C. madagascariensis, an unexplored species of Burseraceae is used by local population for the management of inflammation and throat pain. The disease alleviation by this plant could be due to the presence of rich repository of active compounds with various pharmacological importances. In this study, therefore, the profiling of metabolites and isolation of active compounds of C. madagascariensis was performed. Furthermore, the ethanol, ethyl acetate extracts and a selected active compound was subjected for in vitro and in vivo anti-inflammatory activities. Metabolomic analysis identified and quantified 116 metabolites from leaves, young stem and gum-resins of C. madagascariensis (Burseraceae) followed by multivariate PCA analysis. NMR, GC–MS and HPLC were used to analyze primary and secondary metabolites. Subsequently, five main isolated compounds were identified as trimethoxy tetrahydrobenzo dioxolo isochromene (TTDI), butyl phenol, butyl propionate phenol, germacrone and β-elemenone. Amongst them, TTDI was found to be a novel compound. Hence, a process was developed to obtain the enriched fraction of TTDI in ethanol and ethyl acetate extracts of leaves. Furthermore, TTDI and extracts were subjected for their in vitro anti-inflammatory activity in LPS sensitized murine splenocytes. The results showed that TTDI and both extracts significantly suppressed the levels of pro-inflammatorycytokines (TNF-α, IFN-γ). Interestingly, the suppression of pro-inflammatory cytokines was evenmore significant by the similar concentration of TTDI when compared with colchicine. However, the level of anti-inflammatory cytokine (IL-10) was found to be unchanged. Additionally, in vivo anti-inflammatory study revealed a significant reduction in carrageenan induced paw edema by TTDI and both the extracts. In the docking study, TTDI was more active than colchicine with strong binding affinity to COX-2, PLA2, and 5β reductase. Our results highlighted that the presence of metabolites with medicinal and nutraceutical importance in C. madagascariensis, could provide opportunities for the development of a new plant-based therapeutics for inflammation.

Atmospheric water harvesting (AWH) has consistently emerged as a possible source of fresh water, especially in regions where water and energy are scarce. Harvesting water from ambient air has the potential to be largely powered by renewable energy sources. Renewable energy has demonstrated a greater potential to produce water in arid regions using adsorption-based atmospheric water harvesting (ABAWH). Adsorbent is the only component in the ABAWH process that converts ambient air or moisture to water. In this direction, metal–organic frameworks (MOFs) have recently emerged as effective AWH adsorbents. The chapter focuses on the development of MOF-based adsorbents with excellent adsorption performance. Various parameters, such as adsorption kinetics, climatic conditions, and adsorption–desorption rate, have been covered in this chapter. This chapter also looks at the current advancements in AWH technologies and achievements. It is expected that this chapter will provide the reader with challenges that have been identified that retard the potential practical application of MOFs in AWH technology.

Ingenious nanomedical researches have ameliorated outcomes in cancer theranostics. Though limitations like non specific distribution generating low signal to noise ratio in diagnosis, complicated alignment of molecules, decreased biocompatibility, reduced photostability and intrinsic toxicity induced by nanomaterials require the need for improvement of nano composites by regulating their biological and physicochemical characteristics. Smart nanomaterials respond to specific stimuli like pH, oxidative stress, temperature, enzymes or any specific molecule. These properties of smart nanomaterials enhance their efficacy for use as carriers of therapeutic agents, biosensors and diagnostic tools. Smart nanomaterial drug composites respond to the conditions of tumor micro environment (TME), remaining inactive in normal cells and reducing intrinsic toxicities. Multiple drug resistance (MDR) is a significant factor causing chemotherapeutic failure and can be intrinsic or acquired. Primary/intrinsic resistance arises due to presence of factors before initiation of chemotherapy. Whereas, acquired MDR may arise by inadequate delivery of drugs, heightened expression of drug delivery targets, activation of alternate signaling pathways and constant exposure of neoplastic cells to sublethal concentration of cytotoxic drugs. The current review is focused on the categories of smart nanomaterials used in cancer theranostics and their response to various stimuli in the TME. We present a succinct account of the drug resistance mechanisms and the role of smart nanomaterials in reversing resistance offered by these physiological barriers, with special emphasis on precision and personalized therapy.

