Cytokines induce effector T-helper cells during invasive aspergillosis; what we have learned about T-helper cells?

Invasive aspergillosis caused by Aspergillus species (Aspergillus fumigatus, A. flavus and A. terreus) is life-threatening infections in immunocompromised patients. Understanding the innate and adaptive immune response particularly T-helper cells (TH-cells) against these Aspergillus species and how the different sub-set of TH-cells are regulated by differentiating cytokines at primary target organ site like lung, kidney and brain is of great significance to human health. This review focuses on presentation of Aspergillus through Antigen presenting cells (APCs) to the naive CD4+ T-cells in the host. The production of differentiating/effector cytokines that activate following TH-cells e.g., TH1, TH2, TH9 and TH17 has been reported in association or alone in allergic or invasive aspergillosis. Chemokines (CXCL1, CXCL2, CCL1 and CCL20) and their receptors associated to these TH-cells have also been observed in invasive aspergillosis. Thus, further study of these TH-cells in invasive aspergillosis and other elements of adaptive immune response with Aspergillus species are required in order to have a better understanding of host response for safer and effective therapeutic outcome

Influence of 17β-Estradiol on Gene Expression of Paracoccidioides during Mycelia-to-Yeast Transition

BACKGROUND: Paracoccidioides is the causative agent of paracoccidioidomycosis, a systemic mycosis endemic to Latin America. Infection is initiated by inhalation of conidia (C) or mycelial (M) fragments, which subsequently differentiate into yeast (Y). Epidemiological studies show a striking predominance of paracoccidioidomycosis in adult men compared to premenopausal women. In vitro and in vivo studies suggest that the female hormone (17β-estradiol, E(2)) regulates or inhibits M-or-C-to-Y transition. In this study we have profiled transcript expression to understand the molecular mechanism of how E(2) inhibits M-to-Y transition. METHODOLOGY: We assessed temporal gene expression in strain Pb01 in the presence or absence of E(2) at various time points through 9 days of the M-to-Y transition using an 11,000 element random-shear genomic DNA microarray and verified the results using quantitative real time-PCR. E(2)-regulated clones were sequenced to identify genes and biological function. PRINCIPAL FINDINGS: E(2)-treatment affected gene expression of 550 array elements, with 331 showing up-regulation and 219 showing down-regulation at one or more time points (p≤0.001). Genes with low expression after 4 or 12 h exposure to E(2) belonged to pathways involved in heat shock response (hsp90 and hsp70), energy metabolism, and several retrotransposable elements. Y-related genes, α-1,3-glucan synthase, mannosyltransferase and Y20, demonstrated low or delayed expression in E(2)-treated cultures. Genes potentially involved in signaling, such as palmitoyltransferase (erf2), small GTPase RhoA, phosphatidylinositol-4-kinase, and protein kinase (serine/threonine) showed low expression in the presence of E(2), whereas a gene encoding for an arrestin domain-containing protein showed high expression. Genes related to ubiquitin-mediated protein degradation, and oxidative stress response genes were up-regulated by E(2). CONCLUSION: This study characterizes the effect of E(2) at the molecular level on the inhibition of the M-to-Y transition and is indicative that the inhibitory actions of E(2) may be working through signaling genes that regulate dimorphism

Edible mushroom: occurrence, management and health benefits

Owing to medicinal and nutraceutical properties, mushrooms have been consumed worldwide for many years. They are valued for their unique flavor, texture, and versatility in cooking. Numerous species of edible mushrooms have different habitats, ecological niches, and growth patterns. In a vegetarian diet, mushrooms have been preferred and widely accepted over a non-vegetarian one because of their low-calorie, high-protein content and their good source of carbohydrates and lipids. Edible mushrooms provide various macronutrients, micronutrients, minerals, and vitamins. Bioactive compounds extracted from different species of mushrooms exhibit various medicinal properties, such as antitumor, antioxidant, hypocholesterolemic, antiallergic, anti-inflammatory, and hypoglycemic effects. These properties are mainly due to polysaccharides like β-glucan, polyphenols like phenolic acids and flavonoids, carotenoids, and vitamins. Edible mushrooms are also potential prebiotics and are beneficial for human gut health. Secondary metabolites extracted from edible mushrooms are used to develop drugs to treat chronic diseases.In conclusion, edible mushrooms contain essential food supplements and versatile food sources that provide numerous health benefits. Effective management of edible mushroom production is crucial to ensure their continued availability, quality, and sustainability. The study of edible mushrooms and their health benefits continues to be an area of active research, and additional benefits will likely be further discovered

Resistance mechanism and proteins in Aspergillus species against antifungal agents

