Valproic Acid-Induced Upregulation of Multidrug Efflux Transporter ABCG2/BCRP via PPARα-Dependent Mechanism in Human Brain Endothelial Cells.

Despite the progress made in the development of new antiepileptic drugs (AEDs), poor response to them is a rising concern in epilepsy treatment. Of several hypotheses explaining AED treatment failure, the most promising theory is the overexpression of multidrug transporters belonging to ATP-binding cassette (ABC) transporter family at blood-brain barrier. Previous data show that AEDs themselves can induce these transporters, in turn affecting their own brain bioavailability. Presently, this induction and the underlying regulatory mechanism involved at human blood-brain barrier is not well elucidated. Herein, we sought to explore the effect of most prescribed first- and second-line AEDs on multidrug transporters in human cerebral microvascular endothelial cells, hCMEC/D3. Our work demonstrated that exposure of these cells to valproic acid (VPA) induced mRNA, protein, and functional activity of breast cancer resistance protein (BCRP/ABCG2). On examining the substrate interaction status of AEDs with BCRP, VPA, phenytoin, and lamotrigine were found to be potential BCRP substrates. Furthermore, we observed that siRNA-mediated knockdown of peroxisome proliferator-activated receptor alpha (PPARα) or use of PPARα antagonist, resulted in attenuation of VPA-induced BCRP expression and transporter activity. VPA was found to increase PPARα expression and trigger its translocation from cytoplasm to nucleus. Findings from chromatin immunoprecipitation and luciferase assays showed that VPA enhances the binding of PPARα to its response element in the ABCG2 promoter, resulting in elevated ABCG2 transcriptional activity. Taken together, these in vitro findings highlight PPARα as the potential molecular target to prevent VPA-mediated BCRP induction, which may have important implications in VPA pharmacoresistance. SIGNIFICANCE STATEMENT: Induction of multidrug transporters at blood-brain barrier can largely affect the bioavailability of the substrate antiepileptic drugs in the brains of patients with epilepsy, thus affecting their therapeutic efficacy. The present study reports a mechanistic pathway of breast cancer resistance protein (BCRP/ABCG2) upregulation by valproic acid in human brain endothelial cells via peroxisome proliferator-activated receptor alpha involvement, thereby providing a potential strategy to prevent valproic acid pharmacoresistance in epilepsy.

Confronting the consequences of racism, xenophobia, and discrimination on health and health-care systems.

Racism, xenophobia, and discrimination are key determinants of health and equity and must be addressed for improved health outcomes. We conclude that far broader, deeper, transformative action is needed compared with current measures to tackle adverse effects of racism on health. To challenge the structural drivers of racism and xenophobia, anti-racist action and other wider measures that target determinants should implement an intersectional approach to effectively address the causes and consequences of racism within a population. Structurally, legal instruments and human rights law provide a robust framework to challenge the pervasive drivers of disadvantage linked to caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour. Actions need to consider the historical, economic, and political contexts in which the effects of racism, xenophobia, and discrimination affect health. We propose several specific actions: a commission that explores how we action the approaches laid out in this paper; building a conversation and a series of events with international multilateral agency stakeholders to raise the issue and profile of racism, xenophobia, and discrimination within health; and using our multiple platforms to build coalitions, expand knowledge, highlight inequities, and advocate for change across the world.

CD34 Protein: Its expression and function in inflammation.

CD34 has spear-headed the field of basic research and clinical transplantation since the first reports of its expression on hematopoietic stem cells (HSCs). Expressed in mice, humans, rats and other species, CD34 has been used for more than 40 years as a hematopoietic stem and progenitor cell marker. It was later found that muscle satellite cells and epidermal precursors can also be identified with the aid of CD34. Despite the usefulness of CD34 as a marker of HSCs, its overall purpose in animal physiology has remained unclear. This review recaptures CD34 structure, evolutionary conservation, proposed functions, and role in lung inflammation, to describe current research findings and to provide guidance for future studies on CD34.

Knowledge and Attitudes towards Dementia among the General Public in Singapore: A Comparative Analysis.

