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Background/Objectives: Maternal skin-to-skin contact (MSSC) in neonates has been shown to reduce nosocomial infections. In preterm infants, exposure to maternal skin commensals within the first 24 h may prevent colonization by hospital-acquired pathogens. However, the impact of early MSSC on skin colonization in preterm infants is unknown. Our aim was to compare skin colonization patterns on days 2, 3, and 7 of life in preterm infants (280/7 to 316/7 weeks gestational age) who received MSSC within the first 24 h from birth with those who did not. The primary outcome was the rate of skin colonization with bacterial pathogens. The secondary outcome was the rate of Staphylococcus aureus colonization. Methods: This prospective pre- and post-implementation study was conducted at Mount Sinai Hospital, Toronto. Skin swabs were obtained at 24–36 h, 48–72 h, and day 7 of life. Infant mouth and rectal swabs were collected on day 7. Maternal nasal–rectal swabs were obtained at any time from recruitment to day 7. Results: Twenty-seven infants were included in the pre-implementation group and seventeen were included in the post-implementation group, respectively. Post-implementation infants received an increased duration of SSC during the first week. No differences in colonization with pathogens vs. commensals or Staphylococcus aureus colonization were observed between groups at any time point. Skin was fully colonized in both groups by day 7. Conclusions: No differences in skin colonization patterns were identified in the first week of life for preterm infants receiving early MSSC. Larger studies with longitudinal data are needed to further evaluate the impact of MSSC on skin colonization.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

My article discusses long-distance nationalism which provides numerous Afghan refugees with the chance to bridge the territorial gap between their home and host countries with an aim to develop a re-configured national identity. Working through Nadia Hashmi’s novel When the Moon is Low and Caroline Brothers’ Hinterland, I problematise the national identity of the Afghan refugees. Refugees are people who have left their homeland in the hope of finding protection; however, not only are they marginalised but are also pigeon-holed through the creation of a stereotypical identity of a ‘refugee’ that is bound within national boundaries. This promotes their subjugation and intensifies a re-configured long-distance nationalism in the refugee characters in the novels. Incorporating Roger Zetter’s concept of labeling, Ellen Lammers’ theorisation of categorisation and the concept of long-distance nationalism as presented by Nina Glick Schiller and George Eugene Fouron, I theorise how longdistance nationalism forges a trans-border citizenship among the Afghan refugees as a reaction to their reductive categorisation. In doing so, my article serves as one way of addressing the complexities of the Afghan refugee crisis.

This research was designed to analyze the interactive effects of Pseudomonas putida and salicylic acid on the growth of canola in stress and non-stress conditions. Salicylic acid is a phenolic derivative, that has a direct involvement in various plant stages like growth, and inflorescence. While Pseudomonas putida is a drought-tolerant strain having plant growth-promoting characteristics like phosphate solubilization, indole acetic acid, and catalase production. Combined application of Pseudomonas putida and salicylic acid has the ability to develop stress tolerance in plants and also improve growth of plants. They have significant (p

Two of the limitations associated with cancer treatment are the low efficacy and the high dose-related side effects of anticancer drugs. The purpose of the current study was to fabricate biocompatible multifunctional drug-loaded nanoscale moieties for co-therapy (chemo-photothermal therapy) with maximum efficacy and minimum side effects. Herein, we report in vitro anticancerous effects of doxorubicin (DOX) loaded on gold nanorods coated with the polyelectrolyte poly(sodium-4-styrenesulfonate) (PSS-GNRs) with and without NIR laser (808 nm, power density = 1.5 W/cm2 for 2 min) irradiation. The drug-loading capacity of PSS-GNRs was about 76% with a drug loading content of 3.2 mg DOX/mL. The cumulative DOX release significantly increased after laser exposure compared to non-irradiated samples (p < 0.05). The zeta potential values of GNRs, PSS-GNRs and DOX-PSS-GNRs were measured as 42 ± 0.1 mV, −40 ± 0.3 mV and 39.3 ± 0.6 mV, respectively. PSS-GNRs nanocomplexes were found to be biocompatible and showed higher photothermal stability. The DOX-conjugated nanocomplexes with NIR laser irradiation appear more efficient in cell inhibition (93%) than those without laser exposure (65%) and doxorubicin alone (84%). The IC50 values of PSS-GNRs-DOX and PSS-GNRs-DOX were measured as 7.99 and 3.12 µg/mL, respectively, with laser irradiation. Thus, a combinatorial approach based on chemotherapy and photothermal strategies appears to be a promising platform in cancer management.

Artificial intelligence and machine learning promise to transform cancer therapies by accurately predicting the most appropriate drugs to treat individual patients. Here, the authors present an approach which uses omics data to produce ordered lists of drugs based on their effectiveness in decreasing cancer cell proliferation.

