Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

The effects of short term blue light treatment on promoting nutrition value in Chinese cabbage.

Chinese cabbage is a nutrients-rich vegetable with diverse leaf colors. Here, we used widely-targeted metabolomics technology to study the metabolic responses of three Chinese cabbage varieties with representative leaf colors after blue light treatment. The inner leaf color of orange varieties 20S530 and 15S1094 changed from yellow to golden yellow, while no visible color change occurred in the common variety 14S23 after the treatment. A total of 844 metabolites were measured from the leaf samples of these three varieties in a time course study after short term blue light treatment, with kaempferol-4'-O-glucoside, isoquercitrin, hyperin, arbutin, sulforaphane as enriched nutritional metabolites. Orange Chinese cabbage varieties showed additional nutrition enhancement after the treatment. This study is the first to explore the global metabolic responses of Chinese cabbage after blue light treatment, and our findings provided valuable insights on how to effectively use lighting conditions to enhance specific groups of nutrients in vegetables.

Effects of Chlorella extracts on growth of Capsicum annuum L. seedlings.

The long-term application of chemical fertilizers has caused to the farmland soil compaction, water pollution, and reduced the quality of vegetable to some extent. So, its become a trend in agriculture to find new bio-fertilizers. Chlorella extract is rich in amino acids, peptides, nucleic acids, growth hormones, potassium, calcium, magnesium, iron, zinc ions, vitamin E, B1, B2, C, B6, folic acid, free biotin and chlorophyll. Chlorella extract can promote biological growth, mainly by stimulating the speed of cell division, thereby accelerating the proliferation rate of cells and playing a role in promoting plant growth. Whether Chlorella extract can be used to improve the growth of pepper (Capsicum annuum), needs to be verified. In current study, a pepper variety 'Chao Tian Jiao' was used as experiment material, by determining the changes of the related characteristics after spraying the seedlings with Chlorella extract, and its effect on growth of Capsicum annuum plants was investigated. The results showed that the Chlorella extract significantly increased plant height of pepper seedlings (treatment: 32.2 ± 0.3 cm; control: 24.2 ± 0.2 cm), stem diameter (treatment: 0.57 ± 0.02 cm; control: 0.41 ± 0.03 cm) and leaf area (treatment: 189.6 ± 3.2 cm2; control: 145.8 ± 2.5 cm2). Particularly, the pepper seedlings treated with Chlorella extract, developed the root system in better way, significantly increased the chlorophyll a, and the activities of SOD, POD and CAT enzymes were also improved significantly. Based on our results, we can speculate that it is possible to improve the growth of Capsicum annuum seedlings and reduce the application of chemical fertilizers in pepper production by using Chlorella extract.

Anti-inflammatory and analgesic potential of leaf extract of Justicia adhatoda L. (Acanthaceae) in Carrageenan and Formalin-induced models by targeting oxidative stress.

Plants are regarded as a valuable and inexpensive source of new drug development, and a variety of plant compounds are now being used in clinical trials to treat a variety of ailments. The goal of this work was to characterize and evaluate the anti-inflammatory and antioxidant effects of Justicia adhatoda L. leaf extract (Acanthaceae). The presence of alkaloids, saponins, tannins, phytosterols, phenols, and proteins in the leaf extract of J. adhatoda was determined using phytochemical screening. While the identification of different compounds in the leaf extract was carried out by HPLC analysis. Similarly, the anti-inflammatory potential of the leaf extract was assessed in Carrageenan and Formalin-induced inflammatory mice models. The phytochemical analysis of the leaf extract indicated a positive test for alkaloids, saponins, tannins, phytosterols, phenols, proteins, and amino acids, while the negative test for carbohydrates, and glycosides, flavonoids, and diterpenes. Moreover, among the detected compounds, gallic acid was found in the highest concentration with a 45.42% composition. The leaf extract showed the highest antibacterial activity against E. coli, while the lowest activity against Listeria was observed. The leaf extract of J. adhatoda revealed promising anti-inflammatory, analgesic, and antioxidants activities both in vitro and in vivo. Similarly, the detected compounds portrayed variable pharmacokinetic as well as binding affinities with the target proteins. In conclusion, the leaf extract exhibited significant antioxidants and antibacterial activities using in vitro assays. Similarly, the extract also revealed promising anti-inflammatory activities in vivo while exhibiting variable Pharmacokinetics and binding affinities towards protein target using computational tools.