INTRODUCTION: This paper provides a summary of findings on the public's knowledge and attitudes towards dementia. We aim to investigate if the attitudes of Singaporeans towards dementia have changed over the years by adopting a questionnaire used in a similar study in 2012. METHODS: A cross-sectional, descriptive study was conducted through the dissemination of an existing, online questionnaire to participants above 16 years of age. Out of 1,500 subjects, results from 1,373 participants were analysed. Descriptive statistics were used to analyse and compare results from the 2012 study while a latent class analysis was performed to understand the categories of study participants based on varying levels of attitudes, knowledge and stigma. RESULTS: The mean age of study participants was 43.8 (SD = 15.7). Majority of the participants were females (76.5%), between 51 and 60 years of age (29.6%) and belonged to the Chinese ethnic group (77.8%). Results demonstrated that there were significant differences in attitudes towards dementia between 2012 and 2021. There was a 70.2% improvement in stigma-associated attitudes and an increase in correct responses to 4 out of 5 questions in the knowledge section. CONCLUSION: Findings of this study suggest that the general public has a better knowledge and more positive attitude towards dementia. This could have been attributed to higher literacy levels of the current study population and effectiveness of established outreach initiatives in Singapore. However, further research with a more balanced representation of ethnic and cultural groups would offer more comprehensive insights into dementia health literacy.

The Pharmacological Implications of Flavopiridol: An Updated Overview.

Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.

Microbial CO2 fixation and biotechnology in reducing industrial CO2 emissions.

The rapid acceleration in emissions of inevitably generated CO2 due to numerous activities mainly anthropogenic have devastating environmental effects leading to climatic concerns. Hence, significant, sustainable approaches should be developed for reduction of CO2 emission targets, balancing the existing needs of the current population. Biological carbon acquisition, storage and usage are considered crucial alternative strategies in assimilating inorganic carbon, manifested by diverse variety of microorganisms. Furthermore, central biochemical routes along with associated enzymes serve as considerable factors for understanding molecular microbial CO2 assimilation. Microorganisms exhibit an impeccable capability to facilitate evolved mechanisms in sequestering inorganic carbon at higher pace to produce biomaterials like biofuels, bioplastics etc. This review endorses the importance of microorganisms in reducing the concomitant release of CO2 by providing supervision in biotechnological applications (such as genetic engineering, microbial electrosynthesis, gas fermentation and protein engineering) to mitigate CO2 at an industrial scale.

Multidrug efflux transporter ABCG2: expression and regulation.

The adenosine triphosphate (ATP)-binding cassette efflux transporter G2 (ABCG2) was originally discovered in a multidrug-resistant breast cancer cell line. Studies in the past have expanded the understanding of its role in physiology, disease pathology and drug resistance. With a widely distributed expression across different cell types, ABCG2 plays a central role in ATP-dependent efflux of a vast range of endogenous and exogenous molecules, thereby maintaining cellular homeostasis and providing tissue protection against xenobiotic insults. However, ABCG2 expression is subjected to alterations under various pathophysiological conditions such as inflammation, infection, tissue injury, disease pathology and in response to xenobiotics and endobiotics. These changes may interfere with the bioavailability of therapeutic substrate drugs conferring drug resistance and in certain cases worsen the pathophysiological state aggravating its severity. Considering the crucial role of ABCG2 in normal physiology, therapeutic interventions directly targeting the transporter function may produce serious side effects. Therefore, modulation of transporter regulation instead of inhibiting the transporter itself will allow subtle changes in ABCG2 activity. This requires a thorough comprehension of diverse factors and complex signaling pathways (Kinases, Wnt/ß-catenin, Sonic hedgehog) operating at multiple regulatory levels dictating ABCG2 expression and activity. This review features a background on the physiological role of transporter, factors that modulate ABCG2 levels and highlights various signaling pathways, molecular mechanisms and genetic polymorphisms in ABCG2 regulation. This understanding will aid in identifying potential molecular targets for therapeutic interventions to overcome ABCG2-mediated multidrug resistance (MDR) and to manage ABCG2-related pathophysiology.

Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections.

Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack. The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with COPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were never-smoking normal controls. Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using Image ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.

Loss of Nucleobindin-2/Nesfatin-1 increases lipopolysaccharide-induced murine acute lung inflammation.

