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Boosting the immune system has become a crucial aspect in the global battle against the COVID-19 pandemic and other similar infections to protect oneself against symptoms, especially in the prevention of viral infections of the lower respiratory tract. The importance of conducting more studies to create successful herbal formulations as infection prevention measures is emphasized in this review, which looks at the function of immune-boosting nutrients, medicinal plants, and herbal treatments. We reviewed and analyzed 207 studies published from 1946 to the present using reputable databases like Google Scholar, PubMed, and NCBI. The review examined 115 plant species in total and identified 12 key nutrients, including vitamins A, D, C, omega-3 fatty acids, iron, and zinc, while noting that four plant families, Rosaceae, Asteraceae, Amaryllidaceae, and Acanthaceae, show potential against respiratory infections like influenza, RSV, and SARS-CoV. To lower the risk of infection, it is recommended to consume nutritious meals that have immune-modulating qualities. Information on the bioactive components of medicinal herbs, spices, and plants that have been effective in treating respiratory viral infections and related conditions is compiled in this review, which highlights phytoactive substances with antibacterial and antiviral activity as effective modulators to lower the risk of infections. Furthermore, it is highlighted that ancient knowledge systems, like Ayurveda and Naturopathy, should be integrated to help develop new herbal formulations. To improve immunity and lessen vulnerability to serious respiratory infections, the results highlight the need for including immune-modulating foods and plant-based medicines into everyday routines., Competing Interests: Conflict of interestThe authors declare that there are no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Naringenin (NRG) inhibits the fungal 17β-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn 2+ ) to synthesize NRG-Zn 2+ nanocomposites. The particle size and ζ-potential of NRG-Zn 2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn 2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn 2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm 2 /h. The MIC 50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1β and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Key Message: Fon race 2 resistant QTLs were identified on chromosomes 8 and 9. Families homozygous for resistance alleles at a haplotype of three KASP markers had 42% lower disease severity than those with susceptible alleles in an independent, interspecific validation population confirming their utility for introgression of Fusarium wilt resistance. Fusarium oxysporum f. sp. niveum (Fon) race 2 causes Fusarium wilt in watermelon and threatens watermelon production worldwide. Chemical management options are not effective, and no resistant edible watermelon cultivars have been released. Implementation of marker-assisted selection to develop resistant cultivars requires identifying sources of resistance and the underlying quantitative trait loci (QTL), developing molecular markers associated with the QTL, and validating marker-phenotype associations with an independent population. An intraspecific Citrullus amarus recombinant inbred line population from a cross of resistant USVL246-FR2 and susceptible USVL114 was used for mapping Fon race 2 resistance QTL. KASP markers were developed (N = 51) for the major QTL on chromosome 9 and minor QTL on chromosomes 1, 6, and 8. An interspecific F 2:3 population was developed from resistance donor USVL246-FR2 (C. amarus) and a susceptible cultivar 'Sugar Baby' (Citrullus lanatus) to validate the utility of the markers for introgression of resistance from the wild crop relative into cultivated watermelon. Only 16 KASP markers segregated in the interspecific C. amarus/lanatus validation population. Four markers showed significant differences in the separation of genotypes based on family-mean disease severity, but together explained only 16% of the phenotypic variance. Genotypes that inherited homozygous resistant parental alleles at three KASP markers had 42% lower family-mean disease severity than homozygous susceptible genotypes. Thus, haplotype analysis was more effective at predicting the mean disease severity of families than single markers. The haplotype identified in this study will be valuable for developing Fon race 2 resistant watermelon cultivars., (© 2024. The Author(s).)

