Stress-induced Growth Research Articles

Влияние оксопроизводных азотсодержащих гетероциклов CBR-384 и CBR-386 на дыхательную активность и уровень внеклеточных серосодержащих соединений у бактерий Escherichia coli

The biological activity of two representatives of oxo-derivative nitrogen-containing heterocycles CBR-384 and CBR-386, planned for use as drugs, on growing aerobically gram-negative bacteria Escherichia coli was studied. Compound CBR-384 completely inhibited growth rate and biomass accumulation as measured by optical density (OD600). Continuous recording of dissolved oxygen (dO2) with a Clark electrode directly in the growing culture showed that CBR-384 caused a rapid and irreversible increase in oxygen levels in the medium, which indicated a decrease in the respiratory activity of cells. In time, the phase of rapid decline in respiration coincided with the phase of decreased growth rate. In aerobic cultures of E. coli, respiratory activity is closely related to the generation of membrane potential. However, only a small, but statistically significant, decrease in membrane potential, measured using the fluorescent dye DiBAC4(3), was found with CBR-384. It is known that in aerobic E. coli cultures growing on sulfate as a sulfur source, stress-induced growth inhibition is accompanied by an increase in extracellular glutathione (GSH) and H2S export. The use of a sulfide-specific electrode re-vealed that when E. coli growth is stopped by CBR-384, sulfide is also exported into the medium. Under these conditions, an increase in extracellular GSH was also noted. The effect of CBR-386 on E. coli, assessed by these four parameters, was less pronounced. The differences in the biological activities of CBR-384 and CBR-386 may be due to differences in their structures.

Characterization of Nitrogen Stress-induced Growth, Proximate, and Pigment Contents of Nannochloropsis sp.

Nitrogen is one of the key growth factors and structural constituent of the cellular molecules of Nannochloropsis sp. This study aimed to determine the influence of nitrogen stress in the form of potassium nitrate (KNO3 ) by altering the standard recommended nitrogen concentration to characterize the growth performance, proximate composition, and pigments content. The nitrogen concentration was arranged in following order for the culture of Nannochloropsis sp.: 50 g/L, 75 g/L, 100 g/L (standard), 125 g/L, and 150 g/L of KNO3 . All growth parameters, proximate composition, and pigment contents showed significant (p < 0.05) changes among the treatments. Cell density was increased by 2.48 folds, SGR was increased by 56.9%, and cells were doubled in number at a pace of 12.192 hours faster at the maximum nitrogen concentration (150g/L KNO3 ). The maximum protein content was 54 ± 1.05% at 150 g/L KNO3 while the highest lipid content was 36 ± 0.32% at 75 g/L KNO3 . The highest carbohydrate content was 24 ± 2.51% at 100 g/L KNO3 . The chlorophyll a content was increased to 0.632 ± 0.049 µg/L at 150 g/L KNO3 , while the highest carotenoids content was 3.301 ± 0.052 µg/ml at the 75g/L KNO3 . On the other hand, phycobiliprotein content was the highest 0.028 mg/g for the standard concentration of KNO3 . This study provides the commercial cultivation strategy for Nannochloropsis sp. by revealing the biomass productivity, biochemical and bioactive compounds status at different nitrogen-based culture conditions that will ensure their multipurpose use in aquaculture, pharmaceuticals, and nutraceuticals sectors.

Heterologous overexpression of HIOMT alleviates alkaline stress in apple plants by increasing melatonin concentration

Melatonin is an indole derivative of tryptophan that has an important function in alleviating abiotic stress. Previous studies have reported that exogenous melatonin increases the tolerance of plants to saline-alkali stress in a concentration-dependent manner, but the role of endogenous melatonin metabolism in the response of apple (Malus domestica) plants to alkali stress is unclear. In this study, the human melatonin biosynthesis-related enzyme N-acetyl-5-hydroxytryptamine methyltransferase gene (HIOMT) transformed in ‘GL-3’ apple was used to study the regulation of HIOMT in alkaline stress of apple plants. The heterologous overexpression of HIOMT under alkaline stress increased the concentration of endogenous melatonin in apple leaves, alleviated the stress-induced growth inhibition of the plants, enhanced root development, leaf photosynthesis, and antioxidant capacity, and stabilized cell membrane permeability and ionic balance. In addition, the transgenic lines also increased the concentrations of organic acids, such as oxalic acid, malic acid, malonic acid, citric acid, and succinic acid, which alleviated the high pH stress. These results provide evidence for the critical role of heterologous overexpression of HIOMT in the alkaline stress tolerance of apple plants.