Biosynthesis of iron oxide magnetic nanoparticles using clinically isolated Pseudomonas aeruginosa.

Magnetotactic bacteria are microscale complex natural systems that synthesize magnetic nanoparticles through biologically controlled mineralization. Nanoparticles produced by this process are biocompatible due to the presence of surrounding membranes. The mechanism controlling synthesis is cost-effective and is executed by complex genomes (operons). The results are monodispersed magnetic nanoparticles displaying advantages over polydispersed ones synthesized by physical and chemical methods. In this work, we isolated Pseudomonas aeruginosa from clinical samples and demonstrated its ability to biosynthesize magnetic nanoparticles. P. aeruginosa was thrived in a carbon-minimal medium supplemented with iron at low pH. The cells aligned parallel to a magnetic field, confirming their magnetic properties. The magnetic nanoparticles were extracted, purified, and characterized using electron microscopy, magnetometry, dynamic light scattering, and X-ray diffraction. This work represents the first isolation of a magnetotactic bacterium from clinical samples. The aerobic nature of these bacteria allows them to be easily cultured under laboratory conditions, unlike their well-known microaerophilic counterparts. The biosynthesized magnetic nanoparticles can be used in many applications, including magnetic resonance imaging, diagnostics, and therapeutics (i.e., magnetic hyperthermia).

Recent technologies for nutrient removal and recovery from wastewaters: A review.

Water scarcity and its pollution has become a concern in recent times. The disposal of nutrient-rich (nitrogen and phosphorous) wastewater is also one of the main cause of water pollution through eutrophication, reduced dissolved oxygen that poses threat to aquatic ecosystems. As a result, nutrient removal has become a mandate apart from the removal of organics. However, the removal of nutrients from sewage is a challenging task. Conversely, conventional biological treatment processes provide little relief in nutrient removal. The treated effluents from conventional biological processes do not achieve the stringent nutrient removal disposal standard limits and become primary cause of pollution in the receiving water bodies. This has stressed upon the need for eco-friendly, low-energy and cost-efficient nutrient removal treatment technologies. Various biological treatment combinations or variants are in use for the efficient removal of nutrients. The biological processes in itself or in combination with chemical processes are preferred over technologies based solely on physico-chemical processes for its treatment performance at lower cost. This review summarizes the existing treatment processes and their possible up-gradation with the aim to accomplish the marked effluent standards for the nutrients. The concept of conventional systems and advanced systems for nutrients (nitrogen and phosphorous) removal which are already developed or under development are deeply discussed. Further, the challenges of each treatment systems are abridged. Finally, the possible suggestions for the modification/retrofitting of existing treatment systems for achieving stringent disposal standards are pointed out.

Effects of vibratory massage therapy on grip strength, endurance time and forearm muscle performance.

BACKGROUND: Vibration therapy (VT) causes an increase in motor unit activation tendency, an involuntary recruitment of earlier sedentary motor units, which increases the muscle fiber force generating capacity and muscle performance. OBJECTIVE: To evaluate the effect of vibratory massage therapy at 23 Hz and 35 Hz on grip strength, endurance, and forearm muscle performance (in terms of EMG activity). METHODS: Ten healthy and right-handed men participated voluntarily in this study. The experiment was characterized by the measurement of MVC (maximal voluntary contraction) grip strength and grip endurance time at 50%MVC, accompanied by the corresponding measurement of the EMG signals of the muscles viz., flexor digitorum superficialis (FDS); flexor carpi ulnaris (FCU); extensor carpi radialis brevis (ECRB); and extensor carpi ulnaris (ECU) in supine posture. RESULTS: MANCOVA results showed significant effects of VT frequency on endurance time (p < 0.001); but no significant effect on the grip strength (p = 0.161) and muscle performance (in terms of EMG activities of the forearm muscles). However, VT improves the MVC grip strength and grip endurance time (better at 35 Hz). The Pearson correlation was significant between: weight, palm length, palm circumference, and forearm length with MVC grip strength; and the palm length with the endurance time. In addition, the palm length, palm circumference, and forearm circumference generally serve to better predict MVC grip strength and grip endurance time. CONCLUSIONS: Vibration therapy at 35 Hz for 10 minutes on the forearms had a significant positive effect on the neuromuscular performance to enhance muscle performance of upper extermitites and can be used as the optimal range to study the effect of VT. Findings may be used to prepare guidelines for VT in rehabilitation, healthcare, sports, and medical for therapists.

