Multifactorial pathways in burn injury-induced chronic pain: novel targets and their pharmacological modulation.

Burn injuries are among the highly prevalent medical conditions worldwide that occur mainly in children, military veterans and victims of fire accidents. It is one of the leading causes of temporary as well as permanent disabilities in patients. Burn injuries are accompanied by pain that persists even after recovery from tissue damage which puts immense pressure on the healthcare system. The pathophysiology of burn pain is poorly understood due to its complex nature and lack of considerable preclinical and clinical shreds of evidence, that creates a substantial barrier to the development of new analgesics. Burns damage the skin layers supplied with nociceptors such as NAV1.7, TRPV1, and TRPA1. Burn injury-mediated co-localization and simultaneous activation of TRPA1 and TRPV1 in nociceptive primary afferent C-fibers which contributes to the development and maintenance of chronic pain. Burn injuries are accompanied by central sensitization, a key feature of pain pathophysiology mainly driven by a series of cascades involving aberrations in the glutamatergic system, microglial activation, release of neuropeptides, cytokines, and chemokines. Activation of p38 mitogen-activated protein kinase, altered endogenous opioid signaling, and distorted genomic expression are other pathophysiological factors responsible for the development and maintenance of burn pain. Here we discuss comprehensive literature on molecular mechanisms of burn pain and potential targets that could be translated into near future therapeutics.

Hydrophilic interaction LC-MS/MS method to avoid endogenous interference in the analysis of 4-hydroxy isoleucine from dietary supplementation of fenugreek.

4-Hydroxy isoleucine is one of the potent hypoglycemic active constituents of fenugreek seeds. A method capable of reducing biological interferences is required for bioavailability studies. An isocratic separation of 4-hydroxy isoleucine from endogenous interferences was achieved in ZIC-cHILIC column using 0.1% formic acid in water and acetonitrile (20:80, % v/v) pumped at 0.5 ml/min. Quantification was performed in multiple reaction monitoring mode using the transitions of m/z 148.1→102.1 and m/z 276.1→142.2 for 4-hydroxy isoleucine and homatropine (as internal standard), respectively. After full method validation, 4-hydroxy isoleucine levels in human plasma and commercial fenugreek formulations were determined. This method showed good linearity in the range of 50-2000 ng/mL. Intra- and interday accuracies were in the range of 90.64-109.0% and precision was <4.82% CV. The mean (SD) plasma concentration of 4-hydroxy isoleucine in healthy individuals at 2 h after oral administration of fenugreek tablet was found to be 1590 (260) ng/mL. Half of marketed formulations were found to contain <0.05% of 4-hydroxy isoleucine content. We developed a rapid hydrophilic interaction liquid chromatography-tandem mass spectrometry method for analysis of 4-hydroxy isoleucine in human plasma. This method can be applied directly to conduct the clinical pharmacokinetics studies of 4-hydroxy isoleucine in human population.

Comparative Study to Evaluate the Effect of Low-Protein Diet Supplementation with Taurine and N-Acetylcysteine, N-Acetylcysteine and Pyridoxamine Dihydrochloride in Preventing the Progression of Chronic Renal Failure in Patients with Non-Diabetic Kidney Disease.