Enhanced Survival and Adherence of Melphalan-Induced Senescent-like Dormant Multiple Myeloma Cells Co-Cultured with Bone Marrow Stromal Cells

Introduction: Multiple myeloma (MM) is an incurable plasma cell cancer and the second most common hematological malignancy in the United States. Therapeutic advances have greatly improved patient survival over the last decade; however, all patients are expected to relapse. New treatments are critically needed to overcome relapse and provide durable response. There is evidence that dormant MM cells exist in the bone marrow, where they exhibit reduced proliferative capacity and resistance to treatment. These cells are present over extended periods of time and may regain proliferative capacity to drive disease relapse. Tumor dormancy shares many features with senescence, a state of stress-induced growth arrest. Chemotherapies, including those used in the standard treatment of multiple myeloma such as melphalan, have been shown to cause therapy-induced senescence in a variety of tissues. Dormant MM cells have been shown to be maintained in their non-proliferative state by interactions with bone lining cells. Interestingly, matrix signaling has also been shown to protect against chemotherapy-induced apoptosis in an in vitro ovarian cancer organoid model. Taken together, this suggests that interaction of MM cells with the bone niche maintains both growth arrest and survival. We hypothesize that therapy-induced senescence drives dormancy in MM cells that is dependent on interactions with the mesenchymal bone niche. Methods: GFP-expressing 5TGM1 mouse MM cells were treated with vehicle or melphalan for 48 hours and then cultured in the presence or absence of ex vivo mouse bone marrow stromal cells (BMSCs). Cells were maintained for 12 additional days to allow for the development of a senescent phenotype after the initial stress response. During this period, cells were imaged and quantified during media replacements to assess adherence/survival. Cells were then fixed and assessed for nuclear foci, phospho-γH2AX, and telomeres by immunofluorescence/fluorescence in-situ hybridization (IF/FISH). Results: Melphalan-treated 5TGM1 cells cultured with BMSCs were significantly (p<0.0001) growth arrested over the 2-week monitoring period (mean cumulative doublings: 1.26 ± 0.179) compared to vehicle-treated cells (5.84 ± 0.122). Co-culture with BMSCs significantly (p<0.0001) enhanced melphalan-treated 5TGM1 cell adherence (mean percent of total cells washed-off: 21.7% ± 4.2%) compared to culture without BMSCs (92.2% ± 4.3%) during media replacement. Of note, melphalan-treated 5TGM1 cells did not survive in the absence of BMSCs after a week in culture. Melphalan-treated 5TGM1 cells also exhibited significantly greater (p<0.001) adherence with BMSCs (mean percent of total cells washed-off: 21.7% ± 4.2%) than vehicle-treated cells (48.9% ± 5.1%). Melphalan-treated 5TGM1 cells were significantly (p<0.0001) larger (median area in square microns: 63.96 [7.66-954.05]) than vehicle-treated cells (44.43 [7.66-434.32]) and exhibited both heterochromatin foci and persistent DNA damage foci associated with telomeres, all of which are markers of cellular senescence. Conclusions: Our findings suggest that interactions with BMSCs promote the survival of chemotherapy-treated MM tumor cells. The enhanced adherence of these melphalan-treated MM cells also suggests that current methods for minimal residual disease assessment may be inadequate, as rare populations of MM cells adhered to the marrow stroma may not be captured by routine bone marrow aspiration. These cells exhibit features of therapy-induced senescence which may be key to MM dormancy. Thus, targeting senescence survival pathways via senolytic therapy may be a novel approach to eliminate dormant MM cells and prevent disease relapse.

