Application of ferrous sulfate alleviates negative impact of cadmium in rice (<i>Oryza sativa</i> L.)

Soil contamination with toxic heavy metals [such as cadmium (Cd)] is becoming a serious global problem due to rapid development of social economy. Iron (Fe), being an important element, has been found effective in enhancing plant tolerance against biotic and abiotic stresses. The present study investigated the extent to which different levels of Ferrous sulphate (FeSO₄) modulated the Cd tolerance of rice (Oryza sativa L.), when maintained in artificially Cd spiked regimes. A pot experiment was conducted under controlled conditions for 146 days, by using natural soil, mixed with different levels of CdCl₂ [0 (no Cd), 0.5 and 1 mg/kg] together with the exogenous application of FeSO₄ at [0 (no Fe), 1.5 and 3 mg/kg] levels to monitor different growth, gaseous exchange characteristics, oxidative stress, antioxidative responses, minerals accumulation, organic acid exudation patterns of O. sativa. Our results depicted that addition of Cd to the soil significantly (P < 0.05) decreased plant growth and biomass, gaseous exchange parameters, mineral uptake by the plants, sugars (soluble, reducing, and non-reducing sugar) and altered the ultrastructure of chloroplasts, plastoglobuli, mitochondria, and many other cellular organelles in Cd-stressed O. sativa compared to those plants which were grown without the addition of Cd in the soil. However, Cd toxicity boosted the production of reactive oxygen species (ROS) by increasing the contents of malondialdehyde (MDA), which is the indication of oxidative stress in O. sativa and was also manifested by hydrogen peroxide (H₂O₂) contents and electrolyte leakage to the membrane bounded organelles. Although, activities of various antioxidative enzymes like superoxidase dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) and non-enzymatic antioxidants like phenolics, flavonoid, ascorbic acid, anthocyanin and proline contents increased up to a Cd level of 0.5 mg/kg in the soil but were significantly diminished at the highest Cd level of 1 mg/kg in the soil compared to those plants which were grown without the addition of Cd in the soil. The negative impacts of Cd injury were reduced by the application of FeSO₄ which increased plant growth and biomass, improved photosynthetic apparatus, antioxidant enzymes, minerals uptake together with diminished exudation of organic acids as well as oxidative stress indicators in roots and shoots of O. sativa by decreasing Cd retention in different plant parts. These results shed light on the effectiveness of FeSO₄ in improving the growth and upregulation of antioxidant enzyme activities of O. sativa in response to Cd stress. However, further studies at field levels are required to explore the mechanisms of FeSO₄-mediated reduction of the toxicity of not only Cd, but possibly also other heavy metals in plants.     

Agmatine pretreatment protects retinal ganglion cells (RGC-5 cell line) from oxidative stress <i>in vitro</i>

Agmatine, 2-(4-aminobutyl)guanidine, has been reported to have neuroprotective effects against various neuronal damages. In this study it was investigated whether agmatine pretreatment rescues the retinal ganglion cells from oxidative injury in vitro. After differentiation of transformed rat retinal ganglion cells (RGC-5 cell line) with staurosporine, agmatine (0.0 to 100.0 μM) pretreatment was performed for 2 hours. Subsequently, they were exposed to hydrogen peroxide (0.0 to 2.5 mM) as an oxidative stress. Cell viability was monitored for up to 48 hours with the lactate dehydrogenase (LDH) assay and apoptosis was examined by the terminal deoxynucleotide transferase-mediated terminal uridine deoxynucleotidyl transferase nick end-labeling (TUNEL) method. As a result, differentiated RGC-5 cells were found to have decreased viability after addition of hydrogen peroxide in a dose-dependent manner. This hydrogen peroxide induced cytotoxicity caused apoptosis characterized by DNA fragmentation. Agmatine pretreatment not only increased cell viability but also attenuated DNA fragmentation. In conclusion, agmatine pretreatment demonstrated neuroprotective effects against oxidative stress induced by hydrogen peroxide in differentiated RGC-5 cells in vitro. This suggests a novel therapeutic strategy rescuing retinal ganglion cells from death caused by oxidative injury     