Significance of biopolymersBiopolymer like chitosan and its nanosized derivatives and the procedure of their implementation in various disciplines, particularly in medicine, is continuously increasing. The distinctive biological, physicochemical, physiological and ecological properties like biodegradabilityBiodegradability, biocompatibilityBiocompatibility, reduced toxicity, environmental stability, enhanced metabolic activity, cost-effectiveness, capability to chelate ions and elevated absorption make chitosan a promising prospect for use in various biomedical applicationsBiomedical applications. Hydroxyl and amino functional groups make chitosanChitosan a propitious agent for several biomedical processes like precision carrier of drugs, bone or tissue engineeringTissue engineering, healing of wounds, alternative medicine, haemostasis, dental proceduresDental procedures, cosmetic treatmentCosmetic treatment and in various biotechniques. ChitosanChitosan and derivatives are also involved in mucosal delivery of vaccines. NanoparticlesNanoparticles conjugated with chitosanChitosan have immense scope for development of innovative drugs and vaccines. Based on recent research, the current chapter elaborates the techniques employed for preparation of chitosanChitosan-based nanocompositesComposites.

Water contamination adversely affects the environment and human health and has significant socioeconomic implications. Scarcity of potable water requires effective strategies for wastewater treatment. Conventional strategies release disinfection byproducts (DBPs), consume time and are expensive. Nanotechnology uses molecules or atoms to develop new devices with enhanced optical, conductive, magnetic, mechanical, and electronic characteristics. It is an emerging viable technique for wastewater purification, but its implementation needs to be explored. In this review, we specify nanotechniques for wastewater treatment, formulated on processes of adsorption, biosorption, photocatalysis, nanofiltration, sensing and monitoring technologies. Additionally, we also interpret the future of wastewater treatment through nanotechnology and the risks associated.

1 Department of Orthopaedic Surgery, King George’s Medical University (KGMU), Shahmina Road, Chowk, Lucknow, Uttar Pradesh, India. 2 Department of Biochemistry, King George’s Medical University (KGMU), Shahmina Road, Chowk, Lucknow, Uttar Pradesh, India. 3 Department of Neurology, King George’s Medical University (KGMU), Shahmina Road, Chowk, Lucknow, Uttar Pradesh, India. 4 Centre of Biomedical Research, formerly Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Rae Bareli Road, Lucknow, Uttar Pradesh, India. 5 Department of Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences (RMLIMS), Vibhuti Khand, Gomti Nagar, Lucknow, Uttar Pradesh, India.

Acute spinal cord injury (ASCI) is an extremely overwhelming disease with high morbidity and mortality. Despite significant successes in understanding the pathophysiology of ASCI, little is known about limiting neurological damage and predicting recovery. Biofluid metabolomics by 1H NMR spectroscopy for metabolites quantification specific to nervous tissue injury may determine the injury and progression. This study evaluates the urinary metabolic profile in ASCI cases on two different treatment modalities. One forty participants were enrolled. Group-1, “healthy control, n=70”, ASCI cases in Group-2 “fixation with stem cells therapy, n=35” and ASCI cases in Group-3, “fixation alone n=35”. Urine samples were collected at baseline and regular follow-ups up to the 6th month for 1H NMR spectroscopy. The sample spectra were subjected to multivariate Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) and Variable Importance to the Projection (VIP) analysis. The significant metabolites were correlated with neurological recovery. Acetate, creatinine, creatine, creatine phosphate, urea, and phenylalanine were found to be significant. The 3D scattered score plots in OPLS-DA represented the shifting of cases towards control in the final follow-up. It was further substantiated on VIP score plots. The metabolic aberrations in urine with disease severity in ASCI could be a potential biomarker of neurological recovery. Key words: NMR spectroscopy, metabolomics, acute spinal cord injury (ASCI), Asia impairment scale (AIS), neurological recovery.

Commiphora wightii (Arn.) Bhandari, known as guggul, produces a medicinally important gum resin which is used extensively by Ayurvedic physicians to treat various ailments. However, most of the studies on C. wightii have been limited to its gum resin. Comprehensive metabolic profiling of leaves, stem and gum resin samples was undertaken to analyse aqueous and non-aqueous metabolites from three distinct chemotypes (NBRI-101, NBRI-102 and NBRI-103) shortlisted from different agro-climatic zones. GC-MS, HPLC and NMR spectroscopy were used for comprehensive metabolomics. Multivariate analysis showed characteristic variation in quinic and citric acids, myo-inositol and glycine (aqueous metabolites) and 2,6-di-tert-butyl-phenol, trans-farnesol and guggulsterones (non-aqueous metabolites) amongst the three chemotypes. Quinic acid, citric acid and myo-ionositol were detected in substantial quantities from leaves and stem samples which provide opportunities for novel nutraceutical and pharmaceutical formulations. Quinic acid, from the leaves, was identified as a marker metabolite for early selection of high guggulsterones-yielding cultivars.

