Dynamics of reactive oxygen species and lignin biosynthesis during leaf spot disease of Withania somnifera (L.) Dunal.

Withania somnifera is an important medicinal plant, however, its cultivation and quality are compromised through infestation by leaf spot disease caused by the fungus, Alternaria alternata. To find suitable strategies against this disease, studies on post-infectional changes are important. ROS are critical as they interact with other defence signalling pathways. We analyzed ROS-generating and scavenging systems in healthy and diseased leaf samples of W. somnifera and ROS-driven downstream defence pathways. We used DAB and NBT assays for ROS detection, spectrophotometry and in-gel assays for ROS scavenging enzymes, a thioglycolic acid (TGA) based assay, histochemical staining for lignin, and qRT-PCR for transcript-level expression. Leaf spot infection in W. somnifera increased NADPH oxidase activity and ROS accumulation in infected leaves, together with enhanced antioxidant enzyme activity. Leaf spot-infected leaves had increased lignin content and higher expression of lignin biosynthesis genes. In addition, transcript levels of defence-related genes, NPR1 and PR, were also upregulated. The present work provides insights into responses to leaf spot disease through defence-related signalling in W. somnifera. It demonstrates crosstalk between ROS and lignin biosynthesis. This work identified potential targets for developing strategies to confer disease resistance against A. alternata in W. somnifera.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis.

PURPOSE: To provide a precise summary and collate the hitherto available clinical evidence on the effect of vitamin D supplementation on clinical outcomes in COVID-19 patients. METHODS: PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched using appropriate keywords till June 8, 2021, to identify observational studies and randomized controlled trials (RCTs) reporting adverse clinical outcomes (ICU admission and/or mortality) in COVID-19 patients receiving vitamin D supplementation vs. those not receiving the same. Both prior use and use of vitamin D after COVID-19 diagnosis were considered. Unadjusted/adjusted pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated (PROSPERO registration number CRD42021248488). RESULTS: We identified 13 studies (10 observational, 3 RCTs) pooling data retrieved from 2933 COVID-19 patients. Pooled analysis of unadjusted data showed that vitamin D use in COVID-19 was significantly associated with reduced ICU admission/mortality (OR 0.41, 95% CI: 0.20, 0.81, p = 0.01, I2 = 66%, random-effects model). Similarly, on pooling adjusted risk estimates, vitamin D was also found to reduce the risk of adverse outcomes (pooled OR 0.27, 95% CI: 0.08, 0.91, p = 0.03, I2 = 80%, random-effects model). Subgroup analysis showed that vitamin D supplementation was associated with improved clinical outcomes only in patients receiving the drug post-COVID-19 diagnosis and not in those who had received vitamin D before diagnosis. CONCLUSIONS: Vitamin D supplementation might be associated with improved clinical outcomes, especially when administered after the diagnosis of COVID-19. However, issues regarding the appropriate dose, duration, and mode of administration of vitamin D remain unanswered and need further research.

Bio-therapeutics from human milk: prospects and perspectives.

Human milk is elixir for neonates and is a rich source of nutrients and beneficial microbiota required for infant growth and development. Its benefits prompted research into probing the milk components and their use as prophylactic or therapeutic agents. Culture-independent estimation of milk microbiome and high-resolution identification of milk components provide information, but a holistic purview of these research domains is lacking. Here, we review the current research on bio-therapeutic components of milk and simplified future directions for its efficient usage. Publicly available databases such as PubMed and Google scholar were searched for keywords such as probiotics and prebiotics related to human milk, microbiome and milk oligosaccharides. This was further manually curated for inclusion and exclusion criteria relevant to human milk and clinical efficacy. The literature was classified into subgroups and then discussed in detail to facilitate understanding. Although milk research is still in infancy, it is clear that human milk has many functions including protection of infants by passive immunization through secreted antibodies, and transfer of immune regulators, cytokines and bioactive peptides. Unbiased estimates show that the human milk carries a complex community of microbiota which serves as the initial inoculum for establishment of infant gut. Our search effectively screened for evidence that shows that milk also harbours many types of prebiotics such as human milk oligosaccharides which encourage growth of beneficial probiotics. The milk also trains the naive immune system of the infant by supplying immune cells and stimulatory factors, thereby strengthening mucosal and systemic immune system. Our systematic review would improve understanding of human milk and the inherent complexity and diversity of human milk. The interrelated functional role of human milk components especially the oligosaccharides and microbiome has been discussed which plays important role in human health.