A mini-review on pharmacological effects of ginsenoside Rb3, a marked saponin from <i>Panax genus</i>

Ginsenoside Rb3 (G-Rb3) is one of the primary active compounds isolated from Panax ginseng Meyer, which belongs to protopanaxadiol ginsenosides (PPD). Based on the structure-activity relationship (SAR) of ginsenosides, the pentose structure of G-Rb3 limited itself to possess more pharmacological activity to a certain extent. However, pharmacokinetics show that G-Rb3 is processed through deglycosylation in the intestinal tract and converted into more active rare saponins, such as Compound K, F2, etc. A series of studies focused on neuroprotection and the cardiovascular system demonstrating its therapeutic potentials, which was achieved by diminishing oxidative stress and apoptosis. Therefore, more systematic and in-depth studies are needed to complete the pharmaceutical value and to promote its clinical applications. This article highlights the multiple pharmacological effects and mechanisms of G-Rb3 and prospects for its development.     

Overexpression of a sugarcane<i> ScCaM</i> gene negatively regulates salinity and drought stress responses in transgenic <i>Arabidopsis thaliana</i>

Calmodulin (CaM) proteins play a key role in signal transduction under various stresses. In the present study, the effects of a sugarcane ScCaM gene (NCBI accession number: GQ246454) on drought and salt stress tolerance in transgenic Arabidopsis thaliana and Escherichia coli cells were evaluated. The results demonstrated a significant negative role of ScCaM in the drought and salt stress tolerance of transgenic lines of A. thaliana, as indicated by the phenotypes. In addition, the expression of AtP5CS and AtRD29A, two genes tightly related to stress resistance, was significantly lower in the overexpression lines than in the wild type. The growth of E. coli BL21 cells expressing ScCaM showed weaker tolerance under mannitol and NaCl stress. Taken together, this study revealed that the ScCaM gene plays a negative regulatory role in both mannitol and NaCl stresses, and it possibly exerts protective mechanisms common in both prokaryotes and eukaryotes under stress conditions.     

Screening and evaluation of chilli (<i>Capsicum annuum</i> L.) genotypes for waterlogging tolerance at seedling stage

Waterlogging is an illustrious abiotic stress and the constrictions it enforces on plant roots have negative effects on growth and development. This study was undertaken to investigate waterlogging stress tolerant potential in chilli (Capsicum annum L.) genotypes through evaluating morphological, physiological, biochemical and anatomical parameters. Thirty-five days old seedlings of 10 chilli genotypes were exposed to waterlogging stress maintaining water height 3–5 cm over the soil surface artificially for three days. This duration (36–38 DAE) was termed as waterlogging period, and subsequent withdrawal of waterlogging condition (39–45 DAE) was regarded as a recovery phase. Based on their survival performance, two tolerant genotypes viz., SRC-517 and BARI morich-2 and two susceptible genotypes viz., AHM-206 and RI-1(6) were selected for studying stress tolerance mechanism. Under waterlogging, however, both genotypes (tolerant and susceptible) exhibited reduced root shoot length, dry weight ratio, petiole weight and leaf area, and noticeable reduction regarding these parameters was observed in susceptible genotypes. Moreover, tolerant genotypes displayed a higher recovery than susceptible genotypes after removal of waterlogging stress. Lower reduction of leaf area and photosynthetic pigments as well as higher reduction of relative water content (RWC) were noticed in susceptible genotypes. Higher accumulation of proline and total antioxidant capacity (TAC) during waterlogging condition in tolerant genotypes suggested lower oxidative damage. Although both genotypes lost total soluble sugar (TSS) relative to control at waterlogging stress, better performance was recorded in tolerant genotypes. During the period after the removal of extra water, a similar genotypic response in terms of TSS gain was seen. Undoubtedly, under flooding conditions, the development of aerenchyma cells in tolerant genotypes is a means of tolerance mechanism for long-term survival. Thus, the morpho-physiological and biochemical changes help to understand the tolerance mechanism in chilli under waterlogging stress.     