Effects of vibration therapy on neuromuscular efficiency & features of the EMG signal based on endurance test.

BACKGROUND: Vibration Therapy (VT) stimulate the muscle spindles, which in turn enhances its afferent activities. OBJECTIVE: The present study was designed to investigate the effect of VT at 23 and 35 Hz on muscle performance. The EMG features (six time-domain (TD) and four frequency-domain (FD)) and a new formula for computing neuromuscular performance were used as dependent variables to evaluate the effect of VT. METHOD: The EMG recording was performed at 50% MVC during grip endurance test before and after VT. The EMG features were extracted out of raw EMG signals acquired from four forearm muscles, viz., flexor digitorum superficialis (FDS); flexor carpi ulnaris (FCU); extensor carpi radialis brevis (ECRB); and extensor carpi ulnaris (ECU) in supine position. Fatigue assessments were evaluated based on the pattern of TD and FD features. RESULTS: Statistical analysis showed a significant difference in the effect of vibration exposure frequency on IEMG (p < 0.001), MAV (p = 0.041), SSI (p = 0.032), and WL (p < 0.001) of FCU muscle. In addition, the greatest increase in neuromuscular efficiency (NME) was observed in the performance of ECRB after 35 Hz of VT and ECU muscles after 23 Hz of VT. CONCLUSIONS: The features of EMG signals could be used for fatigue analysis. However, the slope based on the median frequency regression line may be the best feature for fatigue assessment.

Physiological and biochemical response of wheat (Triticum aestivum) to TiO2 nanoparticles in phosphorous amended soil: A full life cycle study.

Nanoparticles (NPs) application in soil as nano-fertilizers to increase crop yield is getting attention due to their higher efficiency and less environmental risks. This study investigated the interactive effects of variable titanium dioxide nanoparticles (TiO2-NPs) levels (0, 30, 50 and 100 mg kg-1) superimposed to phosphorus (P) fertilizer application in soil at the rates of 0, 25 and 50 mg kg-1 on wheat crop. Physiological parameters of plants, their antioxidant enzymes activities (SOD, POD), and contents of crude protein, H2O2, MDA and metals/nutrients (Al, Ca, Mg, Fe, Zn and Cu) were measured. Data on physiological traits revealed that application of 50 mg kg-1 of TiO2-NPs without P fertilizer significantly enhanced the root and shoot length by 63 and 26%, respectively. Increased contents of nutrients in the shoots, viz., Ca (316%), Cu (296%), Al (171%) and Mg (187%) with 50 mg kg-1 TiO2-NPs treatment reflected improvement in crop growth and grain quality. Furthermore, P contents in plant tissues were raised up to 56% with 50 mg kg-1 of TiO2-NPs even in the absence of P fertilizer. In the soil, concentration of phytoavailable P was significantly increased up to 63.3% in the presence of 50 mg kg-1 TiO2-NPs as compared to control. Contents of crude protein in grain were also enhanced by 22.8% (at P50) and 17.4% (at P25) with 50 mg kg-1 TiO2-NPs application. Along with P application, TiO2-NPs triggered the activities of SOD (2.06-33.97%) and POD (up to 13.19%), and H2O2 production (50.6-138.8%). However, MDA contents were not elevated significantly at any level of TiO2-NPs, and remained at par with control. It was noteworthy that highest level of TiO2-NPs, viz., 100 mg kg-1 exhibited plant and nutrients response lower than that with 50 mg kg-1. Further, TiO2-NPs triggered the bioavailability of micronutrient heavy metals (Zn, Cu and Fe) and Al, which could have toxicity at higher concentrations. These results suggested that TiO2-NPs might have some affinities with phosphate compounds and metal ions in the soil to bring them in soluble form, which enhanced their bioavailability. Although it improved the crop yield and quality, but toxic or negative impact of TiO2-NPs was also apparent at higher dose. Therefore, investigations on the potential interactions of NPs with other nutrients and toxic metals are needed to enhance our understanding for the safer application of nano-fertilizer.

