BMP3 Affects Cortical and Trabecular Long Bone Development in Mice

Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female Bmp3−/− mice. To investigate the effect of Bmp3 from birth to maturity, we compared Bmp3−/− mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age. Bmp3 deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The Bmp3 reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of Bmp3−/− mice. Bmp3 deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult Bmp3−/− mice.

The AGT Epistasis Pattern Proposed a Novel Role for ZBED9 In Regulating Blood Pressure: Tehran Cardiometabolic Genetic Study (TCGS)

Backgroung: Hypertension is typically considered as the leading risk factor for cardiovascular disease. Epistasis studies may add another layer of complexity to our understanding of the genetic basis of hypertension. Methods: A nested case-control design was used on 4214 unrelated Tehran Cardiometabolic Genetic Study (TCGS) adults to evaluate 65 SNPs of previously associated genes, including ZBED9, AGT, and TNXB. The integrated effect of each gene was determined using the Sequence-based Kernel Association Test (SKAT). We used model-based multifactor dimension reduction (Mb-MDR) and entropy-based gene-gene interaction (IGENT) methods to determine interaction and epistasis patterns. Results: The integrated effect of each gene has a statistically significant association with blood pressure traits (P-value < 0.05). Single-locus analysis identified two missense variants in ZBED9 (rs450630) and AGT (rs4762) that are associated with hypertension. In the ZBED9 gene, significant local interactions were discovered. The G allele in rs450630 showed an antagonistic effect on hypertension, but interestingly, IGENT analysis revealed significant epistasis effects for different combinations of ZBED9, AGT, and TNXB loci. Conclusion: We discovered a novel interaction effect between a significant variant in an essential gene for hypertension (AGT) and a missense variant in ZBED9, which has shifted our focus to ZBED9's role in blood pressure regulation.

Biocontrol Potential and Catabolic Profile of Endophytic Diaporthe eres Strain 1420S from Prunus domestica L. in Poland—A Preliminary Study

Recently, Diaporthe has been considered the most frequently isolated genera of endophytic fungi, having a broad spectrum of host plants and a worldwide distribution. The endophytic Diaporthe strain used in the present work came from the Fungal Collection of Phytopathology and Mycology Subdepartment, University of Life Sciences in Lublin (Poland), and was isolated from healthy Prunus domestica shoots during previous studies. Due to the possibility of using the Diaporthe endophytes as a promising option for plant disease management, the main goal of the research was to study the antagonistic effect of endophytic Diaporthe strain against six phytopathogens: Verticillium dahliae, Botrytis cinerea, Fusarium avenaceum, F. sprotrichioides, Alternaria alternata, and Trichothecium roseum based on the dual culture assay and to determine the catabolic profile of the endophyte by using Biolog FF Plates. The dual-culture test assay revealed the ability of the endophytic Diaporthe to limit the growth of all tested pathogens. The growth inhibition percentage ranged from 20% (V. dahliae) to 40% (T. roseum). A distinct zone of inhibition occurred between the endophytic Diaporthe and the pathogens T. roseum, V. dahliae, and B. cinerea in the co-growth combinations. As for the catabolic profile results, the most intensive utilization of carbon substrates was observed after 168 h of incubation. The growth of the analyzed strain was observed on 79 media containing carbohydrates, carboxylic acids, amino acids, amines and amides, polymers, and others. The most effective decomposition was observed in the polymers group, the least in amines and amides. Molecular identification indicated that this strain was closely related to the Diaporthe eres species complex.

Effect of Plant Growth Promoting Bacillus spp. on Germination and Seedling Growth of Soybean

Background: Bacillus spp., known to promote growth and reduce disease of various field and vegetable crops, are frequently found in soils. The objective of the study was to select effective Bacillus spp. isolates with multiple plant growth properties and antifungal activities and to examine their effect on germination of soybean. Methods: Bacterial isolates were screened for production of indole-3-acetic acid (IAA) and siderophores and solubilization of phosphate. The ability of bacterial isolates to inhibit the growth of seven phytopathogenic fungi affecting soybean was determined using a dual plate assay. Bacillus spp. were further selected and examined in a seed germination test. Result: All Bacillus spp. isolates were positive for IAA production, while siderophore production and P-solubilization were observed in 80% and 20% bacterial isolates, respectively. Bacillus spp. exhibited the highest antifungal activity against Diaporthe caulivora, followed by Diaporthe sojae, Diaporthe eres, Diaporthe longicolla and Macrophomina phaseolina and the least antagonistic effect toward Fusarium graminearum and Fusarium subglutinans. Selected isolates of B. subtilis significantly affected final germination, shoot length, root length, shoot dry weight and root dry weight of two soybean cultivars. The most effective Bacillus spp. isolates could be used as potential inoculants for improving soybean productivity.