NUCB2/nesfatin-1 is expressed in variety of tissues. Treatment with nesfatin-1 reduces inflammation in rat models of subarachnoid hemorrhage-induced oxidative brain damage and traumatic brain injury as well as myocardial injury. There is only one study showing anti-inflammatory actions of nesfatin-1 on acute lung inflammation. To more precisely determine the role of NUCB2/nesfatin-1 in acute lung inflammation, we conducted a study using NUCB2/nesfatin-1 knockout (NKO) mice as well as neutrophils isolated from the bone marrows of WT and NKO mice. Our findings suggest that the absence of NUCB2/nesfatin-1 significantly increases the accumulation of adherent neutrophils by approximately 3 times compared with WT within LPS-treated lungs. Integrating this with observations from both BALF and neutrophil cytokine expression, we propose that although neutrophils lacking NUCB2/nesfatin-1 individually secrete less pro-inflammatory cytokines compared with stimulated WT cells, the result of knocking out NUCB2/nesfatin-1 is net pro-inflammatory. No change was found in NUCB2/nesfatin-1 mRNA or protein expression comparing WT LPS and PBS-treated samples. Taken together, our results show that NUCB2/nesfatin-1 is constitutively expressed in mouse lungs and neutrophils and demonstrates anti-inflammatory properties in mouse lungs during acute lung injury, by inhibiting adherent neutrophil accumulation and inflammatory cytokine expression.

Research article expression of surfactant protein-A and D, and CD9 in lungs of 1 and 30 day old foals.

BACKGROUND: Respiratory diseases are a major cause of morbidity and mortality in the horses of all ages including foals. There is limited understanding of the expression of immune molecules such as tetraspanins and surfactant proteins (SP) and the regulation of the immune responses in the lungs of the foals. Therefore, the expression of CD9, SP-A and SP-D in foal lungs was examined. RESULTS: Lungs from one day old (n = 6) and 30 days old (n = 5) foals were examined for the expression of CD9, SP-A, and SP-D with immunohistology and Western blots. Western blot data showed significant increase in the amount of CD9 protein (p = 0.0397) but not of SP-A and SP-D at 30 days of age compared to one day. Immunohistology detected CD9 in the alveolar septa and vascular endothelium but not the bronchiolar epithelium in the lungs of the foals in both age groups. SP-A and SP-D expression was localized throughout the alveolar septa including type II alveolar epithelial cells and the vascular endothelium of the lungs in all the foals. Compared to one day old foals, the expression of SP-A and SP-D appeared to be increased in the bronchiolar epithelium of 30 day old foals. Pulmonary intravascular macrophages were also positive for SP-A and SP-D in 30 days old foals and these cells are not developed in the day old foals. CONCLUSIONS: This is the first data on the expression of CD9, SP-A and SP-D in the lungs of foals.

Dynamic methylation of Numb by Set8 regulates its binding to p53 and apoptosis.

Although Numb exhibits its tumor-suppressive function in breast cancer in part by binding to and stabilizing p53, it is unknown how the Numb-p53 interaction is regulated in cells. We found that Numb is methylated in its phosphotyrosine-binding (PTB) domain by the lysine methyltransferase Set8. Moreover, methylation uncouples Numb from p53, resulting in increased p53 ubiquitination and degradation. While Numb promotes apoptosis in a p53-dependent manner, the apoptotic function is abolished when Numb is methylated by Set8 or the Lys methylation sites in Numb are mutated. Conversely, the Numb-p53 interaction and Numb-mediated apoptosis are significantly enhanced by depletion of Set8 from cancer cells or by treating the cells with doxorubicin, a chemotherapeutic drug that causes a reduction in the mRNA and protein levels of Set8. Our work identifies the Set8-Numb-p53 signaling axis as an important regulatory pathway for apoptosis and suggests a therapeutic strategy by targeting Numb methylation.

COVID-19 ARDS: A Multispecialty Assessment of Challenges in Care, Review of Research, and Recommendations.

Physicians and care providers are familiar with the management of ARDS, however, when it occurs as a sequalae of COVID-19, it has different features and there remains uncertainty on the consensus of management. To answer this question on how it compares and contrasts with ARDS from other causes, the authors reviewed the published literature and management guidelines as well as their own clinical experience while managing patients with COVID-19 ARDS. For research, a PubMed search was conducted on 01.04.2021 using the systematic review filter to identify articles that were published using MeSH terms COVID-19 and ARDS. Systematic reviews or meta-analyses were selected from a systematic search for literature containing diagnostic, prognostic and management strategies in MEDLINE/PubMed. Those were compared and reviewed to the existing practices by the various treating specialists and recommendations were made. Specifically, the COVID-19 ARDS, its risk factors and pathophysiology, lab diagnosis, radiological findings, rational of recommendation of drugs proposed so far, oxygenation and ventilation strategies and the psychological ramifications of the disease were. discussed. Because of the high mortality in mechanically ventilated patients, the above recommendations and findings direct the potential for improvement in the management of patients with COVID-19 ARDS.