Context: In contrast to un-catalyzed hydrolysis of organophosphorus (OP) compounds, metal ions or/and their complexes with chelating ligands show catalytic effects in several ways depending upon the nature of the metal, ligand, substrate, and medium. It is known that Cu(II)-en chelate containing copper complexes accelerate the hydrolysis of OP compounds. However, the mechanism for this rate enhancement in the Cu(II)-en chelate catalytic hydrolysis reaction of sarin remains unexplored. We have examined possible mechanisms involving a Cu(II)-en with hydroxide nucleophile for the reaction pathway of the hydrolysis of O-isopropyl methylphosphonofluoridate (sarin) computationally. The density functional (B3LYP) employed in this study has reproduced the experimental Gibb's free energy of activation value 15.5 kcal/mol for alkaline hydrolysis of sarin. Earlier proposal of push-pull mechanism for metal ion chelate-catalyzed hydrolysis of OP compounds has been found to be unfavorable in the present study. The role of water molecules in catalyzing the hydrolysis of sarin with Cu(II)-en chelate is crucial. The catalytic process involving Cu(II)-en chelate with one water molecule is the more plausible pathway to achieve the hydrolysis of sarin with Cu(II)-en chelate complexes., Methods: The most popular B3LYP method was used for optimization of given geometries. Except LANL2DZ for Cu atom, all the atoms are described using the 6-31 + G(d) basis set. The stability test has been performed for the wave functions as we are dealing with the open-shell molecules in order to ensure stable electronic configuration form, and the stable wavefunction is used as the initial configuration for the subsequent optimization. Harmonic frequency calculations and thermodynamic corrections were performed at the same level of theory. PCM method has been used for solvation effects. In order to ensure that each saddle point is linked to a minimum, IRC calculations were performed in forward and reverse directions to ensure the eigenvectors associated with the unique negative eigenvalues of the Hessian matrix. All energies discussed are solvated Gibbs free energies corrected to 298.15 K for the relative stability of the chemical structure. All calculations were performed using the Gaussian 09 code., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The current research was aimed to synthesize a phytomolecule, naringenin (NRG)-mediated silver nanoparticles (NRG-SNPs) to study their antifungal potential against Candida albicans (C. albicans) and Candida glabrata (C. glabrata). The NRG-SNPs were synthesized by using NRG as a reducing agent. The synthesis of NRG-SNPs was confirmed by a color change and surface plasmon resonance (SPR) peak at 425 nm. Furthermore, the NRG-SNPs were analyzed for size, PDI, and zeta potential, which were found to be 35 ± 0.21 nm, 0.19 ± 0.03, and 17.73 ± 0.92 mV, respectively. In silico results demonstrated that NRG had a strong affinity towards the sterol 14α-demethylase. The docking with ceramide revealed the skin permeation efficiency of the NRG-SNPs. Next, the NRG-SNPs were loaded into the topical dermal dosage form (NRG-SNPs-TDDF) by formulating a gel using Carbopol Ultrez 10 NF. The MIC 50 of NRG solution and TSC-SNPs against C. albicans was found to be 50 µg/mL and 4.8 µg/mL, respectively, significantly (P < 0.05) higher than 0.3625 µg/mL of NRG-SNPs-TDDF. Correspondingly, MIC 50 results were calculated against C. glabrata and the results of NRG, TSC-SNPs, NRG-SNPs-TDDF, and miconazole nitrate were found to be 50 µg/mL, 9.6 µg/mL, 0.3625 µg/mL, and 3-µg/mL, respectively. Interestingly, MIC 50 of NRG-SNPs-TDDF was significantly (P < 0.05) lower than MIC 50 of miconazole nitrate against C. glabrata. The FICI (fractional inhibitory concentration index) value against both the C. albicans and C. glabrata was found to be 0.016 and 0.011, respectively, which indicated the synergistic antifungal activity of NRG-SNPs-TDDF. Thus, NRG-SNPs-TDDF warrants further in depth in vivo study under a set of stringent parameters for translating in to a clinically viable antifungal product., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

A reliable and stable Agrobacterium -mediated genetic transformation system for Artemisia pallens has been developed using cell suspension cultures derived from cotyledon explants. Cotyledon, attached cotyledon, and compound leaves were found to be suitable for the induction of callus among five different types of explants tested. The yellow friable callus derived from attached cotyledon was used to initiate suspension cultures in Suspension Culture Medium (SCM) which was supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D) at 2.0 mg L -1 and in combination with different concentrations of Zeatin (ZEA) at 0.25 mg L -1 . Two different shock treatments, cold shock (at 4 ℃) for 20 min and heat shock (at 45 ℃) treatment for 5 min, heat shock treatment increased the transformation efficiency. The supplementation of Pluronic F-68 (0.05%) significantly enhanced the transformation efficiency of suspension cultures, whereas Silwet L-77 (0.05%) leads to more browning of the cells and reduced the transformation efficiency. The maximum GUS intensity was recorded with an optimal intensity of blue spots in the transformed cells. The highest GUS fluorometric activity measured was 879.4 ± 113.7 nmol 4MU/mg/min in transformed cell suspension cultures. The hygromycin-resistant calli showed intense blue color in GUS histochemical assay. The transgene integration into the plant genome was confirmed by polymerase chain reaction (PCR) using uidA specific primers in six hygromycin-resistant cell lines. The partial coding sequence of three candidate reference genes, i.e., ADP-ribosylation factor ( Arf ), β-actin ( Act ), and ubiquitin ( Ubi ), and carotenoid biosynthesis pathway gene, i.e., Phytoene desaturase ( Pds ) were cloned, sequenced, and submitted to NCBI for the first time. The quantitative mRNA expression of the transgene ( uidA ) and internal ApPds gene were evaluated in transgenic callus lines. The present Agrobacterium- mediated genetic transformation protocol could help in better understanding of the metabolic pathways of this medicinally important plant and its genetic improvement., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03251-x., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2022.)

