Pregnenolone derivatives for the treatment of Alzheimer's disease: synthesis, and in vitro inhibition of amyloid ß1-42 peptide aggregation, acetylcholinesterase and carbonic anhydrase-II.

The amyloid state, which is a specific conformation of proteins, offers valuable information about both functional protein structures and the pathological assemblies associated with various diseases. One of the major hallmarks of Alzheimer's disease includes primarily the extracellular build-up of a peptide known as amyloid-ß, which has a sequence consisting of 39 to 42 amino acid residues, and the formation of intracellular neurofibrillary tangles mostly consisting of hyperphosphorylated tau protein. Drugs that are expected to reduce Aß production, prevent Aß aggregation, and promote Aß clearance are promising approaches for treating AD. Current work is focused on identifying the compounds that have balanced even mild biological activities against multiple targets instead of finding one-target compound with high potency. We synthesized pregnenolone derivatives and evaluated their potential against inhibition of eeAChE/eqBChE, hCA-II and self-mediated Aß1-42 peptide aggregation. Our synthesized derivatives 23, and 25-27 exhibited concomitant inhibition of all the tested macromolecular targets. All the active compounds were found to be BBB penetrants in the PAMPA assay. Furthermore, these selected compounds were found to be non-neurotoxic in the MTT assay on neuroblastoma SH-SY5Y cells. Docking studies support dual binding site (PAS and CAS) inhibition of AChE which showed Aß1-42 aggregation and AChE inhibition. Moreover, docking studies carried out on the 3D crystallographic structure of Aß1-42 peptide (PDB ID = 1IYT) showed significant interactions with amino acid residues Asp 23 and Lys 28, and hydrophobic interactions with the Phe19, Phe20, and Ala 30 effectively impeding the formation of ß-sheet structures.

Exploitation of the multitarget role of new ferulic and gallic acid derivatives in oxidative stress-related Alzheimer's disease therapies: design, synthesis and bioevaluation.

Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. GA analog 28 was identified as the most potent antioxidant compound with IC50 values of 1.77 µM and 2.06 µM in DPPH and ABTS assays respectively. In the in vitro enzyme inhibition assays, synthesized derivative 23 emerged as a potent multitarget inhibitor of hMAO-B, eeAChE. COX-2 and 5-LOX with IC50 values of 0.037 µM, 0.071 µM, 14.3 µM and 0.59 µM, respectively. Moreover, selected compounds 23, 25, 26 and 28 displayed good to moderate inhibition of self-mediated amyloid ß1-42 peptide aggregation. More importantly, compounds 23, 25, 28 and 29 showed no neurotoxicity on SH-SY5Y cells and also showed excellent neuroprotective effects against H2O2-induced SH-SY5Y cells. In the in vivo experiment, antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were studied in the brain of male BALB/c mice at the dose of 5 mg kg-1. All the tested compounds, except 29, have shown good to in vivo antioxidant potential. Docking studies on 3D crystallographic structures of AChE and MAO-B showed significant interactions with catalytic amino acid residues. In conclusion, the current study showed that FA/GA derivatives could be further exploited for their multitarget role in oxidative stress-related AD therapies.

Rivaroxaban Failure Presenting With Renal Infarction in a Patient With Persistent Atrial Fibrillation: A Case Report.

Direct oral anticoagulants (DOAC) are the preferred choice of anticoagulation for patients with atrial fibrillation. DOACs are always preferred over vitamin K antagonists due to their better safety profile in terms of life-threatening bleeding and decreased need for INR (international normalised ratio) monitoring. Although the most commonly used anticoagulation, failure to DOAC has been reported. Here we present a rare case of rivaroxaban failure presenting with left renal infarction in a patient who had dense spontaneous echocardiographic contrast in the left atrium visualised by transthoracic echocardiography.

Long non-coding RNAs: a summary of their roles in placenta development and pathology†.

