Insights into phytonutrient profile and postharvest quality management of jackfruit: A review.

Jackfruit (Artocarpus heterophyllus Lam.), also known as 'vegetarian's meat', is an excellent source of carbohydrates, protein, fiber, vitamins, minerals, and several phytochemicals. It is a climacteric fruit that exhibits an increase in ethylene biosynthesis and respiration rate during fruit ripening. The market value of jackfruit is reduced due to the deterioration of fruit quality during storage and transportation. There is a lack of standardized harvest maturity index in jackfruit, where consequently, fruit harvested at immature or overmature stages result in poor quality ripe fruit with short storage life. Other factors responsible for its short postharvest life relate to its highly perishable nature, chilling sensitivity and susceptibility to fruit rot which result in significant qualitative and quantitative losses. Various postharvest management techniques have been adopted to extend the storage life, including cold storage, controlled atmosphere storage, modified atmosphere packaging, edible coatings, chemical treatment, and non-chemical alternatives. Diversified products have been prepared from jackfruit to mitigate such losses. This comprehensive review highlights the nutritional profile, fruit ripening physiology, pre and postharvest quality management, and value addition of jackfruit as well as the way forward to reduce postharvest losses in the supply chain.

Trends in maintaining postharvest freshness and quality of Rubus berries.

Blackberries and raspberries, commonly known as Rubus berries, are commercially grown worldwide across different climates. Rubus berries contain wide array of phytochemicals, vitamins, dietary fibers, minerals, and unsaturated fatty acids. Nevertheless, these berries have short storage life which is the major constraint in their supply chains leading to higher postharvest losses. Inappropriate harvest handling, physical bruising, insect pests, and postharvest diseases lower the acceptability of fruit among consumers and other supply chain stakeholders. Additionally, the susceptibility to microbial decay, fruit softening, higher ethylene production, respiratory activity, and increased oxidation of anthocyanins, phenolics, and flavonoids considerably affects the marketability of Rubus berries at domestic and international markets. To date, several postharvest strategies such as cold storage, precooling, modified and controlled atmospheres, anti-ripening chemicals, edible coatings, biological agents, and nonchemical alternatives (heat treatment, ultrasound, irradiations, ozone) have been reported to prolong storage life, ensure food safety, and maintain the nutritional quality of Rubus berries. This review briefly encompasses multiple aspects including harvest maturity indices, regulation of fruit ripening, pre and postharvest factors affecting fruit quality, and an update on postharvest quality preservation by employing postharvest technologies to extend the storage life and maintaining the bioactive compounds in Rubus berries which are lacking in the literature. Accordingly, this review provides valuable information to the industry stakeholders and scientists offering relevant solutions, limitations in the application of certain technologies at commercial scale, highlighting research gaps, and paving the way forward for future investigations.

1H-1,2,3-triazole grafted tacrine-chalcone conjugates as potential cholinesterase inhibitors with the evaluation of their behavioral tests and oxidative stress in mice brain cells.

The present paper explicates the synthesis of 1H-1,2,3-triazole tethered tacrine-chalcone conjugates and evaluation of their AChE and BuChE inhibitory activity. In-vitroAChE inhibition assay revealed three compounds, 9h, 9i, and 11f, being more potent than the standard drug tacrine and further evaluated against butyrylcholinesterase. The present study was extended to investigate the anti-amnestic effect of promising compoundson scopolamine-induced behavioral and neurochemical changes in mice. Inclined plane model and Elevated plus-maze model were performed to assess general limb motor activity and anxiety-like behavior, respectively, in mice pre-treated with scopolamine. Oxidative stress parameters reduced glutathione contents (GSH) and lipid peroxidation products (TBARS) in the brain homogenates as estimated using ex-vivo studies. Furthermore, molecular docking studies were performed for the potent compounds to decipher the mechanism of observed activities.

Fenofibrate attenuates ischemia reperfusion-induced acute kidney injury and associated liver dysfunction in rats.