Purpose: Heart transplantation is the definitive treatment for end-stage heart failure. With respect to donor-recipient size matching, the problems with undersized heart transplantation have been widely discussed, but there is a paucity of information on oversized transplants due to the presumed advantage of large hearts. We intend to share our center's experience with oversized heart transplantation and its associated problems which would help to expand the knowledge on oversized cardiac allografts., Methods: Patients who underwent isolated heart transplantation at our hospital between March 1, 2008, and March 1, 2020, were included. For adults, a donor-recipient predicted heart mass percentage difference exceeding 30% and for children, a donor-recipient weight ratio < 0.8 and > 2.0 was considered a mismatch. We collected data from the in-patient medical records and analyzed the in-hospital outcomes and survival post-transplant among various other parameters., Results: Out of the 43 patients included in this study, 32 (74.4%) patients received a matched heart and 11 (25.6%) patients received oversized hearts. None of the patients received an undersized heart. The in-hospital mortality rate of oversized transplants was 18.2% whereas that of matched transplants was 9.4% ( p  = 0.432). The post-operative characteristics and 1-year survival were comparable between the groups. We encountered problems specific to oversizing in 5 of the 11 patients (45.4%) which are discussed., Conclusion: With the liberalization of donor criteria to overcome organ shortage, oversized heart transplantation poses certain unique challenges, which when efficiently managed offers acceptable outcomes., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2021.)

India is an agrarian country producing a large amount of rice straw as an agricultural residue. These residues are burnt openly leading to severe environmental pollution and health hazards. Among several options available, anaerobic digestion of rice straw into biomethane gas and digestate is a promising technology. The current paper reviews the characteristics, principles of rice straw and the process variables (temperature, volatile fatty acids, and pH, carbon to nitrogen ratio, metal elements and organic loading rate) that affect the performance of the rice straw digestion and process strategies which may alleviate the barriers and may improve the biomethane yield. Co-digestion of rice straw with nitrogen-rich substrates is proven to be an effective way to balance the carbon to nitrogen ratio, in turn, leads to nutrient balance and enhance the biomethane yields of anaerobic co-digestion system. Moreover, pretreatment is another effective strategy; physical, chemical and biological pretreatments are reviewed in the article which improved the performance of digester. The utilisation of rice straw along with other co-substrates and appropriate pretreatment may be a recommended sustainable solution for preventing environmental and health hazards.

Background: To evaluate the clinical value of the chest CT scan compared to the reference standard real-time polymerase chain reaction (RT-PCR) in COVID-19 patients., Methods: From March 29th to April 15th of 2020, a total of 240 patients with respiratory distress underwent both a low-dose chest CT scan and RT-PCR tests. The performance of chest CT in diagnosing COVID-19 was assessed with reference to the RT-PCR result. Two board-certified radiologists (mean 24 years of experience chest CT), blinded for the RT-PCR result, reviewed all scans and decided positive or negative chest CT findings by consensus., Results: Out of 240 patients, 60% (144/240) had positive RT-PCR results and 89% (213/240) had a positive chest CT scans. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of chest CT in suggesting COVID-19 were 100% (95% CI: 97-100%, 144/240), 28% (95% CI: 19-38%, 27/240), 68% (95% CI: 65-70%) and 100%, respectively. The diagnostic accuracy of the chest CT suggesting COVID-19 was 71% (95% CI: 65-77%). Thirty-three patients with positive chest CT scan and negative RT-PCR test at baseline underwent repeat RT-PCR assay. In this subgroup, 21.2% (7/33) cases became RT-PCR positive., Conclusion: Chest CT imaging has high sensitivity and high NPV for diagnosing COVID-19 and can be considered as an alternative primary screening tool for COVID-19 in epidemic areas. In addition, a negative RT-PCR test, but positive CT findings can still be suggestive of COVID-19 infection.

