Siderophore of plant growth promoting rhizobacterium origin reduces reactive oxygen species mediated injury in Solanum spp. caused by fungal pathogens.

AIMS: The study aims to explore antifungal properties of bacillibactin siderophore produced by the plant growth-promoting rhizobacterium (PGPR) Bacillus subtilis against fungal phytopathogens Alternaria porri and Fusarium equiseti isolated from Solanum lycopersicum and Solanum melongena plants. METHODS AND RESULTS: Alternaria porri and F. equiseti were isolated from infected plants of eggplant and tomato, respectively. A plate assay was employed to assess the effect of bacillibactin against the phytopathogens. The antifungal potential of the PGPR was evaluated by estimation of dry fungal biomass, visualization of cellular deformity using compound and scanning electron microscopy, antioxidative enzyme assay and analysis of membrane damage via using lipid peroxidation. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis was employed to investigate changes in intracellular iron content. The impact of bacillibactin on pathogenesis was evaluated by infecting detached leaves of S. lycopersicum and S. melongena plants with both the pathogens and treating the infected leaves with bacillibactin. Leaves were further investigated for ROS accumulation, extent of necrosis and cell death. Our findings revealed significant damage to the hyphal structure of A. porri and F. equiseti following treatment with bacillibactin. Biomass reduction, elevated antioxidative enzyme levels, and membrane damage further substantiated the inhibitory effects of the siderophore on fungal growth. ICP-AES analysis indicates an increase in intracellular iron content suggesting enhanced iron uptake facilitated by bacillibactin. Moreover, application of 1500 µg ml-1 bacillibactin on infected leaves demonstrated a substantial inhibition of ROS accumulation, necrosis, and cell death upon bacillibactin treatment. CONCLUSIONS: This study confirms the potent antagonistic activity of bacillibactin against both the phytopathogens A. porri and F. equiseti growth, supporting its potential as a promising biological control agent for fungal plant diseases. Bacillibactin-induced morphological, physiological, and biochemical alterations in the isolated fungi and pathogen-infected leaves highlight the prospects of bacillibactin as an effective and sustainable solution to mitigate economic losses associated with fungal infections in vegetable crops.

Screening of potential phytomolecules against MurG as drug target in nosocomial pathogen Pseudomonas aeruginosa: perceptions from computational campaign.

The nosocomial infection outbreak caused by Pseudomonas aeruginosa remains a public health concern. Multi-drug resistant (MDR) strains of P. aeruginosa are rapidly spreading leading to a huge mortality rate because of the unavailability of promising antimicrobials. MurG glycotransferase [UDP-N-acetylglucosamine-N-acetylmuramyl (pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase] is located at the plasma membrane and plays a key role in murein (peptidoglycan) biosynthesis in bacteria. Since MurG is required for bacterial cell wall synthesis and is non-homologous to Homo sapiens; it can be a potential target for the antagonist to treat P. aeruginosa infection. The discovery of high-resolution crystal structure of P. aeruginosa MurG offers an opportunity for the computational identification of its prospective inhibitors. Therefore, in the present study, the crystal structure of MurG (PDB ID: 3S2U) from P. aeruginosa was selected, and computational docking analyses were performed to search for functional inhibitors of MurG. IMPPAT (Indian medicinal plants, phytochemicals and therapeutic) phytomolecule database was screened by computational methods with MurG catalytic site. Docking results identified Theobromine (-8.881 kcal/mol), demethoxycurcumin (-8.850 kcal/mol), 2-alpha-hydroxycostic acid (-8.791 kcal/mol), aurantiamide (-8.779 kcal/mol) and petasiphenol (-8.685 kcal/mol) as a potential inhibitor of the MurG activity. Further, theobromine and demethoxycurcumin were subjected to MDS (molecular dynamics simulation) and free energy (MM/GBSA) analysis to comprehend the physiological state and structural stability of MurG-phytomolecules complexes. The outcomes suggested that these two phytomolecules could act as most favorable natural hit compounds for impeding the enzymatic action of MurG in P. aeruginosa, and thus it needs further validation by both in vitro and in vivo analysis. HIGHLIGHTSThe top phytomolecules such as theobromine, demethoxycurcumin, 2-alpha-hydroxycostic acid, aurantiamide and petasiphenol displayed promising binding with MurG catalytic domain.MurG complexed with theobromine and demethoxycurcumin showed the best interaction and stable by MD simulation at 100 ns.The outcome of MurG binding phytomolecules has expanded the possibility of hit phytomolecules validation.Communicated by Ramaswamy H. Sarma.