Ischemia/reperfusion (I/R) is one of the common reasons for acute kidney injury (AKI) and we need to develop effective therapies for treating AKI. We investigated the role of fenofibrate against I/R-induced AKI and associated hepatic dysfunction in rats. In male wistar albino rats, renal pedicle occlusion for 40 min and 24 h reperfusion resulted in AKI. I/R-induced AKI was demonstrated by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, fractional excretion of sodium and urinary microproteins. Oxidative stress in rat kidneys was quantified by assaying superoxide anion generation, thiobarbituric acid reactive substances, and reduced glutathione levels. AKI-induced hepatic damage was quantified by assaying serum aminotransferases, alkaline phosphatase and bilirubin levels. Moreover, serum cholesterol, high density lipoprotein and triglycerides were quantified. Hematoxylin-eosin staining of renal and hepatic tissues was done and the kidney and liver injury scores were determined. Immunohistology of endothelial nitric oxide synthase (eNOS) was done in rat kidneys. Fenofibrate was administered for 1 week before subjecting rats to AKI. In separate group, the nitric oxide synthase inhibitor, L-nitroarginine methyl ester (L-NAME) was administered prior to fenofibrate treatment. In I/R group, significant alteration in the serum/urine parameters indicated AKI and hepatic dysfunction along with marked increase in kidney and liver injury scores. Treatment with fenofibrate attenuated AKI and associated hepatic dysfunction. Moreover, I/R-induced decrease in renal eNOS expression was abrogated by fenofibrate. Pre-treatment with L-NAME abolished fenofibrate mediated reno- and hepato-protective effects. In conclusion, fenofibrate attenuates I/R-induced AKI and associated hepatic dysfunction putatively through modulation of eNOS expression.

Modification of the lead molecule: Tryptophan and piperidine appended triazines reversing inflammation and hyeperalgesia in rats.

The structural optimization of the molecules making them to fit into the active site pocket of COX-2 occupying the same space as covered by the natural substrate arachidonic acid helped in the emergence of compound 10 as an efficacious anti-inflammatory agent. Selective for COX-2 over COX-1, compound 10 exhibited IC50 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg-1 dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia. As evidenced by the results of molecular modeling studies supported by the nuclear Overhauser enhancement data, the appropriate geometry of the molecule in the active site pocket of COX-2 contributing to its H-bond/hydrophobic interactions with Ser530, Trp387 and Tyr385 seems responsible for the enzyme inhibitory activity of the compound.

Anti-nociceptive and anti-inflammatory effect of imperatorin: evidences for involvement of COX-2, iNOS, NFκB and inflammatory cytokines.

Aim: The objective of the current investigation was to explore the analgesic effect of naturally occurring furanocoumarin, imperatorin and the involvement of inducible cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), NFκB and cytokines in the observed effect.Materials and methods: Anti-nociceptive effect was explored by inducing chemical hyperalgesia using acetic acid and formalin in mice. ED50 of imperatorin was calculated in acetic acid model. Modulation of cyclooxygenase and nitric oxide pathway by imperatorin was examined by stimulator/precursor challenge with substance P and L-arginine, respectively and quantification of COX-2, iNOS and NFκB expression by immunohistochemical analysis in spinal tissues. Involvement of inflammatory cytokines TNF-α and IL-1ß was investigated using LPS challenge and subsequent ELISA analysis of these inflammatory mediators in serum. Carrageenan inflicted paw edema was employed to explore the anti-inflammatory activity of imperatorin.Results: A significant reduction in the nociceptive behaviour was observed with imperatorin treatment in acetic acid and formalin test. ED50 of imperatorin was found to be 4.53 mg/kg. Pre-treatment with substance P and L-arginine significantly attenuated the anti-nociceptive activity of imperatorin in formalin test. Immunohistochemical findings revealed marked decrease in spinal COX-2, iNOS and NFκB expression. Imperatorin administration significantly reduced LPS induced rise in level of TNF-α and IL-1ß dose dependently. In carrageenan-induced paw edema test, maximum possible anti-inflammatory effect of imperatorin was evident after 240 min of carrageenan administration.Conclusion: Current investigation revealed that anti-nociceptive and anti-inflammatory potential of imperatorin is probably mediated through the attenuation of COX-2, iNOS, NFκB activity and reduction in circulatory cytokines.

Bergapten inhibits chemically induced nociceptive behavior and inflammation in mice by decreasing the expression of spinal PARP, iNOS, COX-2 and inflammatory cytokines.