Azoxystrobin, buprofezin, dinocap and hexaconazole are widely used in crop protection of mango from flowering to harvest. Residue assessment of these chemicals on mango fruits was done following treatments at the recommended and double doses as per good agricultural practices (GAP). Mango fruit and soil sample preparation was done by QuEChERS, and analysis was done using LC-MS/MS (liquid chromatography mass spectrometry). Using these techniques, the limit of detection (LOD) determined was 1.5 μg kg -1 and limit of quantification (LOQ) was 0.005 mg kg -1 for all analytes. The residue levels on mango initially were 0.265 and 0.55 mg kg -1 for azoxystrobin, 0.63 and 0.974 mg kg -1 for buprofezin, 0.635 and 0.98 mg kg -1 for dinocap and 0.203 and 0.35 mg kg -1 for hexaconazole from standard and double dose treatments, respectively. The dissipation rate of the pesticides on mango fruits was about the same except for azoxystrobin, which dissipated slowly compared with others. The half-life of degradation (DT 50 ) of azoxystrobin was 10.4-12.1 days; buprofezin, 5.8-8.5 days; dinocap, 5.4-6.2 days; and hexaconazole, 4.4-6.1 days. The pre-harvest interval (PHI) based on European Union (EU) MRL (maximum residue limit) requirements were 1 day for azoxystrobin, 15 and 26 days for buprofezin, 27 and 34 days for dinocap, and 19 and 30 days for hexaconazole. The results of this study can be used to produce mango fruits safe for consumption and to meet the regulatory requirements for export of mango fruits from India.

Background: Technique of surgical ventricular restoration (SVR) may impact its outcomes. Therefore, we conducted a meta-analysis of studies on SVR performed by using different techniques and studied outcomes., Methods: Scientific databases were searched for studies on SVR. End points assessed were NYHA class, left ventricular ejection fraction (LVEF), end-systolic volume index (ESVI), sphericity index, apical rotations, mortality, and re-admissions for heart failure., Results: Circular patch use showed significant increases in LVEF by 9.53% (7.62, 11.45), decreases in ESVI by - 35.16 ml (- 44.97, - 25.34), improvements in NYHA class by - 1.29 (- 1.45, - 1.13), and decreases in sphericity index by - 0.04 (- 0.08, 0.00) . In studies using rectangular patch, the LVEF showed an increase by 5.75% (3.52, 7.98,), the NYHA class improved by - 2.45 (- 2.59, - 2.32). The decrease in ESVI was - 40.36 ml (- 62.2, - 18.52). The apical rotation increased by 3.45 0 ( 0.62, 6.29,). Re-admission for heart failure and mortality was less.When the magnitude of ESVI decrease were compared within studies using rectangular patch, the greatest decrease in ESVI was notedwith use of a rectangular patch. (- 59 ml versus - 40 ml a very narrow patch and - 22 ml use of oval patch) The improvements in sphericity index at 2 years in use of rectangular patch study was - 0.78 ± 0.11 versus 0.00 ± 0.03 in use of oval patch study., Conclusions: Rectangular patch use resulted in maximal decreases in ESVI and sphericity index. Mortality and re-admissions for heart failure were also significantly less at mid-term after SVR., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2020.)

Besides clinical and imaging techniques, there is a lack of molecular makers for the diagnosis of Parkinson's disease (PD). There is an immense need to develop biomarkers associated with the phenotypes which may be valuable for individualized treatment. Single-nucleotide polymorphisms (PARK2: Ser167Asn (G>A) and Val380Leu (G>C); PARK7: IVS4 + 46G>A and IVS4 + 30T>G) in PD-related genes were examined to elucidate its relationship with concentration of serum elements and clinical symptoms of PD. A total of 214 PD patients and 213 controls from Indian population were genotyped using PCR and DNA sequencing methods. The serum element concentrations were detected and clinical symptoms were determined based on UPDRS scale and recorded at the time of sample collection. The IVS4 + 30T>G, Ser167Asn (G>A) and Val380Leu (G>C) polymorphisms appeared to alter element concentrations in PD. The patients with Ser167Asn polymorphism showed significant association with copper, iron and zinc that reinforces the role of A allele as a factor for change in the concentrations of elements, than those patients with G allele. In particular, patients with A allele of Ser167Asn have risk of having high serum iron concentration (OR 11.55, 95% CI 5.59-23.85), which are associated with dementia and postural imbalance. Similar results were observed for Val380Leu (G>C) and IVS4 + 30T>G polymorphisms which suggest their role in element concentration and neurological symptoms. Overall, our study demonstrates the influence of polymorphisms of PD genes on element concentrations and clinical symptoms. Results of this study may be taken into account when considering the contributing factors for PD symptoms.