Abstract Crude oil contamination is a serious environmental threat for soil and plants growing in it. This study provides the first experimental evidence for comparison of the efficacy of pyrochar (slow pyrolysis biochar), thermal desorption and their combined application for degradation of crude oil contaminated soil (0%, 10%, and 20%), and growth of lettuce under glasshouse conditions. Pyrochar was produced by pyrolysis of sawdust at 350 °C, whereas thermal desorption was done by soil pyrolysis at 500 °C. Soil incubations were done for 120 days. The results of soil analysis showed that the crude oil degradation efficiency for the combined application was highest (40%), whereas pyrochar and thermal desorption was 25% and 19.6%, respectively. The maximum degradation products of crude oil were manifested by the detection of low molecular weight hydrocarbons (ranged between 173 and 422) in the soil with combined application treatment using Gas Chromatography-Mass Spectrometry (GC–MS) analysis. Crude oil contamination significantly reduced the germination and growth of the lettuce plants. Similarly, the combined application also improved plant growth by an increase of 24% in germination percentage, 35.5% in seedling vigor index, and 27% in promptness index under 20% crude oil contamination. Remediation caused a significant increase in fresh and dry biomass (40%), leaf area (30%), total chlorophyll (21%), water potential (23.6%), osmotic potential (27%), and membrane stability index (40%). Moreover, there was an increase in the contents of proline (32%), total amino acids (29%), soluble sugars (37%), proteins (27%), and antioxidant enzymes such as superoxide dismutase (19%), catalase (33%) and peroxidase (38%). This study confirmed the efficacy of pyrochar (slow pyrolysis biochar), thermal desorption, and their combined application for crude oil decontamination of soil at laboratory scale and also in improving soil usability by improved germination and growth of lettuce.

Soil contamination with cobalt (Co) negatively impacts plant growth and production. To combat Co toxicity, plant growth-promoting microorganisms for improving plant growth are effectively applied. To this end, unclassified haloarchaeal species strain NRS_31 (OL912833), belonging to Haloferax genus, was isolated, identified for the first time, and applied to mitigate the Co phytotoxic effects on maize plants. This study found that high Co levels in soil lead to Co accumulation in maize leaves. Co accumulation in the leaves inhibited maize growth and photosynthetic efficiency, inducing oxidative damage in the tissue. Interestingly, pre-inoculation with haloarchaeal species significantly reduced Co uptake and mitigated the Co toxicity. Induced photosynthesis improved sugar metabolism, allocating more carbon to defend against Co stress. Concomitantly, the biosynthetic key enzymes involved in sucrose (sucrose-P-synthase and invertases) and proline (pyrroline-5- carboxylate synthetase (P5CS), pyrroline-5-carboxylate reductase (P5CR)) biosynthesis significantly increased to maintain plant osmotic potential. In addition to their osmoregulation potential, soluble sugars and proline can contribute to maintaining ROS hemostasis. Maize leaves managed their oxidative homeostasis by increasing the production of antioxidant metabolites (such as phenolics and tocopherols) and increasing the activity of ROS-scavenging enzymes (such as POX, CAT, SOD, and enzymes involved in the AsA/GSH cycle). Inside the plant tissue, to overcome heavy Co toxicity, maize plants increased the synthesis of heavy metal-binding ligands (metallothionein, phytochelatins) and the metal detoxifying enzymes (glutathione S transferase). Overall, the improved ROS homeostasis, osmoregulation, and Co detoxification systems were the basis underlying Co oxidative stress, mitigating haloarchaeal treatment's impact.

Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC50 value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC50 = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein–ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be −8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors.

Objective: A systematic review was conducted to evaluate recent studies performed on miRNAs as a diagnostic and therapeutic biomarker in breast cancer. Study Design: Online standard databases like PubMed, EMBASE, Web of Science and COCHRANE library were searched to identify research articles relavant to the topic. Place and Duration of Study: All online published studies between 2010-2020, in the scientific electronic databases were analyzed. Materials and Methods: This review was performed according to PRISMA guidelines. Databases were systematically analyzed to explore the diagnostic and therapeutic potentials of miRNAs in breast cancer. Results: We identified twenty-seven studies after literature search. We found six studies focused on diagnosis, sixteen on therapeutics and five on both diagnosis and therapeutics of miRNAs in breast cancer. Conclusion: The combined data obtained in the present systematic review specify that miRNAs could serve as novel diagnostic and therapeutic biomarkers in breast cancer, whereas the practical relevance of the current results has yet to be established.

This research was carried out to evaluate the effect of biochar and compost application on Spinacia oleracea growth in cadmium contaminated soil. Cd toxicity decreased plant growth and biomass significantly and also negatively affected the physiological and biochemical attributes of plants. However, the application of biochar and compost improved the contaminated soil by reducing Cd toxicity and causing its immobilization, which in turn improved plant growth. The combined application of biochar and compost significantly (p < 0.05) enhanced biomass and photosynthetic pigments development in plants. The treatments also increased membrane stability index by 45.12% and enhanced water using efficiency by 218.22%, respectively. The increase in antioxidant activities was 76.03%, 29.02%, and 123.27% in superoxide dismutase, peroxidase, and catalase, respectively. The combined application also reduced the cadmium content (reduced 40.14% in root and 51.16% shoot), its translocation (19.67% decrease), and bioaccumulation (52.63% and 40.32% decrease in Cd content in shoot and root, respectively) in spinach plant. Among the two selected varieties of S. oleracea, Desi palak (V1) performed better as compared to Kanta palak (V2). It can be concluded that the combined application of biochar and compost is one of the best strategies to reduce the toxicity level of Cd in plants and to improve their growth.