Formation of CuO whiskers and facet-controlled oxidation during the oxidation of Au-Cu nanoparticles fabricated by solid-state dewetting

The fabrication of cupric oxide (CuO) nanowires from Cu particles via thermal oxidation provides a simple and scalable method to produce hierarchical structures. A stress-induced growth mechanism is believed to account for the nanowire formation while a slow oxidation rate is favored to sustain the driving force. Here, CuO whiskers are grown from Au-Cu nanoparticles because the formation of Au-Cu phases decreases the Cu diffusion rate and in turn slows down the oxidation rate. The driving force for the whisker growth is attributed to the compressive stress imposed by the CuO shell on the Au-Cu core, which is induced by the significantdifference in their linear thermal expansion coefficients. The contribution of the compressive stress is proved by the calculation. Moreover, preferred oxidation is observed and it is related to the crystalline structures of different facets existing on the surface of Au-Cu nanoparticles. The more compact the plane, the slower the diffusion rate through the plane, resulting in the formation of thinner CuO on the relevant facet. The results open a cost-effect way to fabricate hybrid nanostructures consisting of Cu-based core–shell nanoparticles attached with CuO whiskers and bring new insights into the oxidation behaviors of Cu on different crystal planes.

Exogenous melatonin enhances cell wall response to salt stress in common bean (Phaseolus vulgaris) and the development of the associated predictive molecular markers.

Common bean (Phaseolus vulgaris) is an important food crop; however, its production is affected by salt stress. Salt stress can inhibit seed germination, promote senescence, and modify cell wall biosynthesis, assembly, and architecture. Melatonin, an indole heterocycle, has been demonstrated to greatly impact cell wall structure, composition, and regulation in plants under stress. However, the molecular basis for such assumptions is still unclear. In this study, a common bean variety, "Naihua" was treated with water (W), 70 mmol/L NaCl solution (S), and 100 μmol/L melatonin supplemented with salt solution (M+S) to determine the response of common bean to exogenous melatonin and explore regulatory mechanism of melatonin against salt stress. The results showed that exogenous melatonin treatment alleviated salt stress-induced growth inhibition of the common bean by increasing the length, surface area, volume, and diameter of common bean sprouts. Moreover, RNA sequencing (RNA-seq) and real-time quantitative PCR (qRT-PCR) indicated that the cell wall regulation pathway was involved in the salt stress tolerance of the common bean enhanced by melatonin. Screening of 120 germplasm resources revealed that melatonin treatment improved the salt tolerance of more than 65% of the common bean germplasm materials. Melatonin also up-regulated cell wall pathway genes by at least 46%. Furthermore, we analyzed the response of the common bean germplasm materials to melatonin treatment under salt stress using the key genes associated with the synthesis of the common bean cell wall as the molecular markers. The results showed that two pairs of markers were significantly associated with melatonin, and these could be used as candidate markers to predict whether common bean respond to exogenous melatonin and then enhance salt tolerance at the sprouting stage. This study shows that cell wall can respond to exogenous melatonin and enhance the salt tolerance of common bean. The makers identified in this study can be used to select common bean varieties that can respond to melatonin under stress. Overall, the study found that cell wall could response melatonin and enhance the salt tolerance and developed the makers for predicting varieties fit for melatonin under stress in common bean, which may be applied in the selection or development of common bean varieties with abiotic stress tolerance.

Mechanical stress-caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1.

Sirtuin1 (Sirt1)/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether dioscin functions as an activator of Sirt1/FoxO1 to protect against mechanical stress-induced chondrocyte dysfunction in vitro and in vivo models.HERB and PubChem databases were implemented to predict dioscin-related gene targets. Cell and mouse models of OA were established to determine the pharmacological value of dioscin, a steroidal saponin. Cartilage loss in the knee joint was detected by Safranin O staining. Phosphorylation and nucleocytoplasmic shuttling of FoxO1 was observed in mechanical stress-stimulated chondrocyte and anterior cruciate ligament transection-induced cartilage injury. However, dioscin treatment repressed FoxO1 phosphorylation and cytoplasmic transfer and elevated Sirt1 protein expression. Dioscin treatment reversed mechanical stress-induced growth inhibition and apoptosis of chondrocytes and improved cartilage degradation and bone loss in the epiphysis of the distal femur. Moreover, dioscin could maintain the normal phenotype of chondrocytes via mediating multiple gene expressions. Dioscin inhibited apoptosis and metabolic disorders in OA-like chondrocytes via maintaining the transcriptional activity of FoxO1 and enhancing Sirt1 expression. Dioscin might be a potential Sirt1 activator providing a novel therapeutic schedule for the treatment of OA.

