Search

Salinity is a brutal threat to sustainability of crop production and exhibits injurious effect on major plant processes including protein synthesis, cell division and photosynthetic activity. Germination and early growth of plants are most susceptible to salinity effect in comparison to other growth stages. In this context, the seed emergence and early vegetative growth of flowers needs to be tested properly. The pot based study was conducted in Completely Randomized Design (CRD) with three replicates at Sindh Agriculture University Tandojam. The goal of this investigation was to explore the performance of petunia plants to salt stress environment at early growth stage. Two petunia varieties (V1= Prism blue, V2= Hala lop petunia rose) were evaluated against six levels of salt stress (T1 = Canal irrigation water [Control], T2 = 3 dS m-1, T3 = 5 dS m-1, T4 = 7 dS m-1, T5 = 9 dS m-1, T6 = 11 dS m-1).The results showed that there was an inverse effect of salt stress on all the traits examined and with each increased level of salinity in irrigation water; the values of petunia plant traits were significantly decreased. The petunia grown in pots given only canal water (control) revealed better performance for germination and growth attributes. It was further noted that that salt stress up to 3 dS m-1 level was generally tolerated by petunia. Among petunia varieties, Hala lop petunia rose performance was better and showed relative tolerance to salt stress over Prism blue, but in most cases the differences were insignificant (P>0.05).

The seed of 6 parental cultivars along with 15 F2 Hybrids of hexaploid wheat was planted in randomized complete block design with three replications 6 x 6 half diallel during 2016-2017 sat Southern Wheat Research Station, ARI, Tandojam, Sindh, Pakistan. Mean squares due to General Combining Ability (GCA) and Specific Combining Ability (SCA) variances were highly significant and significant for all morphological traits. It was noticed that additive, as well as nonadditive genes, were there for GCA and SCA. SCA variances were observed greater than those of GCA variances for five traits (PH, TPP, SL, SPS, GYPP) displaying the predominance of nonadditive genes, for some of the characters, nonetheless, GCA variances were more for the rest of the characters (GPS, TGW). Parental cultivars such as Khirman displayed maximum positive and desirable GCA effects for spike length and grains spike-1, Hamal for tillers plant-1 and spikelets spike-1 and Benazir and NIA-Sarang for grain yield plant-1 and seed index. On the other hand, Hamal and NIA-Sarang equally distributed negative, but desirable GCA effects for plant height. The SCA estimates revealed that Sindhu x Hamal manifested maximum positive estimates for spike length and grain yield plant-1, whereas Benazir x Sindhu was found as the best specific combiner for spikelets spike-1 and seed index, Benazir x Khirman and Benazir x NIA-Sarang for tillers plant-1 and grains spike-1. These F2 hybrids may be the best choice as a breeding material for hybrid crop development to improve yield characters. Therefore, it may be possible to take advantage of better general and specific combiners to further selection for the development of a hybrid variety of wheat which can assist to enhance the total production in Pakistan.

The present study aimed to determine the quality parameters of underground drinking water found in Diplo, a sub-district of Tharparkar. The quality parameters examined in the water samples were pH (acidity), total dissolved solids (TDS), and electrical conductivity (EC). A total of 20 samples were randomly collected from different sources of drinking water, namely dug well and hand pump, from the study area. The results showed that the quality parameters of water samples taken from the hand pump were not within the appropriate range (pH range was 5.7-6.0 and TDS range was 1579-2120 mg/L), while those of well water samples were within range (pH range was 5.09-6.60 and TDS range was 497-1182 mg/L). Therefore, it was concluded that water from the well sources was safe for consumption as per the guidelines set by WHO and EPA and could be used for drinking purposes. The findings revealed that water from the hand pump sources had high TDS and EC (greater than WHO limit), which pose several health risks. It was noted that TDS is directly proportional to electrical conductivity and inversely proportional to the pH level of water. Further, it was recommended that future studies need to be conducted at regular intervals to evaluate the quality of drinking water in rural areas of Sindh province, so that authorities can promptly provide solutions to such issues. Copyright (c) The Authors

Drought is a disaster around the world accumulating salt and ero-sion in lands. Presently, a research was conducted to determine the morpho-physiological response in bread wheat under normal and stress irrigations. This experiment was conducted at the experimental field of Sindh Agriculture University, Tandojam, Hy-derabad, Pakistan, for two consecutive years during the Rabi season of the year 2011-12 and 2012-13. Stress was imposed by withhold-ing irrigations at three different growth stages of the plant, i.e. T1: normal irrigations applied, T2: stress at tillering stage, and T3: stress at the booting stage. The progenies Sarsabz x Khirman and Sarsabz x TD-1 contributed the highest heritability% (81.0% and 85.5%) for osmotic potential (-MPa) at stress at booting stage. For grain yield spike-1(g), the progeny Kiran-95 x Khirman showed maximum her-itability as 84.37 in T3. However, the progeny TD-1 x Imdad proved to be the best combiner progeny indicating highest heritability per-centage (91.0%) among the progenies for grain yield at booting stress.