The validation of underexplored traditional plant remedies represents a reservoir of novel leads for drug discovery. In line with this, in vitro total phenolics and flavonoids content, multimode antioxidants, antimicrobial, cytotoxicity, and protein kinase inhibition assays were conducted on C. ambrosioides seed extracts in addition to RP-HPLC. Methanol extract exhibited highest total phenolics (64.6±0.6 μg gallic acid equivalent/mg) and flavonoids (50.9±0.5 μg quercetin equivalent/mg) content. RP-HPLC quantified rutin (1.98 μg/mg) in methanol extract whereas quercetin (0.322 μg/mg) and kaempferol (2.86 μg/mg) in methanol-distilled water extract. Methanol extract exhibited highest ascorbic acid equivalent (AAE) free radical (DPPH) scavenging (IC50 of 110.7±5 μg/ml), total antioxidant capacity (110.6±2.2 μg AAE/mg), and total reducing power (94.30±0.46 μg AAE/mg). Highest antibacterial activity against K. pneumonia (14±1.61 mm ZOI) and antifungal activity against F. solani (17±1.38 mm ZOI) were shown by n-hexane and chloroform extracts, respectively. Ethyl acetate extract exhibited highest brine shrimps cytotoxicity (LC50 of 125 μg/ml). A noteworthy protein kinase inhibitory potential was shown by ethanol extract with a 20±1.27 mm bald zone. Therapeutic potential of medicinal plants can be completely explored by using multiple solvent system. This study makes C. ambrosioides, a resourceful prospect for the bioactivity-guided isolation of lead compounds.

Green nanoparticle synthesis is considered the most efficient and safe nanoparticle synthesis method, both economically and environmentally. The current research was focused on synthesizing zinc oxide nanoparticles (ZnONPs) from fruit and leaf extracts of Citrullus colocynthis. Four solvents (n-hexane, methanol, ethyl acetate, and aqueous) were used to prepare the extracts from both plant parts by maceration and extraction. Zinc acetate was used to synthesize the nanoparticles (NPs), and color change indicated the synthesis of ZnONPs. X-ray diffraction, UV spectroscopy, and scanning electron microscopy were used to study the ZnONPs. UV–visible spectroscopy revealed an absorbance peak in the 350–400 nm range. XRD patterns revealed the face-centered cubic structure of the ZnONPs. SEM confirmed a spherical morphology and a size range between 64 and 82 nm. Phytochemical assays confirmed that the complete flavonoid, phenolic, and alkaloid concentrations were higher in unrefined solvent extracts than in nanoparticles. Nanoparticles of C. colocynthis fruit aqueous extracts showed stronger antioxidant activity compared with the crude extracts. Strong antifungal activity was exhibited by the leaves, crude extracts, and nanoparticles of the n-hexane solvent. In a protein kinase inhibition assay, the maximum bald zone was revealed by nanoparticles of ethyl acetate extracts from leaves. The crude extracts and nanoparticles of leaves showed high cytotoxic activities of the n-hexane solvent, with LC50 values of 42.08 and 46.35, respectively. Potential antidiabetic activity was shown by the n-hexane (93.42%) and aqueous (82.54%) nanoparticles of the fruit. The bioactivity of the plant showed that it is a good candidate for therapeutic use. The biosynthesized ZnONPs showed promising antimicrobial, cytotoxic, antidiabetic, and antioxidant properties. Additionally, the in vivo assessment of a nano-directed drug delivery system for future therapeutic use can be conducted based on this study.

Drought stress is reducing the production of crops globally. This research was designed to evaluate the role of titanium dioxide (TiO2 NPs) nanoparticles and calcium phosphate on wheat facing drought stress. TiO2 NPs were prepared by green synthesis and their characterization (by UV–visible spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX)) was also done. The results showed that TiO2 NPs worked efficiently and improved plant growth under drought. However, the best results were obtained from combined applications of 40 ppm TiO2 NPs and 40 ppm calcium phosphate on plants. They increased root length (33%), shoot length (53%), fresh weight (48%), and dry weight (44%) of wheat as compared to control. The physiological parameters including chlorophyll content, relative water content, membrane stability index, and osmolyte content (proline and sugar) were also improved. The increase in superoxide dismutase, peroxidase and, catalase activity by the combined application of TiO2 NPs and calcium phosphate was 83% and 78%, 74% and 52%, 81%, and 67% in Pakistan-13 and Zincol-16 respectively, as compared to untreated drought exposed plants. They also enhanced the nutrients uptake (including potassium, phosphorus, and nitrogen) that ultimately improved plant biomass. They also maintained the level of growth hormones in plants. These hormones regulate cellular processes and are responsible for germination, development, and plant reaction in drought stress. The increase in the yield was also significant, hence it is recommended that the 40 ppm concentration of TiO2 NPs along with calcium phosphate improves the productivity of wheat under drought stress.

Plants are a promising source of bioactive compounds that can be used to tackle many emerging diseases both infectious and non-infectious. Among different plants, Acacia is a very large genus and exhibits a diverse array of bioactive agents with remarkable pharmacological properties against different diseases. Acacia, a herb found all over the world, contains approximately more than 1200 species of the Fabaceae family. In the present review, we have collected detailed information on biochemical as well as pharmacological properties. The data were retrieved using different databases, such as Elsevier, PubMed, Science Direct, Google Scholar, and Scopus, and an extensive literature survey was carried out. Studies have shown that Acacia possesses several secondary metabolites, including amines, cyanogenic glycosides, flavonoids, alkaloids, seed oils, cyclitols, fluoroacetate, gums, non-protein amino acids, diterpenes, fatty acids, terpenes, hydrolyzable tannins, and condensed tannins. These compounds exhibit a wide range of pharmaceutical applications such as anti-inflammatory, antioxidant, antidiarrheal, antidiabetic, anticancer, antiviral, liver protective effects, and so on. Thus, the literature shows the tremendous phytochemical impact of the genus Acacia in medicine. Overall, we recommend that more research should be conducted on the medicinal value and isolation and purification of the effective therapeutic agents from Acacia species for the treatment of various ailments.