β2-Adrenergic Receptor Signaling Pathway Stimulates the Migration and Invasion of Cancer Cells via Src Activation.

Chronic stress has been reported to stimulate the release of catecholamines, including norepinephrine (NE) and epinephrine (E), which promote cancer progression by activating the adrenergic receptor (AR). Although previous studies showed that β2-AR mediated chronic stress-induced tumor growth and metastasis, the underlying mechanism has not been fully explored. In this study, we aimed to investigate the molecular mechanism by which β2-AR exerts a pro-metastatic function in hepatocarcinoma (HCC) cells and breast cancer (BC) cells. Our results showed that Hep3B human HCC cells and MDA-MB-231 human BC cells exhibited the highest ADRB2 expression among diverse HCC and BC cell lines. NE, E, and isoprenaline (ISO), adrenergic agonists commonly increased the migration and invasion of Hep3B cells and MDA-MB-231 cells. The phosphorylation level of Src was significantly increased by E/NE. Dasatinib, a Src kinase inhibitor, blocked E/NE-induced migration and invasion, indicating that AR agonists enhanced the mobility of cancer cells by activating Src. ADRB2 knockdown attenuated E/NE-induced Src phosphorylation, as well as the metastatic ability of cancer cells, suggesting the essential role of β2-AR. Taken together, our results demonstrate that chronic stress-released catecholamines promoted the migration and invasion of HCC cells and BC cells via β2-AR-mediated Src activation.

Sertraline inhibits stress-induced tumor growth through regulating CD8 + T cell-mediated anti-tumor immunity.

Chronic stress has been reported to be associated with tumor initiation and progression. But the underlying mechanism and the specific role of tumor immunity in this process are still unknown. Herein, we applied the repeated restrain stress model in C57BL/6J mice and found that the tumor growth in stressed mice was accelerated compared with that in control mice. In addition, serotonin, also called 5-hydroxytryptamine (5-HT), in the serum of stressed mice was also elevated. Sertraline, a selective serotonin reuptake inhibitor used in the clinic, can restore the serum 5-HT level in stressed mice and restrain tumor growth. We further explored the distribution of major immune cells, including B lymphocytes cells, T lymphocytes, natural killer cells, dendritic cells, tumor-associated macrophages (TAM) and regulatory T cells (Treg). We found that the infiltration of CD8 + T cells in the tumor microenvironment (TME) decreased significantly in stressed mice. And the extra 5-HT treatment could further decrease the infiltration of CD8 + T cells in the TME. The expression of IFN-γ and Granular enzyme B (GzmB) in CD8 + T cells were also dropped in the stressed mice group, whereas the expression of programmed cell death protein 1 (PD-1) on CD8 + T cells was increased. The T cell deficiency induced by stress can be reversed by sertraline, indicating its promising role in strengthening the efficacy of anti-PDL1/PD-1 immunotherapy. The present study provides new mechanistic insights into the impact of chronic stress on antitumor immunity and implicates a novel combined immunotherapy strategy for cancer patients with chronic stress.

Magnetomechanical Stress-Induced Colon Cancer Cell Growth Inhibition

The application of magnetomechanical stress in cells using internalized magnetic nanoparticles (MNPs) actuated by low-frequency magnetic fields has been attracting considerable interest in the field of cancer research. Recent developments prove that magnetomechanical stress can inhibit cancer cells’ growth. However, the MNPs’ type and the magnetic field’s characteristics are crucial parameters. Their variability allows multiple combinations, which induce specific biological effects. We previously reported the antiproliferative effects induced in HT29 colon cancer cells by static-magnetic-field (200 mT)-actuated spherical MNPs (100 nm). Herein, we show that similar growth inhibitory effects are induced in other colon cancer cell lines. The effect of magnetomechanical stress was also examined in the growth rate of tumor spheroids. Moreover, we examined the biological mechanisms involved in the observed cell growth inhibition. Under the experimental conditions employed, no cell death was detected by PI (propidium iodide) staining analysis. Flow cytometry and Western blotting revealed that G2/M cell cycle arrest might mediate the antiproliferative effects. Furthermore, MNPs were found to locate in the lysosomes, and a decreased number of lysosomes was detected in cells that had undergone magnetomechanical stress, implying that the mechanical activation of the internalized MNPs could induce lysosome membrane disruption. Of note, the lysosomal acidic conditions were proven to affect the MNPs’ magnetic properties, evidenced by vibrating sample magnetometry (VSM) analysis. Further research on the combination of the described magnetomechanical stress with lysosome-targeting chemotherapeutic drugs could lay the groundwork for the development of novel anticancer combination treatment schemes.