In continuation with our previous studies on osthole, bergapten, a closely related furanocoumarin was investigated for its ameliorative effect on chemically induced neurogenic and inflammatory hyperalgesia and inflammation in mice. Chemical hyperalgesia and inflammation was induced by administration of formalin (intraplantar), acetic acid (intraperitoneal) and carrageenan (intraplantar) to different groups of animals. Pain responses were quantified and median effective dose (ED50) of bergapten was calculated. Lipopolysaccharide challenge was administered to study inflammatory cytokines which were analyzed in plasma using ELISA. The expression of poly ADP-ribose polymerase (PARP), cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) was quantified by immnofluorescence staining. Bergapten was found to ameliorate both neurogenic and inflammatory hyperalgesia precipitated by formalin, acetic acid induced writhing and carrageenan induced paw inflammation with ED50 dose of 2.96 mg/kg. Bergapten also significantly decreased the levels of TNF-α and IL-6 and the expression of PARP, COX-2 and iNOS in the spine. It is concluded that bergapten is an interesting molecule with significant analgesic and anti-inflammatory activity emanating through the modulation of multiple pain mediating pathways.

Choices and Challenges With Treatment of Myasthenia Gravis in Pregnancy: A Systematic Review.

Myasthenia gravis (MG) is an autoimmune disease affecting young women in their second and third decades, coinciding with their reproductive years. We aim to explore the choices and challenges in the treatment of MG in pregnancy. Cochrane, PubMed, Google Scholar, and Embase were the four databases systematically searched for studies with patients reporting pregnancy outcomes for women with MG during pregnancy using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) technique. Quality assessment was done using the Joanna Briggs Institute critical tool (JBI, Adelaide, Australia) for methodological quality. From 2000 to 2023, 40 studies from database search results were considered. There is a substantial risk of complications with MG, especially if it appears during pregnancy. In particular, widespread weakness is a cause of severe, life-threatening disorders, but several treatment options are available.

Design, Synthesis, and Activity Evaluation of Stereoconfigured Tartarate Derivatives as Potential Anti-inflammatory Agents In Vitro and In Vivo.

Preclinical and clinical data reveal that inflammation is strongly correlated with the pathogenesis of a number of diseases including those of cancer, Alzheimer, and diabetes. The inflammatory cascade involves a multitude of cytokines ending ultimately with the activation of COX-2/LOX for the production of prostaglandins and leukotrienes. While the available inhibitors for these enzymes suffer from nonoptimal selectivity, in particular for COX-2, we present here the results of purposely designed tartarate derivatives that exhibit favorable selectivity and significant effectiveness against COX-2 and LOX. Integrated approaches of molecular simulation, organic synthesis, and biochemical/physical experiments identified 15 inhibiting COX-2 and LOX with respective IC50 4 and 7 nM. At a dose of 5 mg kg-1 to Swiss albino mice, 15 reversed algesia by 65% and inflammation by 33% in 2-3 h. We find good agreement between experiments and simulations and use the simulations to rationalize our observations.

Two Cases of Crystal-storing Histiocytosis Diagnosed by Morphology, Immunohistochemistry, and Ultrastructural Examination.

Crystal-storing histiocytosis (CSH) is a non-neoplastic histiocytic proliferation containing crystalline material, usually associated with an underlying lymphoproliferative or plasmacytic disorder. The crystalline structures are typically derived from kappa light chain immunoglobulins. The lesions of CSH are comprised of sheets of histiocytes with abundant eosinophilic cytoplasm containing variably prominent, elongated crystals. This rare phenomenon is important to recognize, as it is known to morphologically obscure an underlying neoplasm. Histologically, the cells of CSH may closely mimic Gaucher cells, as well as the "pseudo-Gaucher" cells sometimes encountered in chronic myeloid leukemia. The distinction between the cells of CSH and that of histologic mimics may be made more definitively through the use of electron microscopy, as the crystalline inclusions seen in CSH display characteristic size, shape, and localization within the cells. Here, we report 2 rare cases of CSH diagnosed by morphology, immunohistochemistry, and ultrastructural examination. The first case presented was diagnosed concurrently with plasma cell myeloma, and the second case discussed was diagnosed in association with marginal zone lymphoma.

Differential Antimycotic and Antioxidant Potentials of Chemically Synthesized Zinc-Based Nanoparticles Derived from Different Reducing/Complexing Agents against Pathogenic Fungi of Maize Crop.