Chronic Kidney Disease(CKD) has multifactorial etiology and there are lots of grey zone in understanding its complex pathophysiology. There is no silver bullet for optimal care of CKD. Oxidative stress being well understood and considered as an important common progressive factor for CKD of different etiology. Several research studies focused on reducing oxidative stress and have shown diverse outcomes. In this randomized, open-label, three arms, controlled, single center study we evaluated the role of N acetylcysteine which is a direct scavenger of free radical, in combination with taurine and pyridoxamine in retarding the progression of non-diabetic kidney disease. METHODS: 69 non-dialysis, non-diabetic patients diagnosed with chronic renal failure with GFR more than 15 ml/min/1.73m2 and less than 60ml/min/1.73m2 receiving standard of care were enrolled in the study, of which 22 were in the placebo arm, 23 treated with NT (500 mg Taurine + 150 mg NAC) arm and 24 in the NP (300mg NAC+ 50mg pyridoxamine di-hydrochloride) arm. The subjects in the treatment arm received the study drug twice a day along with low protein (0.6gm protein per Kg body weight) isocaloric diet with 25-30 Kcal/Kg/D and were evaluated monthly up to 6 months. Change in eGFR accorss 3 groups over 6 months were compared. RESULT: Mean age of the subjects was 57 ± 13 years of 56.25% were male and 43.75% were female. 69 patients completed the study. The Empirical Distribution Function (EDF) of NP group was dominant over control and NT group indicating a positive effect of NT on non-diabetic CKD at 10% level of significance. In the subgroup analysis a significant effect was observed in the cases of patients receiving NP with baseline eGFR more than 45 ml/min. The mean increase in eGFR readings over six months was 8.15 units higher in the NP group than in the control group. The two-sided p-values of the t-test, the Wilcoxon test and the Kolmogorov-Smirnov test were 0.0496, 0.0316 and 0.0354, respectively. Thus, all the three tests reject the hypothesis of identical changes in eGFR at the 5% level. In subjects with bicarbonate more than 22 mg/dl, the mean increase in eGFR over six months was 10.86 units higher in the NP group than in the control group indicating NP has a positive effect on increasing eGFR over 6 months, in patients without the presence of any metabolic acidosis. The two-sided p-vales of the t-test, the Wilcoxon test and the Kolmogorov-Smirnov test were 0.0325, 0.0205 and 0.1495, respectively. Thus, two of the three tests reject the hypothesis of identical changes in eGFR at the 5% level which clearly indicates that NP had better efficacy than other groups. CONCLUSION: N-acetyl cysteine along with pyridoxine may be a useful intervention along with a low protein diet in retarding progression of CKD in the nondiabetic population in early CKD.

Retention of freshness and isothiocyanates in fresh-cut radish (Raphanus sativus var. Longipinnatus) through glucose dip treatment.

Experiments were carried out with the objective of enhancing shelf life and maintain quality of fresh-cut radish slices during storage at 8 °C. Dip treatment of radish slices in 20 g/L glucose solution for five minutes retained the quality attributes viz., surface colour, sensory properties and antioxidant capacity of the slices till six days of storage. Isothiocyanates were also retained better due to glucose dip. Biplot generated through principal component analysis of head space volatiles from fresh and stored radish slices showed that fresh and glucose treated slices grouped together with 4-methyl thio-3-butenyl isothiocyanate. Accumulation of sulphurous volatiles such as methyl disulphide, dimethyl trisulphide, 2-pentanethiol was observed in control (undipped) radish slices, indicating their probable role as spoilage indicator volatiles. Thus, glucose pre-treatment can be considered as a practical method for quality retention of fresh-cut radish. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05276-1.

Blood fruit (Haematocarpus validus (Miers.) Bakh. f. ex Forman): a novel source of natural food colourant.

Plant based pigments have widely been used by human beings since ancient times. These pigments, being natural in origin, have better acceptability amongst the consumers and offer diversified applications worldwide. For identification of novel pigment sources, lesser known species need to be studied systematically. In the present report, a tropical fruit species viz. blood fruit was studied for its physicochemical parameters and anthocyanin content. Fruit pulp had total soluble solids of 17 °B with acidic pH (3.01) and total phenolic content of 13.44 mg GAE/100 g of fresh pulp. Pulp of fully ripe fruits contained 8.76 mg/g of total anthocyanins. Pelargonidin was the dominant anthocyanin, followed by Cyanidin, Peonidin and Petunidin. Considering these qualities, the species could be a potential candidate for food and dye industries.

Profiling of anthocyanins and carotenoids in fruit peel of different colored mango cultivars.