Terpenoid phytocompounds from mangrove plant Xylocarpus moluccensis as possible inhibitors against SARS-CoV-2: In silico strategy.

COVID-19 shook the world during the pandemic, where the climax it reached was vaccine manufacturing at an unfathomable pace. Alternative promising solutions to prevent infection from SARS-CoV-2 and its variants will remain crucial in the years to come. Due to its key role in viral replication, the major protease (Mpro) enzyme of SARS-CoV-2 can be an attractive therapeutic target. In the present work, natural terpenoids from mangrove medicinal plant Xylocarpus moluccensis (Lam.) M. Roem. were screened using computational methods for inhibition of Mpro protein. Out of sixty-seven terpenoids, Angolensic acid methyl ester, Moluccensin V, Thaixylomolin F, Godavarin J, and Xylomexicanolide A were shortlisted based on their docking scores and interaction affinities (- 13.502 to - 15.52 kcal/mol). The efficacy was validated by the 100 ns molecular dynamics study. Lead terpenoids were within the acceptable range of RMSD and RMSF with a mean value of 2.5 Å and 1.5 Å, respectively indicating that they bound tightly within Mpro and there was minimal fluctuation and stability of Mpro upon binding of these terpenoids. The utmost favorable binding strengths as calculated by MM-GBSA, were of Angolensic acid methyl ester and Moluccensin V with binding free energies (ΔGbind) of - 39.084, and - 43.160 kcal/mol, respectively. The terpenoids showed no violations in terms of Drug Likeliness and ADMET predictions. Overall, the findings indicate that Angolensic acid methyl ester and Moluccensin V are effective terpenoids having strong binding interaction with Mpro protein, which must be tested in vitro as an effective anti-SARS-CoV-2 drug.

A systematic review and meta-analysis of the surgical outcomes in patients with osteochondroma of mandibular condyle.

Many options exist in the diagnosis and management of condylar osteochondroma. The purpose of this study was to provide a congregate information concerning treatment of the osteochondroma involving the mandibular condyle. The search was conducted in PubMed, Google Scholar, Semantic Scholar, and Cochrane database until February 2022. Twenty-seven studies were included for the final review. The review included 439 patients who underwent surgical management for mandibular condylar osteochondroma. The position of osteochondroma was mentioned in 13 studies. Preauricular, retromandibular, endaural, submandibular, transzygomatic, and intraoral approaches were used for approaching the tumor. Surgical techniques included resection, conservative condylectomy, and total condylectomy. Concomitant orthognathic surgery was performed along with tumor resection in 19 studies. In the entire review, the recurrence rate was 0.22% (1/439). The results of the meta-analysis showed that 2 studies reported significant malocclusion events after surgical therapy. Total joint replacement after tumor resection has a higher improvement in maximal mouth opening (8 mm) compared with vertical ramus osteotomy and no reconstruction groups, which have similar improvements (6 mm). The mainstay of treatment of osteochondroma is surgical excision either as condylectomy or conservative condylectomy. Among the various reconstruction modalities, total joint replacement showed better improvement in mouth opening. Adjunct procedures like orthodontic and orthognathic surgery have an important role in holistic management of severe cases. The treating surgeon must choose the surgical procedures in a pragmatic way.

Green extraction of bioactive components from carrot industry waste and evaluation of spent residue as an energy source.