A <i>Brachypodium distachyon</i> calcineurin B-like protein-interacting protein kinase,BdCIPK26, enhances plant adaption to drought and high salinity stress

As sessile organisms, plants possess a complex system to cope with environmental changes. Ca²⁺ functions as a vital second messenger in the stress signaling of plants, and the CBL-interacting protein kinases (CIPKs) serve as essential elements in the plant Ca²⁺ signaling pathway. In this study, calcineurin B-like protein-interacting protein kinase 26 (BdCIPK26) from Brachypodium distachyon was characterized. Overexpression of BdCIPK26 enhanced tolerance to drought and salt stress of transgenic plants. Further investigations revealed that BdCIPK26 participated in abscisic acid (ABA) signaling, conferred hypersensitivity to exogenous ABA in transgenic plants, and promoted endogenous ABA biosynthesis. Moreover, BdCIPK26 was found to maintain ROS homeostasis in plants under stress conditions. Therefore, this study indicates that BdCIPK26 functions as a positive regulator in drought and salt stress response.     

An extract of <i>Hypericum perforatum</i> induces wound healing through inhibitions of Ca²⁺ mobilizations,mitochondrial oxidative stress and cell death in epithelial cells: Involvement of TRPM2 channels

The wound is induced by several mechanical and metabolic factors. In the etiology of the wound recovery, excessive oxidative stress, calcium ion (Ca²⁺) influx, and apoptosis have important roles. Ca²⁺-permeable TRPM2 channel is activated by oxidative stress. Protective roles of Hypericum perforatum extract (HP) on the mechanical nerve injury-induced apoptosis and oxidative toxicity through regulation of TRPM2 in the experimental animals were recently reported. The potential protective roles in HP treatment were evaluated on the TRPM2-mediated cellular oxidative toxicity in the renal epithelium (MPK) cells. The cells were divided into three groups as control, wound, and wound + HP treatment (75 µM for 72 h). Wound diameters were more importantly decreased in the wound+HP group than in the wound group. In addition, the results of laser confocal microscopy analyses indicated protective roles of HP and TRPM2 antagonists (N-(p-Amylcinnamoyl) anthranilic acid and 2-aminoethyl diphenylborinate) against the wound-induced increase of Ca²⁺ influx and mitochondrial ROS production. The wound-induced increase of early (annexin V-FITC) apoptosis and late (propidium iodide) apoptosis were also decreased in the cells by the HP treatment. In conclusion, HP treatment acted protective effects against wound-mediated oxidative cell toxicity and apoptosis through TRPM2 inhibition. These effects may be attributed to their potent antioxidant effect.     

Thyme oil and thymol abrogate doxorubicin-induced nephrotoxicity and cardiotoxicity in Wistar rats <i>via</i> repression of oxidative stress and enhancement of antioxidant defense mechanisms

This study aimed to assess the preventive effects of thyme oil and thymol on doxorubicin (DOX)-induced renotoxicity, cardiotoxicity, and oxidative stress in Wistar rats. Thyme oil was subjected to GC-MS analysis, which indicated that thymol was the major constituent representing 33.896%. Rats intraperitoneally injected with DOX at a dose of 2 mg/kg b.w./one per week for 7 weeks were co-treated with thyme oil and its major constituent, thymol, at doses 250 and 100 mg/kg b.w./every other day, respectively, by oral gavage for the same period. Thyme oil and thymol markedly ameliorated the raised levels of serum urea, uric acid, and creatinine in DOX-administered rats. They also reduced the elevated activities of serum CK-MB and LDH. Thyme oil was more effective than thymol in decreasing the elevated serum creatinine level and serum CK-MB activity in DOX-administered rats, thereby reflecting its more potent effect on kidney and heart functions. Lipid peroxidation significantly decreased while GSH level and GST and GPx activities significantly increased in kidney and heart of DOX-administered rats treated with thyme oil and thymol. The DOX-induced perturbed kidney histological changes including congestion of glomerulus tuft, inflammatory cells infiltration, protein cast in lumina of the renal tubule, and thickening of the parietal layer of Bowman’s capsule were remarkably ameliorated as a result of treatment with thyme oil and thymol; thyme oil was more effective. In addition, DOX-induced deleterious heart histological alterations, including intramuscular infiltration of inflammatory cells, focal necrosis of cardiac myocytes, and edema, were remarkably reduced by treatment with thyme oil and thymol. Thus, it can be concluded that DOX could induce marked toxicity in kidney and heart, and the treatment with thyme oil or thymol produced potential improvement of kidney and heart function and histological integrity via repression of oxidative stress and enhancement of antioxidant defense mechanisms.     