Ischemic cardiomyopathy often presents with advanced heart failure necessitating an intensive multidisciplinary approach to management. These patients constitute a very difficult population presenting with angina and ventricular tachyarrhythmias sometimes presenting as sudden cardiac death. In those patients presenting with spontaneous ventricular tachyarrhythmias, treatment with automated intracardiac defibrillator implantation has a significant mortality benefit. In patients with significant left ventricular (LV) dilatation and a left ventricular ejection fraction ≤ 30%, guidelines state that device implantation should be preceded by programmed electrical stimulation, which demonstrates inducible ventricular tachyarrhythmia. The treatment options for patients with moderate LV dilatation and ejection fraction ≥ 30% is individualized. Devices have their associated problems. Radiofrequency ablation has mixed results. Surgical cryoablation when performed concomitantly with surgical ventricular restoration has shown promising results. But, this option remains isolated to patients eligible for surgical ventricular restoration. Programmed electrical stimulation for inducibility of ventricular tachyarrhythmias in these patients also has a questionable role. The need for programmed electrical stimulation prior to cryoablation also seems highly individualized. In this review, we discuss the mechanisms of ischemic ventricular tachyarrhythmias and treatment options in heart failure. The mechanisms of ventricular arrhythmogenesis in ischemic cardiomyopathy help in formulating novel technical modifications for cryoablation when performed concomitantly with surgical ventricular restoration., Competing Interests: Conflict of interestNo, (© Indian Association of Cardiovascular-Thoracic Surgeons 2019.)

Hypertrophic cardiomyopathy (HCM) is an inherited heart failure condition, mostly found to have genetic abnormalities, and is a leading cause of sudden death in young adults. Whole exome sequencing should be given consideration as a molecular diagnostic tool to identify disease-causing mutation/s. In this study, a HCM family with multiple affected members having history of sudden death were subjected to exome sequencing along with unaffected members. Quality passed variants obtained were filtered for rarity (MAF > 0.5%), evolutionary conservation, pathogenic prediction, and segregation in affected members after removing shared variants present in unaffected members. Only one non-synonymous mutation (p. Glu186Lys or E186K) in exon 6 of P2X7 gene segregated in HCM-affected individuals which was absent in unaffected family members and 100 clinically evaluated controls. The site of the mutation is highly conserved and led to complete loss of function which is in close vicinity to ATP-binding site-forming residues, affecting ATP binding, channel gating, or both. Mutations in candidate genes which were not segregated define clinical heterogeneity within affected members. P2X7 gene is highly expressed in the heart and shows direct interaction with major candidate genes for HCM. Our results reveal a significant putative HCM causative gene, P2X7, for the first time and show that germ-line mutations in P2X7 may cause a defective phenotype, suggesting purinergic receptor involvement in heart failure mediated through arrhythmias which need further investigations to be targeted for therapeutic interventions.

The present study describes the uptake and distribution of fungicides, fluopyram, and tebuconazole in tomato and bell pepper plant tissues from the soil drench application of their combination product fluopyram17.7% + tebuconazole 17.7%. For extraction and cleanup of fluopyram, its metabolite fluopyram benzamide, and tebuconazole samples, the QuEChERS method was used in conjunction with LC-MS/MS. The limit of detection (LOD) and limit of quantification (LOQ) of the method determined were 1.5 μg kg -1 and 0.005 mg kg -1 , respectively, and recoveries of all analytes from sample matrices remained within the acceptable range of 70-120%. Rapid uptake of the fungicides by tomato and bell pepper plants was observed from the first day onwards. In the tomato plant, the major part of the fungicides accumulated in the roots, whereas in bell pepper plant, it accumulated both in the roots and in the leaves. Accumulation of fluopyram and tebuconazole residues was lowest in tomato and bell pepper fruits which were much below their respective maximum residue limits (MRLs). The highest residue concentration of fluopyram and tebuconazole in tomato fruits was 0.060 and 0.009 mg kg -1 ; the corresponding values in bell pepper fruits were 0.080 and 0.013 mg kg -1 . In field soil, fluopyram residues were 3.18-3.570 mg kg -1 initially which dissipated at the half-life of 36 days. Tebuconazole concentration was 1.57-1.892 mg kg -1 initially, and it dissipated at the half-life of 44.5-49.5 days. The major metabolite of fluopyram, fluopyram benzamide, was detected in plant tissues as well as in soil, and remained within 12% of the parent compound. The results of the study indicated that fluopyram and tebuconazole are less likely of entry into food chain through intake of tomato and bell pepper fruits if these crops are grown on soil contaminated with these fungicides.

