[Genome-wide identification of bZIP family genes and screening of candidate AarbZIPs involved in terpenoid biosynthesis in Artemisia argyi].

Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.

Implications of the Cultivation of Rosemary and Thyme (Lamiaceae) in Plant Communities for the Development of Antioxidant Therapies.

Oxidative stress is the most critical factor in multiple functional disorders' development, and natural antioxidants could protect the human body against it. Our study aims to investigate the polyphenol content of four extracts of two medicinal plants (Rosmarinus officinalis L. and Thymus vulgaris L.) and analyze the correlation with their antioxidant activity. The research was carried out on extracts of rosemary and thyme obtained from species cultivated together in plant communities. Both were compared with extracts from species cultivated in individual crops (control crops). Their polyphenols were determined by spectrophotometric methods (dosage of flavones, phenol carboxylic acids, and total polyphenols) and chromatography (UHPLC-MS and FT-ICR MS). Triterpenic acids were also quantified, having a higher concentration in the thyme extract from the culture. The antioxidant activity of the dry extracts was evaluated in vitro (DPPH, ABTS, and FRAP) and in silico (prediction of interactions with BACH1/BACH2 transcription factors). The concentrations of polyphenols are higher in the extracts obtained from the sources collected from the common crops. These observations were also validated following the chromatographic analysis for some compounds. Statistically significant differences in the increase in the antioxidant effect were observed for the extracts from the common batches compared to those from the individual ones. Following the Pearson analysis, the IC50 values for each plant extract were strongly correlated with the concentration of active phytoconstituents. Molecular docking studies revealed that quercetin could bind to BTB domains of BACH1 and BACH2 transcription factors, likely translating into increased antioxidant enzyme expression. Future studies must validate the in silico findings and further investigate phytosociological cultivation's effects.

Role of bZIP transcription factors in the regulation of plant secondary metabolism.

MAIN CONCLUSION: This study provides an overview of the structure, classification, regulatory mechanisms, and biological functions of the basic (region) leucine zipper transcription factors and their molecular mechanisms in flavonoid, terpenoid, alkaloid, phenolic acid, and lignin biosynthesis. Basic (region) leucine zippers (bZIPs) are evolutionarily conserved transcription factors (TFs) in eukaryotic organisms. The bZIP TFs are widely distributed in plants and play important roles in plant growth and development, photomorphogenesis, signal transduction, resistance to pathogenic microbes, biotic and abiotic stress, and secondary metabolism. Moreover, the expression of bZIP TFs not only promotes or inhibits the accumulation of secondary metabolites in medicinal plants, but also affects the stress response of plants to the external adverse environment. This paper describes the structure, classification, biological function, and regulatory mechanisms of bZIP TFs. In addition, the molecular mechanism of bZIP TFs regulating the biosynthesis of flavonoids, terpenoids, alkaloids, phenolic acids, and lignin are also elaborated. This review provides a summary for in-depth study of the molecular mechanism of bZIP TFs regulating the synthesis pathway of secondary metabolites and plant molecular breeding, which is of significance for the generation of beneficial secondary metabolites and the improvement of plant varieties.

BACH1 regulates erythrophagocytosis and iron-recycling in ß-thalassemia.

Macrophages play essential roles in erythrophagocytosis and iron recycling. ß-thalassemia is characterized by a genetic defect in hemoglobin synthesis, which increases the rate of iron recycling. We previously showed that reduced expression of the BTB and CNC homolog 1 (BACH1) gene leads to increased phagocytosis of abnormal RBCs by activated monocytes. However, the mechanisms underlying this abnormal RBC clearance remained unclear. Herein, the spleen and bone marrow cells of ß-thalassemic mice were examined for erythrophagocytosis CD markers and iron-recycling genes. Higher expression levels of CD47 and CD163 on RBCs and macrophages, respectively, were observed in ß-thalassemic mice than in wild-type cells. The decreased expression of BACH1 caused an increase in Nrf2, Spic, Slc40a1, and HMOX1 expression in splenic red pulp macrophages of thalassemic mice. To investigate BACH1 regulation, a macrophage cell line was transfected with BACH1-siRNA. Decreased BACH1 expression caused an increase in CD163 expression; however, the expression levels were lower when the cells were cultured in media supplemented with ß-thalassemia/HbE patient plasma. Additionally, the iron recycling-related genes SPIC, SLC40A1, and HMOX1 were significantly upregulated in BACH1-suppressed macrophages. Our findings provide insights into BACH1 regulation, which plays an important role in erythrophagocytosis and iron recycling in thalassemic macrophages.

