A series of indole-derived γ-hydroxy propiolate esters as potent anti-inflammatory agents: Design, synthesis, in-vitro and in-vivo biological studies.

A variety of novel indole-derived γ-hydroxy propiolate esters were designed, synthesized, and evaluated for their anti-inflammatory activity in-vitro and in-vivo. According to the nitric oxide (NO) inhibitory analysis, all compounds showed potent NO inhibitory ability in a dose-dependent manner, with no apparent cytotoxicity. The model compound, L-37, also exhibited significant potency in PGE2 inhibition. In addition, compounds L-37 and L-39 can downregulate the expression of COX-2 enzyme at 5 µM via ELISA experiment. Compound L-37 (1 µM) also inhibited the PGF1 production as well as the expression of COX-1, but displayed weak inhibition activity towards the Leukotrienes (LT) and Thromboxane-B2 (TXB-2) production. However, the expression of 5-LOX was significantly inhibited by compound L-39 at 5 µM. Xylene-induced ear edema model was explored for in-vivo anti-inflammatory evaluation, compound L-37 showed similar inhibitory activity compared with celecoxib, approximately 80% at 50 mg/kg dosage. Every outcome showed that the newly synthesized compounds can effectively inhibit inflammation.

A DUF966 gene family member OsDSR3 positively regulates alkali stress tolerance in rice.

Rice growth and production are severely constrained by alkali stress. However, the mechanism underlying the rice tolerance to alkali stress is unclear. OsDSR3, a novel gene from the domains of unknown function 966 (DUF966) family, was identified and characterized for its function in the response of rice to alkali stress. The result of this study clearly showed that alkali stress significantly induced OsDSR3 expression level. Moreover, the expression of OsDSR3 was up-regulated by drought, salt, cold, H2O2 and abscisic acid (ABA), and down-regulated by gibberellic acid (GA3), and 2,4-Dichlorophenoxyacetic acid (2,4-D) treatments. Subcellular localization exhibited that OsDSR3 was detected in the nucleus and membrane. OsDSR3-overexpressing (OsDSR3-OE) plants showed higher tolerance to alkali stress than the wild-type (WT). In contrast, OsDSR3 knockout (OsDSR3-KO) mutants were more vulnerable to alkali stress. The differentially expressed genes (DEGs) among OsDSR3-OE and WT seedlings were mainly enriched in porphyrin and chlorophyll, starch and sucrose, and carotenoid metabolic pathways. Among these DEGs, 26 were identified as potential alkali stress-responsive genes, including several up-regulated genes like OsHAK5, OsGRX23 and OsNIR2. Consistent with the expression profiles of metabolic pathways-related genes, most of the metabolite contents and metabolite synthases activities were improved in OsDSR3-OE lines and decreased in OsDSR3-KO lines compared to WT. This may explain the higher tolerance of OE lines and lower tolerance of KO lines to alkali stress. These findings suggested that OsDSR3 positively regulates rice tolerance to alkali stress, which will help to elucidate the molecular mechanism underlying rice alkali tolerance.

Chemical Characterization Analysis, Antioxidants, and Anti-Diabetic Activity of Two Novel Acidic Water-Soluble Polysaccharides Isolated from Baobab Fruits.

This study explores the isolation and characterization of two acidic polysaccharides from baobab (Adansonia digitata) fruits, named ADPs40-F3 and ADPs60-F3; the two types of acidic polysaccharides exhibited high sugar content and chemical structural features characterized by O-H, C-H, carbonyl C=O, and COOH carboxyl functional groups. The two fractions showed molecular weights of 1.66 × 105 and 9.59 × 104 Da. ADPs40-F3 residues consist of arabinose (2.80%), galactose (0.91%), glucose (3.60%), xylose (34.70%), and galacturonic acid (58.10%). On the other hand, ADPs60-F3 is composed of rhamnose (1.50%), arabinose (5.50%), galactose (2.50%), glucose (3.10%), xylose (26.00%), and galacturonic acid (61.40%). Furthermore, NMR analysis showed that the main acidic structures of ADPs40-F3 and ADPs60-F3 are formed by 4,6)-α-d-GalpA-(1→, →4)-ß-d-Xylf-(1→, →4,6)-ß-d-Glcp-(1→, →5)-α-L-Araf-(1→, →4,6)-α-d-Galp-(1→ residues and 4)-α-d-GalpA-(1→, →4)-ß-d-Xylf-(1→, →6)-ß-d-Glcp-(1→, →5)-α-l-Araf-(1→ 4,6)-α-d-Galp-(4,6→, →2)-α-Rhap- residues, respectively, based on the observed signals. Antioxidant assays against DPPH, ABTS+, and FRAP revealed significant antioxidant activities for ADPs40-F3 and ADPs60-F3, comparable to ascorbic acid (VC). Additionally, both polysaccharides exhibited a dose-dependent inhibition of α-glucosidase and α-amylase activities, suggesting potential anti-diabetic properties. In vivo evaluation demonstrated that ADPs60-F3 significantly reduced blood glucose levels, indicating promising therapeutic effects. These findings underscore the potential utility of baobab fruit polysaccharides as natural antioxidants and anti-diabetic agents.