Combretaceae, an immense family involving species (500) or genera (20), originates in tropical and subtropical regions. This family has evinced medicinal values such as anti-leishmanial, cytotoxic, antibacterial, antidiabetic, antiprotozoal, and antifungal properties. Conocarpus lancifolius (C. lancifolius) methanol extract (CLM) was prepared, then compound isolation performed by open column chromatography, and compound structure was determined by spectroscopic techniques (13C NMR, IR spectroscopy, 1H-NMR, mass spectrometry UV-visible, and 2D correlation techniques). Molecular docking studies of ligand were performed on transcriptional regulators 4EY7 and 2GV9 to observe possible interactions. Phytochemical screening revealed the presence of secondary metabolites including steroids, cardiac glycosides, saponins, anthraquinones, and flavonoids. The isolated compound was distinguished as lancifolamide (LFD). It showed cytotoxic activity against human breast cancer, murine lymphocytic leukemia, and normal cells, human embryonic kidney cells, and rat glioma cells with IC50 values of 0.72 µg/mL, 2.01 µg/mL, 1.55 µg/mL, and 2.40 µg/mL, respectively. Although no cytotoxic activity was noticed against human colon cancer and human lung cancer, LFD showed 24.04% inhibition against BChE and 60.30% inhibition against AChE and is therefore beneficial for Alzheimer’s disease (AD). AChE and LFD interact mechanistically in a way that is optimum for neurodegenerative disorders, according to molecular docking studies. Methanol and dichloromethane extract of C. lancifolius and LFD shows antibacterial and antifungal activity against antibiotic resistance Bacillus subtilis, Streptococcus mutans, Brevibacillus laterosporus, Salmonella Typhi, Candida albicans, and Cryptococcus neoformans, respectively. LFD shows antiviral activity against HSV-1 with 26% inhibition IP. The outcomes of this study support the use of LFD for cognitive disorders and highlight its underlying mechanism, targeting AChE, DNA-POL, NF-KB, and TNF-α, etc., for the first time.

Water stress affects the growth, development, and yield of crops. The objective of this study is to evaluate the positive effects of nutrients (calcium, potassium, and boron) on durum wheat facing drought stress. Two treatments of calcium, potassium, and boron were used under drought and well-watered conditions on two varieties of durum wheat (V1—Preco; V2—Kronos). The data depict that the exogenous application of these nutrients gave significantly different (p < 0.05) results. The percentage increase in shoot length and root length was 29% and 35% compared to the untreated, drought-facing plants. There is also an increase in the synthesis of photosynthetic pigments and osmolytes. The foliar spray of nutrients enhances the synthesis of antioxidants, including superoxide dismutase, catalase, and peroxidase, which reduce the production of free radicals. It also helps to maintain the stability of membranes and other cell organelles. The spray application enhances the yield of durum wheat, i.e., the percentage increase in the number of grains per spike and 1000-grain weight was 23% and 25% compared to the untreated, drought-facing plants. The use of these nutrients considerably improves the functioning of antioxidant machinery, helping combat the adverse effects of drought. Additionally, they improve the growth- and yield-related parameters. Hence, these sprays can be used as a plant growth regulator.

Background: The aim of the present research was to formulate and evaluate curcumin hydrogel and to investigate the potential of natural essential oils as permeation enhancers. Methods: Curcumin 2% w/w hydrogel containing various concentrations of eucalyptus oil, aloe vera oil and clove oil was developed using carboxy methyl cellulose (CMC) as a gelling agent. Differential scanning calorimetry and Fourier Transform infrared spectroscopy were used to evaluate the compatibility between the drug and the excipients. In order to assess the efficacy of the formulation; rheological properties, skin irritation studies, in vitro release, ex vivo permeation and retention studies were conducted. Results: DSC and FTIR suggest no in-compatibility between curcumin and excipients. Studies proved that addition of suitable natural permeation enhancers to the hydrogels improved the in vitro release and ex vivo permeation and retention of curcumin. From the various natural essential oils, the aloe vera oil at a concentration of 3% w/w had the greatest effect on the permeability rate and skin retention of the Curcumin and produces the highest enhancement ratio amongst all the concentrations of essential oils examined. Conclusion: Aloe vera oil enhances the permeation of curcumin across the skin by altering the complex structure of the stratum corneum without itself undergoing any change. The developed curcumin hydrogels along with natural essential oils may present an effective choice regarding skin infection/wound healing.

