A novel case of limbal stem cell deficiency in a patient with acrodermatitis enteropathica.

An 18-year-old male diagnosed with acrodermatitis enteropathica (AE) since early childhood presented with worsening of dermatitis along with photophobia and watering in both eyes. Systemic evaluation by dermatology and gastroenterology specialists confirmed a diagnosis of acute exacerbation of AE, and oral zinc supplements were initiated. A best-corrected visual acuity of 20/20 was documented in both eyes. Slit-lamp examination revealed bilateral subepithelial corneal opacities in a radial fan-like pattern extending from the superior limbus toward the center. A whorled appearance of fluorescein staining and small epithelial erosions was noted in both eyes. Ocular involvements in AE such as blepharitis, cataracts, and radial corneal opacities have been reported previously. We report a new association of AE with limbal stem cell deficiency with its classical features of linear subepithelial corneal opacities with a whorling uptake of fluorescein stain and corneal erosions.

Findings from a feasibility study of estradiol for hypogonadal women with cystic fibrosis-related bone disease.

BACKGROUND: Advancements in therapies for patients with cystic fibrosis (CF) have decreased mortality, leading to increased prevalence of chronic complications including bone disease. CF-related bone disease (CFBD) is characterized by low bone mineral density (BMD) and fragility fractures. Estrogen deficiency increases bone resorption, resulting in decreased BMD that can be restored with estrogen replacement. Current CF guidelines recommend treating female hypogonadal patients with CFBD with estrogen replacement, but no prospective study has investigated the effects of estrogen supplementation on CFBD. Estrogen is known to modulate inflammatory markers and autoimmune diseases. We proposed to test the hypothesis that estrogen status plays a critical role in optimizing bone health, modulating inflammation, preserving lung function, and maximizing quality of life in premenopausal women with CF. METHODS: We planned a randomized, placebo-controlled, investigator- and patient-blinded, pilot trial with two parallel arms. Eligible subjects were women with CF 18-50 years old with hypogonadism and low BMD who were not taking systemic glucocorticoids, had not had a prior transplant, and did not have contraindications to oral estradiol. Subjects would be block randomized to receive oral estradiol or placebo for 6 months. The primary outcome was feasibility metrics. Secondary outcomes included relative changes in estradiol, bone turnover markers, lung function, inflammatory markers, and quality of life metrics. The study was funded through departmental funds. RESULTS: Of 233 subjects screened, 86 subjects were women with CF 18-50 years old and none were eligible for participation. Most subjects were excluded due to absent DXA report (24%), normal BMD (22%), or use of systemic estrogen (16%). Due to difficulty recruiting the planned 52 subjects, the trial was closed for recruitment and no subjects were randomized. CONCLUSION: This study was designed to investigate the feasibility of a safety and efficacy trial of estrogen therapy for women with CF. Unfortunately, due to eligibility criteria, the study was unable to recruit subjects. This feasibility study highlights the need for improved BMD screening in young women with CF. Future study designs may require the incorporation of a screening DXA as part of subject recruitment. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov ( NCT03724955 ).

Insights into the physiology of Chlorella vulgaris cultivated in sweet sorghum bagasse hydrolysate for sustainable algal biomass and lipid production.

Supplementing cultivation media with exogenous carbon sources enhances biomass and lipid production in microalgae. Utilization of renewable organic carbon from agricultural residues can potentially reduce the cost of algae cultivation, while enhancing sustainability. In the present investigation a medium was developed from sweet sorghum bagasse for cultivation of Chlorella under mixotrophic conditions. Using response surface methodology, the optimal values of critical process parameters were determined, namely inoculum cell density (O.D.750) of 0.786, SSB hydrolysate content of the medium 25% v/v, and zero medium salinity, to achieve maximum lipid productivity of 120 mg/L/d. Enhanced biomass (3.44 g/L) and lipid content (40% of dry cell weight) were observed when the alga was cultivated in SSB hydrolysate under mixotrophic conditions compared to heterotrophic and photoautotrophic conditions. A time course investigation revealed distinct physiological responses in terms of cellular growth and biochemical composition of C. vulgaris cultivated in the various trophic modes. The determined carbohydrate and lipid profiles indicate that sugar addition to the cultivation medium boosts neutral lipid synthesis compared to structural lipids, suggesting that carbon flux is channeled towards triacylglycerol synthesis in the cells. Furthermore, the fatty acid profile of lipids extracted from mixotrophically grown cultures contained more saturated and monosaturated fatty acids, which are suitable for biofuel manufacturing. Scale-up studies in a photobioreactor using SSB hydrolysate achieved a biomass concentration of 2.83 g/L consisting of 34% lipids and 26% carbohydrates. These results confirmed that SSB hydrolysate is a promising feedstock for mixotrophic cultivation of Chlorella and synthesis of algal bioproducts and biofuels.