Lack of CD34 produces defects in platelets, microparticles, and lung inflammation.

Lung innate immune activation results in acute lung inflammation, which is characterized by alveolar barrier disruption and accumulation of cellular lung aggregates comprising neutrophils, platelets, mononuclear cells, and microparticles. CD34 is a sialomucin, with pan-selectin affinity and recently shown to protect the endothelial barrier in a bleomycin-induced lung injury model. However, there is very little information about the fundamental role of CD34 in regulation of the lung innate immune response. We hypothesized that CD34 regulates leukocyte recruitment by promoting optimal platelet activation (aggregation and spread) during bacterial lipopolysaccharide (LPS)-induced acute lung injury. Therefore, we utilized CD34 knock-out (KO) and wild-type (WT) mice to analyze and compare the morphology and expression of leukocyte subsets from the pulmonary and systemic compartments. We utilized the chemotactic N-formylated tri-peptide, fMLP, to understand platelet aggregation in vitro, and the fundamental immune stimulant, LPS, to induce lung injury and understand platelet activation ex vivo. Our data reveal that under steady-state conditions, KO mice possess large aggregates of integrin ß3 (CD61)-positive microparticles in peripheral blood. Moreover, the KO mice recruit a large number of neutrophils to lungs, which are not cleared even at 36-h post-LPS exposure. The KO mice display an increased platelet CD61 expression, which aggregates, but does not spread normally in response to in vitro fMLP treatment. The KO platelets display similar deficits in their spreading ability even after ex vivo LPS exposure. Thus, our data demonstrate that CD34 modulates platelet biology, microparticle aggregation, and neutrophil recruitment during murine lung inflammation.

Comparison of efficacy of thoracic paravertebral block with oblique subcostal transversus abdominis plane block in open cholecystectomy.

BACKGROUND AND AIMS: Sensory afferent nerve branches of lower six thoracic and upper lumbar nerves innervate the anterior abdominal wall and are the therapeutic focus of local anesthetics to provide analgesia for the abdominal surgical incision. Central neuraxial and regional analgesia can provide better control of pain due to right subcostal incision used in open cholecystectomy and attenuate the need for opioids. The earlier studies which showed the benefit of the thoracic paravertebral block (TPVB) for analgesia after upper abdominal surgeries did not compare TPVB with oblique subcostal transversus abdominis plane (OSTAP) block. Therefore, the current study compares the analgesic efficacy of TPVB and OSTAP block in open cholecystectomy. MATERIAL AND METHODS: Seventy consenting adults scheduled for open cholecystectomy were allocated to one of the two groups: ultrasound-guided TPVB (Group I) and ultrasound-guided OSTAP block (Group II). The primary objective of this study is to assess and compare tramadol consumption in 48 h in both the groups along with VAS in post anesthesia care unit, and then at 2, 4, 6, 8, 12, 24, and 48 h. The secondary objective of the study is to assess the incidence of PONV. RESULTS: The number of doses of rescue analgesia required was less in Group I when compared with Group II (P < 0.001). Patients in Group I had significantly lower pain scores than Group II. Although in the initial 8 h, both groups had comparable pain scores, after 8 h, these scores were significantly lower in patients in Group I. Less postoperative nausea and vomiting was seen in Group I patients (11.7%) in comparison to Group II (18.1%). CONCLUSION: Ultrasound-guided TPVB is superior to OSTAP block because of its association with decreased postoperative opioid consumption, lower VAS score, and reduction in opioid-related side effects. Thus, it should be strongly considered as a part of multimodal analgesia regimen in upper abdominal surgeries.

Usability of Health Information Websites Designed for Adolescents: Systematic Review, Neurodevelopmental Model, and Design Brief.