Potential of Hibiscus Rosa-Sinensis L. and Baccaurea Racemosa Extract as a Hair Growth with Tail Suspension Test Stress-Induced Alopecia

Alopecia is the loss of excess hair that causes baldness, either temporarily or permanently. Physical and emotional stress are the most common causes. This study aims to determine the activity of H. rosa-sinensis L. and B. racemosa extracts on stress-induced hair growth in alopecia. Stress induction in male Wistar albino rats was obtained using the tail suspension test (TST) method. The results of the chemical content test were the total phenol content test (4,223.06 mg/100 g), total flavonoid (10,383.12 mg/100 g) and DPPH free radical reduction of B. racemosa (EB) extracts (1,593.17 mg/L GAEAC) were greater than those of the H. rosa-sinensis L. (EH) extract. The longest hair and highest hair density were obtained in the Minoxidil 2% group. While the most hair follicles were found in the group given the combination of EH and EB = 1: 1. The content of phenolic and flavonoid substances affects the hair growth activity.&#x0D; KEYWORDS: alopecia, stress, hibiscus, baccaurea, DPPH

The Exogenous Application of Brassinosteroids Confers Tolerance to Heat Stress by Increasing Antioxidant Capacity in Soybeans

Heat stress is an important factor affecting soybean yield. Brassinosteroids (BRs) play a crucial role in plant growth, development, and defense. In the present study, the regulatory effects of 24-epibrassinolide (EBR, one of the bioactive BRs) on heat tolerance in soybeans, and its underlying physiological mechanisms were investigated. The results show that foliar spraying with EBR significantly alleviate heat stress-induced water loss and oxidative damage in soybean leaves. The activities of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and the contents of antioxidant substances (ascorbic acid and reduced glutathione) were markedly increased in EBR-treated leaves compared with water-treated leaves, which contributed to maintaining reactive oxygen species homeostasis and relieving oxidative injury under heat stress. However, EBR-treated leaves showed a significant decrease in free proline and total soluble sugar content under heat stress compared to water-treated leaves. In addition, EBR treatment showed obviously higher photosystem II activity under heat stress, and higher net photosynthetic rate and biomass accumulation after recovery from heat stress compared to water treatment. Collectively, these results indicated that EBR could significantly improve the capacity of antioxidant defense systems to protect photosynthetic apparatus under heat stress, thereby effectively alleviating heat stress-induced growth inhibition in soybean plants.

Nodosin Exerts an Anti-Colorectal Cancer Effect by Inhibiting Proliferation and Triggering Complex Cell Death in Vitro and in Vivo

Colorectal cancer (CRC) is one of the most common digestive system cancer in the world. Its incidence and mortality are increasing annually. Presently, CRC lacks long-term effective treatment methods and drugs. Therefore, finding new treatment methods and drugs is of great significance for CRC treatment. Compounds derived from natural plants have been widely used in tumor research and treatment because of their good antitumor activity these years. This study found that nodosin, a diterpenoid extracted from the medicinal plant Rabdosia serra (Maxim.) Hara, inhibited the growth of CRC cells SW480, HT-29 and LoVo in a dose- and time-dependent manner, with inhibitory concentrations (IC50) of 7.4, 7.7, and 6.6 μM respectively. We selected highly metastatic and poorly differentiated SW480 cells for further studies. We found that nodosin could inhibit cell proliferation by inhibiting DNA synthesis and induce cell death by inducing oxidative stress, apoptosis and autophagy in cells. Through in vitro assays combined with transcriptomic analysis, it was found that nodosin could downregulate tribbles pseudokinase 3 and upregulate oxidative stress-induced growth inhibitor 1 to induce oxidative stress in cells; nodosin-induced reactive oxygen species were able to upregulate the expression of heme oxygenase 1 to induce apoptosis and the expression of cathepsin L. and light chain-3 to induce autophagy. In vivo, we found that nodosin inhibited tumor growth and induced cells to undergo apoptosis and autophagy without significant toxic effects. In conclusion, our findings suggest that nodosin exerts anti-CRC effects mainly through its ability to induce apoptosis and autophagy in vitro and in vivo. Therefore, our study contributes to the development of nodosin-based potential CRC therapeutic drugs.