BACKGROUND:Acute Spinal Cord Injury (ASCI) is still having substantial morbidity and mortality despite of advanced therapeutics. Major obstacles are paucity of monitoring tools or biomarkers for severity determination, recovery and prognostication. A prospective case control pilot study with serum 1H NMR spectroscopic metabolic profiling was carried out to evaluate metabolites perturbations and its relationship with recovery and to see role of stem cells in facilitating neurological recovery. METHODOLOGY:Twenty subjects with ASCI were classified on the basis of therapeutic modality into surgical fixation alone (Group-1, n = 10), stem cell adjuvant (Group-2, n = 10) and healthy controls (Group-0, n = 10). Serum samples were collected at admission (baseline) and after six months (follow-up). NMR data of serum sample were quantified and subjected to Wilcoxon and ANOVA tests. Further validation was performed using supervised OSC-PCA and OPLS-DA by incorporating substantial control samples. RESULT:Twenty-eight metabolites were identified; well resolved resonances of fifteen metabolites were quantified wherein seven were statistically significant. Predominantly amino acids and ketone bodies played vital role in the differentiation of groups. CONCLUSIONS:Serum NMR spectroscopy reveals certain metabolites perturbations having clear correlation with pattern of recovery in treated ASCI subject. Stem cells treatment group had comparatively effective recovery.

Aim of the study was to undertake comprehensive metabolic profiling of plant parts of Commiphora wightii during two contrasting seasons i.e. summer and winter; compared seasonal metabolic variations; and assess antioxidant activity of fractions for commercial applications. Leaves, young stems and gum-resin extracts from summer and winter seasons were analyzed using GC-MS, HPLC and NMR spectroscopy. The antioxidant activity on each set was determined by DPPH free radical scavenging assay. Complete metabolic profiling from two contrasting seasons identified one hundred and four major known and unknown metabolites. Also, two alkylated phenols, 2,4-di- tert-butyl phenol and 3-(3,5-di- tert-butyl-4-hydroxyphenyl) propanoic acid not reported earlier from this taxon were isolated from the vegetative part. Comparative analysis of seasonal metabolic profiles of leaves, young stems and gum-resin revealed significant variations in concentrations of several metabolites. Multivariate principal component analysis (PCA) showed significant qualitative and quantitative variations in the polar (glycine, quinic acid and myo-inositol) and non-polar metabolites (alkylated phenols, guggulsterones and α-tocopherol) between the two seasons. Variation amongst metabolites such as myo-inositol, quinic acid α- tocopherol and alkylated phenols that are important for nutraceutical industry in the two contrasting seasons is a useful finding. These metabolites are of medicinal and nutraceutical importance and are commonly used in nutraceuticals and dietary supplement industry. DPPH radical scavenging activity (IC50 values) of polar and non-polar extracts varied significantly between summer and winter seasons. The antioxidant activity can be attributed to major polar metabolite, quinic acid biosynthesized in excess during winter, and to non-polar metabolites like alkylated phenols and α-tocopherol present during the summer season. The study shall be useful for medicinal, nutraceutical and dietary supplement industry for selection of polar or non-polar extracts from a particular season for obtaining targeted products with optimized functionality.

Aim of the study was to undertake comprehensive metabolic profiling of plant parts of Commiphora wightii during two contrasting seasons i.e. summer and winter; compared seasonal metabolic variations; and assess antioxidant activity of fractions for commercial applications. Leaves, young stems and gum-resin extracts from summer and winter seasons were analyzed using GC-MS, HPLC and NMR spectroscopy. The antioxidant activity on each set was determined by DPPH free radical scavenging assay. Complete metabolic profiling from two contrasting seasons identified one hundred and four major known and unknown metabolites. Also, two alkylated phenols, 2,4-di- tert -butyl phenol and 3-(3,5-di- tert -butyl-4-hydroxyphenyl) propanoic acid not reported earlier from this taxon were isolated from the vegetative part. Comparative analysis of seasonal metabolic profiles of leaves, young stems and gum-resin revealed significant variations in concentrations of several metabolites. Multivariate principal component analysis (PCA) showed significant qualitative and quantitative variations in the polar (glycine, quinic acid and myo -inositol) and non-polar metabolites (alkylated phenols, guggulsterones and α-tocopherol) between the two seasons. Variation amongst metabolites such as myo -inositol, quinic acid α- tocopherol and alkylated phenols that are important for nutraceutical industry in the two contrasting seasons is a useful finding. These metabolites are of medicinal and nutraceutical importance and are commonly used in nutraceuticals and dietary supplement industry. DPPH radical scavenging activity (IC 50 values) of polar and non-polar extracts varied significantly between summer and winter seasons. The antioxidant activity can be attributed to major polar metabolite, quinic acid biosynthesized in excess during winter, and to non-polar metabolites like alkylated phenols and α-tocopherol present during the summer season. The study shall be useful for medicinal, nutraceutical and dietary supplement industry for selection of polar or non-polar extracts from a particular season for obtaining targeted products with optimized functionality.