Expression analysis of <i>OsSERK</i>, <i>OsLEC1</i> and <i>OsWOX4</i> genes in rice (<i>Oryza</i> sativa L.) callus during somatic embryo development

Somatic embryogenesis is an asexual reproduction process that occurs in many plant species, including rice. This process contains several totipotency markers such as Somatic Embryogenesis Receptor-like Kinase (SERK), Leafy Cotyledon1 (LEC1) and WUSCHEL-Related Homeobox4 (WOX4) and also a helpful model for embryo development and clones and transformations. Here, we report the gene expression during somatic embryo development correlates with regeneration frequency in 14 Javanica rice (pigmented and non-pigmented) using modifified N6 media supplemented with Kinetin (2.0 mg/L) and NAA (1.0 mg/L). Although there have been advances in understanding the genetic basis of somatic embryogenesis in other varieties, rice is still unexplored, especially during somatic embryo development. Moreover, for the formation of callus induction from immature embryos, 2,4-D (2.0 mg/L, 3.0 mg/L) was used. This study analysed the gene expression of OsSERK, OsWOX4 and OsLEC1 genes through RT-PCR analysis. Higher expression of the OsLEC1 gene indicates that their function may correlate in the in vitro with the high response of rice after transfer to regeneration media. This study found that rice varieties of pigmented rice (MS Pendek and Gogoniti II) and non-pigmented rice (Pandan Ungu) showed high regeneration frequency, showing higher OsLEC1 expression than other varieties because OsLEC1 promotes the maturation of somatic embryos in plant regeneration on day 14. However, the contrast with Genjah nganjuk may be effective because of other regulatory genes. RT-PCR analysis showed OsSERK had less expression level than OsLEC1 and OsWOX4 in the varieties, which correlate with the percentage of plant regeneration, but not for Gogoniti II. In conclusion, the higher percentage of plant regeneration correlates with the higher expression level of OsLEC1 at day 14 of media regeneration of rice.     

Butein imparts free radical scavenging,anti-oxidative and proapoptotic properties in the flower extracts of <i>Butea monosperma</i>

The flower of Butea monosperma (Lam.) (Fabaceae) has been used in traditional Indian medicine in the treatment of many ailments including liver disorders. To understand the pharmacological basis of its beneficial effects, the extracts of dried flowers in water, methanol, butanol, ethyl acetate and acetone were evaluated for free radical scavenging and pro-apoptotic activities in cell cultures (human hepatoma Huh-7 cell line and immortalized AML-12 mouse hepatocytes). Butrin and butein -the active constituents of flower extracts- were used as reference molecules. The levels of cell injury markers like lactate dehydrogenase, glutathione and lipid peroxidation and primary antioxidant enzymes glutathione S-transferase and catalase were also measured. The aqueous and butanolic extracts exhibited better 2,2-diphenyl-1-picrylhydrazyl scavenging and cytotoxic activities in hepatoma cells than in immortalized hepatocytes. Interestingly, butein inhibited 2,2-diphenyl-1-picrylhydrazyl radical better than butrin. The aqueous and butanolic extracts were further investigated for hepatoprotection against carbon tertrachloride-induced biochemical changes and cell death. Both extracts, just as butrin and butein, significantly reversed the cellular glutathione levels and lipid peroxidation, and glutathione–S-transferase activity. Lactate dehydrogenase leakage and cell death were also prevented. However, only butein revived the catalase activity. Thus, the butein content of Butea monosperma flower extracts is important for free radical scavenging activity, apoptotic cell death and protection against oxidative injury in hepatic cells.     