Comparative study of oxidative status and some biochemical parameters in subjects suffered of intermediate and major Thalassemia

In the β-thalassemia’s, oxidative stress, resulting from chronic hemolysis, globin chain imbalance, iron overload and depleted antioxidant defenses, likely contributes to cell death, organ damage, anemia, hypoxia and inflammation. Between November 2020 and June 2021, the study assessed adults aged (25-35 years) attending to Hiwa Cancer Hospital/ Sulaimaniah Thalassemia and congenital blood disorders center/ Iraq: 60 patients with HbE β-thalassemia, 30 β-thalassemia major, 30 β-thalassemia intermediate and 30 control subjects. ferritin were measured as sources of oxidants; plasma antioxidants: Glutathione Reductase (GR) and Oxidative stress-induced growth inhibitor 2 (OSGIN2) , plasma D-dimer assessed thrombosis status and serum C-reactive protein assessed inflammation, the results showed increased in the levels of ferritin, plasma D-dimer and CRP in both β-thalassemia major and β-thalassemia intermediate (2789±789 ; 2657±725.8 ng/ml) , (175.4±54.02; 188.7±62.01 ng/ml) and (15.6±2.6; 13.3±3.1 mg/l) compared to control group (178.7±58.9 ng/ml) , (79.8±34.8 ng/ml) and (2.3± 0.7 mg/l) respectively. Whereas decreased in the levels of GR and OSGIN2 (38.4±12.7; 35±8.8 pg/ml) and (58±18.3; 78±20.5 mg/dl) compared to control group (96±17.3 pg/ml) and (156±65.6 mg/dl ) respectively.

Naringenin in Si-Ni-San formula inhibits chronic psychological stress-induced breast cancer growth and metastasis by modulating estrogen metabolism through FXR/EST pathway

IntroductionChronic psychological stress is a well-established risk factor for breast cancer development. Si-Ni-San (SNS) is a classical traditional Chinese medicine formula prescribed to psychological disorder patients. However, its action effects, molecular mechanisms, and bioactive phytochemicals against breast cancer are not yet clear. ObjectivesThis study aimed to explore the modulatory mechanism and bioactive compound of SNS in regulating estrogen metabolism during breast cancer development induced by chronic psychological stress. MethodsMouse breast cancer xenograft was used to determine the effect of SNS on breast cancer growth and metastasis. Metabolomics analysis was conducted to discover the impact of SNS on metabolic profile changes in vivo. Multiple molecular biology experiments and breast cancer xenografts were applied to verify the anti-metastatic potentials of the screened bioactive compound. ResultsSNS remarkably inhibited chronic psychological stress-induced breast cancer growth and metastasis in the mouse breast cancer xenograft. Meanwhile, chronic psychological stress increased the level of cholic acid, accompanied by the elevation of estradiol. Mechanistic investigation demonstrated that cholic acid activated farnesoid X receptor (FXR) expression, which inhibited hepatocyte nuclear factor 4α (HNF4α)-mediated estrogen sulfotransferase (EST) transcription in hepatocytes, and finally resulting in estradiol elevation. Notably, SNS inhibited breast cancer growth by suppressing estradiol level via modulating FXR/EST signaling. Furthermore, luciferase-reporting gene assay screened naringenin as the most bioactive compound in SNS for triggering EST activity in hepatocytes. Interestingly, pharmacokinetic study revealed that naringenin had the highest absorption in the liver tissue. Following in vivo and in vitro studies demonstrated that naringenin inhibited stress-induced breast cancer growth and metastasis by promoting estradiol metabolism via FXR/EST signaling. ConclusionThis study not only highlights FXR/EST signaling as a crucial target in mediating stress-induced breast cancer development, but also provides naringenin as a potential candidate for breast cancer endocrine therapy via promoting estradiol metabolism.