The present study aimed for the synthesis, characterization, and comparative evaluation of anti-oxidant and anti-fungal potentials of zinc-based nanoparticles (ZnNPs) by using different reducing or organic complexing-capping agents. The synthesized ZnNPs exhibited quasi-spherical to hexagonal shapes with average particle sizes ranging from 8 to 210 nm. The UV-Vis spectroscopy of the prepared ZnNPs showed variation in the appearance of characteristic absorption peak(s) for the various reducing/complexing agents i.e., 210 (NaOH and NaBH4), 220 (albumin, and thiourea), 260 and 330 (starch), and 351 nm (cellulose) for wavelengths spanning over 190-800 nm. The FT-IR spectroscopy of the synthesized ZnNPs depicted the functional chemical group diversity. On comparing the antioxidant potential of these ZnNPs, NaOH as reducing agent, (NaOH (RA)) derived ZnNPs presented significantly higher DPPH radical scavenging potential compared to other ZnNPs. The anti-mycotic potential of the ZnNPs as performed through an agar well diffusion assay exhibited variability in the extent of inhibition of the fungal mycelia with maximum inhibition at the highest concentration (40 mg L-1). The NaOH (RA)-derived ZnNPs showcased maximum mycelial inhibition compared to other ZnNPs. Further, incubation of the total genomic DNA with the most effective NaOH (RA)-derived ZnNPs led to intercalation or disintegration of the DNA of all the three fungal pathogens of maize with maximum DNA degrading effect on Macrophomina phaseolina genomic DNA. This study thus identified that differences in size and surface functionalization with the protein (albumin)/polysaccharides (starch, cellulose) diminishes the anti-oxidant and anti-mycotic potential of the generated ZnNPs. However, the NaOH emerged as the best reducing agent for the generation of uniform nano-scale ZnNPs which possessed comparably greater anti-oxidant and antimycotic activities against the three test maize pathogenic fungal cultures.

Characterization and Mapping of Spot Blotch in Triticum durum-Aegilops speltoides Introgression Lines Using SNP Markers.

Spot blotch (SB) of wheat is emerging as a major threat to successful wheat production in warm and humid areas of the world. SB, also called leaf blight, is caused by Bipolaris sorokiniana, and is responsible for high yield losses in Eastern Gangetic Plains Zone in India. More recently, SB is extending gradually toward cooler, traditional wheat-growing North-Western part of the country which is a major contributor to the national cereal basket. Deployment of resistant cultivars is considered as the most economical and ecologically sound measure to avoid losses due to this disease. In the present study, 89 backcross introgression lines (DSBILs) derived from Triticum durum (cv. PDW274-susceptible) × Aegilops speltoides (resistant) were evaluated against SB for four consecutive years, 2016-2020. Phenotypic evaluation of these lines showed a continuous variation in disease severity indicating that the resistance to SB is certainly quantitative in nature. Phenotypic data of DSBILs were further used for mapping QTLs using SNPs obtained by genotyping by sequencing. To identify QTLs stable across the environments, Best Linear Unbiased Estimates (BLUEs) and Predictions (BLUPs) were used for mapping QTLs based on stepwise regression-based Likelihood Ratio Test (RSTEP-LRT) for additive effect of markers and single marker analysis (SMA). Five QTLs, Q.Sb.pau-2A, Q.Sb.pau-2B, Q.Sb.pau-3B, Q.Sb.pau-5B, and Q.Sb.pau-6A, linked to SB resistance were mapped across chromosomes 2A, 2B, 3B, 5B, and 6A. Genes found adjacent to the SNP markers linked to these QTLs were literature mined to identify possible candidate genes by studying their role in plant pathogenesis. Further, highly resistant DSBIL (DSBIL-13) was selected to cross with a susceptible hexaploidy cultivar (HD3086) generating BC2F1 population. The QTL Q.Sb.pau-5B, linked to SNP S5B_703858864, was validated on this BC2F1 population and thus, may prove to be a potential diagnostic marker for SB resistance.

Interactions of an Emerging Fungal Pathogen Scedosporium aurantiacum with Human Lung Epithelial Cells.

Scedosporium fungi are found in various natural and host-associated environments, including the lungs of cystic fibrosis patients. However, their role in infection development remains underexplored. Here the attachment of conidia of a virulent S. aurantiacum strain WM 06.482 onto the human lung epithelial A549 cells in vitro was visualized using microscopy to examine the initial steps of infection. We showed that 75-80% of fungal conidia were bound to the A549 cells within four hours of co-incubation, and started to produce germ tubes. The germinating conidia seemed to invade the cells through the intercellular space, no intracellular uptake of fungal conidia by the airway epithelial cells after conidial attachment. Transcriptomic analysis of the A549 cells revealed that the up-regulated genes were mainly associated with cell repair and inflammatory processes indicating a protective response against S. aurantiacum infection. Network analysis of the differentially expressed genes showed activation of the innate immune system (NF-kB pathway) leading to the release of pro-inflammatory cytokines. We believe this is the first report showing the transcriptomic response of human alveolar epithelial cells exposed to S. aurantiacum conidia paving a way for better understanding of the mechanism of the infection process.