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Pelargonium graveolens, rose-scented geranium, is commonly used in the perfume industry. P. graveolens is enriched with essential oils, phenolics, flavonoids, which account for its tremendous biological activities. Laser light treatment and arbuscular mycorrhizal fungi (AMF) inoculation can further enhance the phytochemical content in a significant manner. In this study, we aimed to explore the synergistic impact of these two factors on P. graveolens. For this, we used four groups of surface-sterilized seeds: (1) control group1 (non-irradiated; non-colonized group); (2) control group2 (mycorrhizal colonized group); (3) helium-neon (He-Ne) laser-irradiated group; (4) mycorrhizal colonization coupled with He-Ne laser-irradiation group. Treated seeds were growing in artificial soil inculcated with Rhizophagus irregularis MUCL 41833, in a climate-controlled chamber. After 6 weeks, P. graveolens plants were checked for their phytochemical content and antibacterial potential. Laser light application improved the mycorrhizal colonization in P. graveolens plants which subsequently increased biomass accumulation, minerals uptake, and biological value of P. graveolens. The increase in the biological value was evident by the increase in the essential oils production. The concomitant application of laser light and mycorrhizal colonization also boosted the antimicrobial activity of P. graveolens. These results suggest that AMF co-treatment with laser light could be used as a promising approach to enhance the metabolic content and yield of P. graveolens for industrial and pharmaceutical use.

Drastic changes in the climate and ecosystem due to natural or anthropogenic activities have severely affected crop production globally. This concern has raised the need to develop environmentally friendly and cost-effective strategies, particularly for keeping pace with the demands of the growing population. The use of nanobiofertilizers in agriculture opens a new chapter in the sustainable production of crops. The application of nanoparticles improves the growth and stress tolerance in plants. Inoculation of biofertilizers is another strategy explored in agriculture. The combination of nanoparticles and biofertilizers produces nanobiofertilizers, which are cost-effective and more potent and eco-friendly than nanoparticles or biofertilizers alone. Nanobiofertilizers consist of biofertilizers encapsulated in nanoparticles. Biofertilizers are the preparations of plant-based carriers having beneficial microbial cells, while nanoparticles are microscopic (1–100 nm) particles that possess numerous advantages. Silicon, zinc, copper, iron, and silver are the commonly used nanoparticles for the formulation of nanobiofertilizer. The green synthesis of these nanoparticles enhances their performance and characteristics. The use of nanobiofertilizers is more effective than other traditional strategies. They also perform their role better than the common salts previously used in agriculture to enhance the production of crops. Nanobiofertilizer gives better and more long-lasting results as compared to traditional chemical fertilizers. It improves the structure and function of soil and the morphological, physiological, biochemical, and yield attributes of plants. The formation and application of nanobiofertilizer is a practical step toward smart fertilizer that enhances growth and augments the yield of crops. The literature on the formulation and application of nanobiofertilizer at the field level is scarce. This product requires attention, as it can reduce the use of chemical fertilizer and make the soil and crops healthy. This review highlights the formulation and application of nanobiofertilizer on various plant species and explains how nanobiofertilizer improves the growth and development of plants. It covers the role and status of nanobiofertilizer in agriculture. The limitations of and future strategies for formulating effective nanobiofertilizer are mentioned.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography–Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance.

In view of the wide traditional uses of legume sprouts, several strategies have been approved to improve their growth, bioactivity, and nutritive values. In this regard, the present study aimed at investigating how priming with selenium nanoparticles (SeNPs, 25 mg L−1) enhanced the effects of β-amino butyric acid (BABA, 30 mM) on the growth, physiology, nitrogen metabolism, and bioactive metabolites of Medicago interexta sprouts. The results have shown that the growth and photosynthesis of M. interexta sprouts were enhanced by the treatment with BABA or SeNPs, being higher under combined treatment. Increased photosynthesis provided the precursors for the biosynthesis of primary and secondary metabolites. In this regard, the combined treatment had a more pronounced effect on the bioactive primary metabolites (essential amino acids), secondary metabolites (phenolics, GSH, and ASC), and mineral profiles of the investigated sprouts than that of sole treatments. Increased amino acids were accompanied by increased nitrogen metabolism, i.e., nitrate reductase, glutamate dehydrogenase (GDH), glutamate synthase (GOGAT), glutamine synthase (GS), cysteine synthesis serine acetyltransferase, arginase, threonine synthase, and methionine synthase. Further, the antioxidant capacity (FRAP), the anti-diabetic activities (i.e., α-amylase and α-glucosidase inhibition activities), and the glycemic index of the tested sprouts were more significantly improved by the combined treatment with BABA and SeNPs than by individual treatment. Overall, the combined effect of BABA and SeNPs could be preferable to their individual effects on plant growth and bioactive metabolites.

Solubility of phytoconstituents depends on the polarity of the extraction medium used, which might result in the different pharmacological responses of extracts. In line with this, ethnomedicinally important food plant (i.e., Caralluma tuberculata extracts) have been made in fourteen distinct solvent systems that were then analyzed phytochemically via total phenolic amount estimation, total flavonoid amount estimation, and HPLC detection and quantification of the selected polyphenols. Test extracts were then subjected to a battery of in vitro assays i.e., antioxidants (DDPH scavenging, antioxidant capacity, and reducing power estimation), antimicrobial (antibacterial, antifungal, and antileishmanial), cytotoxic (brine shrimps, THP-1 human leukemia cell lines and normal lymphocytes), and protein kinase inhibition assays. Maximum phenolic and flavonoid contents were computed in distilled water–acetone and acetone extracts (i.e., 16 ± 1 μg/mg extract and 8 ± 0.4/mg extract, respectively). HPLC-DAD quantified rutin (0.58 µg/mg extract) and gallic acid (0.4 µg/mg extract) in methanol–ethyl acetate and methanol extracts, respectively. Water–acetone extract exhibited the highest DPPH scavenging of 36 ± 1%. Total reducing potential of 76.0 ± 1 μg/mg extract was shown by ethanol chloroform while maximum total antioxidant capacity was depicted by the acetone extract (92.21 ± 0.70 μg/mg extract). Maximal antifungal effect against Mucor sp., antileishmanial, brine shrimp cytotoxicity, THP-1 cell line cytotoxicity, and protein kinase inhibitory activities were shown by ethyl acetate-methanol (MIC: 50 µg/disc), n-hexane (IC50: 120.8 ± 3.7 µg/mL), ethyl acetate (LD50: 29.94 ± 1.6 µg/mL), distilled water–acetone (IC50: 118 ± 3.4 µg/mL) and methanol–chloroform (ZOI: 19 ± 1 mm) extracts, respectively. Our findings show the dependency of phytochemicals and bioactivities on the polarity of the extraction solvent and our preliminary screening suggests the C. tuberculata extract formulations to be tested and used in different ailments, however, detailed studies remain necessary for corroboration with our results.