Numerical simulations of the nonsymmetric growth and remodeling of arteries under axial twisting

Blood vessels are often subjected to axial twisting during body movement or surgery. Sustained twisting may lead to blood vessel growth and remodeling, however, it remains unclear how the extracellular matrix in the blood vessels remodel under sustained axial twisting. This study aimed to develop a computational model to simulate stress-induced growth and remodeling (G&R) of thin-walled blood vessels under axial twisting. Cylindrical vessels were subjected to a step increase in axial torque while the axial stretch and lumen pressure remained constant. The vessel walls were modeled based on the constrained mixture theory given as microstructure-based discrete fiber families with isotropic matrix structure models. Simulation results demonstrated that in response to a constant twist angle loading, arterial wall thickness, mass, and twisting torque gradually increase towards a new steady state. However, the stress and mass decrease in one diagonal fiber family while increasing in the other diagonal fiber family before reaching plateaus. A novel finding was that the two helical collagen fiber families showed different growth rates and patterns during remodeling, driven by the different fiber stresses generated by the twisting, and led to non-symmetric material properties. This study sheds new light on arterial wall remodeling under axial twisting.

Oxidative Stress-Induced Growth Inhibitor (OSGIN1), a Target of X-Box-Binding Protein 1, Protects Palmitic Acid-Induced Vascular Lipotoxicity through Maintaining Autophagy.

Saturated free fatty acids (FFAs) strongly correlate with metabolic syndromes and are well-known risk factors for cardiovascular diseases (CVDs). The mechanism of palmitic acid (PA)-induced vascular lipotoxicity under endoplasmic reticulum (ER) stress is unknown. In the present paper, we investigate the roles of spliced form of X-box-binding protein 1 (XBP1s) target gene oxidative stress-induced growth inhibitor 1 (OSGIN1) in PA-induced vascular dysfunction. PA inhibited the tube formation assay of primary human umbilical vein endothelial cells (HUVECs). Simultaneously, PA treatment induced the XBP1s expression in HUVECs. Attenuate the induction of XBP1s by silencing the XBP1s retarded cell migration and diminished endothelial nitric oxide synthase (eNOS) expression. OSGIN1 is a target gene of XBP1s under PA treatment. The silencing of OSGIN1 inhibits cell migration by decreasing phospho-eNOS expression. PA activated autophagy in endothelial cells, inhibiting autophagy by 3-methyladenine (3-MA) decreased endothelial cell migration. Silencing XBP1s and OSGIN1 would reduce the induction of LC3 II; therefore, OSGIN1 could maintain autophagy to preserve endothelial cell migration. In conclusion, PA treatment induced ER stress and activated the inositol-requiring enzyme 1 alpha–spliced XBP1 (IRE1α–XBP1s) pathway. OSGIN1, a target gene of XBP1s, could protect endothelial cells from vascular lipotoxicity by regulating autophagy.

Mycobacterium tuberculosis PknK Substrate Profiling Reveals Essential Transcription Terminator Protein Rho and Two-Component Response Regulators PrrA and MtrA as Novel Targets for Phosphorylation.