Long non-coding RNAs are cellular transcripts that have ˃200 nucleotides in length and do not code for proteins. Due to their low expression levels, long non-coding RNAs were previously considered as mere transcriptional noise. However, current evidence indicates that they regulate a myriad of biological processes such as cell proliferation, invasion, and apoptosis. Hence, their expression patterns are crucial indicators of the physiological or pathological states of cells, tissues, and organs. The utilization of long non-coding RNAs as biomarkers and therapeutic targets for the clinical management of several diseases have been suggested. Gradually, long non-coding RNAs are gaining a substantial attention in the field of feto-maternal medicine. After embryo implantation, the interactions between the trophoblast cells from the embryo and the uterus of the mother facilitate placenta development and pregnancy progression. These processes are tightly regulated, and their impairments result in pregnancy pathologies such as miscarriage and preeclampsia. Accumulating evidence implicates long non-coding RNAs in these processes. Herein, we have summarized the roles of several long non-coding RNAs in human placenta development, have proposed some mechanisms by which they participate in physiological and pathological placentation, have revealed some knowledge deficits, and have recommended ideal experimental approaches that will facilitate the clarification of the mechanistic actions of each long non-coding RNA at the feto-maternal interface during healthy and pathological pregnancies.

Secondary traumatic stress and death anxiety in healthcare professionals: Moderating role of social support.

Background & Objective: It's hard to deny the buffering impact of social support as it provides much-needed assistance to counter untoward circumstances that individuals face in their daily life. By focusing on the moderating role of social support, the present investigation studied the relationship between secondary traumatic stress and death anxiety that healthcare professionals encounter in their regular work life. Method: Through a cross-sectional correlational design, 200 participants were included from various hospitals in Lahore (from June-August, 2022) by employing a non-probability purposive sampling technique. They provided basic sociodemographic information along with their responses on self-reported questionnaires for the current investigation. Results: Results were analyzed through SPSS 21 which indicated that secondary traumatic stress had a positive association with death anxiety, unlike social support which had a negative relationship with death anxiety. Findings also revealed social support as a significant moderator for secondary traumatic stress and death anxiety. Conclusions: It can be concluded that increased social support could benefit healthcare professionals as it weakened the association between secondary traumatic stress and death anxiety. Other than academia and research, these findings have implications across a variety of professional settings including physical and mental healthcare professionals who can benefit from these indigenous findings.

Comparative analysis of multiorgan toxicity induced by long term use of disease modifying anti-rheumatic drugs.

The constant use of disease modifying anti rheumatic drugs affects the functioning of multiple organs inside the body. Some drugs are more toxic than others. The present case control investigation was designed to evaluate the comparative toxicity of methotrexate and leflunomide on multiple organs in rheumatoid arthritis patients. For this purpose, 100 subjects with confirmed rheumatoid arthritis condition were recruited form tertiary care center. Whereas 50 age matched controls were recruited from the local healthy population. Participants of the study were categorized into three groups with equal numbers of subjects in each group (n = 50). Group 1 comprised rheumatoid arthritis patients on methotrexate treatment, group 2 included rheumatoid arthritis patients on leflunomide treatment and group 3 were healthy subjects. Cardiac and respiratory response was evaluated by monitoring blood pressure, pulse and breathing rate and spot oxygen saturation. Stress on liver was estimated by measuring change in liver enzymes (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and total bilirubin. While, degree of renal impairment was assessed by calculating glomerular filtration rate, serum creatinine, urinary urea and uric acid. For statistical interpretation, data was subjected to independent student "t" test and analysis of variance (one way ANOVA) for mean variations. Both methotrexate and leflunomide elevated the systolic and diastolic blood pressure and pulse rate. Leflunomide maintained the oxygen saturation at 96.7%, whereas methotrexate exerted serious effect on spot oxygen saturation by reducing it significantly to 93.25% than healthy subjects. Hepatotoxicity manifested by sustained use of leflunomide was perceptible in this study group. Whereas, both methotrexate and leflunomide influenced renal function as indicated by marked increase in blood urea nitrogen (P = 0.001), serum creatinine (P = 0.007) and reduced glomerular filtration rate (P<0.0001). However, use of methotrexate demonstrated significant (P<0.0001) reduction in serum uric acid and urinary urea levels. Methotrexate is more injurious to heart, blood vessels and kidneys than leflunomide but it is less noxious to hepatic parenchyma. Contrarily, leflunomide usage is comparatively better option for respiratory, cardiovascular, and renal health but dangerous to liver. Thus, a single drug can't be prescribed for the treatment of rheumatoid arthritis for longer management of arthritis patients.