The present study aimed to determine the quality parameters of underground drinking water found in Diplo, a sub-district of Tharparkar. The quality parameters examined in the water samples were pH (acidity), total dissolved solids (TDS), and electrical conductivity (EC). A total of 20 samples were randomly collected from different sources of drinking water, namely dug well and hand pump, from the study area. The results showed that the quality parameters of water samples taken from the hand pump were not within the appropriate range (pH range was 5.7-6.0 and TDS range was 1579-2120 mg/L), while those of well water samples were within range (pH range was 5.09-6.60 and TDS range was 497-1182 mg/L). Therefore, it was concluded that water from the well sources was safe for consumption as per the guidelines set by WHO and EPA and could be used for drinking purposes. The findings revealed that water from the hand pump sources had high TDS and EC (greater than WHO limit), which pose several health risks. It was noted that TDS is directly proportional to electrical conductivity and inversely proportional to the pH level of water. Further, it was recommended that future studies need to be conducted at regular intervals to evaluate the quality of drinking water in rural areas of Sindh province, so that authorities can promptly provide solutions to such issues. Copyright (c) The Authors

Background Dengue virus (DENV) is an increasing global health threat and associated with induction of both a long-lived protective immune response and immune-suppression. So far, the potency of treatment of DENV via antiviral drugs is still under investigation. Recently, increasing evidences suggest the potential role of microRNAs (miRNAs) in regulating DENV. The present study focused on the function of miRNAs in innate insusceptible reactions and organization of various types of immune cells and inflammatory responses for DENV. Three drugs were tested including antiviral herbal medicine ReDuNing (RDN), Loratadine (LRD) and Acetaminophen. Results By the microarray expression of miRNAs in 165 Patients. Results showed that 89 active miRNAs interacted with 499 potential target genes, during antiviral treatment throughout the critical stage of DENV. Interestingly, reduction of the illness threats using RDN combined with LRD treatment showed better results than Acetaminophen alone. The inhibitions of DENV was confirmed by decrease concentrations of cytokines and interleukin parameters; like TNF-α, IFN-γ, TGF-β1, IL-4, IL-6, IL-12, and IL-17; after treatment and some coagulants factors increased. Conclusions This study showed a preliminary support to suggest that the herbal medicine RDN combined with LRD can reduce both susceptibility and the severity of DENV.

Drug target interactions (DTIs) are crucial in pharmacology and drug discovery. Presently, experimental determination of compound-protein interactions remains challenging because of funding investment and difficulties of purifying proteins. In this study, we proposed two in silico models based on support vector machine (SVM) and random forest (RF), using 1589 molecular descriptors and 1080 protein descriptors in 9948 ligand-protein pairs to predict DTIs that were quantified by Ki values. The cross-validation coefficient of determination of 0.6079 for SVM and 0.6267 for RF were obtained, respectively. In addition, the two-dimensional (2D) autocorrelation, topological charge indices and three-dimensional (3D)-MoRSE descriptors of compounds, the autocorrelation descriptors and the amphiphilic pseudo-amino acid composition of protein are found most important for Ki predictions. These models provide a new opportunity for the prediction of ligand-receptor interactions that will facilitate the target discovery and toxicity evaluation in drug development.

BackgroundAddition and subtraction theory (AST), a basic theory of herb combination in traditional Chinese medicine (TCM), is often used to add or subtract the "fundamental formulae" to generate more targeted prescriptions. This theory plays a core role in individualized medicine and compound compatibility of TCM. However, the mechanisms underlying AST have largely remained elusive. MethodsAn integrated platform of systems pharmacology was proposed for revealing how the oral administration, drug half-life, and target interactions affect the pharmacological functions of herbal medicines. This platform was further applied on two classical prescriptions, i.e., Xiao Chaihu decoction (XCHD) and Da Chaihu decoction (DCHD) to dissect the addition and subtraction theory (AST). ResultsWe uncovered the candidate compounds, key molecular targets and interaction network involved in XCHD and DCHD, and summarized its pharmacological characters and therapeutic indications. The results show that the "fundamental formula" is responsible for the major therapeutic effects, whereas the "additive herbs" synergistically enhance the treatment outcomes by targeting the same or complementary proteins between the foundational and additive herbs. ConclusionThis work has established a novel method to comprehensively understand the mechanism of AST, which would be beneficial for the TCM recipe optimization as well as the production of new herbal formula with desirable therapeutic effects. Candidate compounds, targets and interaction network involved in XCHD and DCHD."Fundamental formula" is mainly responsible for basic therapeutic effects."Additive herbs" exhibit reinforced function to the foundational formula.