Current Progress of Phytomedicine in Glioblastoma Therapy.

Glioblastoma multiforme, an intrusive brain cancer, has the lowest survival rate of all brain cancers. The chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling pathways. These complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy resistance. Therefore, the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound importance. Medicinal plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers, modulate anti-cancer pathways and immunological responses to facilitate their eradication, and induce apoptosis. These phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis, chemotherapy resistance and angiogenesis. These plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and recurrence. In this review, we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics, and also highlighted their mode of action and pharmacological profile.

CRISPR/Cas9: Nature's gift to prokaryotes and an auspicious tool in genome editing.

Clustered regularly interspaced short palindromic repeats (CRISPR) is a family of DNA direct repeats found in many prokaryotic genomes. It was discovered in bacteria as their (adaptive) immune system against invading viruses. Cas9 is an endonuclease enzyme linked with the CRISPR system in bacteria. Bacteria use the Cas9 enzyme to chop viral DNA sequences by unwinding it and then finding the complementary base pairs to the guide RNA. CRISPR/Cas9 is a modern and powerful molecular biology approach that is widely used in genome engineering (to activate/repress gene expression). It can be used in vivo to cause targeted genome modifications with better efficiency as compared to meganucleases, zinc-finger nucleases and transcription activator-like effector nucleases. CRISPR/Cas9 is a simple, reliable, and rapid method for causing gene alterations that open new horizons of gene editing in a variety of living organisms, including humans, for the treatment of several diseases. In this short review, we explored the basic mechanisms underlying its working principles along with some of its current applications in a number of diverse fields.

Investigative evaluation of Cassia absus for antibacterial capacity and biomimetic synthesis of silver nanoparticles.

Cassia absus is used for medicinal purposes for a long time all over the world. In this study, the authors report the antimicrobial potential of C. absus extracts obtained with different solvents. The extract(s) obtained with ethyl acetate yielded the best antibacterial effects because of a rich supply of oxalates and alkaloids in it. The same extract was also exploited for reducing Ag+ ions (to metallic Ag0) for the synthesis of nanoparticles. Electron microscopy revealed that the silver nanoparticles were ∼18-25 nm in diameter. The Fourier-transform infrared evaluation pointed towards the fact that flavonoids present in the plant extract were acting as reductants while amino groups were the bound stabilisation agents to the synthesised nanoparticles limiting the diameter to a certain threshold and avoiding aggregation naturally. A comparative antibacterial assay of C. absus versus Ag nanoparticles showed that the nanoparticles as well as organic (ethyl acetate) extract of the plant checked the growth of selected (MDR) superbugs. However, the biosynthesised Ag nanoparticles returned better antibacterial efficacies than ethyl acetate extract.

Respiring cellular nano-magnets.

Magnetotactic bacteria provide an interesting example for the biosynthesis of magnetic (Fe3O4 or Fe3S4) nanoparticles, synthesized through a process known as biologically controlled mineralization, resulting in complex monodispersed, and nanostructures with unique magnetic properties. In this work, we report a novel aerobic bacterial strain isolated from sludge of an oil refinery. Microscopic and staining analysis revealed that it was a gram positive rod with the capability to thrive in a medium (9K) supplemented, with Fe2+ ions at an acidic pH (~3.2). The magnetic behaviour of these cells was tested by their alignment towards a permanent magnet, and later on confirmed by magnetometry analysis. The X-ray diffraction studies proved the cellular biosynthesis of magnetite nanoparticles inside the bacteria. This novel, bio-nano-magnet, could pave the way for green synthesis of magnetic nanoparticles to be used in industrial and medical applications such as MRI, magnetic hyperthermia and ferrofluids.