ABSTRACTThe Mycobacterium tuberculosis protein kinase K regulates growth adaptation by facilitating mycobacterial survival in response to a variety of in vitro and in vivo stress conditions. Here, we further add that pknK transcription is responsive to carbon and nitrogen starvation signals. The increased survival of an M. tuberculosis ΔpknK mutant strain under carbon- and nitrogen-limiting growth conditions compared to the wild-type (WT) H37Rv suggests an integral role of PknK in regulating growth during metabolic stress. To identify the downstream targets of PknK-mediated signaling, we compared phosphoproteomic and transcription profiles of mycobacterial strains overexpressing WT and phosphorylation-defective PknK. Results implicate PknK as a signaling protein that can regulate several enzymes involved in central metabolism, transcription regulation, and signal transduction. A key finding of this study was the identification of two essential two-component response regulator (RR) proteins, PrrA and MtrA, and Rho transcription terminator, as unique targets for PknK. We confirm that PknK interacts with and phosphorylates PrrA, MtrA, and Rho in vivo. PknK-mediated phosphorylation of MtrA appears to increase binding of the RR to the cognate probe DNA. However, dual phosphorylation of MtrA and PrrA response regulators by PknK and their respective cognate sensor kinases in vitro showed nominal additive effect on the mobility of the protein-DNA complex, suggesting the presence of a potential fine-tuning of the signal transduction pathway which might respond to multiple cues.IMPORTANCE Networks of gene regulation and signaling cascades are fundamental to the pathogenesis of Mycobacterium tuberculosis in adapting to the continuously changing intracellular environment in the host. M. tuberculosis protein kinase K is a transcription regulator that responds to diverse environmental signals and facilitates stress-induced growth adaptation in culture and during infection. This study identifies multiple signaling interactions of PknK and provides evidence that PknK can change the transcriptional landscape during growth transitions by connecting distinctly different signal transduction and regulatory pathways essential for mycobacterial survival.

Physiological, biochemical and metabolomic mechanisms of mitigation of drought stress-induced tobacco growth inhibition by spermidine

Drought is a multifaceted environmental stress condition that limits crop productivity worldwide. Spermidine (Spd), one of the types of polyamines (PAs), is involved in plant stress tolerance. However, the molecular mechanism underlying the changes in the abundance of metabolites induced by Spd in drought stress tolerance is poorly understood. We aimed to examine the effects of Spd on the endogenous PA content, growth, photosynthesis, antioxidant system, and metabolite profiles as well as the expression of stress-responsive genes (NtP5CS, NtHsp18 and NtLEA5) in N. tabacum under drought stress and to investigate the underlying mechanisms with which Spd is involved. The results revealed that Spd application significantly increased the Spd, putrescine (Put), and spermine (Spm) contents and plant biomass under drought stress. Biochemical assays indicated that, under water-deficit conditions, plants treated with Spd presented increased chlorophyll contents, photosynthesis rate, and activities of antioxidant enzymes (SOD, POD, CAT and APX), but reduced O2•− production speed, H2O2 content, MDA content and electrolyte leakage. Furthermore, metabolite profiles revealed that Spd significantly promoted the contents of carbohydrates, unsaturated fatty acids, IAA and ABA phytohormone, but decreased most amino acid levels compared to those in drought-exposed plants. This study provides a comprehensive understanding of Spd-mediated drought stress tolerance from physiological, biochemical and metabolic perspectives.

Strain states and unique properties in cold-rolled TiNi shape memory alloys

Martensitic transformation (MT), strain glass transition (SGT) and the corresponding stress-strain responses in cold-rolled Ti49.2Ni50.8 shape memory alloys (SMAs) at various amounts of cold-rolling deformation are investigated. A phase diagram describing all the strain states and transitions among them is established in the temperature – deformation space. It shows a normal sharp, strong first-order B2 to B19′ MT at low deformation levels (cold-rolling thickness reduction εp < 27%), but a continuous B2 to B19′ SGT at high deformation levels (εp ≥ 27%) upon cooling. Superelasticity with small hysteresis, tunable modulus and functional-fatigue resistance properties are achieved by altering the transition behavior from MT to SGT at εp ≥ 27%. Nanodomains of single variant B19′ martensite at the atomic scale are observed by using aberration-corrected scanning transmission electron microscopy in samples with εp = 27%. Further in-situ loading synchrotron-based high energy X-ray diffraction technique shows that the quasi-linear superelasticity associated with the SGT can be attributed to stress-induced continuous growth of B19′ nanodomains. Geometrical phase analysis of high-resolution transmission electron microscopy image reveals a nanoscale network of severe lattice distortion associated with the accumulated high-density of defects at εp ≥ 27%, which is the microstructural origin of the B19′ strain glass state. This work provides a detailed explanation for the longstanding puzzle of unique quasi-linear superelastic response in plastically deformed TiNi SMAs, and may shed light on achieving novel mechanical properties through defect engineering.