Carrot processing industries produce 25-30% of waste in the form of carrot rejects, peels, and pomace which contain a large amount of high-value bioactive components. Green extraction of the bioactive components from carrot rejects with green solvents using closed-vessel energy-intensive microwave-assisted extraction was the objective of this work. In this work, three experimental studies were implemented. One uses 8 different green solvents for maximum yield of bioactive using green technology, and the other for the optimization of Microwave-assisted Extraction (MAE) parameters to enhance the bioactive components yield. Response Surface Methodology was employed to optimize the processing parameters including temperature, time, solid to solvent ratio, and solvent type. The optimized extraction conditions: treatment temperature of 50 °C for 5 min gave a significantly higher yield of total carotenoids (192.81 ± 0.32 mg carotenoids/100 g DW), total phenolic (78.12 ± 0.35 g GAE/100 g DW), and antioxidants by FRAP (5889.63 ± 0.47 mM TE/100 g DW), ABTS (1143.65 ± 0.81 mM TE/100 g DW), and DPPH (823.14 ± 0.54 mM TE/100 g DW) using a solvent combination of hexane and ethanol (1:3) with solid to solvent ratio of 1:40 (w/v). This green technology in combination with GRAS solvents promoted the best recovery of bioactive from carrot rejects. Moreover, the solid residue remained after the extraction of bioactive components exhibited higher carbon content (46.5%) and calorific value (16.32 MJ/kg), showcasing its potential to be used as an energy source.

Consequence of cyclic pollen selection for heat tolerance on the performance of different generations in maize (Zea mays L.).

The reproductive stage in many crops, including maize, is very sensitive to heat stress and the genetic overlap between gametophytic and sporophytic phase gives an opportunity to select superior stress tolerant genotype at gametophytic stage. An attempt was made to evaluate the response of cyclic pollen selection in the F1 and F2 generations on the performance of F3 generation progenies for seed yield and yield contributing traits under natural heat stress conditions. In this direction three groups of F3 progenies, namely (i) pollen selection in F1 and F2 generations (GG), (ii) pollen selection only in F2 generation (CG), (iii) no pollen selection in F1 and F2 generations (CC) were screened for heat stress at Agricultural Research Station (ARS), Bheemarayanagudi. The GG progenies recorded significantly higher chlorophyll content, more number of pollen grains per anther and less pollen sterility compared to CG and CC group of progenies under heat stress. Further, the F4 progenies obtained through cyclic pollen selection (in F1, F2 and F3) were also tested for heat stress tolerance at seedling stage. The significant improvement for heat stress tolerance was recorded in F4 progenies derived through cyclic pollen selection as compared to control (no pollen selection for heat tolerance in any generation) F4 progenies. The results indicated that cyclic pollen selection in F1, F2 and F3 generations improved the heat stress tolerance of the progenies in the succeeding generations. To provide genetic evidence for the effect of pollen selection for heat tolerance, the control F2 (C) and selected F2 (G) populations were compared for the segregation of SSR markers. The selected F2 (G) population showed significant deviation from normal Mendelian ratio of 1:2:1 and showed skewness towards the alleles selected from male parent. The results provide strong evidence for an increase in the frequency of parental alleles in the progenies that impart heat stress tolerance.

How effective is 5-Fluorouracil as an adjuvant in the management of odontogenic keratocyst? A systematic review and meta-analysis.