Genome-wide identification of <i>U-box</i> gene family and expression analysis under abiotic stresses in <i>Salvia miltiorrhiza</i>

Plant U-box (PUB) E3 ubiquitin ligases play important roles in hormone signaling pathways and in response to different abiotic stresses, but little is known about U-box genes in Danshen (root of Salvia miltiorrhiza Bunge). Here, we identified and characterized 70 SmPUB genes based on its genome sequence. Phylogenetic analysis of U-box genes from S. miltiorrhiza and Arabidopsis suggested that they can be clustered into seven subgroups (I–VII). Typical U-box domains were found in all identified SmPUB genes through the analysis of conserved motifs. Moreover, qRT-PCR was applied to analyze the relative expression levels of U-box genes in S. miltiorrhiza roots and leaves under PEG-induced water deficit and salt stresses. Results revealed that the SmPUB genes exhibited stronger response to drought than to salt stress. To the best of our knowledge, this report is the first to perform genome-wide identification and analysis of the U-box gene family in S. miltiorrhiza, and the results provide valuable information for better understanding of the function of U-box in S. miltiorrhiza.     

Oxidative effects of glyphosate on the lipophobic intracellular environment in the microalgae <i>Chlorella vulgaris</i>

The studied hypothesis is that the herbicide glyphosate (GLY) can affect the oxidative balance in the hydrophobic intracellular medium in non-target Chlorella vulgaris cells. Analytical GLY and RoundUp (RUP) supplementation, affected the growth profile. A significant 42% decrease in the cellular biomass in stationary (St) phase was observed in cultures supplemented with either 5 µM of GLY or RUP, as compared to control cultures. The treatment with 0.3 µM of GLY generated non-significant effects on the oxidation rate of 2’, 7’ dichlorofluorescein diacetate (DCFH-DA), neither in exponential (Exp) nor in St phase of development, as compared to control cultures. However, the treatment with either 5 µM GLY or 0.3 and 5 µM RUP lead to a significant decrease in the DCFH-DA oxidation rate, as compared to control cultures. The lipid radical (LR^●) generation rate, detected by Paramagnetic Resonance Spectroscopy (EPR), was significantly increased in the presence of RUP, in Lag and Exp phase of growth. The non-enzymatic antioxidants, α-Tocopherol (α-T) and β-Carotene (β-C), are aimed to protect membranes against the damage produced by the radical reactions. The content of β-C was not significantly affected, as compared to control cultures, by any of the treatments, in both growth phases of cellular development. The content of α-T was significantly decreased by the supplementation with either 0.3 or 5 µM of RUP or 5 µM GLY. The LR^●/α-T ratio, used as indicator of the oxidative balance in the hydrophobic cellular media, was significantly different between samples obtained from control and RUP-exposed microalgae in both, Exp and St phase of development, with either 0.3 or 5 μM RUP. The data presented here showed evidence that suggested that oxidative balance in the hydrophobic environment was affected by either GLY or RUP.

     

Association between preterm birth risk and polymorphism and expression of the DNA repair genes <i>OGG1</i> and <i>APE1</i> in Saudi women

Genomic instability and mutations caused by increases in oxidative stress during pregnancy can damage the fetoplacental unit and can upshot preterm birth. Oxidative damage to DNA may possibly be involved in etiology of preterm birth (PTB) which can be repaired by DNA repair gene. In the present study, we assessed the association of base excision repair gene family by analyzing the association of single nucleotide polymorphisms and genes expression in 8-oxoguanine glycosylase-1 (OGG1) and apurinic-apyrimidinic endonuclease 1 (APE1) genes with risk of preterm birth in Saudi women. We analyzed genotypes of four single nucleotide polymorphisms (SNPs) (rs1052133, rs293795, rs2072668 and rs2075747) in OGG1 gene and three SNPs (rs1130409, rs3136814, and rs3136817) in APE1 gene using TaqMan Genotyping assay kits in 50 pairs of preterm cases and individually matched controls. Also, gene expression level was explored by RT-PCR in 10 pairs of preterm placental tissues and individually matched normal placental tissues. Two OGG1 SNP, rs1052133 (OR=0.497; c2=1.11; p=0.292) and rs2072668 (OR=0.408; c2=1.90; p=0.167) and one APE1 SNP rs3136817 (OR=0.458; c2=0.40; p=0.527) showed nonsignificant protective effect against PTB development. The expression of both genes under study was found lower in the PTB patients. Genotype and allele frequencies of both gene SNPs did not show any association with the risk of preterm delivery in Saudi women (P˃0.05). However, synthesis and release of OGG1 and APE1 proteins decreased in preterm placental tissues compared to term delivery reflects the probability of being one of the mechanisms leading to preterm birth.     