Relationship Between Estrogen Treatment and Skeletal Health in Women With Cystic Fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at risk for CF-related bone disease. Women with CF may use estrogen supplementation for reasons other than skeletal health. It is unknown whether estrogen therapy has a beneficial impact on skeletal health in women with CF. METHODS: In this retrospective cohort study of women with CF followed at a single CF center, the lumbar spine bone mineral density (BMD) of women with CF exposed to supplemental and not exposed to supplemental estrogen were compared. Spline function models included the main effect of estrogen exposure and the interaction between age and estrogen supplementation. RESULTS: Of the 145 subjects analyzed, 44 subjects were exposed to supplemental estrogen. The baseline characteristics of estrogen exposed and unexposed subjects were similar except for use of CF transmembrane conductance regulator modulators and anti-osteoporosis medications. Women exposed to estrogen reached peak BMD around 21 years of age, but women not exposed to estrogen reached peak BMD around 25 years of age. A significant interaction of age and estrogen supplementation indicated that the lumbar spine BMD trajectories differed by exposure group. CONCLUSIONS: Our study demonstrates that few women with CF of reproductive age are prescribed estrogen therapy. Furthermore, estrogen exposure up to age 21 is associated with improved BMD, but estrogen exposure after age 21 does not appear to be associated with improved BMD. Further studies are needed to understand the reasons for the low rates of estrogen use in young women with CF and the optimal timing, dose and formulation of estrogen prescription.

Assessing the robust growth and lipid-accumulating characteristics of Scenedesmus sp. for biodiesel production.

In the present investigation, different salts of nitrogen and carbon sources were tested for their potential to boost biomass and lipid content in Scenedesmus sp. IITRIND2. Among the nitrogen sources, ammonium bicarbonate/nitrate cultures showed maximum dry cell weight (DCW) of ~ 1.8 g/L and lipid yield (~ 40%) while the addition of C6 sugars (glucose and mannose) and sodium acetate enhanced the DCW (~ 3 g/L) and lipid accumulation (~ 40%) compared with disaccharides, C4 and C5 sugars. On evaluating the synergistic effects of the nitrogen and carbon sources, maximum DCW (3.66 g/L) was obtained in ammonium bicarbonate + sodium acetate cultures with a lipid yield of 37.15%. The fatty acid profile of the derived biodiesel was similar to that of plant oils. The results clearly established the robust capability of the novel microalga to efficiently adapt, sustain, and grow in different carbon and nitrogen sources along with high lipid productivity, making it a potential source for biodiesel production.

Chemistry and Biology of Farnesol and its Derivatives: Quorum Sensing Molecules with Immense Therapeutic Potential.

BACKGROUND: Farnesol is an acyclic sesquiterpene alcohol, endogenously synthesized via the ergosterol pathway. It is a quorum sensing molecule (QSM) that was first discovered in C. albicans, and is involved in the inhibition of hyphae formation. METHODS: This review focuses on the comprehensive details of occurrence, chemical/biological synthesis of farnesol and its derivatives, and the factors involved in the regulation of their production. Further, the review also presents their cellular functions and diversified biomedical applications. RESULTS: Large-scale production of farnesol can be achieved using chemical synthesis and metabolic engineering approach. Farnesol is involved in the regulation of various physiological processes including filamentation, biofilm development, drug efflux, and apoptosis, etc. Farnesol and its derivatives/ analogues have also been reported to exhibit anti-biofilm, anti-cancer, anti-tumor and fungicidal properties. The antimicrobial potential of farnesol has been enhanced by synergizing it with known antifungal drugs, and also through nano-formulation(s). CONCLUSION: Apart from its quorum sensing activity, farnesol can be used as an effective anti-microbial, anti-inflammatory, ant-allergic, anti-cancerous, and anti-obesity agent.

Anticoagulant mechanism, pharmacological activity, and assessment of preclinical safety of a novel fibrin(ogen)olytic serine protease from leaves of Leucas indica.