Mango cultivars are broadly categorized into green, yellow, and red types based on their peel colors. Anthocyanins and carotenoids are the most important pigments responsible for the color of fruits. The information available on the composition of pigments on mango peel was scanty, and the exact role of anthocyanins and carotenoids in imparting peel color was not clear. The present study was aimed at profiling anthocyanin and carotenoid pigments in the peels of green ('Langra', 'Amrapali', 'Hamlet' and 'Bombay No. 1'), yellow ('Arka Anmol', 'Lazzat Baksh', 'Peach' and 'Banganapalli') and red ('Tommy Atkins', 'Lalmuni', 'Gulabi' and 'Janardhan Pasand') colored mango cultivars through liquid chromatography and mass spectrometry at different stages of ripening. The analysis helped in the identification of eight carotenoids and 24 anthocyanins in mango peel. Higher levels of carotenoids were observed in yellow colored cultivars, and major compounds were ß-carotene and violaxanthin. Further, the red colored types were found to possess the higher anthocyanin content than green and yellow types. The major groups of anthocyanin compounds include cyanidin, peonidin, petunidin, delphinidin and pelargonidin. During fruit ripening, a significant increase in carotenoids content, and no or marginal rise in anthocyanin content was observed in mango peels. The results, show the status of carotenoids and anthocyanins in mango peel of different colored cultivars and their developmental pattern during ripening.

Effect of pretreatments and modified atmosphere packaging on the shelf life and quality of fresh- cut green bell pepper.

Present study was aimed at understanding the effect of pretreatments and modified atmosphere packaging on the quality of fresh-cut green bell pepper (Capsicum annuum L.) during low temperature storage. Dip treatment of freshly cut green bell pepper pieces in 2 % calcium propionate followed by surface drying and subsequent packing in cryovac PD961 film which maintained an equilibrium modified atmosphere of 13-14 % O2 and 7 % CO2 helped to extend the marketability till 9 days storage at 8 °C. The microbiological quality was at the best level up to 6 days of storage, as evidenced by a surge in aerobic plate count, pectinolysers and pseudomonads on subsequent days. Head space volatile analysis of the produce at regular intervals showed a reduction in monoterpenoids and simultaneous increase of aldehydes and ketones, sesquiterpenoids, esters, furans and pyrazines during storage. Principal component analysis of the head space volatiles identified, cis - ocimene, 1,3,8-paramenthatriene, trans 3- caren 2-ol, bergamotene, 2-hexenal, ethyl 1- decanol, (E)-3- hexenol and heptane thiol as the markers of freshness in minimally processed green bell pepper.

Computational reverse chemical ecology: virtual screening and predicting behaviorally active semiochemicals for Bactrocera dorsalis.

BACKGROUND: Semiochemical is a generic term used for a chemical substance that influences the behaviour of an organism. It is a common term used in the field of chemical ecology to encompass pheromones, allomones, kairomones, attractants and repellents. Insects have mastered the art of using semiochemicals as communication signals and rely on them to find mates, host or habitat. This dependency of insects on semiochemicals has allowed chemical ecologists to develop environment friendly pest management strategies. However, discovering semiochemicals is a laborious process that involves a plethora of behavioural and analytical techniques, making it expansively time consuming. Recently, reverse chemical ecology approach using odorant binding proteins (OBPs) as target for elucidating behaviourally active compounds is gaining eminence. In this scenario, we describe a "computational reverse chemical ecology" approach for rapid screening of potential semiochemicals. RESULTS: We illustrate the high prediction accuracy of our computational method. We screened 25 semiochemicals for their binding potential to a GOBP of B. dorsalis using molecular docking (in silico) and molecular dynamics. Parallely, compounds were subjected to fluorescent quenching assays (Experimental). The correlation between in silico and experimental data were significant (r2 = 0.9408; P < 0.0001). Further, predicted compounds were subjected to behavioral bioassays and were found to be highly attractive to insects. CONCLUSIONS: The present study provides a unique methodology for rapid screening and predicting behaviorally active semiochemicals. This methodology may be developed as a viable approach for prospecting active semiochemicals for pest control, which otherwise is a laborious process.

Optimization of foaming process for development of modified aloe polysaccharide (MAP) juice and powder using foam-mat drying.

The present study was performed to optimize the modified aloe polysaccharide (MAP) foaming process and to determine the effect of drying process parameters on the quality of obtained MAP powder. The studied process parameters were glycerol monostearate (GMS), carboxymethyl cellulose (CMC), and whipping time (WT) which was varied between 1 and 4% w/v, 0.1-0.5% w/v, and 1-5 min, respectively. The optimized values of foaming process parameters were 3.87% GMS, 0.39% CMC, and 4.89 min WT with a desirability of 0.889. The optimized foamed MAP juice was dried at different foam thicknesses (FT) (1, 3, and 5 mm) and drying temperatures (DT) (50, 60, and 70 °C) to develop MAP powder and compared with non-foamed aloe powder developed under the same drying condition. Based on functional properties, the best GMS foamed MAP powder was achieved at 50 °C DT and 1 mm FT, recording powder yield (16%), solubility (20.85%), and polysaccharide content (282 mg/L). Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01354-6.

