(TME)and immune effects.Furthermore,some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory,anti-oxidation and apoptosis inhibition.In conclusion,the prospect of bacteria in radiotherapy will be very extensive,but its biological safety and mechanism need to be further evaluated and studied.
基金This work was supported by the National Natural Science Foundation of China(NSFC 32171318 and 32101069)the Faculty of Health Sciences,University of Macao,the Science and Technology Development Fund,Macao SAR(File no.0109/2018/A3,0011/2019/AKP,0113/2019/A2,0103/2021/A,and 0002/2021/AKP)+1 种基金the Multi-Year Research Grant(MYRG)of University of Macao(File no.MYRG2022-00011-FHS)Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004).
文摘Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis,angiogenesis,and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression.Interdicting melanoma intrinsic growth signals,including the blockade of PD-L1 and mTOR signaling concurrently,cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance.Thence,we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody(aPD-L1)for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication.The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1:PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling;corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis,respectively.Further,high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy.Hereto,the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy.Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.