<i>Claroideoglomus etunicatum</i> improved the growth and saline– alkaline tolerance of <i>Potentilla anserina</i> by altering physiological and biochemical properties

To investigate the effects of arbuscular mycorrhizal (AM) fungi on the growth and saline–alkaline tolerance of Potentilla anserina L., the seedlings were inoculated with Claroideoglomus etunicatum (W.N. Becker & Gerd.) C. Walker & A. Schüßler in pot cultivation. After 90 days of culture, saline–alkaline stress was induced with NaCl and NaHCO₃ solution according to the main salt components in saline–alkaline soils. Based on the physiological response of P. anserina to the stress in the preliminary experiment, the solution concentrations of 0 mmol/L, 75 mmol/L, 150 mmol/L, 225 mmol/L and 300 mmol/L were treated with stress for 10 days, respectively. The mycorrhizal colonization rate, mycorrhizal dependence, chlorophyll content, malondialdehyde content, antioxidant enzyme activities, osmoregulation substances content and water status were measured. The results showed that with the increase of NaCl and NaHCO₃ stress concentration, mycorrhizal colonization rate, colonization intensity, arbuscular abundance and vesicle abundance decreased, and reached the lowest value at 300 mmol/L. Strong mycorrhizal dependence was observed after the symbiosis with AM fungus, and the dependence was higher under NaHCO₃ treatment. Under NaCl and NaHCO₃ stress, inoculation with AM fungus could increase chlorophyll content, decrease malondialdehyde content, increase activities of superoxide dismutase, peroxidase and catalase, increase contents of proline, soluble sugar and soluble protein, increase tissue relative water content and decrease water saturation deficit. It was concluded that salt–alkali stress inhibited the colonization of AM fungus, but the mycorrhiza still played a positive role in maintaining the normal growth of plants under salt–alkali stress.     

Nicotinic acid induces apoptosis of glioma cells <i>via</i> the calcium-dependent endoplasmic reticulum stress pathway

Malignant glioma is one of the most common and deadly tumors in the central nervous system while developing effective treatments for this devastating disease remains a challenge. Previously, we demonstrated that the vitamin nicotinic acid (NA) inhibits glioma invasion. Here, we show that high-dose NA induces apoptosis of malignant glioma cells in vitro and in vivo. In cultured U251 glioma cells treated with NA, we detected ER stress that was likely caused by elevated intracellular calcium levels. The elevated calcium can be attributed to the activation of TRPV1, a cation channel that has been implicated in cutaneous flushing caused by NA administration. Our data further suggested that NA-induced apoptosis is mediated by the calcium-dependent proteases called calpains, whose activities are drastically upregulated by NA. NA-induced apoptosis of U251 cells can be attenuated by blocking calpain activity or knocking down TRPV1. These results reveal a novel function of NA in regulating glioma cell apoptosis via the calcium-dependent ER stress pathway and imply a potential application of NA for the treatment of malignant glioma.     

Exploring the attenuation mechanisms of <i>Dalbergia odorifera</i> leaves extract on cerebral ischemia-reperfusion based on weighted gene co-expression network analysis