Emerging encapsulation strategies for vitamin A fortification in food sector: an overview.

Micro- and nano-encapsulation techniques, such as microfluidization, spray drying, and centrifugal extrusion, have been widely utilized in various industries, including pharmaceuticals, food, cosmetics, and agriculture, to improve the stability, shelf life, and bioavailability of active ingredients, such as vitamin A. Emulsion-based delivery platforms offer feasible and appropriate alternatives for safeguarding, encapsulating, and transporting bioactive compounds. Therefore, there is a need to enrich our basic diet to prevent vitamin A deficiency within a population. This review focused on addressing vitamin A shortages, encapsulation techniques for improving the delivery of vital vitamins A and their food applications. Additionally, more studies are required to guarantee the security of nano-delivery strategies, as they proliferate in the food and beverage sector.

Infusion of active compound into sliced button mushrooms through vacuum impregnation to improve functionality: Comparing response surface methodology and artificial neural network.

The present study explores the infusion of active compounds (ascorbic acid and calcium lactate) into sliced button mushrooms (Agaricus bisporus) to increase the nutritional value and reduce the browning effect of sliced mushrooms using the vacuum impregnation (VI) technique. The aim was to functionalize the vacuum-infused sliced mushrooms and evaluate the physicochemical properties of button mushrooms for diversifying food use. The central composite design was implemented to determine the optimized condition for the process with four independent factors, that is, immersion time (IT) 30-90 min, solution temperature (ST) 35-55°C, solution concentration (SC) 4%-12%, and vacuum pressure (VP) 50-170 mbar. The optimum VI processes obtained were ST-40°C, SC-8%, VP-140 mbar, and IT-65 min with a desirability function of 0.77. Statistically, two models (response surface methodology [RSM] and artificial neural network [ANN]) were employed to compare the better performance for the prediction of VI operational process parameters. The RSM model showed a better prediction of VI process parameters than the ANN model, with a higher R2 value (0.9228 vs. 0.8160) and lower root mean square error value (1.4004 vs. 2.1751), χ2 (2.4491 vs. 5.2762), mean absolute error (1.1177 vs. 1.1611), and absolute average deviation (4.3532 vs. 5.6746) for water loss. A similar pattern was observed for solute gain, ascorbic acid, titratable acidity, color change, firmness, and pH. Therefore, the VI process was found to be an effective method for enhancing the nutritional properties of sliced mushrooms. These findings concluded that the RSM model is more efficient for better prediction with good accuracy of the VI process than the ANN model.

Implementation of RSM and ANN Optimization Approach for Natural Deep Eutectic Solvents-Based Extraction of Bioactive Compounds from Orange Peel.

The present investigation has focused on developing an eco-friendly method to extract bioactive compounds from orange peel using natural deep eutectic solvents (NADES). NADES-II composed of choline chloride (ChCl) and ethylene glycol (1:2) and 50% water shows the maximal extraction yield with higher antioxidant activity in terms of DPPH and ABTS scavenging activity with a high total phenolic content (TPC) and total flavonoid content (TFC). The microwave-assisted extraction (MAE) process was optimized using response surface methodology (RSM) and an artificial neural network (ANN). ANN showed a higher value of R 2 and lower values of other statistical parameters when compared to RSM. The ideal extraction conditions were optimized as a 13 min rising time, 52 °C temperature, a 21 min holding time, and a 20 mL/g liquid-to-solid ratio. MAE was compared with the conventional heating-stirring extraction (HSE) method using the NADES-II solvent under optimum conditions. The results show that higher extraction yield and antioxidant capacities (DPPH and ABTS), TPC, and TFC can be obtained from orange peel using the MAE process compared to the HSE process. Overall, this study shows an optimiztic approach for the extraction of bioactive compounds from an orange peel using eco-friendly solvents and microwave technology. It also highlights the potential of this approach for valorizing orange peel waste.