Though cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs) are different diseases associated with different organs, they are highly correlated clinically. Importantly, in Traditional Chinese Medicine (TCM), similar treatment strategies have been applied in both diseases. However, the etiological mechanisms underlying them remain unclear. Here, an integrated systems pharmacology approach is presented for illustrating the molecular correlations between CVDs and GIDs. Firstly, we identified pairs of genes that are associated with CVDs and GIDs and found that these genes are functionally related. Then, the association between 115 heart meridian (HM) herbs and 163 stomach meridian (SM) herbs and their combination application in Chinese patent medicine was investigated, implying that both CVDs and GIDs can be treated by the same strategy. Exemplified by a classical formula Sanhe Decoration (SHD) treating chronic gastritis, we applied systems-based analysis to introduce a drug-target-pathway-organ network that clarifies mechanisms of different diseases being treated by the same strategy. The results indicate that SHD regulated several pathological processes involved in both CVDs and GIDs. We experimentally confirmed the predictions implied by the effect of SHD for myocardial ischemia. The systems pharmacology suggests a novel integrated strategy for rational drug development for complex associated diseases.

Designing maximally selective ligands that act on individual drug targets with high binding affinity has been the central dogma of drug discovery and development for the past two decades. However, many low-affinity drugs that aim for several targets at the same time are found more effective than the high-affinity binders when faced with complex disease conditions, such as cancers, Alzheimer's disease and cardiovascular diseases. The aim of this study was to appreciate the importance and reveal the features of weak-binding drugs and propose an integrated strategy for discovering them. Weak-binding drugs can be characterized by their high dissociation rates and transient interactions with their targets. In addition, network topologies and dynamics parameters involved in the targets of weak-binding drugs also influence the effects of the drugs. Here, we first performed a dynamics analysis for 33 elementary subgraphs to determine the desirable topology and dynamics parameters among targets. Then, by applying the elementary subgraphs to the mitogen-activated protein kinase (MAPK) pathway, several optimal target combinations were obtained. Combining drug-target interaction prediction with molecular dynamics simulation, we got two potential weak-binding drug candidates, luteolin and tanshinone IIA, acting on these targets. Further, the binding affinity of these two compounds to their targets and the anti-inflammatory effects of them were validated through in vitro experiments. In conclusion, weak-binding drugs have real opportunities for maximum efficiency and may show reduced adverse reactions, which can offer a bright and promising future for new drug discovery.

A system-level identification of drug-target direct interactions is vital to drug repositioning and discovery. However, the biological means on a large scale remains challenging and expensive even nowadays. The available computational models mainly focus on predicting indirect interactions or direct interactions on a small scale. To address these problems, in this work, a novel algorithm termed weighted ensemble similarity (WES) has been developed to identify drug direct targets based on a large-scale of 98,327 drug-target relationships. WES includes: (1) identifying the key ligand structural features that are highly-related to the pharmacological properties in a framework of ensemble; (2) determining a drug’s affiliation of a target by evaluation of the overall similarity (ensemble) rather than a single ligand judgment; and (3) integrating the standardized ensemble similarities (Z score) by Bayesian network and multi-variate kernel approach to make predictions. All these lead WES to predict drug direct targets with external and experimental test accuracies of 70% and 71%, respectively. This shows that the WES method provides a potential in silico model for drug repositioning and discovery.

The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at http://lsp.nwsuaf.edu.cn/CancerHSP.php.

As a rich natural resource for drug discovery, Traditional Chinese Medicine (TCM) plays an important role in complementary and alternative medical systems. TCM shows a daunting complexity of compounds featuring multi-components and multi-targets to cure diseases, which thus always makes it extremely difficult to systematically explain the molecular mechanisms adequately using routine methods. In the present work, to reveal the systematic mechanism of herbal formulae, we developed a pathway-based strategy by combining the pathways integrating, target selection, reverse drug targeting and network analysis together, and then exemplified it by Reduning injection (RDN), a clinically widely used herbal medicine injection, in combating inflammation. The anti-inflammatory effects exerted by the major ingredients of RDN at signaling pathways level were systematically investigated. More importantly, our predicted results were also experimentally validated. Our strategy provides a deep understanding of the pharmacological functions of herbal formulae from molecular to systematic level, which may lead to more successful applications of systems pharmacology for drug discovery and development.