Background: The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion (I/R) is little known. The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chromatography. The molecular mechanism of D. odorifera leaves on cerebral I/R was investigated. Methods: Serial affinity chromatography based on D. odorifera leaves extract (DLE) affinity matrices were applied to find specific binding proteins in the brain tissues implemented on C57BL/6 mice by intraluminal middle cerebral artery occlusion for 1 h and reperfusion for 24 h. Specific binding proteins were subjected to mass-spectrometry to search for the differentially expressed proteins between control and DLE-affinity matrices. The hub genes were screened based on weighted gene co-expression network analysis (WGCNA). Then, predictive biology and potential experimental verification were performed for the candidate genes. The protective role of DLE in blood-brain barrier damage in cerebral I/R mice was evaluated by the leakage of Evans blue, western blotting, immunohistochemistry, and immunofluorescent staining. Results: 952 differentially expressed proteins were classified into seven modules based on WGCNA under soft threshold 6. Based on WGCNA, AKT1, PIK3CA, NOS3, SMAD3, SMAD1, IL6, MAPK1, TGFBR2, TGFBR1, MAPK3, IGF1R, LRG1, mTOR, ROCK1, TGFB1, IL1B, SMAD2, and SMAD5 18 candidate hub proteins were involved in turquoise module. TGF-β, MAPK, focal adhesion, and adherens junction signaling pathway were associated with candidate hub proteins. Gene ontology analysis demonstrated that candidate hub proteins were related to the TGF-β receptor signaling pathway, common-partner SMAD protein phosphorylation, etc. DLE could significantly reduce the leakage of Evans blue in mice with cerebral I/R, while attenuating the expression of occludin, claudin-5, and zonula occludens-1. Western blotting demonstrated that regulation of TGF-β/SMAD signaling pathway played an essential role in the protective effect of DLE. Conclusion: Thus, a number of candidate hub proteins were identified based on DLE affinity chromatography through WGCNA. DLE could attenuate the dysfunction of blood-brain barrier in the TGF-β/SMAD signaling pathway induced by cerebral I/R.     

Role of foliar spray of plant growth regulators in improving photosynthetic pigments and metabolites in <i>Plantago ovata</i> (Psyllium) under salt stress–A field appraisal

Salinity is one of the major abiotic factors that limit the growth and productivity of plants. Foliar application of plant growth regulators (PGRs) may help plants ameliorate the negative impacts of salinity. Thus, a field experiment was conducted at the Botanical Garden University of Balochistan, Quetta, to explore the potential role of PGRs, i.e., moringa leaf extract (MLE; 10%), proline (PRO; 1 µM), salicylic acid (SA; 250 µM), and thiourea (TU; 10 mM) in ameliorating the impacts of salinity (120 mM) on Plantago ovata, an important medicinal plant. Salinity hampered plant photosynthetic pigments and metabolites but elevated oxidative parameters. However, foliar application of PGRs enhanced photosynthetic pigments, including Chl b (21.11%), carotenoids (57.87%) except Chl a, activated the defense mechanisms by restoring and enhancing the metabolites, i.e., soluble sugars (49.68%), soluble phenolics (33.34%), and proline (31.47%), significantly under salinity stress. Furthermore, foliar supplementation of PGRs under salt stress led to a decrease of about 43.02% and 43.27% in hydrogen peroxide and malondialdehyde content, respectively. Thus, PGRs can be recommended for improved photosynthetic efficiency and metabolite content that can help to get better yield under salt stress, with the best and most effective treatments being those of PRO and MLE to predominately ameliorate the harsh impacts of salinity.     

Targeting the “undruggable” cancer driver genes: <i>Ras</i>, <i>myc</i>, and <i>tp53</i>

The term “undruggable” is to describe molecules that are not targetable or at least hard to target pharmacologically. Unfortunately, some targets with potent oncogenic activity fall into this category, and currently little is known about how to solve this problem, which largely hampered drug research on human cancers. Ras, as one of the most common oncogenes, was previously considered “undruggable”, but in recent years, a few small molecules like Sotorasib (AMG-510) have emerged and proved their targeted anti-cancer effects. Further, myc, as one of the most studied oncogenes, and tp53, being the most common tumor suppressor genes, are both considered “undruggable”. Many attempts have been made to target these “undruggable” targets, but little progress has been made yet. This article summarizes the current progress of direct and indirect targeting approaches for ras, myc, two oncogenes, and tp53, a tumor suppressor gene. These are potential therapeutic targets but are considered “undruggable”. We conclude with some emerging research approaches like proteolysis targeting chimeras (PROTACs), cancer vaccines, and artificial intelligence (AI)-based drug discovery, which might provide new cues for cancer intervention. Therefore, this review sets out to clarify the current status of targeted anti-cancer drug research, and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such “undruggable” molecules.