Withaferin A (WA) is a pivotal withanolide that has conquered a conspicuous place in research, owning to its multidimensional biological properties. It is an abundant constituent in Withania somnifera Dunal. (Ashwagandha, WS) that is one of the prehistoric pivotal remedies in Ayurveda. This article reviews the literature about the pharmacological profile of WA with special emphasis on its anticancer aspect. We reviewed research publications concerning WA through four databases and provided a descriptive analysis of literature without statistical or qualitative analysis. WA has been found as an effective remedy with multifaceted mechanisms and a broad spectrum of pharmacological profiles. It has anticancer, anti-inflammatory, antiherpetic, antifibrotic, antiplatelet, profibrinolytic, immunosuppressive, antipigmentation, antileishmanial, and healing potentials. Evidence for wide pharmacological actions of WA has been established by both in vivo and in vitro studies. Further, the scientific literature accentuates the role of WA harboring a variable therapeutic spectrum for integrative cancer chemoprevention and cure. WA is a modern drug from traditional medicine that is necessary to be advanced to clinical trials for advocating its utility as a commercial drug.

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 μg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli. Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P. roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation.

Palm date pits as a source of bioactive chemicals have received only a limited amount of attention. This study was conducted to determine the bioactive components of Ajwa date pits, as well as their antibacterial and antimutagenic activities. Therefore, chromatographic techniques were used to extract and isolate the phenolic compounds in date pits, which were further elucidated by using spectroscopic techniques (FTIR and NMR) for identification of most abundant bioactive metabolites. Data showed that the methanolic extract of date pits contained high levels of total phenols (17.38 mg GA/g) and flavonoids (5.324 mg QE/g). The HPLC analysis of date pits’ extract showed the presence of six phenolic compounds. Interestingly, there was a significant amount of gallic acid (11.85 mg GA/gFW), which was isolated via chromatography (thin layer chromatography) and identified by spectroscopic investigation (FTIR, MS, 1H, and 13C NMR). An inhibitory effect on Gram-positive and Gram-negative bacteria was observed for date pit gallic acid purified. S. aureus cell viability was completely inhibited at 200 µg/mL of acid for 6 h. Moreover, gallic acid was found to have a significant antimutagenic activity against Salmonella typhimurium at all tested concentrations, with a decrease in percent mutagenicity from 52 to 32 in the case of test substance TA98, and from 39 to 15 for test substance TA100 in terms of percent antimutagenicity. Gallic acid at a dose of 3000 g/plate had the greatest antimutagenic effect on S. typhimurium TA98, with the lowest toxicity. Overall, the bioactive properties of date pits’ extracts were investigated, with a particular attention to their chemical composition, biological activity, and pharmaceutical applications.

Molybdenum ions (Mo) can improve plants’ nutritional value primarily by enhancing nitrogenous metabolism. In this study, the comparative effects of seed priming using Mo were evaluated among sproutings of Canavalia species/cultivars, including Canavalia ensiformis var. gladiata (CA1), Canavalia ensiformis var. truncata Ricker (CA2), and Canavalia gladiata var. alba Hisauc (CA3). Mo impacts on growth, metabolism (e.g., nitrogen and phenolic metabolism, pigment and total nutrient profiles), and biological activities were assayed. Principal component analysis (PCA) was used to correlate Mo-mediated impacts. The results showed that Mo induced photosynthetic pigments that resulted in an improvement in growth and increased biomass. The N content was increased 0.3-fold in CA3 and 0.2-fold in CA1 and CA2. Enhanced nitrogen metabolism by Mo provided the precursors for amino acids, protein, and lipid biosynthesis. At the secondary metabolic level, phenolic metabolism-related precursors and enzyme activities were also differentially increased in Canavalia species/cultivars. The observed increase in metabolism resulted in the enhancement of the antioxidant (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP)) and antidiabetic potential (Glycemic index (GI) and inhibition activity of α-amylase, and α-glucosidase) of species. The antioxidant activity increased 20% in CA3, 14% in CA1, and 8% in CA2. Furthermore, PCA showed significant variations not only between Mo-treated and untreated samples but also among Canavalia species. Overall, this study indicated that the sprouts of Canavalia species have tremendous potential for commercial usage due to their high nutritive value, which can be enhanced further with Mo treatment to accomplish the demand for nutritious feed.