Odontogenic keratocyst (OKC) is known for its benign but aggressive clinical behaviour, and presents a challenge in its management due to high recurrence rate following surgical intervention. The sourcing of Carnoy's solution, the widely used adjunct in OKC treatment, has lately become difficult especially after its banning by the United States Food and Drugs Agency (FDA). This has generated interest in exploring alternative chemical agents such as 5-Fluorouracil (5-FU) and Modified Carnoy's solution (MCS). We conducted a systematic review and meta-analysis to assess the effectiveness of 5-FU as an adjunct following surgical intervention of OKC. A protocol was registered in PROSPERO prior to the literature search. All studies reporting the use of 5-FU in OKC treatment were included in the initial search of multiple literature databases. Of the 148 initially identified articles, three met the criteria for the final appraisal. The relevant data were extracted and a meta-analysis was undertaken in relation to recurrence rate and nerve paraesthesia. There were no recurrence observed in cases treated with 5-FU (n=56), and the incidence of nerve paraesthesia was 20% (none permanent). This systematic review has revealed early encouraging results for 5-FU as an adjunct, however a caution is recommended due to overall low quality of evidence related to individual studies. We present the cumulative evidence on the effectiveness of 5-FU in OKC treatment with discussion on its mechanism of action, safety profile, application protocol, and the implications for clinical practice.

Drug Screening Assays on Medulloblastoma Stem Cells Using Compound Libraries.

Conventional chemotherapies for medulloblastoma are restricted to only proliferative population leaving the cancer stem cells unscathed. This shortcoming of the traditional therapies is attributed to the relapse and metastasis of the cancer. The current research is entirely focused on the screening of therapeutic agents that can restrict and target the self-renewal potential of the cancer stem cells. The advances in drug screening strategies have led to high-throughput screening which provide a robust and expeditious platform to screen potential compounds against cancer stem cells. In this book chapter, we describe two in vitro assays that are routinely used to measure the cell killing and anti-self-renewal activity of the compounds against the cancer stem cells. Combining these assays with high-throughput screening offers a rapid, reliable, and inexpensive approach to screen potential compounds against cancer stem cells and to overcome the limitation of conventional chemotherapeutic agents.

Promising traditional Indian medicinal plants for the management of novel Coronavirus disease: A systematic review.

Traditional Indian medical practices (Ayurveda, Siddha, Unani, and homeopathy) are a vast reservoir of knowledge about medicinal plants. The promising pharmacological properties of these plants have paved the way for developing therapy against novel Coronavirus (CoV) infection. The current review will summarize published works of literature on the effects of traditional Indian medicinal plants against acute respiratory infection (COVID-19, SARS, Influenza, and Respiratory syncytial virus infection) and registered clinical trials of traditional Indian herbal medicines in COVID-19. The current study aims to comprehensively evaluate the data of traditional Indian medicinal plants to warrant their use in COVID-19 management. PubMed, Embase, and Cochrane databases were searched along with different clinical trial databases. A total of 22 relevant traditional Indian medicinal plants (35 relevant studies) were included in the current study having potential antiviral properties against virus-induced respiratory illness along with promising immunomodulatory and thrombolytic properties. Further, 36 randomized and nonrandomized registered clinical trials were also included that were aimed at evaluating the efficacy of herbal plants or their formulations in COVID-19 management. The antiviral, immunomodulatory, and thrombolytic activities of the traditional Indian medicinal plants laid down a strong rationale for their use in developing therapies against SARS-CoV-2 infection. The study identified some important potential traditional Indian medicinal herbs such as Ocimum tenuiflorum, Tinospora cordifolia, Achyranthes bidentata, Cinnamomum cassia, Cydonia oblonga, Embelin ribes, Justicia adhatoda, Momordica charantia, Withania somnifera, Zingiber officinale, Camphor, and Kabusura kudineer, which could be used in therapeutic strategies against SARS-CoV-2 infection.

Current status of in silico, preclinical and clinical study registries across the globe: A systematic review and meta-analysis.