An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities.

Objective: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. Methods: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. Results: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1ß and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. Conclusion: Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Efficacy of Pemafibrate Versus Fenofibrate Administration on Serum Lipid Levels in Patients with Dyslipidemia: Network Meta-Analysis and Systematic Review.

BACKGROUND: Pemafibrate is a novel fibrate class drug that is a highly potent and selective agonist of peroxisome proliferator-activated receptor α (PPARα). We performed the first ever network meta-analysis containing the largest ever group of patients to test the efficacy of pemafibrate in improving lipid levels compared with fenofibrate and placebo in patients with dyslipidemia. METHODS: Potentially relevant clinical trials were identified in Medline, PubMed, Embase, clinicaltrials.gov, and Cochrane Controlled Trials registry. Nine randomized controlled trials met the inclusion criteria out of 40 potentially available articles. The primary effect outcome was a change in the levels of triglycerides (TG), high-density lipoproteins (HDL), or low-density lipoproteins (LDL) before and after the treatment. RESULTS: A total of 12,359 subjects were included. The mean patient age was 54.73 (years), the mean ratio for female patients was 18.75%, and the mean examination period was 14.22 weeks. The dose for pemafibrate included in our study was 0.1, 0.2, or 0.4 mg twice daily, whereas the dose for fenofibrate was 100 mg/day. Data showed a significant reduction in TG and a mild increase in HDL levels across the pemafibrate group at different doses and fenofibrate 100 mg group (with greatest effect observed with pemafibrate 0.1 mg twice daily). A mild increase in LDL was also observed in all groups, but the increase in LDL in the 0.1 mg twice daily dose group was statistically insignificant. CONCLUSION: Pemafibrate 0.1 mg twice daily dose led to highest reduction in TG levels and the highest increase in HDL levels compared with other doses of pemafibrate, fenofibrate, and placebo.

The conformation of glutenin polymers in wheat grain: some genetic and environmental factors associated with this important characteristic.

In a previous study we used asymmetric-flow field-flow fractionation to determine the polymer mass (Mw), gyration radius (Rw) and the polydispersity index of glutenin polymers (GPs) in wheat (Triticum aestivum). Here, using the same multi-location trials (4 years, 11 locations, and 192 cultivars), we report the factors that are associated with the conformation (Conf) of the polymers, which is the slope of Log(Rw) versus a function of Log(Mw). We found that Conf varied between 0.285 and 0.740, it had low broad-sense heritability (H2=16.8), and it was significantly influenced by the temperature occurring over the last month of grain filling. Higher temperatures were found to increase Rw and the compactness and sphericity of GPs. Alleles for both high- and low-molecular-weight glutenin subunits had a significant influence on the Conf value. Assuming a Gaussian distribution for Mw, the number of polymers present in wheat grains was computed for different kernel weights and protein concentrations, and it was found to exceed 1012 GPs per grain. Using atomic force microscopy and cryo-TEM, images of GPs were obtained for the first time. Under higher average temperature, GPs became larger and more spherical and consequently less prone to rapid hydrolysis. We propose some orientations that could be aimed at potentially reducing the impact of numerous GPs on people suffering from non-celiac gluten sensitivity.

Evaluation of pharmaceutically compounded oral caffeine on the impact of medication adherence and risk of readmission among preterm neonates: A single-center quasi-experimental study.