Chloroplast transformation vectors require an expression cassette flanked by homologous plastid sequences to drive plastome recombination. The rrn 16- rrn 23 plastome region was selected and using this region, a new species-specific plastid transformation vector CuIA was developed with pKS + II as a backbone by inserting the rrn 16- trnI and trnA - rrn 23 sequences from Cucumis sativus L. An independent expression cassette with aadA gene encoding aminoglycoside 3'-adenylyltransferase with psbA controlling elements is added into the trnI - trnA intergenic region that confers resistance to spectinomycin. An efficient plastid transformation in bitter melon ( Momordica charantia L.) was achieved by bombardment of petiole segments. The frequency of transplastomic plants yielded using standardized biolistic parameters with CuIA vector was two per 15 bombarded plates, each containing 20 petiole explants. Integration of aadA gene was verified by PCR analysis in transplastomes. Transplastomic technology developed may be a novel approach for high level expression of pharmaceutical traits., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Identification of isoform-specific histone deacetylase inhibitors (HDACi) is a significant advantage to overcome the adverse side effects of pan-HDACi for the treatment of various diseases, including cancer. We have designed, and synthesized novel 1,3,4 oxadiazole with glycine/alanine hybrids as HDAC8-specific inhibitors and preliminary evaluation has indicated that 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)propanamide (10b)] to be a potent HDAC8 inhibitor. In the present study, the in vitro efficacy of the molecule in inhibiting the cancer cell proliferation and the underlying molecular mechanism was studied. 10b inhibited the growth of MDA-MB-231 and MCF7 breast cancer cells, with a lower IC 50 of 230 and 1000 nM, respectively, compared to K562, COLO-205 and HepG2 cells and was not cytotoxic to normal breast epithelial cells, MCF10A. 10b was specific to HDAC8 and did not affect the expression of other class I HDACs. Further, a dose-dependent increase in H3K9 acetylation levels demonstrated the HDAC-inhibitory activity of 10b in MDA-MB-231 cells. Flow cytometric analysis indicated a dose-dependent increase and decrease in the percent apoptotic cells and mitochondrial membrane potential, respectively, when treated with 10b. Immunoblot analysis showed a modulation of Bax/Bcl2 ratio with a decrease in Bcl2 expression and no change in Bax expression. 10b treatment resulted in induction of p21 and inhibition of CDK1 proteins along with cytochrome c release from mitochondria, activation of caspases-3 and -9 and cleavage of poly ADP-ribose polymerase leading to apoptotic death of MDA-MB-231 and MCF7 cells. In conclusion, our results clearly demonstrated the efficacy of 10b as an anticancer agent against breast cancer.

Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract. The antioxidative activity of SEA extract at IC 50 (200 ± 0.6 μg/mL) is equal to that of ascorbic acid at IC 50 (50 ± 0.6 μg/mL), and the anti-inflammatory activity of SEA extract at IC 50 (150 ± 0.2 μg/mL) was inhibited significantly by nitric oxide (NO) production. The SEA extract significantly reduced the sprouting of new blood vessels at ID 50 500 ± 0.13 μg/mL in the CAM assay. Gas chromatography-mass spectrometry analysis of the SEA extract detected 34 secondary metabolites, of which 6a,12a-dihydro-6H-(1,3)dioxolo(5,6)benzofuro(3,2-c)chromen-3-ol (maackiain) and funiculosin formed strong hydrogen bond interactions with Lys 920, Thr 916 and Cys 919 (2H), as well as Glu 917 of VEGFR2, and these interactions were similar to those of the anti-angiogenic compound axitinib. Significant findings in all the assays performed indicate that SEA extract has potential anti-angiogenic compounds that may interfere with VEGF-induced cancer malignancy.

Proteins are playing a vital role in maintaining the cellular integrity and function, as well as for brain cells. Protein intake and supplementation of individual amino acids can affect the brain functioning and mental health, and many of the neurotransmitters in the brain are made from amino acids. The amino acid supplementation has been found to reduce symptoms, as they are converted into neurotransmitters which in turn extenuate the mental disorders. The biosynthesis of amino acids in the brain is regulated by the concentration of amino acids in plasma. The brain diseases such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD) are the most common mental disorders that are currently widespread in numerous countries. The intricate biochemical and molecular machinery contributing to the neurological disorders is still unknown, and in this chapter, we revealed the involvement of dietary amino acids on neurological diseases.

Gravity associated with postural changes has a strong bearing on haemodynamics of blood flow in arteries. Its effect on stenosed cases has not been widely investigated. In the present study, variation observed in blood flow during postural changes is investigated for different conditions like standing, sleeping and head-down position. A fluid structure interaction study is carried out for idealized normal and 75% eccentric and concentric stenosed common carotid normal artery. The results clearly indicate the effects of altered gravity on flow conditions. It was found to be very significant during head-down position and demonstrated very high arterial blood pressure in stenosed common carotid when compared with normal carotid.