The harnessing of medicinal plants containing a plethora of bioactive molecules may lead to the discovery of novel, potent and safe therapeutic agents to treat thrombosis-associated cardiovascular diseases. A 35 kDa (m/z 34747.5230) serine protease (lunathrombase) showing fibrin(ogen)olytic activity and devoid of N- and O- linked oligosaccharides was purified from an extract of aqueous leaves from L. indica. The LC-MS/MS analysis, de novo sequencing, secondary structure, and amino acid composition determination suggested the enzyme's novel characteristic. Lunathrombase is an αß-fibrinogenase, demonstrating anticoagulant activity with its dual inhibition of thrombin and FXa by a non-enzymatic mechanism. Spectrofluorometric and isothermal calorimetric analyses revealed the binding of lunathrombase to fibrinogen, thrombin, and/or FXa with the generation of endothermic heat. It inhibited collagen/ADP/arachidonic acid-induced mammalian platelet aggregation, and demonstrated antiplatelet activity via COX-1 inhibition and the upregulation of the cAMP level. Lunathrombase showed in vitro thrombolytic activity and was not inhibited by endogenous protease inhibitors α2 macroglobulin and antiplasmin. Lunathrombase was non-cytotoxic to mammalian cells, non-hemolytic, and demonstrated dose-dependent (0.125-0.5 mg/kg) in vivo anticoagulant and plasma defibrinogenation activities in a rodent model. Lunathrombase (10 mg/kg) did not show toxicity or adverse pharmacological effects in treated animals.

Amaranth seeds (Amaranthus palmeri L.) as novel feedstock for biodiesel production by oleaginous yeast.

The potential of lipid accumulation by oleaginous yeast Cryptococcus vishniaccii grown on amaranth seed aqueous extract (AAE) media was assessed. Maximum cell biomass productivity of 104 mg/L/h, lipid productivity of 54 mg/L/h, and lipid content of 52.31% were recorded on AAE when carbon to nitrogen (C:N) ratio increased from 134 to 147 after removal of ammonia nitrogen. The lipid droplet (LD) size (2.32 ± 0.38 µm) was visualized by fluorescence microscopy using Nile red stain indicating maximum accumulated triacylglycerol (TAG) at C:N 147. Fatty acid methyl ester (FAME) profile obtained after transesterification of extracted lipid revealed the presence of palmitic acid (16:0), palmitoleic acid (16:1), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2). Data showed the presence of high monounsaturated fatty acid (MUFA) content (68.17%) depicting improved winter operating conditions of biodiesel. Various quality parameters of biodiesel were evaluated and compared to the American and European biodiesel standards specifications. Based on the lipid productivity, distribution of fatty acids, and evaluated properties obtained; the lipid accumulation by C. vishniaccii utilizing amaranth seeds as substrate could serve as a feasible feedstock for biodiesel production.

Bioremediation of domestic and industrial wastewaters integrated with enhanced biodiesel production using novel oleaginous microalgae.

The study illustrates the synergistic potential of novel microalgal, Chlamydomonas debaryana IITRIND3, for phycoremediation of domestic, sewage, paper mill and dairy wastewaters and then subsequent utilisation of its biomass for biodiesel production. Among these wastewaters, maximum lipid productivity (87.5 ± 2.3 mg L-1 day-1) was obtained in dairy wastewater with removal efficiency of total nitrogen, total phosphorous, chemical oxygen demand and total organic carbon to be 87.56, 82.17, 78.57 and 85.97 %, respectively. Metal ions such as sodium, calcium, potassium and magnesium were also removed efficiently from the wastewaters tested. Pigment analysis revealed loss of chlorophyll a while increase in carotenoid content in algal cells cultivated in different wastewaters. Biochemical data of microalgae grown in different wastewaters showed reduction in protein content with an increase in carbohydrate and lipid contents. The major fatty acids in algal cells grown in dairy wastewater were C14:0, C16:0, C16:1, C18:0, C18:2 and C18:3. The physical properties of biodiesel derived from microalgae grown in dairy wastewater were in compliance with the ASTM D6751 and EN 14214 fuel standards and were comparable to plant oil methyl esters.

Boosting TAG Accumulation with Improved Biodiesel Production from Novel Oleaginous Microalgae Scenedesmus sp. IITRIND2 Utilizing Waste Sugarcane Bagasse Aqueous Extract (SBAE).