Antioxidant and Antifungal Activity of the Cynophalla flexuosa (L.) J. Presl (Capparaceae) against Opportunistic Fungal Pathogens

The chemical composition of the Cynophalla flexuosa hydroethanolic extract (CFHEE) was identified and its antioxidant, antifungal and antipleomorphic activities against C. albicans and C. tropicalis strains were evaluated. Phytochemical prospecting evidenced polyphenolic and triterpenoid compounds while UPLC-MS analysis revealed the presence of Isopropyl/n-propyl-GLS; Methylpropyl-GLS/butyl-GLS; Methylbutyl-GLS; Quercetin O-di-hexoside; Quercetin-pentosyl-hexoside; Rutin; Quercetin O-glucoside; Kaempferol O-rhamnosyl-hexoside; Kaempferol O-pentosyl-hexoside and Lariciresinol hexoside. The CFHEE inhibited the effect of the DPPH● free radical, both when evaluated individually and in combination with the antifungal fluconazole. When associated with 256 μg/mL fluconazole, the extract, at concentrations from 128 μg/mL, reduced the effect of the DPPH● free radical with values ranging from 37.7% to 95.8%. The extract’s antifungal effect was considered clinically irrelevant and its combination with the antifungal triggered an antagonistic effect against the two strains, thus indicating the popular use of bravo beans in the form of teas or infusions should not be combined with the intake of the drug Fluconazole as this may lead to a reduction of its clinical effect. The extract, however, inhibited morphological changes (pleomorphism) in Candida species, preventing the development of hyphae. The CFHEE possesses an antioxidant effect and a potential pharmacological activity for the inhibition of one of the Candida spp. virulence factors.

Duality of Interactions Between TGF-β and TNF-α During Tumor Formation

The tumor microenvironment is essential for the formation and development of tumors. Cytokines in the microenvironment may affect the growth, metastasis and prognosis of tumors, and play different roles in different stages of tumors, of which transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α) are critical. The two have synergistic and antagonistic effect on tumor regulation. The inhibition of TGF-β can promote the formation rate of tumor, while TGF-β can promote the malignancy of tumor. TNF-α was initially determined to be a natural immune serum mediator that can induce tumor hemorrhagic necrosis, it has a wide range of biological activities and can be used clinically as a target to immune diseases as well as tumors. However, there are few reports on the interaction between the two in the tumor microenvironment. This paper combs the biological effect of the two in different aspects of different tumors. We summarized the changes and clinical medication rules of the two in different tissue cells, hoping to provide a new idea for the clinical application of the two cytokines.

Acute and chronic toxicity of mixtures of bisphenol A and trace metals (Cd and Pb) to micro-crustacean, Daphnia magna

The occurrence of plastic additives and their ecological impacts have attracted much attention in recent years globally. Among plastic additives, the trace metals (e.g., Cd, Pb) are widely used as color pigments and stabilizers, whereas bisphenol A (BPA) is added to enhance the desired physical characteristics of plastic products. However, these additives can easily leach out of plastic materials and enter the aquatic environment causing risks to aquatic ecosystems. Although the toxicity of a single additive on various aquatic organisms has been studied, the responses of zooplankton exposed to the mixed plastic additives have not been fully understood. Therefore, this study aims to evaluate the effects of the binary mixtures (BPA+Cd, BPA+Pb) and trinary mixture (BPA+Pb+Cd) at the metal concentrations of 5 µg/L and BPA level of 50 µg/ L on the life history traits and food feeding rate of the freshwater micro-crustacean, Daphnia magna. The results showed exposures to these mixtures for 24h could significantly enhance the food feeding rate of D. magna from 2.5 – 5.8 times higher than the control. The survival rate was decreased from 50 – 90% in the organisms exposed to these mixtures after 18 incubated days. We found a synergistic effect of BPA+Pb but an antagonistic effect of BPA+Pb+Cd on the survivorship of D. magna. Similarly, the organisms in the exposures delayed their maturity age and reduced their reproduction. The potent impact order of the mixtures on D. magna was BPA+Cd > BPA+Pb+Cd > BPA+Pb. Our results evidenced the adverse effects of plastic additive mixtures on aquatic organisms. Therefore, the use and disposal of plastic materials and plastic additives should be paid more attention to protect the environment, ecosystem, and human health. Moreover, our findings proved that the toxicity of multi-contaminants on organisms could be unpredictable even the toxicity of a single contaminant is known.