Add-on effect of Ayurvedic treatment protocol for diabetic retinopathy: A randomized controlled clinical study.

Background: Diabetic retinopathy (DR), the leading cause of visual disability in diabetics, is a significant complication of diabetes mellitus. Currently available conventional treatments for DR have certain limitations, considering which Ayurvedic treatment protocol was designed. Aim: The aim of this study was to evaluate the clinical efficacy of the Ayurvedic treatment protocol for DR. Materials and methods: This was a randomized, controlled, black box design clinical study conducted from April 2016 to September 2017 by the department of Shalakya Tantra of a tertiary academic hospital in Western India. A hundred patients of DR in the age group 30-70 years were randomly divided into two groups by simple random sampling using computer-generated random number tables. In the trial group (n = 70), the preparatory phase included Dipana-Pachana (stomachic and digestant), Koshtha Shodhana (mild therapeutic purgation), and Shiro Virechana (eliminative nasal medication). The treatment phase included Marsha Nasya (nasal medication) and Pratimarsha Nasya (nasal medication of mild dose) with Durvadi Ghrita, Takra Dhara (pouring medicated buttermilk over the scalp) with Siddha Takra, and intake of Rasayana Yoga (treatment duration - 3 months). In the control group (n = 30), patients were kept under conservative treatment and observed during the trial period of 3 months. Patients of both groups continued with their treatment for diabetes and DR if any. Two follow-ups were done at an interval of 15 days. The primary outcomes were objective signs like best-corrected visual acuity (BCVA); ophthalmoscopic signs such as superficial hemorrhages, dot-blot hemorrhages, hard exudates, cotton wool spots, neovascularization disc, neovascularization elsewhere, and fibrovascular proliferation; subjective symptoms such as diminished vision, blurred vision, frequent changes in presbyopia glasses, perception of flashes of light, floaters, and problem for dark adaptation. The secondary outcomes were fasting blood sugar (FBS), postprandial blood sugar (PPBS), urine sugar, serum cholesterol, hemoglobin (Hb), glycosylated HbA1C, liver function test, and renal function test outcomes were assessed before and after the treatment. Results: Ninety participants were included in the analysis of the primary outcome (62 in the trial and 28 in the control group). The trial group provided better results which were statistically significant on dot-blot hemorrhages, superficial hemorrhages, hard exudates, BCVA, FBS, and serum cholesterol. Both the groups provided almost similar effects in PPBS, Hb, HbA1C, and urine sugar which were statistically insignificant. Adverse effects were not reported in any of the patient among either groups. Conclusion: Ayurvedic treatment protocol is safe and effective in DR.

Understanding salt tolerance mechanism using transcriptome profiling and de novo assembly of wild tomato Solanum chilense.