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, −9.4 and −8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

Herbal and traditional medicines can play a pivotal role in combating cancer and neglected tropical diseases. Ajuga bracteosa, family Lamiaceae, is an important medicinal plant. The genetic transformation of A. bracteosa with rol genes of Agrobacterium rhizogenes further enhances its metabolic content. This study aimed at undertaking the molecular, phytochemical, and in vitro biological analysis of A. bracteosa extracts. We transformed the A. bracteosa plant with rol genes and raised the regenerants from the hairy roots. Transgenic integration and expression of rolB were confirmed by conventional polymerase chain reaction (PCR) and qPCR analysis. The methanol: chloroform crude extracts of wild-type plants and transgenic regenerants were screened for in vitro antibacterial, antihemolytic, cytotoxic, anticancer, and leishmanial activity. Among all plants, transgenic line 3 (ABRL3) showed the highest expression of the rolB gene. Fourier transform infra-red (FTIR) analysis confirmed the enhanced number of functional groups of active compounds in all transgenic lines. Moreover, ABRL3 exhibited the highest antibacterial activity, minimum hemolytic activity (CC50 = 7293.05 ± 7 μg/mL) and maximum antileishmanial activity (IC50 of 56.16 ± 2 μg/mL). ABRL1 demonstrated the most prominent brine shrimp cytotoxicity (LD5039.6 ± 4 μg/mL). ABRL3 was most effective against various human cancer cell lines with an IC50 of 57.1 ± 2.2 μg/mL, 46.2 ± 1.1 μg/mL, 72.4 ± 1.3 μg/mL, 73.3 ± 2.1 μg/mL, 98.7 ± 1.6 μg/mL, and 97.1 ± 2.5 μg/mL against HepG2, LM3, A549, HT29, MCF-7, and MDA-MB-231, respectively. Overall, these transgenic extracts may offer a cheaper therapeutic source than the more expensive synthetic drugs.

Autism is a group of neuro-developmental disabilities. It has an early-onset and can be diagnosed up to 3 years of age. It is characterized by disturbances in child's socialization, communication and cognitive abilities, and an unusual repetitive and restricted behavior. The majority of subjects have comorbid conditions. Males are more 1 affected than females.1 The prevalence of autism is increasing in the world that could be due to improvement in1 diagnostic procedures and awareness in public and its worldwide prevalence is around 1%.1 In Pakistan, there is a lack of widespread awareness and understanding about autism. We do not have exact prevalence data on this disease in Pakistan. However, according to the Autism Society of Pakistan, there are 2 probably 350,000 children with this disease in the country.2 But the actual prevalence is believed to be much higher. Many cases remain undiagnosed because of unawareness, lack of medical facilities and stigma that is 3 attached to mental conditions in Pakistan. In Pakistan, the distribution of disabilities includes mental retardation (MR), hearing impairment, visual impairment and physical disability. Autism is not considered as a disability in Pakistani society. Moreover, the term mental disability or cognition problem is considered as a social stigma or disgrace. Therefore, many people do not disclose the condition to avoid stigma. Another important reason of undiagnosed cases is lack of medical facilities and untrained doctors that categories autism under intellectual disability that is another condition. Many people especially from rural areas opt traditional therapies or go to preachers for healing.

Ajuga bracteosa Wall. ex Benth. is an endangered medicinal herb traditionally used against different ailments. The present study aimed to create new insight into the fundamental mechanisms of genetic transformation and the biological activities of this plant. We transformed the A. bracteosa plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. These transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, elemental analysis, polyphenol content, and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was most abundant in all transgenic lines. Furthermore, transgenic line 3 (ABRL3) showed maximum phenolics and flavonoids content among all tested plant extracts. ABRL3 also demonstrated the highest total antioxidant capacity (8.16 ± 1 μg AAE/mg), total reducing power, (6.60 ± 1.17 μg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8 μg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 μg/mL), and iron-chelating power (IC50 = 154.8 ± 2 μg/mL). Moreover, transformed plant extracts produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant activities in BALB/c mice models. In conclusion, transgenic regenerants of A. bracteosa pose better antioxidant and pharmacological properties under the effect of rol genes as compared to wild-type plants.

Plant growth-promoting rhizobacteria (PGPR) mediate heavy metal tolerance and improve phytoextraction potential in plants. The present research was conducted to find the potential of bacterial strains in improving the growth and phytoextraction abilities of Brassica nigra (L.) K. Koch. in chromium contaminated soil. In this study, a total of 15 bacterial strains were isolated from heavy metal polluted soil and were screened for their heavy metal tolerance and plant growth promotion potential. The most efficient strain was identified by 16S rRNA gene sequencing and was identified as Bacillus cereus. The isolate also showed the potential to solubilize phosphate and synthesize siderophore, phytohormones (indole acetic acid, cytokinin, and abscisic acid), and osmolyte (proline and sugar) in chromium (Cr+3) supplemented medium. The results of the present study showed that chromium stress has negative effects on seed germination and plant growth in B. nigra while inoculation of B. cereus improved plant growth and reduced chromium toxicity. The increase in seed germination percentage, shoot length, and root length was 28.07%, 35.86%, 19.11% while the fresh and dry biomass of the plant increased by 48.00% and 62.16%, respectively, as compared to the uninoculated/control plants. The photosynthetic pigments were also improved by bacterial inoculation as compared to untreated stress-exposed plants, i.e., increase in chlorophyll a, chlorophyll b, chlorophyll a + b, and carotenoid was d 25.94%, 10.65%, 20.35%, and 44.30%, respectively. Bacterial inoculation also resulted in osmotic adjustment (proline 8.76% and sugar 28.71%) and maintained the membrane stability (51.39%) which was also indicated by reduced malondialdehyde content (59.53% decrease). The antioxidant enzyme activities were also improved to 35.90% (superoxide dismutase), 59.61% (peroxide), and 33.33% (catalase) in inoculated stress-exposed plants as compared to the control plants. B. cereus inoculation also improved the uptake, bioaccumulation, and translocation of Cr in the plant. Data showed that B. cereus also increased Cr content in the root (2.71-fold) and shoot (4.01-fold), its bioaccumulation (2.71-fold in root and 4.03-fold in the shoot) and translocation (40%) was also high in B. nigra. The data revealed that B. cereus is a multifarious PGPR that efficiently tolerates heavy metal ions (Cr+3) and it can be used to enhance the growth and phytoextraction potential of B. nigra in heavy metal contaminated soil.