A novel actinomycete strain, designated VRC07(T), was isolated from a Callistemon citrinus rhizosphere sample collected from Hyderabad, India. Its taxonomic status was determined by using polyphasic approach. It is a Gram-positive, aerobic, non-motile, weakly acid-fast strain. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain VRC07(T) is a member of the genus Nocardia. The highest levels of 16S rRNA gene sequence similarity was found between the strains Nocardia niwae W9241(T) (99.6 %), Nocardia amikacinitolerans W9988(T) (99.3 %) and Nocardia arthritidis IFM 10035(T) (98.9 %); similarity to other type strains of the genus Nocardia was below 98.7 %. The organism had chemical and morphological features consistent with its classification in the genus Nocardia such as meso-diaminopimelic acid as the diagnostic diamino acid in the cell wall peptidoglycan. Arabinose and galactose as the diagnostic sugars. Diagnostic polar lipids were phosphatidylinositol, diphosphatidylglycerol, and phosphatidylglycerol. The predominant menaquinone was MK-8(H4, ω-cycl). The major fatty acids were C16:0, C18:0, C18:1 w9c, C18:0 10-methyl TBSA and sum in feature 3 (16:1 w7c/16:1 w6c). The G+C content of the genomic DNA was 68.5 mol%. The DNA-DNA relatedness data, together with phenotypic differences clearly distinguished the isolate from its closest relatives. On the basis of these phenotypic and genotypic data, the isolate represents a novel species, for which the name Nocardia bhagyanesis sp. nov., is proposed. The type strain is VRC07(T) (=KCTC 29209(T) = MTCC 11725(T) = ATCC BAA-2548).

Marine sediments of the Gulf of Mannar (GoM), India are contaminated by potential toxic elements (PTEs) due to anthropogenic activities posing a risk to the existing fragile coral ecosystem and human health. The current study aimed to assess the distribution of PTEs (arsenic--As; cobalt--Co; copper--Cu, molybdenum--Mo; lead--Pb; and zinc--Zn) in marine sediments of different grain size fractions, viz., medium sand (710 μm), fine sand (250 μm), and clay (<63 μm) among the different coastal regions of Pamban, Palk Bay, and Rameswaram coasts of GoM, using grain size as one of the key factor controlling their concentrations. The concentrations of PTEs were measured in the different size fractions of sediment using inductively coupled plasma mass spectrophotometer. The order of accumulation of all PTEs in the three fractions was ranked as Zn > Cu > Pb > As > Co > Mo and in the three locations as Rameswaram > Palk Bay > Pamban. The concentration of PTEs in Palk Bay and Rameswaram coast was significantly different (P < 0.05), when compared to Pamban coast. Measured geoaccumulation index (I(geo)) and contamination factor (CF) indicated significant enrichment of Co and Pb from Rameswaram coast when compared to other two coasts. Although the concentration of Co was low but the measured I(geo) and CF values indicated significant enrichment of this PTE in Rameswaram coast. The increased input of PTEs in the coastal regions of GoM signifies the need to monitor the coast regularly using suitable monitoring tools such as sediments to prevent further damage to the marine ecosystem.

Despite existing aggressive treatment modalities, the prognosis for advanced stage neuroblastoma remains poor with significant long-term illness in disease survivors. Advance stage disease features are associated with tumor vascularity, and as such, angiogenesis inhibitors may prove useful along with current therapies. The matricellular protein, secreted protein acidic and rich in cysteine (SPARC), is known to inhibit proliferation and migration of endothelial cells stimulated by growth factors. Here, we sought to determine the effect of SPARC on neuroblastoma tumor cell-induced angiogenesis and to decipher the molecular mechanisms involved in angiogenesis inhibition. Conditioned medium from SPARC-overexpressed neuroblastoma cells (pSPARC-CM) inhibited endothelial tube formation, cell proliferation, induced programmed cell death and suppressed expression of pro-angiogenic molecules such as VEGF, FGF, PDGF, and MMP-9 in endothelial cells. Further analyses revealed that pSPARC-CM-suppressed expression of growth factors was mediated by inhibition of the Notch signaling pathway, and cells cultured on conditioned medium from tumor cells that overexpress both Notch intracellular domain (NICD-CM) and SPARC resumed the pSPARC-CM-suppressed capillary tube formation and growth factor expression in vitro. Further, SPARC overexpression in neuroblastoma cells inhibited neo-vascularization in vivo in a mouse dorsal air sac model. Furthermore, SPARC overexpression-induced endothelial cell death was observed by co-localization studies with TUNEL assay and an endothelial marker, CD31, in xenograft tumor sections from SPARC-overexpressed mice. Our data collectively suggest that SPARC overexpression induces endothelial cell apoptosis and inhibits angiogenesis both in vitro and in vivo.

In this work, we explore the idea of using mathematical models to build design space for the primary drying portion of freeze-drying process. We start by defining design space for freeze-drying, followed by defining critical quality attributes and critical process parameters. Then using mathematical model, we build an insilico design space. Input parameters to the model (heat transfer coefficient and mass transfer resistance) were obtained from separate experimental runs. Two lyophilization runs are conducted to verify the model predictions. This confirmation of the model predictions with experimental results added to the confidence in the insilico design space. This simple step-by-step approach allowed us to minimize the number of experimental runs (preliminary runs to calculate heat transfer coefficient and mass transfer resistance plus two additional experimental runs to verify model predictions) required to define the design space. The established design space can then be used to understand the influence of critical process parameters on the critical quality attributes for all future cycles.