Evaluation of the cytotoxic potential of a new pentacyclic triterpene from Rhododendron arboreum stem bark.

CONTEXT: Traditionally, Rhododendron arboreum Sm. (Ericaceae) is a very important medicinal plant having oxytocic, estrogenic, anti-inflammatory, analgesic and hepatoprotective activities; it also inhibits the prostaglandin synthetase. OBJECTIVES: This study determines the cytotoxic potential of 15-oxoursolic acid isolated from R. arboreum against selected human cancer cell lines. MATERIALS AND METHODS: Extraction from stem bark (5 kg) of R. arboreum was performed with methanol, which was successively partitioned into hexane, dichloromethane and ethyl acetate fractions, respectively. The new antitumor agent [15-oxoursolic acid (1)] was isolated from ethyl acetate fraction through column chromatography. Structure elucidation of new compound was performed through extensive spectroscopy i.e., IR, MS and 1D and 2D NMR. Cytotoxicity of isolated compound was determined at doses 5-100 µM for a period of 72 h on specified human cancer cell lines [renal cell carcinoma (A498), non-small cell lung (NCI-H226), squamous cell carcinoma (H157) and human ovarian carcinoma (MDR-2780AD)]. RESULTS: Structure of isolated compound was characterized as 15-oxoursolic acid on the basis of various extensive spectroscopic techniques. 15-Oxoursolic acid revealed considerable anticancer activity with IC50 values of 2.3 ± 0.1 µM, 4.9 ± 0.2 µM, 9.2 ± 0.2 µM and 10.3 ± 0.1 µM against MDR 2780AD, Hep G2, H157 and NCI-H226, respectively, while in the case of A498, the activity was good (IC50 32.8 ± 1.2 µM). CONCLUSIONS: This study highlighted the potential of 15-oxoursolic acid to be further explored as a new lead compound for cancer chemotherapy.

Empty nano and micro-structured lipid carriers of virgin coconut oil for skin moisturisation.

Virgin coconut oil (VCO) is the finest grade of coconut oil, rich in phenolic content, antioxidant activity and contains medium chain triglycerides (MCTs). In this work formulation, characterisation and penetration of VCO-solid lipid particles (VCO-SLP) have been studied. VCO-SLP were prepared using ultrasonication of molten stearic acid and VCO in an aqueous solution. The electron microscopy imaging revealed that VCO-SLP were solid and spherical in shape. Ultrasonication was performed at several power intensities which resulted in particle sizes of VCO-SLP ranged from 0.608 ± 0.002 µm to 44.265 ± 1.870 µm. The particle size was directly proportional to the applied power intensity of ultrasonication. The zeta potential values of the particles were from -43.2 ± 0.28 mV to -47.5 ± 0.42 mV showing good stability. The cumulative permeation for the smallest sized VCO-SLP (0.608 µm) was 3.83 ± 0.01 µg/cm(2) whereas for larger carriers it was reduced (3.59 ± 0.02 µg/cm(2)). It is concluded that SLP have the potential to be exploited as a micro/nano scale cosmeceutical carrying vehicle for improved dermal delivery of VCO.

Green Tropical Phytoextracts - Promising Anticancer Alternative

ABSTRACT The anticancer potential of aqueous extracts of tropical plants Ficus deltoidea and Labisia pumila were tested on human prostate carcinoma (DU145) cells. The effects of these extracts on the cells were observed through several tests such as cytotoxicity MTT assay, trypan blue exclusion assay (for cell viability), fluorescence and morphological observations. Both of the plant extracts had a growth repression effect on the cells with different concentrations. The best concentration (1x10-3 μg/mL) was chosen by determining their cytotoxic effects on human prostate cancer as well as fibroblast (normal) cells. The F. deltoidea extract showed more potency and killed the cells faster than L. pumila. Morphologically both extracts affected the cells in a similar way, i.e. the cells became irregular shaped, detached themselves and kept floating in the medium.

Metabolomics - the complementary field in systems biology: a review on obesity and type 2 diabetes.

Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.