Domain of unknown function (DUF) proteins in plants: function and perspective.

Domains of unknown function (DUFs), which are deposited in the protein family database (Pfam), are protein domains with conserved amino acid sequences and uncharacterized functions. Proteins with the same DUF were classified as DUF families. Although DUF families are generally not essential for the survival of plants, they play roles in plant development and adaptation. Characterizing the functions of DUFs is important for deciphering biological puzzles. DUFs were generally studied through forward and reverse genetics. Some novelty approaches, especially the determination of crystal structures and interaction partners of the DUFs, should attract more attention. This review described the identification of DUF genes by genome-wide and transcriptome-wide analyses, summarized the function of DUF-containing proteins, and addressed the prospects for future studies in DUFs in plants.

Multiple-Criteria Decision-Making (MCDM) techniques to study the behavior of dendrimers using topological indices.

Topological indices provide a mathematical language for capturing molecular structure, symmetry, and predicting properties. Dendrimers are microscopic bilaterally symmetrical molecules with a well-defined homogeneous nanoparticles structure, often consisting of a symmetric center, inner shell, and outer shell. In this work, first we compute some degree-based topological indices of Porphyrin (DnPn),Poly (Propyl) Ether Imine(PETIM), Zinc porphyrin (DPZn), and Polyamidoamine (PAMAM) dendrimers. Then, we use multi-criteria decision making (MCDM) techniques to establish the weighted evaluation of dendrimer classes based on certain topological indices. For weighted analysis we correlate the properties of benzene derivatives with topological invariants. Finally, based on the multi-criteria decision making techniques namely TOPSIS, SAW and MOORA method, we have ranked the dendrimer structures based on their properties.

Anti-inflammatory efficacy and relevant SAR investigations of novel chiral pyrazolo isoquinoline derivatives: Design, synthesis, in-vitro, in-vivo, and computational studies targeting iNOS.

Isoquinoline alkaloids are a rich source of multimodal agents with distinctive structural specificity and various pharmacological activities. In the present report, we propose a combination of design, synthesis, computational study, primary in-vitro screening using the lipopolysaccharide (LPS)-induced RAW 264.7 cell line, and in-vivo evaluation in mice models as a novel approach to speed up anti-inflammatory drugs discovery. The nitric oxide (NO) inhibitory effect of new compounds revealed that all of them displayed the potent NO inhibitory ability in a dose-dependent manner with no obvious cytotoxicity. A series of the model compounds 7a, 7b, 7d, 7f, and 7g have been identified as the most promising, with IC50 values of 47.76 µM, 33.8 µM, 20.76 µM, 26.74 µM, and 47.8 µM respectively in LPS-induced RAW 264.7 cell line. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. Western blotting data of 7d identified that our synthesized compounds can down-regulate and suppress the expression of the key inflammatory enzyme, inducible nitric oxide synthase (iNOS). These results suggested that synthesized compounds may be potent anti-inflammatory agents, inhibiting the NO-release, in turn, iNOS inflammatory pathways. Furthermore, in-vivo anti-inflammatory detection via xylene-induced ear edema in mice revealed that these compounds could also inhibit swelling in mice, with model compound 7h showing an inhibition activity (64.4%) at a concentration of 10 mg/kg comparable to the reference drug celecoxib. Molecular docking results showed that shortlisted compounds (7b, 7c, 7d, 7e, and 7h) had a potential binding affinity for iNOS with low energies, with S-Score to be -7.57, -8.22, -7.35, -8.95, -9.94 kcal/mol, respectively. All results demonstrated that the newly synthesized chiral pyrazolo isoquinoline derivatives are highly potential anti-inflammatory agents.

The suppressed expression of a stress responsive gene 'OsDSR2' enhances rice tolerance in drought and salt stress.