Pseudomonas aeruginosa inhibits the growth of Scedosporium aurantiacum, an opportunistic fungal pathogen isolated from the lungs of cystic fibrosis patients.

The filamentous fungus Scedosporium aurantiacum and the bacterium Pseudomonas aeruginosa are opportunistic pathogens isolated from lungs of the cystic fibrosis (CF) patients. P. aeruginosa has been known to suppress the growth of a number of CF related fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. However, the interactions between P. aeruginosa and S. aurantiacum have not been investigated in depth. Hence we assessed the effect of P. aeruginosa reference strain PAO1 and two clinical isolates PASS1 and PASS2 on the growth of two clinical S. aurantiacum isolates WM 06.482 and WM 08.202 using solid plate assays and liquid cultures, in a synthetic medium mimicking the nutrient condition in the CF sputum. Solid plate assays showed a clear inhibition of growth of both S. aurantiacum strains when cultured with P. aeruginosa strains PASS1 and PAO1. The inhibitory effect was confirmed by confocal microscopy. In addition to using chemical fluorescent stains, strains tagged with yfp (P. aeruginosa PASS1) and mCherry (S. aurantiacum WM 06.482) were created to facilitate detailed microscopic observations on strain interaction. To our knowledge, this is the first study describing successful genetic transformation of S. aurantiacum. Inhibition of growth was observed only in co-cultures of P. aeruginosa and S. aurantiacum; the cell fractions obtained from independent bacterial monocultures failed to initiate a response against the fungus. In the liquid co-cultures, biofilm forming P. aeruginosa strains PASS1 and PAO1 displayed higher inhibition of fungal growth when compared to PASS2. No change was observed in the inhibition pattern when direct cell contact between the bacterial and fungal strains was prevented using a separation membrane suggesting the involvement of extracellular metabolites in the fungal inhibition. However, one of the most commonly described bacterial virulence factors, pyocyanin, had no effect against either of the S. aurantiacum strains. This study shows that P. aeruginosa has a substantial inhibitory effect on the growth of the recently described CF fungal pathogen S. aurantiacum. The findings also highlighted that P. aeruginosa biofilm formation is important but not crucial for inhibiting the growth of S. aurantiacum in a lung- mimicking environment.

Proteomics of hosts and pathogens in cystic fibrosis.

Cystic fibrosis (CF) is a congenital disease that results in great morbidity and mortality mainly in the Caucasian population. Although CF is a monogenic disease caused by mutation in the CF conductance transmembrane regulator (CFTR) gene, most of the related mortality can be attributed to infection mediated by opportunistic bacterial and fungal pathogens. Over the past decade, advancements in the field of proteomics have helped to gain insight into the repertoire of host and pathogen proteins involved in CF pathophysiology. This review provides an overview of the contributions of proteomic studies in advancing our knowledge of the biology of CF and disease progression associated with pathogen infection and host defense responses.

Phenotypic profiling of Scedosporium aurantiacum, an opportunistic pathogen colonizing human lungs.

Genotyping studies of Australian Scedosporium isolates have revealed the strong prevalence of a recently described species: Scedosporium aurantiacum. In addition to occurring in the environment, this fungus is also known to colonise the respiratory tracts of cystic fibrosis (CF) patients. A high throughput Phenotype Microarray (PM) analysis using 94 assorted substrates (sugars, amino acids, hexose-acids and carboxylic acids) was carried out for four isolates exhibiting different levels of virulence, determined using a Galleria mellonella infection model. A significant difference was observed in the substrate utilisation patterns of strains displaying differential virulence. For example, certain sugars such as sucrose (saccharose) were utilised only by low virulence strains whereas some sugar derivatives such as D-turanose promoted respiration only in the more virulent strains. Strains with a higher level of virulence also displayed flexibility and metabolic adaptability at two different temperature conditions tested (28 and 37°C). Phenotype microarray data were integrated with the whole-genome sequence data of S. aurantiacum to reconstruct a pathway map for the metabolism of selected substrates to further elucidate differences between the strains.

Draft Genome of Australian Environmental Strain WM 09.24 of the Opportunistic Human Pathogen Scedosporium aurantiacum.

We report here the first genome assembly and annotation of the human-pathogenic fungus Scedosporium aurantiacum, with a predicted 10,525 genes, and 11,661 transcripts. The strain WM 09.24 was isolated from the environment at Circular Quay, Sydney, New South Wales, Australia.