Soil salinity affects the plant growth and productivity detrimentally, but Solanum chilense, a wild relative of cultivated tomato (Solanum lycopersicum L.), is known to have exceptional salt tolerance. It has precise adaptations against direct exposure to salt stress conditions. Hence, a better understanding of the mechanism to salinity stress tolerance by S. chilense can be accomplished by comprehensive gene expression studies. In this study 1-month-old seedlings of S. chilense and S. lycopersicum were subjected to salinity stress through application of sodium chloride (NaCl) solution. Through RNA-sequencing here we have studied the differences in the gene expression patterns. A total of 386 million clean reads were obtained through RNAseq analysis using the Illumina HiSeq 2000 platform. Clean reads were further assembled de novo into a transcriptome dataset comprising of 514,747 unigenes with N50 length of 578 bp and were further aligned to the public databases. Genebank non-redundant (Nr), Viridiplantae, Gene Ontology (GO), KOG, and KEGG databases classification suggested enrichment of these unigenes in 30 GO categories, 26 KOG, and 127 pathways, respectively. Out of 265,158 genes that were differentially expressed in response to salt treatment, 134,566 and 130,592 genes were significantly up and down-regulated, respectively. Upon placing all the differentially expressed genes (DEG) in known signaling pathways, it was evident that most of the DEGs involved in cytokinin, ethylene, auxin, abscisic acid, gibberellin, and Ca2+ mediated signaling pathways were up-regulated. Furthermore, GO enrichment analysis was performed using REVIGO and up-regulation of multiple genes involved in various biological processes in chilense under salinity were identified. Through pathway analysis of DEGs, "Wnt signaling pathway" was identified as a novel pathway for the response to the salinity stress. Moreover, key genes for salinity tolerance, such as genes encoding proline and arginine metabolism, ROS scavenging system, transporters, osmotic regulation, defense and stress response, homeostasis and transcription factors were not only salt-induced but also showed higher expression in S. chilense as compared to S. lycopersicum. Thus indicating that these genes may have an important role in salinity tolerance in S. chilense. Overall, the results of this study improve our understanding on possible molecular mechanisms underlying salt tolerance in plants in general and tomato in particular.

Ethnobotany of medicinal plants used by the Zeliangrong ethnic group of Manipur, northeast India.

ETHNOPHARMACOLOGICAL RELEVANCE: The Zeliangrong people with their yearlong experiences still depend on the medicinal plants for primary healthcare. Some of the medicinal plants used by the community exhibits established pharmacological activities which signify the importance of the traditional knowledge of the tribes. Besides, many other species traditionally used by the tribes assume to have pharmacological potentiality. AIM OF THE STUDY: The study aimed to identify the medicinally and pharmacologically important species with understanding the traditional healing practices and to compare medicinal plant knowledge among the informants of the three tribes under Zeliangrong group. MATERIAL AND METHODS: Data were collected by interviewing selected 27 herbal healers using modified semi-structured questionnaires. Identification and documentation of all the species have been made using standard taxonomic procedure. Ethnomedicinal uses of all the recorded species was analyzed with computation of the use reports for each species and Informant Consensus Factor. RESULTS: The study recorded 145 medicinal plants used in healing practices by the Zeliangrong tribes. Except 2 species, all are Angiospermic plants found mostly in wild condition. These medicinal plants are used for treating about 59 different health ailments categorized under 13 ICPC disease categories. Highest ICF (0.75) was found in Digestive disorder with 174 use reports for 44 plant species. Besides the established medicinal plants in the Indian System of medicine like Acorus calamus, Centella asiatica, Oroxylum indicum and Phyllanthus emblica, a number of other species like Ageratum conizoides, Blumeopsis flava, Clerodendrum glandulosum, Gynura cusimbua, Hedyotis scandens and Paederia foetida also has maximum use reports. Among the species with higher use reports, 2 species namely Clerodendrum glandulosum and Paederia foetida are exclusively used for the treatment of hypertension, and bone fracture and sprain respectively indicating their remarkable medicinal values and acceptability. Out of the total 145 species, only 24 are shared by all the three tribes with 11 species used for similar diseases. CONCLUSION: The medicinal plants with higher use reports can be evaluated for validation of pharmacological activities and their toxicity. The Indigenous Knowledge System of Zeliangrong community for herbal remedies may be of immense value in pharmacological experimentation particularly for the uses like malaria, health tonic, cancer, jaundice, hypertension and diabetes.