Rice is a crucial staple food crop in many countries, yet, abiotic factors like salt and drought impact its growth. The Domain of Unknown Function 966 (DUF966) gene family may be crucial in how rice plants respond to abiotic stress. Our earlier research showed that overexpression of OsDSR2 (DUF966-stress repressive gene 2 in Oryza sativa) decreased resistance to salt and drought stress. To further understand how OsDSR2 negatively affects rice tolerance to salt and drought stress, transgenic rice plants with decreased OsDSR2 expression levels were created employing the RNAi technique. We investigated alterations in rice phenotype, physiology, and differentially expressed genes (DEGs) using a combination of physio-biochemical measurement and RNA-seq analysis. The results of the study demonstrated that rice seedling lines with OsDSR2 knockdown exhibited improved salt and drought stress tolerance. Statistical analysis revealed that the transgenic plants' survival rate (56-68%) was higher than the control plants (30%), in addition to a roughly 3 fold, 3.5 fold, 20% and 10.5% reduction in cell membrane permeability, malondialdehyde (MDA), superoxide anion radical (O2-) and hydrogen peroxide (H2O2) contents, respectively. However, the proline content and antioxidant enzymes (superoxide dismutase (SOD) and peroxidase (POD)) activities were considerably increased by about 5.5 fold, 3.5 fold, and 4.5 fold, respectively, at physiological levels. There were 115 up-regulated and 173 down-regulated DEGs in the leaves of the transgenic lines on the transcriptional regulation under the combined salt-drought stress. Among these, both up-regulation DEGs (e.g., OsHAK5, OsIAA25) and the down-regulation DEGs (e.g., OsbZIP23, OsERF48, OsAP2-39, etc.) may be related to the enhanced tolerance of the transgenic lines under combined salt-drought stress. This possibly depended on the involvement of abscisic acid (ABA) and indoleacetic acid (IAA) signaling pathways. These findings further confirmed that OsDSR2 negatively affected rice's ability to withstand salt and drought, suggesting that it could be a helpful gene for CRISPR-Cas9 technology-based genetic modification of rice's ability to withstand abiotic stress.

Melatonin Enhances Drought Tolerance in Rice Seedlings by Modulating Antioxidant Systems, Osmoregulation, and Corresponding Gene Expression.

Rice is the third largest food crop in the world, especially in Asia. Its production in various regions is affected to different degrees by drought stress. Melatonin (MT), a novel growth regulator, plays an essential role in enhancing stress resistance in crops. Nevertheless, the underlying mechanism by which melatonin helps mitigate drought damage in rice remains unclear. Therefore, in the present study, rice seedlings pretreated with melatonin (200 µM) were stressed with drought (water potential of -0.5 MPa). These rice seedlings were subsequently examined for their phenotypes and physiological and molecular properties, including metabolite contents, enzyme activities, and the corresponding gene expression levels. The findings demonstrated that drought stress induced an increase in malondialdehyde (MDA) levels, lipoxygenase (LOX) activity, and reactive oxygen species (ROS, e.g., O2- and H2O2) in rice seedlings. However, the melatonin application significantly reduced LOX activity and the MDA and ROS contents (O2- production rate and H2O2 content), with a decrease of 29.35%, 47.23%, and (45.54% and 49.33%), respectively. It activated the expression of ALM1, OsPOX1, OsCATC, and OsAPX2, which increased the activity of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), respectively. Meanwhile, the melatonin pretreatment enhanced the proline, fructose, and sucrose content by inducing OsP5CS, OsSUS7, and OsSPS1 gene expression levels. Moreover, the melatonin pretreatment considerably up-regulated the expression levels of the melatonin synthesis genes TDC2 and ASMT1 under drought stress by 7-fold and 5-fold, approximately. These improvements were reflected by an increase in the relative water content (RWC) and the root-shoot ratio in the drought-stressed rice seedlings that received a melatonin application. Consequently, melatonin considerably reduced the adverse effects of drought stress on rice seedlings and improved rice's ability to tolerate drought by primarily boosting endogenous antioxidant enzymes and osmoregulation abilities.

Implication of scanning electron microscopy as a tool for identification of novel, nonedible oil seeds for biodiesel production.