BACKGROUND: Caffeine is available in an ampoule, used via parenteral and enteral routes in preterm neonates to treat apnea of prematurity (AOP) in neonates of gestational age ≥ 35-40 weeks. A longer duration of therapy has a higher risk of medication non-adherence due to higher costs and inappropriate dosage forms. Pharmaceutically compounded oral caffeine (PCC) could be an appropriate alternate dosage form. The researchers aimed to determine the impact of PCC on medication-related factors influencing medication adherence (MA) and the frequency of hospital readmission with apnea (HRA) in preterm neonates. METHODS: We conducted a single-center quasi-experimental study for this quality improvement project using PCC among the preterm neonates admitted in a tertiary care level-III NICU at the Aga Khan University Hospital Karachi, Pakistan, received caffeine therapy, and survived at discharge. The researchers compared pre-PCC data (April-December 2017) with post-PCC data (April-Dec 2018) each for nine months, with three months intervals (January-March 2018) of PCC formulation and implementation phase. The study was conducted according to the SQUIRE2.0 guidelines. The Data were collated on factors influencing MA, including the cost of therapy, medication refill rates, and parental complaints as primary outcome measures. The Risk factors of HRA were included as secondary outcomes. RESULTS: After PCC implementation cost of therapy was reduced significantly from Rs. 97000.0 (729.0 USD) to Rs. 24500.0 (185.0 USD) (p<0.001), significantly higher (p<0.001) number of patients completed remaining refills (77.6% pre-phase vs 97.5% post-phase). The number of parental complaints about cost, ampoule usage, medication drawing issue, wastage, inappropriate dosage form, and longer duration of therapy reduced significantly in post-phase. HRA reduced from 25% to 6.6% (p<0.001). Post-implementation of PCC (RR 0.14; 95% CI: 0.07-0.27) was a significant independent risk factor for reducing HRA using a multivariate analysis model. Longer duration of caffeine therapy after discharge (RR 1.05; 95% CI: 1.04-1.04), those who were born in multiple births (RR 1.15; 95% CI: 1.15-1.15), and those who had higher number of siblings were other significant independent risk factors for HRA. CONCLUSIONS: PCC dispensation in the appropriate dosage form at discharge effectively reduced cost, non-adherence to therapy, and risk of hospital readmissions. This neonatal clinical and compounding pharmacist-led model can be replicated in other resource-limiting setting.

Exploring the effect of Jasmonic Acid for Aphids control for improving the yield of Triticum aestivum varieties.

Many biotic and abiotic factors influence the production of wheat (Triticum aestivum L.). Among biological agents, aphids are destructive pests effecting wheat yield drastically. This study was designed to evaluate the impact of foliar Jasmonic acid spray on aphid population as well as on plant growth during aphid infestation in two wheat varieties i.e., Borlaug-2015 and Zincol-2015. Plants are cultivated in pots and treated with jasmonic acid at concentrations of 0.1 and 1 mM (JA). The results revealed that length of shoot and roots decreased after aphid stress and was improved (21-24%) by JA spray. Photosynthetic pigments increased after applying the jasmonic acid spray compared to control plants. Jasmonic acid spray helped the plants to recover from aphid stress by enhanced production of antioxidant enzymes CAT (Catalase) (65-71%), SOD (Superoxide dismutase) (71-74%) and POD (Peroxidase) (61-65%). Consequent to improved defence system, plants treated with JA had fewer aphids as compared to control (60-73% reduction), 24 h after spray. The higher concentration of JA (1 mM) proved more effective as compared to 0.1 mM jasmonic acid. Moreover, Zincol-2015 appeared tolerant as compared to Borlaug-2015 against aphid infestation. The application of jasmonic acid as an exogenous foliar application showed an overall positive impact on the physiological and biochemical attributes of both varieties. It helps the plants to enhance resistance against the biotic stress and can be adopted as future alternative for aphid management. However, detailed studies regarding understanding of underlying molecular mechanisms are needed to optimize the mode for field application.

Estimating genetic variability among diverse lentil collections through novel multivariate techniques.