Acute myeloid leukemia (AML) is an aggressive disease and, despite advances, its treatment remains challenging. Therefore, it remains important to identify new agents for the management of this disease. Withanolides, a group of steroidal lactones found in Solanaceae plants are of potential interest due to their reported anticancer activities in different settings. In this study we investigated the anti-proliferative effects and mode of action of Solanaceae-derived withanolides in AML cell models; these metabolites include withametelin (WTH) and Coagulansin A (CoA) isolated from Datura innoxia and Withania coagluanse, respectively. Both withanolides inhibited the proliferation of AML cells and induced cell death, with WTH being more potent than CoA in the AML models tested. Quantitative label-free proteomics and phosphoproteomics were employed to define the mechanism of action of the studied withanolides. We identified and quantified 5269 proteins and 17,482 phosphosites in cells treated with WTH, CoA or vehicle control. Withanolides modulated the expression of proteins involved in regulating key cellular processes including cell cycle, metabolism, signaling, protein degradation and gene expression. Enrichment analysis of the phosphoproteomics data against kinase substrates, kinase-kinase relationships and canonical pathways showed that the withanolides decreased the activity of kinases such as phosphoinositide 3-kinase (PI3K), protein kinase B (PKB; also known as RAC-alpha serine/threonine-protein kinase or AKT), mammalian target of rapamycin (mTOR), extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and the serine/threonine-protein kinase A-Raf (ARAF), while increasing the activation of DNA repair kinases. These results indicate that withanolide metabolites have pleiotropic effects in the modulation of oncogenic pro-survival and pro-apoptotic signaling pathways that regulate the induction of apoptosis. Withanolide mediated apoptosis was confirmed by immunoblotting showing increased expression of cleaved PARP and Caspases 3, 8 and 9 as a result of treatment. Overall, our results suggest that WTH and CoA have therapeutic potential against AML with WTH exhibiting more potent effects and should be explored further.

Type 2 diabetes is a metabolic disorder, characterized by hyperglycemia and glucose intolerance. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. In present study we investigated the antidiabetic potential of Ficus microcarpa and isolated bioactive compounds i.e., Plectranthoic acid (PA) and 3,4,5,7-Flavantetrol (FL). Anti-hyperglycemic potential was evaluated via α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) assays. 5’AMP-activated kinase (AMPK) activation potential was assessed by using primary hepatocytes. Distribution of PA in different parts of Ficus microcarpa was evaluated by using rapid high-performance liquid chromatography (HPLC). Ethyl acetate fraction (FME) exhibited significant inhibition of α-glucosidase, α-amylase, and DPP-4, therefore, was selected for isolation of bioactive compounds. Among isolated compounds PA was more potent and possessed pleotropic inhibitory activity with IC50 values of 39.5, 55.5, and 51.4 μM against α-glucosidase, α-amylase, and DPP-4, respectively. Our results showed that PA is also a potent activator of AMPK which is a central hub of metabolic regulation. Molecular docking studies confirmed the activity of PA against α-glucosidase, α-amylase, and DPP-4. Rapid HPLC method revealed that maximum concentration of PA is present in the stem (2.25 μg/mg dry weight) of Ficus microcarpa. Both in vitro and in silico studies proposed that Ficus microcarpa and its isolated compound PA could be an important natural source for alleviating the symptoms of type 2 diabetes mellitus and we suggest that PA should be explored further for its ultimate use for the treatment of type 2 diabetes.

Five heteroleptic palladium(II) complexes of the general formula Pd(PR3)(tu)Cl2, where PR3 = triphenylphosphine (1), diphenyl-o-tolylphosphine (2), diphenyl-p-tolylphosphine (3), diphenyl-t-butylphosphine (4), and diphenyl-o-methoxyphenylphosphine (5), and tu = 1,3-bis(2-methoxyphenyl) thiourea. They all have been synthesized and characterized by various spectroscopic techniques (elemental analysis, FTIR, and 1H NMR and the ligand 1,3-bis(2-methoxyphenyl) thiourea was synthesized by single crystal X-ray diffraction technique). The synthesized compounds were screened for their antibacterial activity against four strains of bacteria (Escherichia coli, Shigella flexneri, Staphylococcus aureus, and Bacillus subtilis). The antitumor potential was evaluated in terms of activity against brine shrimp eggs and DNA interaction. The mixed ligand complexes have exhibited moderate antibacterial activity and promising antitumor potential.