This investigation utilized sugarcane bagasse aqueous extract (SBAE), a nontoxic, cost-effective medium to boost triacylglycerol (TAG) accumulation in novel fresh water microalgal isolate Scenedesmus sp. IITRIND2. Maximum lipid productivity of 112 ± 5.2 mg/L/day was recorded in microalgae grown in SBAE compared to modified BBM (26 ± 3 %). Carotenoid to chlorophyll ratio was 12.5 ± 2 % higher than in photoautotrophic control, indicating an increase in photosystem II activity, thereby increasing growth rate. Fatty acid methyl ester (FAME) profile revealed presence of C14:0 (2.29 %), C16:0 (15.99 %), C16:2 (4.05 %), C18:0 (3.41 %), C18:1 (41.55 %), C18:2 (12.41), and C20:0 (1.21 %) as the major fatty acids. Cetane number (64.03), cold filter plugging property (-1.05 °C), and oxidative stability (12.03 h) indicated quality biodiesel abiding by ASTM D6751 and EN 14214 fuel standards. Results consolidate the candidature of novel freshwater microalgal isolate Scenedesmus sp. IITRIND2 cultivated in SBAE, aqueous extract made from copious, agricultural waste sugarcane bagasse to increase the lipid productivity, and could further be utilized for cost-effective biodiesel production.

Synergistic dynamics of nitrogen and phosphorous influences lipid productivity in Chlorella minutissima for biodiesel production.

The study synergistically optimized nitrogen and phosphorous concentrations for attainment of maximum lipid productivity in Chlorella minutissima. Nitrogen and phosphorous limited cells (N(L)P(L)) showed maximum lipid productivity (49.1±0.41mg/L/d), 1.47 folds higher than control. Nitrogen depletion resulted in reduced cell size with large sized lipid droplets encompassing most of the intracellular space while discrete lipid bodies were observed under nitrogen sufficiency. Synergistic N/P starvations showed more prominent effect on photosynthetic pigments as to individual deprivations. Phosphorous deficiency along with N starvation exhibited 17.12% decline in carbohydrate while no change in nitrogen sufficient cells were recorded. The optimum N(L)P(L) concentration showed balance between biomass and lipid by maintaining intermediate cell size, pigments, carbohydrate and proteins. FAME profile showed C14-C18 carbon chains in N(L)P(L) cells with biodiesel properties comparable to plant oil methyl esters. Hence, synergistic N/P limitation was effective for enhancing lipid productivity with reduced consumption of nutrients.

Inhibition of imiquimod-induced psoriasis-like dermatitis in mice by herbal extracts from some Indian medicinal plants.

Psoriasis is a chronic autoimmune human skin disorder that is characterized by excessive proliferation of keratinocytes, scaly plaques, severe inflammation and erythema. The pathophysiology of psoriasis involves interplay between epidermal keratinocytes, T lymphocytes, leukocytes and vascular endothelium. Increased leukocyte recruitment and elevated levels of cytokines, growth factors and genetic factors like interleukin (IL)-1ß, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-ß, toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2, coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR) and vitamin D receptor (VDR) are the most critical factors governing the exacerbation of psoriasis. In the present study, an attempt was made to elucidate the preventive role of herbal extracts of four dermo-protective Ayurvedic plants, Tinospora cordifolia (TC), Curcuma longa (CL), Celastrus paniculatus (CP) and Aloe vera (AV), against psoriasis-like dermatitis. Parkes (P) strain mice were initially induced with psoriasis-like dermatitis using topical application of imiquimod (IMQ, 5 %), followed by subsequent treatment with the herbal extracts to examine their curative effect on the psoriasis-like dermatitis-induced mice. The extracts were orally/topically administered to mice according to their ED/LD50 doses. Phenotypical observations, histological examinations, and semi-quantitative reverse transcription PCR (RT-PCR) analyses of the skin and blood samples of the control, IMQ-treated and herbal extract-treated psoriasis-like dermatitis-induced mice lead to the conclusion that the combination extract from all the plants was instrumental in downregulating the overexpressed cytokines, which was followed by the CL extract. Moreover, lesser yet positive response was evident from CP and TC extracts. The results suggest that these plants can prove to have tremendous preventive potential against the disease and can open the way to new therapeutic strategies for psoriasis treatment.

Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action.

A 'complex solution' to a 'complex' problem: tackling the complexity of cancer with botanicals.

Several biological and physical factors confer complexity on cancer, which may be responsible for its associated morbidity. The successful management of this hyperproliferative disease is beyond the realm of therapeutics that may include the use of a single or at times a combination of treatment modalities. It is apparent that prevention with complex agents such as botanicals could serve as a possible potential solution. The present review focuses on the aspects of cancer that contribute toward making it an extremely complex disease and that may be tackled effectively with the use of 'multicomponent' botanicals.