The quality of life of caregivers of children with atopic dermatitis in a South African setting

Background. Atopic dermatitis (AD) is known to adversely affect patients' quality of life (QOL). However, less is known about the extent to which caregivers are affected, particularly in developing countries. Objectives. To investigate factors affecting QOL in caregivers of children with AD in the South African (SA) setting and to document the associated effect of disease severity. Methods. This was a prospective study of 142 AD patients and their caregivers attending Grey's Hospital in KwaZulu-Natal, SA, between May and September 2016. Disease severity was assessed according to the Objective Scoring of Atopic Dermatitis (Objective SCORAD) index. The Dermatitis Family Impact (DFI) questionnaire was used to assess QOL. Results. The study population included 119 (84%) black, 20 (14%) Indian and 3 (2%) coloured patients. Among the group, 44% of cases (n=62) were classified as mild, 53% (n=76) as moderate and 3% (n=4) as severe. The DFI score was significantly associated with the Objective SCORAD index (p<0.0001). QOL factors significantly affected were emotional distress of the caregiver (p<0.0001), tiredness of the caregiver (p<0.0001) and family leisure activities (p<0.0001). Involvement in treatment (p=0.016), food preparation and feeding (p=0.003), the family's sleep (p=0.001) and the caregiver's relationships (p=0.025) were moderately affected. Conclusion. The QOL of caregivers of children with AD in this setting was adversely affected and declined with increasing disease severity. An evaluation of the psychosocial health of caregivers and appropriate referral where necessary are important for holistic management of both the patient and the caregiver and to improve disease outcome

Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis.

BACKGROUND & AIMS: Protein-Energy Wasting (PEW) is the depletion of protein/energy stores observed in the most advanced stages of Chronic Kidney Disease (CKD). PEW is highly prevalent among patients on chronic dialysis, and is associated with adverse clinical outcomes, high morbidity/mortality rates and increased healthcare costs. This narrative review was aimed at exploring the pathophysiology of PEW in end-stage renal disease (ESRD) on hemodialysis. The main aspects of nutritional status evaluation, intervention and monitoring in this clinical setting were described, as well as the current approaches for the prevention and treatment of ESRD-related PEW. METHODS: An exhaustive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, nutritional intervention and outcome of PEW in ESRD on hemodialysis. RESULTS AND CONCLUSION: The pathogenesis of PEW is multifactorial. Loss of appetite, reduced intake of nutrients and altered lean body mass anabolism/catabolism play a key role. Nutritional approach to PEW should be based on a careful and periodic assessment of nutritional status and on timely dietary counseling. When protein and energy intakes are reduced, nutritional supplementation by means of specific oral formulations administered during the hemodialysis session may be the first-step intervention, and represents a valid nutritional approach to PEW prevention and treatment since it is easy, effective and safe. Omega-3 fatty acids and fibers, now included in commercially available preparations for renal patients, could lend relevant added value to macronutrient supplementation. When oral supplementation fails, intradialytic parenteral nutrition can be implemented in selected patients.

Selenium and other mineral concentrations in feed and sheep's blood in Kosovo.

The aim of this study was to assess the concentration of Se and other minerals in sheep and the supplied feed. Four macrominerals (Ca, P, Mg, and S), 7 microminerals (Se, Fe, Zn, Cu, Mn, Co, and Mo), and 2 toxic minerals (Cd and Pb) were analyzed in 69 feed and 292 sheep blood samples from 30 farms in different regions of Kosovo. The samples were analyzed using inductively coupled plasma mass spectrometry, and mineral concentrations in whole blood were measured to assess their status in animals. Concentrations of the different minerals in feed were found in the following ranges: 1.9 to 9.5 g Ca/kg DM, 0.8 to 3.2 g P/kg DM, 0.8 to 3.2 g Mg/kg DM, 1.0 to 2.8 g S/kg DM, 6 to 82 µg Se/kg DM, 33 to 970 mg Fe/kg DM, 15 to 42 mg Zn/ kg DM, 2.6 to 7.5 mg Cu/kg DM, 26 to 250 mg Mn/kg DM, 0.04 to 0.88 mg Co/kg DM, 0.05 to 0.86 mg Mo/ kg DM, 0.07 to 2.02 mg Pb/kg DM, and 0.02 to 0.19 mg Cd/kg DM. Concentrations of the microminerals analyzed in whole blood were found in the following ranges: 15 to 360 µg Se/L, 190 to 500 mg Fe/L, 1.4 to 3.8 mg Zn/L, 0.3 to 2.6 mg Cu/L, 6 to 243 µg Mn/L, 0.1 to 19.6 µg Co/L, and 1.8 to 66.0 µg Pb/L. Among all minerals, the largest deficiency was found for Se both in feed and sheep blood, with 82% of feed samples and 83% blood samples being inadequate, and its supplementation is necessary. Selenium-supplemented sheep had significantly higher Se concentration in blood than non-supplemented sheep (P < 0.01). In addition, other macro- and microminerals in feed such as P, S, Cu, and Co were at inadequate concentrations at some of the farms, and supplementation may also be needed for these minerals.