BACKGROUND:Parkinson's disease (PD) is the result of progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. METHODS:We included 17 patients with PD along with 7 patients of progressive supranuclear palsy (PSP), 6 patients of multiple system atrophy (MSA) and 22 age and sex-matched healthy controls. We analyzed metabolite profiles in the serum of these patients and controls using 1H NMR spectroscopy. RESULTS:Isoleucine, valine, alanine, glutamine and histidine in PD, PSP and MSA were significantly (P < 0.001) higher than controls, whereas, glutamate and glucose were significantly increased in PD (P < 0.001), PSP and MSA (P < 0.05) vs. CONTROL:Citrate was increased in PD, PSP and MSA (P < 0.05) vs. CONTROL:While, acetone, lactate and formate were higher at P < 0.001, threonine is increased at P < 0.05. The 3D scattered score plot of OPLS-DA model revealed clear differentiation among the groups, R2 = 0.92 and Q2 = 0.78. CONCLUSION:Significant differences in various metabolite levels were found between control and disease groups. Common amino acids that are significantly higher in all groups include branched chain amino acids, which could increase neuronal excitability.

Background: Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls).Methods: The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discritninant Analysis (PLS-DA).Results: The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R-2 of 0.97 and Q(2) of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R-2 of 0.80 and Q(2) of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations.Conclusion: On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. (C) 2017 Elsevier B.V. All rights reserved.

Meningitis, a morbidly infectious central nervous system pathology is accompanied by acute inflammation of the meninges, causing raised intracranial pressure linked with serious neurological sequelae.

Introduction: The identification of a drug candidate and its structural determination is the most important step in the process of the drug discovery and for this, nuclear magnetic resonance (NMR) is one of the most selective analytical techniques.Area covered: The present review illustrates the various perspectives of absolute quantitative H-1 NMR spectroscopy in drug discovery and development. It deals with the fundamentals of quantitative NMR (qNMR), the physiochemical properties affecting qNMR, and the latest referencing techniques used for quantification. The precise application of qNMR during various stages of drug discovery and development, namely natural product research, drug quantitation in dosage forms, drug metabolism studies, impurity profiling and solubility measurements is elaborated. To achieve this, the authors explore the literature of NMR in drug discovery and development between 1963 and 2015. It also takes into account several other reviews on the subject.Expert opinion: qNMR experiments are used for drug discovery and development processes as it is a non-destructive, versatile and robust technique with high intra and interpersonal variability. However, there are several limitations also. qNMR of complex biological samples is incorporated with peak overlap and a low limit of quantification and this can be overcome by using hyphenated chromatographic techniques in addition to NMR.

Objective: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out whether any association existed among structural changes, SIP, and nutritional status.Method: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n = 15 and extrahepatic portal venous obstruction n = 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake.Results: Among children with PHT, 48% had PHTD defined as presence of villous atrophy (villous to crypt ratio < 2.5:1), dilated capillaries (capillary diameter > 16.8 mu m, capillary area > 151 mu m(2), capillary perimeter > 56 mu m), and thickened muscularis mucosae (>22.2 mu m). Lactulose excretion alone was increased in children with PHT as compared with healthy children (median %: 0.03, 0.02, and 0.01 for cirrhosis, extrahepatic portal venous obstruction, and controls, respectively [P < 0.01]) signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight, and triceps skin-fold thickness (<-2SD), whereas no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise, and PHTD in our patients had no correlation.Conclusions: PHT is often associated with duodenopathy. SIP does occur as a result of increased paracellular permeability. Factors of increased SIP, undernutrition, and PHTD do not have correlation in childhood PHT.

Background: Urosepsis, a severe form of sepsis requires immediate medical attention for prognosis. It is clinically diagnosed by estimating serum procalcitonin (PCT) levels along with time taking urine and blood cultures. We explored NMR based profiling, deriving metabolites that could potentially aid diagnosis.Methods: The proton NMR of serum and urine samples of healthy control subjects (n = 32) and urosepsis cases (n = 35) based on PCT levels, were analyzed. Four clinically identified non-urosepsis cases with high PCT levels were also differentiated through principal component analysis (PCA) of the serum samples.Results: Quantification of serum and urine through Discriminant Function Analysis (DFA) afforded 93.7% and 91.7% correct classification respectively, along with identification of malonate and urea as potential biomarkers for the disease in both urine and serum samples. The partial least square discriminant analysis (PLS-DA) showed an R-2 value of 0.97 in both biofluids with Q(2) = 0.87 and 0.85 for serum and urine respectively. The training set of serum samples provided precise prediction of the test set in a small cohort through random re-sampling method, while in urine samples, the predictions were inconclusive.Conclusions: Our pilot study reveals that H-1 NMR of serum metabolic profiling in combination with PCT levels may provide a rapid method for differentiation of urosepsis. (C) 2015 Elsevier B.V. All rights reserved.