While poorly soluble drugs such as corticosteroids sustain drug delivery in the vitreous humor by virtue of slow dissolution, macromolecules such as antibodies and their fragments sustain their levels due to their slow clearance. However, currently there are no approaches to sustain the delivery of well water soluble small molecule drugs in the vitreous. In this study we optimized a PLA microparticle formulation for sustained intravitreal delivery of TG-0054, a well water soluble anti-angiogenic drug that is of potential value in treating choroid neovascularization. After determining the influence of process parameters on particle size and drug loading, spherical microparticles syringeable through a 27 G needle, with a mean diameter of 7.6 μm, 10% w/w TG-0054 loading, sustained in vitro drug release for at least 6 months, and low residual organic solvent content (~ 1 ppb/mg) were prepared. Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits. Drug levels in the microparticle dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, 62.8 ± 22.6 μg/g vitreous, retina, and choroid-RPE, respectively, and similar to levels at one month. Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye, with the levels being 0.8 ± 0.5, 2.7 ± 2.8, and 4.9± 4.2 μg/g in vitreous, retina, and choroid-RPE, respectively, at one month, with no detectable drug at three months. Although surface degradation was evident, microparticles maintained their spherical structure during the 6 months in vitro study and the 3 months in vivo study, with the vitreal particle retention at 1 and 3 months being 60% and 27%, respectively. Thus, PLA microparticles capable of sustaining retinal and choroidal delivery of TG-0054 for three to six months were developed.

Pleiotrophin (Ptn) is a secreted, developmentally regulated growth factor associated with the extracellular matrix. During mammalian embryogenesis, Ptn has been suggested to play a role in the development of various embryonic structures including nervous system and skeleton. In the avian embryo, Ptn has been proposed to be involved in limb cartilage development, but embryonic Ptn expression has not been comprehensively studied. We isolated a cDNA fragment containing the full-length coding sequence of chick Ptn and studied the expression of Ptn in detail until embryonic day 10. We, furthermore, isolated a 6,385-bp phage clone containing the Ptn cDNA of 2,551 bp and additional 3,787 bp downstream of the published Ptn cDNA sequence classifying a yet Ptn-unrelated chEST clone as the 3' untranslated region of Ptn. Our studies revealed novel expression domains in developing somites and during limb formation. We found prominent expression in the somitocoel cells of epithelial somites, and in a sclerotomal subcompartment, the syndetome, which gives rise to the axial tendons in the vertebral motion segment. In the limbs, Ptn was markedly expressed in tendon anlagen and in phalangeal joints. Our results introduce Ptn as a novel marker gene in avian somite and tendon development.

A 67-year-old man presented with acute monoarthritis of the right knee. Aspiration was carried out under aseptic precautions. This yielded a milky appearing fluid. Polarized microscopic examination confirmed uric acid crystals. The patient had a history of trauma to the joint. Acute monoarthritis of the knee can occur due to gout. Chylous effusions in the knee are rare. This combination of findings in the same joint has not been described in the literature. We emphasise the importance of history of trauma in acute monoarthritis. We discuss the unusual features of this case.

Identification of hibernating myocardium and its differentiation from scar tissue is an important clinical task for implementing different treatment options. The recognition of combined criteria in spiral-CT and PET for hibernating myocardium and scar will be important as hybrid CT-PET moves into the main stream of routine oncologic and cardiovascular imaging. A review of three cases, initially referred for CT evaluation of cardiac or pulmonary conditions with subsequent F-18 FDG body PET imaging, was presented for illustration as a combined CT-PET cardiac evaluation. The real value of this combined anatomical and functional evaluation will be with the upcoming concurrent CT and PET imaging using dedicated multi-slice CT-PET scanners.

Polymethyl methacrylate (PMMA) microspheres were used as an embolic agent to reduce the vascularity in eight patients with intracranial vascular tumours. Post embolization angiograms showed 30-60% reduction in the vascularity of the tumours. No patient developed any neurological complications in the immediate post-embolization period. These eight patients subsequently underwent surgery for the removal of their tumours. During surgery there was minimal blood loss and a good plane of cleavage was obtained between the tumour and the adjacent brain. The surgical specimens were examined histopathologically for the effects of PMMA. PMMA microspheres, in contrast to other cyanoacrylates--isobutyl-2-cyanoacrylate (IBCA)--did not elicit either inflammatory reaction or mural angionecrosis within the wall of the embolised vessels. The histopathological studies suggest that PMMA microspheres are an inert material and can be used as an adjunct in the management of intracranial vascular tumours.