Leaf spot disease adversely affects human health-promoting constituents and withanolide biosynthesis in Withania somnifera (L.) Dunal.

AIMS: The present work investigates the implication of leaf spot disease on the antioxidant potential and commercial value of pharmaceutically important constituents of Withania somnifera, a high-valued medicinal plant. METHODS AND RESULTS: Leaf spot disease was induced in W. somnifera by inoculating Alternaria alternata (Fr.) Keiss. pathogen. Total polyphenolic content and antioxidant potential showed a significant decrease during leaf spot disease. Evaluation of pharmaceutically active constituents withaferin A, withanone and withanolide A utilizing high-performance liquid chromatography showed a significant decrease in diseased samples as compared to healthy ones. Quantitative expression of major genes involved in withanolide biosynthesis also showed down-regulation in diseased samples. Alterations in the ultra-structure of chloroplasts were also analysed under transmission electron microscopy to get a better insight into the changes of withanolide biosynthesis in leaf during disease infestation. CONCLUSIONS: The present work suggests that when the pathogenic fungus invades the host plants, it evokes multiple responses, which could be studied at various levels. The knowledge gained from this work will provide appropriate rationale for controlling the bio-deterioration of the pharmaceutically active metabolites in W. somnifera and development of suitable strategies against leaf spot disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to investigate the effect of leaf spot disease on the human health-promoting constituents and withanolide biosynthesis in this high-valued medicinal plant.

Synergistic protective effect of picrorhiza with honey in acetaminophen induced hepatic injury.

Rhizome of picrorhiza along with honey prevents hepatic damage and cure the acetaminophen (paracetamol) induced hepatotoxicity by modulating the activity of hepatic enzymes. Here, we studied the in vivo effects of Picrorhiza kurroa and honey on acetaminophen induced hepatotoxicity Balb/c mice model. Hepatic histopathological observations of acetaminophen fed (day-6) group showed more congestion, hemorrhage, necrosis, distorted hepatic architecture and nuclear inclusion. Such damages were recompensed to normal by picrorhiza or honey alone or both in combinations. We observed increased activity of SGPT and SGOT in injured liver tissues, and that too was compensated to normal with picrorhiza or honey alone or both in combinations. We observed 1.27 and 1.23-fold enhanced activity of SGPT in serum and liver lysate, respectively while SGOT showed 1.66 and 1.11 fold enhanced activity. These two enzymes are signature enzymes of liver damage. Thus, our results support that honey may be used with drug picrorhiza due to its synergistic role to enhance hepatoprotective and hepatoregenerative ability along with allopathic drugs to mitigate the hepatotoxic effects.

In vitro antimicrobial activity of crude ethanol extracts and fractions of Terminalia catappa and Vitex doniana.