Lentil is an important food legume throughout the world and Pakistan stands at 18th position with 8,610 tons production from 17,457 hectares. It is rich in protein, carbohydrates, fat, fiber, and minerals that can potentially meet food security and malnutrition issues, particularly in South Asia. Two hundred and twenty lentil genotypes representing Pakistan (178), Syria (14), and the USA (22) including 6 from unknown origins were studied for yield, yield contributing traits, and cooking time (CT). Genotype 6122 (Pakistan) performed the best during both years with seed yield per plant (SY) 68±1.7 g, biological yield per plant (BY) 264±2.8 g, pod size (PS) 0.61±0.01 cm, number of seeds per pod (NSP) 2, cooking time (CT) 11 minutes, with no hard seed (HS). The genotypes 6122 (Pakistan) and 6042 (Syria) produced the highest BY, hence these have the potential to be an efficient source of fodder, particularly during extreme winter months. The genotypes 5698 (Pakistan) and 6015 (USA) were late in maturity during 2018-19 while 24783 and 5561 matured early in 2019. A minimum CT of 10 minutes was taken by the genotypes 6074 and 5745 of Pakistani origin. The lowest CT saves energy, time, and resources, keeps flavor, texture, and improves protein digestibility, hence the genotypes with minimum CT are recommended for developing better lentil cultivars. Pearson correlation matrix revealed significant association among several traits, especially SY with BY, PS, and NSP which suggests their use for the future crop improvement program. The PCA revealed a considerable reduction in components for the selection of suitable genotypes with desired traits that could be utilized for future lentil breeding. Structural Equational Model (SEM) for SY based on covariance studies indicated the perfect relationship among variables. Further, hierarchical cluster analysis establishes four clusters for 2017-18, whereas seven clusters for 2018-19. Cluster 4 of 2017-18 and cluster 5 of 2018-19 exhibited the genotypes with the best performance for most of the traits (SY, BY, PS, NSP, CT, and HS). Based on heritability; HSW, SY, BY, NSP were highly heritable, hence these traits are expected for selecting genotypes with genes of interest and for future lentil cultivars. In conclusion, 10 genotypes (5664, 5687, 6084, 6062, 6122, 6058, 6087, 5689, 6042 and 6074) have been suggested to evaluate under multi-location environments for selection of the best one/s or could be utilized in hybridization in future lentil breeding programs.

Alleviation of temperature stress in maize by integration of foliar applied growth promoting substances and sowing dates.

Temperature is a key factor influencing plant growth and productivity, but its sudden rise can cause severe consequences on crop performances. Early sowing and application of growth promoting agents as a foliar spray can be a sustainable approach to cope with high temperature stress at grain filling stage of cereal crops. Therefore, a test was designed to explore the potential of different growth helping agents including sorghum water extract (SWE, 10 ml L-1), moringa leaf extract (MLE, 3%), hydrogen peroxide (H2O2, 2 µM), salicylic acid (SA, 50 mg L-1) and ascorbic acid (ASA, 50 mg L-1) as foliar agents at different sowing dates (early and optimum) to cope with temperature stress in maize. The results stated that foliar application of growth promoting substances successfully persuaded high temperature tolerance at reproductive phase of maize in early and optimum sowings when compared to control. However, SWE + ASA, MLE + H2O2 and SWE + ASA + SA + H2O2 were the best combinations for improving growth, development, and physiological variables under both sowing dates even under suboptimal temperature. All foliar applications significantly increased maize grain and biological yields while maximum was observed in SWE + ASA followed by SWE + ASA + SA + H2O2 or MLE + H2O2 that were statistically at par with ASA + SA + H2O2 but plants without spray or distilled water application did not improve grain and biological yields. Overall, the foliar applications of growth promoting substances enable the plant to enhance its growth, development, morphology, yield and biochemical variables.

Transcriptome analysis provides new insights into plants responses under phosphate starvation in association with chilling stress.

BACKGROUND: Chilling temperature reduces the rate of photosynthesis in plants, which is more pronounced in association with phosphate (Pi) starvation. Previous studies showed that Pi resupply improves recovery of the rate of photosynthesis in plants much better under combination of dual stresses than in non-chilled samples. However, the underlying mechanism remains poorly understood. RESULTS: In this study, RNA-seq analysis showed the expression level of 41 photosynthetic genes in plant roots increased under phosphate starvation associated with 4 °C (-P 4 °C) compared to -P 23 °C. Moreover, iron uptake increased significantly in the stem cell niche (SCN) of wild type (WT) roots in -P 4 °C. In contrast, lower iron concentrations were found in SCN of aluminum activated malate transporter 1 (almt1) and its transcription factor, sensitive to protein rhizotoxicity 1 (stop1) mutants under -P 4 °C. The Fe content examined by ICP-MS analysis in -P 4 °C treated almt1 was 98.5 ng/µg, which was only 17% of that of seedlings grown under -P 23 °C. Average plastid number in almt1 root cells under -P 4 °C was less than -P 23 °C. Furthermore, stop1 and almt1 single mutants both exhibited increased primary root elongation than WT under combined stresses. In addition, dark treatment blocked the root elongation phenotype of stop1 and almt1. CONCLUSIONS: Induction of photosynthetic gene expression and increased iron accumulation in roots is required for plant adjustment to chilling in association with phosphate starvation.