Biodiesel is a promising, bio-based, renewable, nontoxic, environment friendly, and alternative fuel for petroleum derived fuels which helps to reduce dependency on conventional fossil fuels. In this study, six novel, nonedible seed oil producing feedstock were explored for their potential for sustainable production of biodiesel. It is very important to correctly identify oil yielding plant species. Scanning electron microscopy (SEM) was used as reliable tool for authentic identification of oil yielding seeds. Macromorphological characters of seeds were studied with light microscopy (LM). Outcomes of LM of seeds exposed distinctive variation in seed size from 16.3 to 3.2 mm in length and 12.4 to 0.9 mm in width, shape varied from oval to triangular, and color from black to light brown. Oil content of nonedible seed ranged from 25 to 30% (w/w). Free fatty acid content of seed oil varied from 0.32 to 2.5 mg KOH/g. Moreover, ultra structural study of seeds via SEM showed variation in surface sculpturing, cell arrangement, cell shape, periclinal wall shape, margins, protuberances, and anticlinal wall shape. Surface sculpturing varied from rugged, reticulate, varrucose, papillate, and striate. Periclinal wall arrangements confirmed variation from rough, wavy, raised, depressed, smooth, and elevated whereas, anticlinal walls pattern showed variation from profuse undulating, smooth, raised, grooved, deep, curved, and depressed. It was concluded that SEM could be a latent and advanced technique in unveiling hidden micromorphological characters of nonedible oil yielding seeds which delivers valuable information to researchers and indigenous people for precise and authentic identification and recognition.

Implication, visualization, and characterization through scanning electron microscopy as a tool to identify nonedible oil seeds.

Second-generation biofuels prove to be a distinctive and renewable source of sustainable energy and cleaner environment. The current study focuses on the exploration and identification of four nonedible sources, that is, Brassica oleracea L., Carthamus oxyacantha M.Bieb., Carthamus tinctorius L., and Beaumontia grandiflora Wall., utilizing light microscopy (LM) and scanning electron microscopy (SEM) for studying the detailed micromorphological features of these seeds. LM revealed that size ranges from 3 to 20 mm. furthermore, a great variety of color is observed from pitch black to greenish gray and yellowish white to off white. Seeds ultrastructure study with the help of SEM revealed a great variety in shape, size, color, sculpturing and periclinal wall shape, and so on. Followed by the production of fatty acid methyl esters from a novel source, that is, seeds oil of Brassica oleracea L. (seed oil content 42.20%, FFA content 0.329 mg KOH/g) using triple metal impregnated montmorillonite clay catalyst (Cu-Mg-Zn-Mmt). Catalyst was characterized using SEM-EDX, FT-IR. Maximum yield of Brassica oleracea L. biodiesel (87%) was obtained at the conditions; 1:9 of oil to methanol ratio, 0.5 g of catalyst, 5 hr reaction time, and 90°C of temperature. Synthesized biodiesel was characterized by FT-IR, GC-MS, and NMR. Fuel properties of the Brassica oleracea L. FAMES were determined and found in accordance with ASTM standards.

Knowledge and Attitude Regarding Telemedicine Among Doctors in Karachi.

Background Telemedicine is an affordable use of information and communication technology (ICT) to enable long-distance patient care and health care services. While the developed world continues to take advantage of this technology, its concept remains new to Pakistan. This study aims to assess the knowledge and perceptions regarding telemedicine among health care professionals in Karachi, Pakistan. Methods  This cross-sectional study was carried out among doctors employed in the public health sector in Karachi from June 2018 to August 2018. Data were collected using a self-designed well-structured questionnaire using a five-point Likert scale, built after an extensive literature review. Statistical analysis was carried out using SPSS version 22. Categorical data were reported as frequencies and percentages. Results A total of 224 doctors, working in the Department of Internal Medicine (27.6%), Pediatrics (9.8%), Cardiology (6.6%), Gynecology (5.35%), Neurology (5.8%), and other specialties (44.6%), participated in the study. A total of 80.7 % of the doctors were aware of the definition of telemedicine. A total of 28.1% of them believed telemedicine to be effective in providing faster medical care while 23.2% thought of it as a means of reducing the white coat syndrome. A total of 42.9% believed that telemedicine disrupts the doctor-patient relationship and causes a breach of patient privacy. A total of 34.8% of the doctors favored the idea of introducing national standards for practicing telemedicine while 33.5% of doctors also agreed that providing a legal explanation of telemedicine to patients was of paramount importance. Poverty and lack of education (90.6%) was thought to be the biggest barrier to the practice of telemedicine in the developing world. Conclusions The knowledge regarding telemedicine among doctors in Karachi was found to be average. However, the perceptions about and attitude towards the introduction and implementation of this new technology were welcomed by the majority of participants with an emphasis on increasing awareness. Conferences and workshops are needed to increase knowledge about telemedicine in Pakistan.