Polygalacturonase inhibitor protein from fruits of anthracnose resistant and susceptible varieties of Chilli (Capsicum annuum L).

Chilli fruit is highly susceptible to anthracnose infection at the stage of harvest maturity, due to which the fruit yield in the leading commercial variety Byadgi is severely affected. Field studies on screening of several varieties for resistance to anthracnose have shown that a variety of chilli AR-4/99K is resistant to anthracnose infection. In many crops, resistance to fungal attack has been correlated with PGIP activity in developing fruits based on which transgenic varieties have been developed with resistance to fungi. The present study was carried out to determine whether anthracnose resistance in AR-4/99K was due to the increased levels of PGIP alone and/ or due to differences, if any, in the properties of PGIP. Hence, a comparative study of the properties of polygalacturonase inhibitor protein (PGIP) isolated from fruits of anthracnose resistant chilli var AR-4/99K and a susceptible variety Byadgi was conducted with the objective of utilizing the information in genetic transformation studies. Both the PGIPs from anthracnose resistant and susceptible varieties of chilli exhibited similarities in the elution pattern on Sephadex gel, DEAE cellulose, PAGE and SDS-PAGE. The two PGIPs were active over a wide range of pH and temperature. Both PGIPs showed differential inhibitory activity against polygalacturonase (PG) secreted by Colletotrichum gleosporoides, C. capsici, C. lindemuthianum, Fusarium moniliforme and Sclerotium rolfsii. The inhibitory activity of PGIP from both resistant and susceptible varieties was the highest (82% and 76%, respectively) against the PG from Colletotrichum capsici, a pathogen causing anthracnose rot of chilli, while the activity was lower (1.27 to 12.3%) on the other fungal PGs. Although PGIP activity decreased with fruit maturation in both the varieties, the resistant variety maintained a higher activity at 45 days after flowering (DAF) as compared to the susceptible variety which helped it to overcome the infection by anthracnose as against the susceptible variety (Byadgi) in which PGIP activity was drastically reduced at maturity. The molecular mass of PGIP as determined by SDS-PAGE was found to be 37 kDa. N-terminal sequence analysis of the PGIP showed the first six amino acid residues from N-terminal end were Asp-Thr-His-Lys-Ser-Glu (DTHKSE), respectively. The similarities in properties of the two PGIPs support the earlier findings that resistance of AR-4/99K to anthracnose fungus is a result of its higher PGIP activity at maturity.

Antiproliferative effect of Acacia nilotica (L.) leaf extract rich in ethyl gallate against human carcinoma cell line KB.

OBJECTIVES: The objective of this study is to analyze the antiproliferative activity of Acacia nilotica (L.) leaf ethanolic extract against cancer KB cells and to determine the mode of cancer cytotoxicity. MATERIALS AND METHODS: In this study, high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis were done to confirm the presence of ethyl gallate as a major bioactive phenolic in the leaf ethanolic extract of A. nilotica, further dose-dependent (0-120 µg/mL) antiproliferative effect was investigated in human carcinoma cell line KB. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, reactive oxygen species, mitochondrial membrane potential loss, DNA damage, and apoptosis were evaluated. RESULTS: A. nilotica leaf ethanolic extract (ANLEE) showed effective concentration (EC50) of 40 µg/mL. Interference of growth was significantly (P < 0.05) high in KB cells treated with ANLEE when compared to untreated control, but less when compared to the reference drug paclitaxel. In addition, the in vivo acute toxicity study demonstrated the safe limit of administration of 2000 mg/kg body weight ANLEE by the histological analysis in rats. The results from the present study indicate that mitochondria and DNA of KB cells are severely affected leading to apoptosis. CONCLUSIONS: ANLEE is a prospective source for cancer therapy and therefore should be highlighted to explore on its wide range of safety in rats and efficacy against human carcinoma cell line KB.

Probing the Manipulated Neurochemical Drive in Alcohol Addiction and Novel Therapeutic Advancements.