Plant phosphate nutrition: sensing the stress.

Phosphorus (P) is obtained by plants as phosphate (Pi) from the soil and low Pi levels affects plant growth and development. Adaptation to low Pi condition entails sensing internal and external Pi levels and translating those signals to molecular and morphophysiological changes in the plant. In this review, we present findings related to local and systemin Pi sensing with focus the molecular mechanisms behind root system architectural changes and the impact of hormones and epigenetic mechanisms affecting those changes. We also present some of the recent advances in the Pi sensing and signaling mechanisms focusing on inositol pyrophosphate InsP8 and its interaction with SPX domain proteins to regulate the activity of the central regulator of the Pi starvation response, PHR.

River Tea Tree Oil: Composition, Antimicrobial and Antioxidant Activities, and Potential Applications in Agriculture.

Melaleuca is one of the genera of the Myrtaceae family enriched in tea tree oil (TTO). Tea tree oils of Melaleuca bracteata and Melaleuca alternifolia are of prime importance and have antioxidant and antimicrobial properties. Terpinen-4-ol and 1-8 cineole are major constituents of M. alternifolia oil. The percentages of the compounds in the oils can slightly vary according to the region of plant harvest, the distillation technique, or the part of the plant used for oil extraction. TTO has a bactericidal effect against various bacterial species such as Bacillus cereus, B. subtilis, E. coli, Pseudomonas putida, and S. aureus. Several reports proved that this essential oil is also effective against fungal strains of Fusarium, Aspergillus, and Candida species. It also has antioxidant properties such as radical scavenging activity and reducing power. The antioxidant properties of TTO at a concentration of 30 mM were observed to be greater than those of butylated hydroxytoluene (BHT), commonly used as a synthetic antioxidant. TTO is also an effective organic fungicide, herbicide, and insecticide for use in the agriculture sector. Postharvest application of the oil has been found efficient on sweet basil, citrus, and strawberry. It is concluded that tea tree oil has the potential to be used in the food, agriculture, and pharmaceutical industries as a natural antimicrobial and preservative agent. This review provides comprehensive information regarding the antioxidant and antimicrobial activities of tea tree oil and its potential applications in agriculture.

Applications of nanotechnology in virus detection, tracking, and infection mechanisms.

Viruses are among the most infectious pathogens, responsible for the highest death toll around the world. Lack of effective clinical drug for most of the viruses emphasizes the rapid and accurate diagnosis at early stages of infection to prevent rapid spread of the pathogens. Nanotechnology is an emerging field with applications in various domains, where nano-biomedical science has many significant contributions such as effective delivery of drugs/therapeutic molecules to specific organs, imaging, sensitive detection of virus, and their accurate tracking in host cells. The nanomaterials reported for virus detection and tracking mainly include magnetic and gold NPs, ZnO/Pt-Pd, graphene, and quantum dots (QDs). In addition, the single virus tracking technology (SVT) allowed to track the life cycle stages of an individual virus for better understanding of their dynamics within the living cells. Inorganic as well as non-metallic fluorescent materials share the advantages of high photochemical stability, a wide range of light absorption curves and polychromatic emission. Hence, are considered as potential fluorescent nano-probes for SVT. However, there are still some challenges: (i) clinical false positive rate of some detection methods is still high; (ii) in the virus tracking process, less adaptability of QDs owing to larger size, flicker, and possible interference with virus function; and (iii) in vivo tracking of a single virus, in real time needs further refinement. In the future, smaller, non-toxic, and chemically stable nanomaterials are needed to improve the efficiency and accuracy of detection, and monitoring of virus infections to curb the mortalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

Salinity Effects on Guard Cell Proteome in Chenopodium quinoa.