BACKGROUND: The spread of microorganisms resistant to some antimicrobial agents necessitates the need to search for novel and effective antimicrobial agents. In this study, the antimicrobial activity of Terminalid catappa Linn. (Combretaceae) and Vitex doniana Sweet. (Verbenaceae), two Nigerian medicinal plants used in folk medicines for the management of various ailments related to microbial infections were evaluated. OBJECTIVES: To evaluate the antimicrobial activity of the crude ethanol extracts and fractions of the leaves and stem bark of T. catappa and V. doniana. METHODOLOGY: Four crude ethanol extracts and 16 (n-hexane, ethylacetate, n-butanol and aqueous) fractions of leaves and stem bark of T. catappa and V doniana were evaluated for in vitro antimicrobial activity against fifteen (15) strains of bacteria and fungi. The antimicrobial activity was determined in a 96-well plate using a resazurin based broth microdilution method. Two standard antimicrobial drugs ampicillin and nystatin were included as positive control. RESULTS: The butanoL fraction of stem bark of T. catappa and ethanol crude extract of leaf of V don iana displayed the highest antibacterial activity with similar minimum inhibitory concentration (MIC) value of 93.75 microg/mL against S. aureus and B. subtilis. Furthermore, the ethyl acetate fraction of stem bark of T. catappa showed the highest antifungal activity with MIC of 187.5 microg/mL against A. sydowi. Amp icillin had MIC of 15.6 and 31.3 microg/mL against S. aureus and B. subtili, respectively while nystatin produced MIC of 3.9 microg/mL against A. sydowi. CONCLUSION: Termninalia catappa and Vitex doniana may serve as useful sources of plant derived antimicrobial agents.

Peripheral neuron plasticity is enhanced by brief electrical stimulation and overrides attenuated regrowth in experimental diabetes.

Peripheral nerve regrowth is less robust than commonly assumed, particularly when it accompanies common clinical scenarios such as diabetes mellitus. Brief extracellular electrical stimulation (ES) facilitates the regeneration of peripheral nerves in part through early activation of the conditioning injury response and BDNF. Here, we explored intrinsic neuronal responses to ES to identify whether ES might impact experimental diabetes, where regeneration is attenuated. ES altered several regeneration related molecules including rises in tubulin, Shh (Sonic hedgehog) and GAP43 mRNAs. ES was associated with rises in neuronal intracellular calcium but its strict linkage to regrowth was not confirmed. In contrast, we identified PI3K-PTEN involvement, an association previously linked to diabetic regenerative impairment. Following ES there were declines in PTEN protein and mRNA both in vitro and in vivo and a PI3K inhibitor blocked its action. In vitro, isolated diabetic neurons were capable of mounting robust responsiveness to ES. In vivo, ES improved electrophysiological and behavioral indices of nerve regrowth in a chronic diabetic model of mice with pre-existing neuropathy. Regrowth of myelinated axons and reinnervation of the epidermis were greater following ES than sham stimulation. Taken together, these findings identify a role for ES in supporting regeneration during the challenges of diabetes mellitus.

Host-mediated gene silencing of a single effector gene from the potato pathogen Phytophthora infestans imparts partial resistance to late blight disease.

RNA interference (RNAi) has proved a powerful genetic tool for silencing genes in plants. Host-induced gene silencing of pathogen genes has provided a gene knockout strategy for a wide range of biotechnological applications. The RXLR effector Avr3a gene is largely responsible for virulence of oomycete plant pathogen Phytophthora infestans. In this study, we attempted to silence the Avr3a gene of P. infestans through RNAi technology. The P. infestans inoculation resulted in lower disease progression and a reduction in pathogen load, as demonstrated by disease scoring and quantification of pathogen biomass in terms of Pi08 repetitive elements, respectively. Transgenic plants induced moderate silencing of Avr3a, and the presence and/or expression of small interfering RNAs, as determined through Northern hybridization, indicated siRNA targeted against Avr3a conferred moderate resistance to P. infestans. The single effector gene did not provide complete resistance against P. infestans. Although the Avr3a effector gene could confer moderate resistance, for complete resistance, the cumulative effect of effector genes in addition to Avr3a needs to be considered. In this study, we demonstrated that host-induced RNAi is an effective strategy for functional genomics in oomycetes.