INTRODUCTION: Registration of study protocols brings about transparency and traceability and the amount of publication bias can be estimated. In this study, we have collected and presented data regarding clinical study registries, preclinical, in vitro and in silico study registries across the globe. MATERIALS AND METHODS: We searched via Google Search Engine with appropriate keywords e.g. name of country (n = 198), name of continent (n = 7), registry, study registry, animal, in silico, virtual, simulation, preclinical, animal, clinical trial. The overall pooled prevalence of clinical study registries and WHO primary registries in per continent was calculated using Medcalc software. RESULTS: The overall pooled prevalence of clinical study registries were 13% in each continent. The prevalence of WHO primary study registries were 8.9% of the countries per continent. Overall, there are 17 primary registries associated with WHO ICTRP as primary registries, 2 partner registries and 6 registries are affiliated to ICMJE. However, the amount of preclinical animal study registry was quite less (n = 4). Regarding in vitro studies, only country specific in vitro fertilization registries were available, however, in other research domains, registries were absent. Only one simulation study registry was available. CONCLUSION: At priori study registration is essential to deal with selective reporting. Comparison between study protocol and final report allows us to know the protocol deviations and allows us to evaluate risk of bias and internal validity of the research findings. Although trialists are responsible for the completeness of records, yet the registries must have some measures for their periodic update and quality control of the data.

Stimuli responsive and receptor targeted iron oxide based nanoplatforms for multimodal therapy and imaging of cancer: Conjugation chemistry and alternative therapeutic strategies.

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Microbiome and host crosstalk: A new paradigm to cancer therapy.

The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs.

In recent years, there have been significant advancements in the nanotechnology for cancer therapy. Even though molybdenum disulphide (MoS2)-based nanocomposites demonstrated extensive applications in biosensing, bioimaging, phototherapy, the review article focusing on MoS2 nanocomposite platform has not been accounted for yet. The review summarizes recent strategies on design and fabrication of MoS2-based nanocomposites and their modulated properties in cancer treatment. The review also discussed several therapeutic strategies (photothermal, photodynamic, immunotherapy, gene therapy and chemotherapy) and their combinations for efficient cancer therapy along with certain case studies. The review also inculcates various diagnostic techniques viz. magnetic resonance imaging, computed tomography, photoacoustic imaging and fluorescence imaging for diagnosis of cancer.

Phosphorene-gold nanocomposite based microfluidic aptasensor for the detection of okadaic acid.

Okadaic acid (OA) is one of the most prevalent and largely distributed bio-toxin in the world. Consumption of OA results in a series of digestive ailments such as nausea and diarrhea. This study demonstrates the preparation and functioning of an electrochemical microfluidic biochip for the detection of OA. The screen-printed carbon electrode (SPCE) was modified by phosphorene-gold nanocomposite onto which an aptamer specific to OA was immobilized. BP-Au nanocomposites were synthesized by an in-situ, one-step method without the use of a reducing agent. Potassium ferro-ferri cyanide was used as a redox pair to quantify signal strength. To improve reaction time, increase sensitivity and portability, a microfluidic platform was designed and developed. This device comprised of channels identified for specific purposes such as sample mixing and incubation. Overall, the integrated system consisted of a polydimethylsiloxane microfluidic chip housing an aptamer modified SPCE, as a single detection module for Okadaic acid. The nanomaterials and the microfluidic channels prepared were spectroscopically and electrochemically analyzed. Differential pulse voltammograms revealed a detection limit of 8 pM, while a linear range was found between 10 nM-250 nM. Selectivity studies were also performed with spiked mussel samples and other interfering species. This point-of-care device can be deployed to perform on-farm assays in fishing units.

Contribution of glomalin to dissolve organic carbon under different land uses and seasonality in dry tropics.

