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.

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.

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.

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.

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.

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.

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.

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.

Determinants of contraceptive practices among eligible couples of urban slum in bankura district, west bengal.

BACKGROUND: Primary care physicians should be aware of the alarming population growth in the developing countries including India. OBJECTIVES: To find couple protection rate (CPR) and risk variables that affect contraceptive practice among eligible couples in an urban slum of Bankura district. MATERIALS AND METHODS: A cross-sectional observational study of 3 months was undertaken on 200 eligible couples in Bakultala urban slum, Lokepur, Bankura district, West Bengal to get relation between various factors that could affect contraceptive practices. RESULTS: Majority of the study population (59%) was young adults (20-29 years age); 65% belonged to nuclear families; one-third were married in less than 18 years of their age. CPR was 67.50%; 49% used permanent methods. Among contraceptive users, significantly higher numbers of couples were married during 18-24 years of age (75%), belonged to nuclear family (70%), literate up to class 10 (73%), having three or more living children (77.50%), and from socioeconomic status of class II (80%). Female literacy rate was higher than national average; 92.50%wives of eligible couple were literate; and tubectomy was commonest contraceptive methods. CONCLUSION: CPR was high, though different factors like age at marriage, type of family, number of living children, literacy status of female partner, and socioeconomic status significantly affected contraceptive behavior of the study population.