Quercetin sensitizes fluconazole-resistant candida albicans to induce apoptotic cell death by modulating quorum sensing.

Quorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZ-resistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections.

Colostrum hexasaccharide, a novel Staphylococcus aureus quorum-sensing inhibitor.

The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in Staphylococcus aureus. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD), (1)H and (13)C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against S. aureus and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in S. aureus. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial.

Veterinary public health in India: current status and future needs.

Veterinary public health (VPH) assumes huge significance in developing countries such as India. However, the implementation of VPH services throughout the country is still in its infancy. From 1970 onwards, many institutes, national and international organisations, professional societies, policies and personalities have contributed towards the development of VPH in India. Nevertheless, there is an urgent need to develop VPH still further as there are many issues, such as high population density, the re-emergence of zoonotic pathogens, environmental pollution and antimicrobial resistance, that require attention. The time has surely come to involve all stakeholders, ranging from primary producers (e.g., farmers) to policy-makers, so as to garner support for the holistic implementation of VPH services in India. To improve VPH activities and services, science-based policies enforced through stringent regulation are required to improve human, animal and environmental health. The emergence of the 'One Health' concept has ushered in new hopes for the resurrection of VPH in India. Applying tools such as the World Organisation for Animal Health (OlE) Day One Competencies and the OlE Tool for the Evaluation of Performance of Veterinary Services (PVS Tool) is essential to improve the quality of national Veterinary Services and to identify gaps and weaknesses in service provision, which can be remedied to comply with the OlE international standards. VPH initiatives started modestly but they continue to grow. The present review is focused on the current status and future needs of VPH in India.

Fungal phytases: characteristics and amelioration of nutritional quality and growth of non-ruminants.

Fungal phytases are histidine acid phosphatases, a subclass of acid phosphatases, which catalyse the hydrolysis of phytic acid resulting in the release of phosphate moieties and thus mitigate its antinutritional properties. The supplementation of feed with phytases increases the bioavailability of phosphorus and minerals in non-ruminant animals and reduces the phosphorus pollution due to phosphorus excretion in the areas of intensive livestock production. Although phytases are reported in plants, animals and micro-organisms, fungal sources are used extensively for the production of phytases on a commercial scale. Phytases have been produced by fungi in both solid-state fermentation (SSF) and submerged fermentation (SmF). The fungal phytases are high molecular weight proteins ranging from 35 to 500 kDa. They are optimally active within pH and temperature ranges between 4.5 and 6.0, and 45 and 70 °C respectively. Phytate degradation leads to amelioration in the nutritional status of foods and feeds by improving the availability of minerals, phosphorus and proteins in non-ruminant animals and human beings and thus mitigates the environmental phosphorus pollution. Our article focuses on the role of fungal phytases in improving nutritional value of foods and feeds with concomitant increase in growth of non-ruminant animals and mitigating environmental phosphorus pollution.

Screening of novel microorganisms for biosurfactant and biocontrol activity against Phytophthora infestans.

In the present study, 95 isolates of bacteria were tested for their biosurfactant as well as biocontrol activity against Phytophthora infestans. The results revealed that only 15.8% isolates showed biosurfactant activity. The emulsification index ranged from 0-68% and 24.2% isolates showed positive reaction for biosurfactant properties. In emulsification assay and oil spreading test, 18.95% and 5.26% isolates, respectively scored positive for biosurfactant production. Among all, only five isolates were found effective against P. infestans, for biocontrol properties. Pseudomonas aeruginosa-1 showed 62.22% inhibition zone after 72 hrs while P. aeruginosa-3 showed 46.42%. Forty-eight hrs old culture supernatants were highly effective in food-poisoning test, tuber slice test and detached leaf method against P. infestans. In whole potato plant test, bacterial cell based formulation, culture supernatant and bacterial cell suspension of P. aeruginosa-1 showed 10.42%, 9.94% and 17.96% diseases severity respectively, as against 53.96% in control. This isolate holds promise as biological control agent against P. infestans in field.