Glomalin related soil protein (GRSP) is a hydrophobic glycoprotein that is significant for soil organic carbon (SOC) persistence and sequestration, owing to its large contribution to SOC pool and long turnover time. However, the contribution of GRSP to dissolve OC (DOC) leach from soil is not yet comprehensively explored, though it could have implication in understanding SOC dynamics. We, therefore, aim to measure the contribution of GRSP to DOC, in a range of land uses and climatic seasons in the dry tropical ecosystem. Our results demonstrated that a significant proportion of GRSP (water soluble GRSP; WS-GRSP) leached with DOC (7.9-21.9 mg kg-1), which accounts for 0.2-0.23% of soils total GRSP (T-GRSP). Forest exhibited significantly higher WS-GRSP and DOC leaching than fallow and agriculture. WS-GRSP and DOC accumulations were higher in the dry season (summer and winter) than in rainy. The extent of seasonal variations was higher in forest than in other two land uses, indicating the role of vegetation and biological activity in soil dissolve organic matter (DOM) dynamics. The regression analysis among WS-GRSP, T-GRSP, DOC and SOC prove that the accumulations and leaching of GRSP and other soil OM (SOM) depend on similar factors. The ratio of WS-GRSP-C to DOC was higher in agriculture soil than in forest and fallow, likely a consequence of altered soil chemistry, and organic matter quantity and quality due to soil management practices. Multivariate analysis reflects a strong linkage among GRSP and SOC storage and leaching, soil nutrients (nitrogen and phosphorus) and other important soil properties (pH and bulk density), suggesting that improving GRSP and other SOM status is an urgent need for the both SOC sequestration and soil health in dry tropical agro-ecosystems.

Sphingolipids as targets for treatment of fungal infections.

Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids.

Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids.

UNLABELLED: Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N'-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N'-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE: Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.

Inositol phosphosphingolipid phospholipase C1 regulates plasma membrane ATPase (Pma1) stability in Cryptococcus neoformans.

Cryptococcus neoformans is a facultative intracellular pathogen, which can replicate in the acidic environment inside phagolysosomes. Deletion of the enzyme inositol-phosphosphingolipid-phospholipase-C (Isc1) makes C. neoformans hypersensitive to acidic pH likely by inhibiting the function of the proton pump, plasma membrane ATPase (Pma1). In this work, we examined the role of Isc1 on Pma1 transport and oligomerization. Our studies showed that Isc1 deletion did not affect Pma1 synthesis or transport, but significantly inhibited Pma1 oligomerization. Interestingly, Pma1 oligomerization could be restored by supplementing the medium with phytoceramide. These results offer insight into the mechanism of intracellular survival of C. neoformans.

Sitosterol as an antioxidant in frying oils.

The antioxidative effect of sitosterol at 1, 2 and 5% levels, in triolein, refined canola, high oleic sunflower and flaxseed oils, continuously heated for a period of up to 72 h at frying temperature of 180 °C, was studied. High Pressure Size Exclusion Chromatography (HPSEC) was used to monitor changes in peak areas of triacylglycerol (TG) polymer, monomer and ester hydrolysis products. The presence of enhanced levels of sitosterol was found to significantly decrease TG polymer formation in triolein and the vegetable oil samples after heating at 180 °C for a period of 72 h. A corresponding increase in the level of intact TG monomer and the extent of TG ester hydrolysis was observed in all samples with enhanced levels of sitosterol. Conversion of sterol to steradiene, by the 1, 2 elimination of water, may be responsible for the antioxidative effect of sitosterol at frying temperatures.

Hypercalcemic crisis induced by calcium carbonate.

We report a rare case of drug-induced hypercalcemic crisis in an elderly male resulting from calcium-containing supplements facilitated by thiazide diuretic and angiotensin-converting enzyme inhibitor. A 61-year-old male presented with hypercalcemic crisis along with renal insufficiency and metabolic alkalosis, mimicking the 'calcium-alkali syndrome'. The patient responded to aggressive intravenous hydration along with emergent hemodialysis and salmon calcitonin. He did not have hyperparathyroidism or malignancy. History revealed an average daily intake of only 1200 mg of calcium carbonate along with vitamin D 1000 U/day over an extended period of time. The patient completely recovered in 3 days and had normal serum calcium, parathyroid hormone and phosphorous level at 3-month follow-up. The case highlights the life-threatening perils of indiscriminate and often excessive intake of calcium-containing supplements in an appropriate clinical setting. We also briefly discuss the epidemiology, clinical and laboratory features along with the recent advances in the understanding of the pathophysiology of calcium-alkali syndrome.