Genome-wide identification of bZIP family genes and screening of candidate AarbZIPs involved in terpenoid biosynthesis in Artemisia argyi / 中国中药杂志

Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.

Genome-wide identification and analysis of bZIP gene family reveal their roles during development and drought stress in Wheel Wingnut (Cyclocarya paliurus).

BACKGROUND: The bZIP gene family has important roles in various biological processes, including development and stress responses. However, little information about this gene family is available for Wheel Wingnut (Cyclocarya paliurus).  RESULTS: In this study, we identified 58 bZIP genes in the C. paliurus genome and analyzed phylogenetic relationships, chromosomal locations, gene structure, collinearity, and gene expression profiles. The 58 bZIP genes could be divided into 11 groups and were unevenly distributed among 16 C. paliurus chromosomes. An analysis of cis-regulatory elements indicated that bZIP promoters were associated with phytohormones and stress responses. The expression patterns of bZIP genes in leaves differed among developmental stages. In addition, several bZIP members were differentially expressed under drought stress. These expression patterns were verified by RT-qPCR. CONCLUSIONS: Our results provide insights into the evolutionary history of the bZIP gene family in C. paliurus and the function of these genes during leaf development and in the response to drought stress. In addition to basic genomic information, our results provide a theoretical basis for further studies aimed at improving growth and stress resistance in C. paliurus, an important medicinal plant.

Genomic characterization of bZIP transcription factors related to andrographolide biosynthesis in Andrographis paniculata.

The basic leucine zipper (bZIP) transcription factor family plays an important role in various biological processes in plants. Andrographis paniculata (Burm.f) Nees, belonging to the family Acanthaceae, has been widely used as an important traditional herb with a wide range of pharmacological activities, such as antivenom, antiretroviral, anticancer and so on. However, there was no comprehensive analysis of bZIP gene family in the Andrographis paniculata been reported. In this study, we identified 62 bZIPs in Andrographis paniculata and grouped them into 12 subfamilies through the phylogenetic tree analysis. The bZIPs in the same groups have similar motif composition, exon-intron structure and domain distribution. In addition, the RNA-seq data gave a reference for selecting candidate bZIPs to make further function verification. Lastly, qRT-PCR analyses revealed seven ApbZIPs (ApbZIP4, ApbZIP19, ApbZIP30, ApbZIP42, ApbZIP50, ApbZIP52, ApbZIP62) were the most highly expressed in leaf and significantly up-regulated with MeJA and ABA treatment which may be involved in biosynthesis regulation of andrographolide. These data pave the way for further revealing the function of the bZIPs in Andrographis paniculata.

Genome-Wide Identification and Salt Stress Response Analysis of the bZIP Transcription Factor Family in Sugar Beet.

As one of the largest transcription factor families in plants, bZIP transcription factors play important regulatory roles in different biological processes, especially in the process of stress response. Salt stress inhibits the growth and yield of sugar beet. However, bZIP-related studies in sugar beet (Beta vulgaris L.) have not been reported. This study aimed to identify the bZIP transcription factors in sugar beet and analyze their biological functions and response patterns to salt stress. Using bioinformatics, 48 BvbZIP genes were identified in the genome of sugar beet, encoding 77 proteins with large structural differences. Collinearity analysis showed that three pairs of BvbZIP genes were fragment replication genes. The BvbZIP genes were grouped according to the phylogenetic tree topology and conserved structures, and the results are consistent with those reported in Arabidopsis. Under salt stress, the expression levels of most BvbZIP genes were decreased, and only eight genes were up-regulated. GO analysis showed that the BvbZIP genes were mainly negatively regulated in stress response. Protein interaction prediction showed that the BvbZIP genes were mainly involved in light signaling and ABA signal transduction, and also played a certain role in stress responses. In this study, the structures and biological functions of the BvbZIP genes were analyzed to provide foundational data for further mechanistic studies and for facilitating the efforts toward the molecular breeding of stress-resilient sugar beet.

Lead exposure represses mitochondrial metabolism by activation of heme-binding protein BACH1 in differentiated SH-SY5Y cell.