Aspergillus species contain pathogenic and opportunistic fungal pathogens which have the potential to cause mycosis (invasive aspergillosis) in humans. The existing antifungal drugs have limitation largely due to the development of drug-resistant isolates. To gain insight into the mechanism of action and antifungal drug resistance in Aspergillus species including biofilm formation, we have reviewed protein data of Aspergillus species during interaction with antifungals drugs (polynes, azoles and echinocandin) and phytochemicals (artemisinin, coumarin and quercetin). Our analyses provided a list of Aspergillus proteins (72 proteins) that were abundant during interaction with different antifungal agents. On the other hand, there are 26 proteins, expression level of which is affected by more than two antifungal agents, suggesting the more general response to the stress induced by the antifungal agents. Our analysis showed enzymes from cell wall remodelling, oxidative stress response and energy metabolism are the responsible factors for providing resistance against antifungal drugs in Aspergillus species and could be explored further in clinical isolates. Also, these findings have clinical importance since the effect of drug targeting different proteins can be potentiated by combination therapy. We have also discussed the opportunities ahead to study the functional role of proteins from environmental and clinical isolates of Aspergillus during its interaction with the antifungal drugs. Abbreviations IPA: invasive pulmonary aspergillosis; IA: invasive aspergillosis; AmB: Amphotericin B; CAS: Caspofungin; VRC: Voriconazole; ITC: Itraconazole; POS: Posaconazole; ART: Artemisinin; QRT: Quercetin; CMR: Coumarin; MIC: minimal inhibitory concentratio

Detection of Candida albicans in the screening of cervical cancer in rural population of Lucknow: Detection of Candida albicans in the screening of cervical cancer

Background Study of Candidal infection is very essential in rural women who being illiterate and financially weak are not aware of personal genital hygiene and thus harbour persistent vaginal infections due to poor availability of medical amenities. Method Rural cervical cancer screening is in progress in the western region of Lucknow, India since May 2013 through camp approach and till date, a total of 2949 women have been cytologically examined. Candidal infection has been observed in the 143 cervical smears of women and  findings have been analyzed in relation to the different predisposing factor of cervical carcinogenesis. Result The incidence of Candida albicans seen in cervical smears of the total 2949 women examined was found to be 4.8% which is much higher than in their urban counterparts (1.2%). The Candida was seen more in the inflammatory smears (9.4%) and those showing squamous intraepithelial lesions of cervix (SIL). –  (8.2%). The fungus was found more prevalent in the reproductive age group and women complaining of vaginal discharge and was result of persistent vaginal infections in the rural women which should be treated.  The Candida was commonly seen in erosion cervix cases but its incidence was high in women with cervicitis and cervix bleeds on touch. Conclusions This persistent  vaginal infections were seen in the illiterate and poor rural women who are not aware of personal genital hygiene. There is a need to create awareness for personal genital hygiene through health workers for making any cancer screening program meaningful and successful

Cervical cancer screening in rural India: Status & current concepts

Cervical carcinoma is one of the most common and dreaded diseases of women, and in India, it accounts for 16 per cent of total cervical cancer cases occurring globally. The situation is more alarming in the rural areas where the majority of women are illiterate and ignorant about the hazards of cervical cancer. Different screening strategies such as rural cancer registries and camp approach for cancer detection have been found useful in minimizing the problem of cervical cancer in the villages. Various screening techniques such as visual inspection with acetic acid, visual inspection with Lugol's iodine, visual inspection with magnification devices-magnavisualizer, Pap smear and HPV-DNA testing have been suggested and tried under low-resource settings of our country, and cervical cytology screening has been found effective in reducing incidence of the disease. In the present review, feasibility of different screening methods has been assessed to find out the most suitable mode applicable at the rural level. Single lifetime screening particularly of high-risk women along with analysis of cost-effective tumour markers such as Argyrophilic nucleolar organizer regions (AgNOR) counts to discriminate high-risk dysplasia cases appears to be an appropriate approach in fighting against cervical cancer

Molecular Insights Into Development and Virulence Determinants of Aspergilli: A Proteomic Perspective

Aspergillus species are the major cause of health concern worldwide in immunocompromised individuals. Opportunistic Aspergilli cause invasive to allergic aspergillosis, whereas non-infectious Aspergilli have contributed to understand the biology of eukaryotic organisms and serve as a model organism. Morphotypes of Aspergilli such as conidia or mycelia/hyphae helped them to survive in favorable or unfavorable environmental conditions. These morphotypes contribute to virulence, pathogenicity and invasion into hosts by excreting proteins, enzymes or toxins. Morphological transition of Aspergillus species has been a critical step to infect host or to colonize on food products. Thus, we reviewed proteins from Aspergilli to understand the biological processes, biochemical, and cellular pathways that are involved in transition and morphogenesis. We majorly analyzed proteomic studies on A. fumigatus, A. flavus, A. terreus, and A. niger to gain insight into mechanisms involved in the transition from conidia to mycelia along with the role of secondary metabolites. Proteome analysis of morphotypes of Aspergilli provided information on key biological pathways required to exit conidial dormancy, consortia of virulent factors and mycotoxins during the transition. The application of proteomic approaches has uncovered the biological processes during development as well as intermediates of secondary metabolite biosynthesis pathway. We listed key proteins/ enzymes or toxins at different morphological types of Aspergillus that could be applicable in discovery of novel therapeutic targets or metabolite based diagnostic markers