Alcohol addiction is one of the highly prevalent neurological disorders and a major threat to public health in the 21st century. Alcohol addiction affects people from all age groups and often leads to other serious comorbidities. The pathophysiology of alcohol addiction involves imbalance between the excitatory and inhibitory neurotransmitters in the brain. These changes occur in various regions of the brain including reward circuit such as the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex. In this review, we have discussed several neurochemical circuitries which get manipulated and maladapted during alcohol addiction. To date there is no effective therapeutic intervention in clinics devoid of side effects that can successfully treat the patients suffering from alcohol addiction. Understanding the neurobiological intricacies of alcohol addiction is critical for the development of novel anti-addiction therapeutics. Apart from this, we have also discussed the recent therapeutic milestones for the management of alcohol addiction including vasopressin receptors, corticotrophin-releasing factor, GABA receptors, glucocorticoid receptors, brain stimulation and mindfulness-oriented recovery enhancement.

Hepatitis E-Induced Acute Myocarditis in an Elderly Woman.

Hepatitis E is a common, mainly water-borne hepatotropic virus prevalent mainly in Southeast Asia, Africa, the Middle East, and Central America. In the eastern part of India epidemics of acute hepatitis E are well reported. Hepatitis E commonly presents as self-limiting acute viral hepatitis among young adults, except for some critical clinical complications during pregnancy. In epidemiological research, subclinical acute hepatitis E infection is also reported from different parts of the world, including developed nations such as the USA (predominantly in the population aged >60 years). Though primarily hepatotropic, in the literature there are reports of rare extrahepatic manifestation of acute hepatitis E. Here we present an elderly lady with acute hepatitis E who primarily presented with acute myocarditis.

Barrier against water loss: relationship between epicuticular wax composition, gene expression and leaf water retention capacity in banana.

In the present study we examined 13 banana (Musa spp.) genotypes belonging to different genomic groups with respect to total leaf cuticular wax concentration, chemical composition, carbon chain length and their relationship with leaf water retention capacity (LWRC). A positive correlation between epicuticular wax content and LWRC clearly indicated that the cuticular wax plays an important role in maintaining banana leaf water content. The classification of hexane soluble cuticular wax components into different classes based on functional group and their association with LWRC showed that alcohol and ester compounds have a positive correlation. Further, the compounds with >C28 carbon chain length had a positive correlation with LWRC, indicating the role of longer carbon chain length in maintaining the water status of banana leaves. Also, the gene expression analysis showed higher expression of the wax biosynthetic genes FATB and KCS11 in higher wax load genotypes whereas lower expression was seen in low wax banana genotypes. Here, we report for the first time the compositional variations of cuticular wax in different banana genotypes, followed by their association with leaf water retention capacity. The results were also supported by variation in gene expression analysis of cuticular wax biosynthetic genes - FATB and KCS11.

Salicylic Acid Induces Changes in Mango Fruit that Affect Oviposition Behavior and Development of the Oriental Fruit Fly, Bactrocera dorsalis.

The Oriental fruit fly, Bactrocera dorsalis (Hendel) is an important quarantine pest around the globe. Although measures for its control are implemented worldwide through IPM and male annihilation, there is little effect on their population. Hence, there is a need for new strategies to control this minacious pest. A strategy that has received negligible attention is the induction of 'natural plant defenses' by phytohormones. In this study, we investigated the effect of salicylic acid (SA) treatment of mango fruit (cv. Totapuri) on oviposition and larval development of B. dorsalis. In oviposition choice assays, gravid females laid significantly less eggs in SA treated compared to untreated fruit. Headspace volatiles collected from SA treated fruit were less attractive to gravid females compared to volatiles from untreated fruit. GC-MS analysis of the headspace volatiles from SA treated and untreated fruit showed noticeable changes in their chemical compositions. Cis-ocimene and 3-carene (attractants to B. dorsalis) were reduced in the headspace volatiles of treated fruit. Further, reduced pupae formation and adult emergence was observed in treated fruit compared to control. Increased phenol and flavonoid content was recorded in treated fruit. We also observed differential expression of anti-oxidative enzymes namely catalase (CAT), polyphenoloxidase (PPO) and peroxidase (POD). In summary, the results indicate that SA treatment reduced oviposition, larval development and adult emergence of B. dorsalis and suggest a role of SA in enhancing mango tolerance to B. dorsalis.