Exposure to lead (Pb), a known toxin causing developmental neurotoxicity, can impair neurogenesis and oxidative phosphorylation (OXPHOS), but the mechanism is not clarified. In the current study, we aim to explore the effects of Pb on the differentiation of SH-SY5Y cells and investigate the role of heme and heme-binding protein BACH1 during differentiation. We found that Pb exposure caused a shift from OXPHOS to glycolysis, resulting in neurogenesis impairment by decreasing neurite growth and downregulation of PSD95 and Synapsin-1 in differentiated SH-SY5Y cells. Heme reduction mediated this mitochondria metabolism repression caused by Pb depending on BACH1 activation. Hemin supplement alleviated Pb-induced OXPHOS damage and adenosine triphosphate (ATP) reduction in differentiated SH-SY5Y cells, and further protected for Pb-induced damage of synapse. Heme binding factor BACH1 was negatively regulated by heme content and BACH1 knockout rescued the Pb-induced transcription and expression decline of genes related to OXPHOS and abrogated Pb-induced growth inhibition of axon promotion and synapse formation. Collectively, the present study demonstrates that heme deficiency mediates OXPHOS damage caused by Pb through BACH1 activation, resulting in neurogenesis impairment.

Multi-algorithm cooperation comprehensive research of bZIP genes under nitrogen stress in Panax notoginseng.

Basic leucine zipper (bZIP) transcription factors play an irreplaceable position in the regulation of plant secondary metabolism, growth and development, and resistance to abiotic stress. Panax notoginseng is a traditional medicinal plant in China, but the systematic identification and the resistance of Panax notoginseng bZIP (PnbZIP) family under nitrogen stress have not been reported before, considering the excessive application of N fertilizers. In this study, we conducted a genome-wide identification of the PnbZIP family and analyzed its phylogeny, tissue selectivity, and abiotic resistence. 74 PnbZIPs were distributed on 12 chromosomes and 8 were not successfully located. Through phylogenetic analysis of Arabidopsis and Panax notoginseng, we divided them into 14 subgroups. In the same subgroup, bZIPs had similiar intron/exon structure and conserved motifs. In the analysis of chromosome structure, two PnbZIP genes were duplicated in tandem on chromosome 3. Intraspecific collinearity analysis showed that 28 PnbZIPs participated in segmental replication. Each PnbZIP promoter contained at least one stress response element or stress-related hormone response element. RNA-seq and qRT-PCR methods were used to analyze the expression patterns of the PnbZIP gene in different tissues (roots, flowers, and leaves) and under different nitrogen stresses. The results showed that the PnbZIP gene had the highest expression level in flowers and reflected tissue-specific expressions. Meanwhile, under the stress of ammonium nitrogen fertilizer and nitrate nitrogen fertilizer, PnbZIPs in roots were differently expressed. 10 PnbZIP stress-responsive genes were screened for significant expression, among which PnbZIP46 was significantly up-regulated, which could be a candidate gene for resistance to Nitrogen stress. This study laid the foundation for functional identification of PnbZIPs and improved the cultivation of Panax notoginseng.

A bZIP transcription factor, PqbZIP1, is involved in the plant defense response of American ginseng.

American ginseng (Panax quinquefolius L.) is a perennial medicinal plant that has a long usage history in China. However, root rot, which is mainly caused by Fusarium solani can severely reduce the yield and quality of American ginseng, but no disease-resistant variety of American ginseng exists, and the resistance against this disease is not yet well understood. Thus, it is very urgent to analyze the interaction mechanism regulating the interactions between American ginseng and F. solani to mine disease resistance genes. Using transcriptome data and quantitative polymerase chain reaction (qPCR), we screened the transcription factor PqbZIP1 in response to induction by chitin. Yeast self-activation and subcellular localization experiments proved that PqbZIP1 showed transcriptional activity and was localized in the plant nucleus. In addition, qPCR showed that the highest relative expression level was in the roots, wherein chitin and F. solani inhibited and activated the expression of PqbZIP1, respectively, in American ginseng. Additionally, PqbZIP1 significantly inhibited the growth of the Pseudomonas syringae pv. tomato D36E strain in Nicotiana benthamiana, where expressing PqbZIP1 in N. benthamiana increased the jasmonic acid, salicylic acid, and abscisic acid content. Furthermore, PqbZIP1 expression was continually increased upon inoculation with F. solani. Hence, this study revealed that the PqbZIP1 transcription factor might mediate multiple hormonal signaling pathway to modulate root rot disease resistance in American ginseng, and provided important information to breed disease-resistant American ginseng.