Epidermal fragments enriched in guard cells (GCs) were isolated from the halophyte quinoa (Chenopodium quinoa Wild.) species, and the response at the proteome level was studied after salinity treatment of 300 mM NaCl for 3 weeks. In total, 2147 proteins were identified, of which 36% were differentially expressed in response to salinity stress in GCs. Up and downregulated proteins included signaling molecules, enzyme modulators, transcription factors and oxidoreductases. The most abundant proteins induced by salt treatment were desiccation-responsive protein 29B (50-fold), osmotin-like protein OSML13 (13-fold), polycystin-1, lipoxygenase, alpha-toxin, and triacylglycerol lipase (PLAT) domain-containing protein 3-like (eight-fold), and dehydrin early responsive to dehydration (ERD14) (eight-fold). Ten proteins related to the gene ontology term "response to ABA" were upregulated in quinoa GC; this included aspartic protease, phospholipase D and plastid-lipid-associated protein. Additionally, seven proteins in the sucrose-starch pathway were upregulated in the GC in response to salinity stress, and accumulation of tryptophan synthase and L-methionine synthase (enzymes involved in the amino acid biosynthesis) was observed. Exogenous application of sucrose and tryptophan, L-methionine resulted in reduction in stomatal aperture and conductance, which could be advantageous for plants under salt stress. Eight aspartic proteinase proteins were highly upregulated in GCs of quinoa, and exogenous application of pepstatin A (an inhibitor of aspartic proteinase) was accompanied by higher oxidative stress and extremely low stomatal aperture and conductance, suggesting a possible role of aspartic proteinase in mitigating oxidative stress induced by saline conditions.

Network Pharmacology Combined with Transcriptional Analysis to Unveil the Biological Basis of Astaxanthin in Reducing the Oxidative Stress Induced by Diabetes Mellitus.

PURPOSE: Astaxanthin (Ast) has been reported to reduce oxidative stress induced by diabetes mellitus (DM). The aim of this research was to give a systematic overview of the biological basis for this process. METHODS: Ast-targeted proteins were collected from the BATMAN database, Comparative Toxicogenomics Database, and STITCH database. Putative DM-related protein targets were collected from the GeneCards database. A DM-rat model was then built with streptozotocin (STZ) combined with a high-sugar, high-fat diet for 30 days. Total cholesterol (TC), triglycerides (TGs), and insulin levels were examined using whole tail-vein blood from overnight-fasted rats. SOD, GSH, and MDA activy was detected in liver tissue (p<0.05). In addition, we used RNA-sequencing analysis to detect gene-transcription level in liver tissue of rats and GO biological process analysis to show all the log2FC≥2 genes in the Ast-fed DM rats compared with the DM group using the STRING database. Ast-intersecting targets were collected with Venn analysis. Docking analysis between Ast and targeted proteins was down with the SwissDock server. Ast targets-pathway networks were built using Cytoscape 3.7.2 software. RESULTS: A total of 120 Ast-targeted proteins and 13,784 DM-related targets were collected. Ast functioned in reducing TC, TG, and MDA levels, promoting SOD activity and GSH expression, and alleviating islet-cell injury in Ast-fed DM rats compared with DM control rats. Furthermore, genes involved in MAPK, TNF, AMPK, and FOXO signaling pathways were differently expressed in Ast-treated DM rats compared with DM rats. The differentially expressed genes were enriched in euchromatin, thyroid cancer, and metaphase-plate congression. Three Ast-intersecting targets - Col5A1, Nqo1, and Notch2 - were then identified. We found possible binding patterns of Ast with Nqo1 and Notch2, respectively. Ast targets-pathway networks were finally built to show a systematic overview of how Ast works in multiple pathways to reduce oxidative stress. Taken together, Ast is predicted to target Col5A1, Nqo1, and Notch2 to form a network of systemic pharmacological effects to: 1) promote insulin-releasing balance and relieve insulin resistance, 2) reduce testicular cell apoptosis, and 3) maintain normal size in marginal-zone B cells and inhibit autoimmune DM, all of which contribute to the balance of lipid metabolism and reduction of oxidative stress in DM patients. CONCLUSION: Ast functions in reducing oxidative stress in DM rats by regulating a variety of targets to form a comprehensive antioxidative network.