Detection of HAC1 mRNA Splicing by RT-PCR in Saccharomyces cerevisiae.

HAC1 mRNA remains translationally repressed in the cytoplasm of the budding yeast Saccharomyces cerevisiae. Under conditions of cellular stress, a dual kinase RNase IRE1 (Inositol Requiring Enzyme-1) cleaves out an intervening sequence from the HAC1 mRNA. Cleaved mRNAs are then ligated by tRNA ligase, thus generating a spliced mRNA that translates an active transcription factor. This unconventional splicing of HAC1 mRNA in the cytoplasm is a molecular marker for various cellular stresses including oxidative stress and endoplasmic reticulum (ER) stress. This article describes a PCR-based protocol to detect the HAC1 mRNA splicing.

BACH2 inhibition reverses ß cell failure in type 2 diabetes models.

Type 2 diabetes (T2D) is associated with defective insulin secretion and reduced ß cell mass. Available treatments provide a temporary reprieve, but secondary failure rates are high, making insulin supplementation necessary. Reversibility of ß cell failure is a key translational question. Here, we reverse engineered and interrogated pancreatic islet-specific regulatory networks to discover T2D-specific subpopulations characterized by metabolic inflexibility and endocrine progenitor/stem cell features. Single-cell gain- and loss-of-function and glucose-induced Ca2+ flux analyses of top candidate master regulatory (MR) proteins in islet cells validated transcription factor BACH2 and associated epigenetic effectors as key drivers of T2D cell states. BACH2 knockout in T2D islets reversed cellular features of the disease, restoring a nondiabetic phenotype. BACH2-immunoreactive islet cells increased approximately 4-fold in diabetic patients, confirming the algorithmic prediction of clinically relevant subpopulations. Treatment with a BACH inhibitor lowered glycemia and increased plasma insulin levels in diabetic mice, and restored insulin secretion in diabetic mice and human islets. The findings suggest that T2D-specific populations of failing ß cells can be reversed and indicate pathways for pharmacological intervention, including via BACH2 inhibition.

Bach1 derepression is neuroprotective in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of nigrostriatal dopaminergic neurons. Mounting evidence suggests that Nrf2 is a promising target for neuroprotective interventions in PD. However, electrophilic chemical properties of the canonical Nrf2-based drugs cause irreversible alkylation of cysteine residues on cellular proteins resulting in side effects. Bach1 is a known transcriptional repressor of the Nrf2 pathway. We report that Bach1 levels are up-regulated in PD postmortem brains and preclinical models. Bach1 knockout (KO) mice were protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity and associated oxidative damage and neuroinflammation. Functional genomic analysis demonstrated that the neuroprotective effects in Bach1 KO mice was due to up-regulation of Bach1-targeted pathways that are associated with both Nrf2-dependent antioxidant response element (ARE) and Nrf2-independent non-ARE genes. Using a proprietary translational technology platform, a drug library screen identified a substituted benzimidazole as a Bach1 inhibitor that was validated as a nonelectrophile. Oral administration of the Bach1 inhibitor attenuated MPTP neurotoxicity in pre- and posttreatment paradigms. Bach1 inhibitor-induced neuroprotection was associated with the up-regulation of Bach1-targeted pathways in concurrence with the results from Bach1 KO mice. Our results suggest that genetic deletion as well as pharmacologic inhibition of Bach1 by a nonelectrophilic inhibitor is a promising therapeutic approach for PD.

Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY.

The central nervous system regulates activity of peripheral organs through interoception. In our previous study, we have demonstrated that PGE2/EP4 skeleton interception regulate bone homeostasis. Here, we show that ascending skeleton interoceptive signaling downregulates expression of hypothalamic neuropeptide Y (NPY) and induce lipolysis of adipose tissue for osteoblastic bone formation. Specifically, the ascending skeleton interoceptive signaling induces expression of small heterodimer partner-interacting leucine zipper protein (SMILE) in the hypothalamus. SMILE binds to pCREB as a transcriptional heterodimer on Npy promoters to inhibit NPY expression. Knockout of EP4 in sensory nerve increases expression of NPY causing bone catabolism and fat anabolism. Importantly, inhibition of NPY Y1 receptor (Y1R) accelerated oxidation of free fatty acids in osteoblasts and rescued bone loss in AvilCre:Ptger4fl/fl mice. Thus, downregulation of hypothalamic NPY expression lipolyzes free fatty acids for anabolic bone formation through a neuroendocrine descending interoceptive regulation.

Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea.

BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

Basic leucine zipper (bZIP) transcription factor genes and their responses to drought stress in ginseng, Panax ginseng C.A. Meyer.

BACKGROUND: Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng. RESULTS: Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress. CONCLUSIONS: These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.

Genome-wide identification and expression profiling of basic leucine zipper transcription factors following abiotic stresses in potato (Solanum tuberosum L.).

Potato (Solanum tuberosum L.) is an important food crop that is grown and consumed worldwide. The growth and productivity of this crop are severely affected by various abiotic stresses. Basic leucine zipper (bZIP) transcription factors (TFs) in plants are well known for their function during growth and development. However, systematic and in-depth identification and functional characterization of the bZIP gene family of potato is lacking. In the current study, we identified a total of 90 bZIPs (StbZIP) distributed on 12 linkage groups of potato. Based on the previous functional annotation and classification of bZIPs in Arabidopsis, wheat, and rice, a phylogenetic tree of potato bZIPs was constructed and genes were categorized into various functional groups (A to I, S, and U) as previously annotated in Arabidopsis thaliana. Analyses of the transcript sequence (RNA-seq) data led to identifying a total of 18 candidate StbZIPs [four in roots, eight in the tuber, six in mesocarp and endocarp] that were expressed in a tissue-specific manner. Differential expression analysis under the various abiotic conditions (salt, mannitol, water, and heat stress) and treatment with phytohormones (ABA, GA, IAA, and BAP) led to the identification of forty-two [thirteen under salt stress, two under mannitol stress, ten under water stress, and eighteen under heat stress], and eleven [eight and three StbZIPs upon treatment with ABA, and IAA, respectively] candidate StbZIPs, respectively. Using sequence information of candidate StbZIPs, a total of 22 SSR markers were also identified in this study. In conclusion, the genome-wide identification analysis coupled with RNA-Seq expression data led to identifying candidate StbZIPs, which are dysregulated, and may play a pivotal role under various abiotic stress conditions. This study will pave the way for future functional studies using forward and reverse genetics to improve abiotic stress tolerance in potato.

Nanomicellar Curcumin Supplementation Improves the Clinical Manifestations of HAM/TSP Patients.

BACKGROUND: HTLV-1 infection causes a chronic, progressive, demyelinating, neuroinflammatory disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Treatment of HAM/TSP patients which have high levels of proviral load and pro-inflammatory markers is a challenge for clinicians. Therefore, we aimed to investigate the immunomodulatory, anti-inflammatory, and antiviral effects of curcumin in HAM/TSP patients. METHODS: In this study, 20 newly diagnosed HAM/TSP patients (2 men and 18 women) were enrolled and evaluated for clinical symptoms, HTLV-1 proviral load, Tax and HBZ expression, neopterin serum concentration, and complete blood count (CBC) before and 12 weeks after treatment with nanomicellar curcumin (80 mg/day, orally). RESULTS: Clinical symptoms such as the mean Osame Motor Disability Score and Ashworth Spasticity Scale Score were significantly improved after the treatment (P = 0.001 and P = 0.001). Sensory symptoms such as pain and paresthesia were significantly decreased in all of the patients (P = 0.001). Furthermore, urinary disorders, including urinary frequency, incontinence, and the feeling of incomplete bladder emptying, were significantly improved (P = 0.001, P = 0.003, and P = 0.03). However, the mean HTLV-1 proviral load (P = 0.97) and CBC were similar, whereas Tax, HBZ, and neopterin levels tend to increase after the treatment (P = 0.004, P = 0.08, and P = 0.04). CONCLUSION: Results suggest that curcumin can safely improve the clinical symptoms of HAM/TSP patients but has no observable positive effects on the HTLV-1 proviral load, Tax, and HBZ expression. Therefore, prolonged use or the use of curcumin with antiviral agents in addition to clinical signs and symptoms can reduce the HTLV-1 proviral load and the expression of functional viral factors such as Tax and HBZ.