BACKGROUND: Adolescence is a unique developmental period characterized by biological, social, and cognitive changes, as well as an interest in managing one's own health care. Many adolescents use the internet to seek health care information. However, young people face barriers before they can understand and apply the health information that they access on the web. It is essential that usability of adolescent health websites on the internet is improved to help adolescents overcome these barriers and allow them to engage successfully with web-based health care content. OBJECTIVE: The aim of this review was to synthesize the usability of specific health information websites. These findings were mapped onto the adolescent neurodevelopmental profile, and a design brief based on the findings was developed to tailor future websites for specific adolescent requirements. METHODS: A systematic search conducted using PubMed, PsycINFO, and Education Resources Information Center (ERIC) identified 25 studies that assessed the usability of health information websites. Adolescent feedback was collected by a mixture of surveys, focus groups, interviews, and think-aloud procedures. RESULTS: A majority of the information websites were developed for specific health issues that may be relevant to adolescents. The most preferred website features were interactive content such as games and quizzes, as well as videos, images, audio clips, and animations. Participants also preferred communicating with other adolescents with similar conditions or learning about their experience through real stories and testimonials. Adolescents found it difficult to use health information websites if they contained too much text, were too cluttered, or had features that made it difficult to access. The findings are considered in the context of adolescent social processes, low tolerance of delayed gratification, and attraction to novelty and mapped onto a neurodevelopmental model of adolescence. CONCLUSIONS: Young people's feedback can determine usability and content that make a health information website easy or informative to use. Neurodevelopmental profiles and the users' specific preferences and skills should be addressed in future development of health information websites for adolescents.

Neutrophils in the lung: "the first responders".

Neutrophils, constituting the first line of defense, perform vital functions during immune surveillance. A key feature that assists in their prompt response to an inflammatory signal is rapid migration to the affected site. They are normally short-lived but can be activated to live longer under the influence of an inflammatory stimulus. They can, thereby, release their toxic granule contents that are differentially housed inside the cytoplasm. Although these events are well characterized in the peripheral circulation, we are still far from fully understanding their recruitment in lungs. Lungs are a reservoir of neutrophils under steady-state. In the event of an infection or injury, they promptly activate and recruit to the alveolar compartment as well as the airways. Lung intravital microscopy has revealed that neutrophils display novel features during steady- and activated-state highlighting key differences in the lung vasculature compared to peripheral sites. This review will discuss neutrophil biology in lung inflammation and will highlight the role of angiostatin, an anti-angiogenic molecule, as well as vitronectin, an acute phase secreted plasma protein, in lung neutrophil recruitment.

Direct measurement of radiation pressure and circulating power inside a passive optical cavity.

A mechanical force sensor coupled to two optical cavities is developed as a metrological tool. This system is used to generate a calibrated circulating optical power and to create a transfer standard for externally coupled optical power. The variability of the sensor as a transfer standard for optical power is less than 2%. The uncertainty in using the sensor to measure the circulating power inside the cavity is less than 3%. The force measured from the mechanical response of the sensor is compared to the force predicted from characterizing the optical spectrum of the cavity. These two forces are approximately 20% different. Potential sources for this disagreement are analyzed and discussed. The sensor is compact, portable, and can operate in ambient and vacuum environments. This device provides a pathway to novel nanonewton scale force and milliwatt scale laser power calibrations, enables direct measurement of the circulating power inside an optical cavity, and enhances the sensitivity of radiation pressure-based optical power transfer standards.

Effectiveness of community pharmacies in improving seasonal influenza uptake-an evaluation using the Donabedian framework.

Background: Community pharmacies are now commissioned nationally in England to provide a seasonal influenza vaccination service. However, there is little evidence about the effectiveness of a pharmacy-based immunization service in improving uptake. Methods: The Donabedian framework was used to evaluate a community pharmacy service in the West Midlands from a commissioning perspective. A mixed methods approach was adopted, including provider and patient surveys, data from the national influenza vaccination returns and an electronic pharmacy data recording system. Results: Patient satisfaction with the service was high. There was no increase in uptake rates. Impact on reaching new patients was limited. The service had an appropriate information system to record activity. Promotion and signposting for the service was weak. Poor engagement with stakeholders led to dissatisfaction and General Practitioner complaints. Commissioners responded to emerging issues to ensure the pharmacies' set up was compliant with the Service Level Agreement. Conclusions: Improvements in convenience and choice for patients did not result in an increase in uptake rates. With a national pharmacy influenza programme, local arrangements to optimize the service may be limited. Clear arrangements for activity transfer and recording, partnership working and a good communications strategy are crucial in achieving a positive outcome.

Process, optimization, and characterization of budesonide-loaded nanostructured lipid carriers for the treatment of inflammatory bowel disease.

The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box-Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66 ± 3.42% and particle size of 284.0 ± 4.53 nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit® S100-coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs during palletization process, with f2 value of 75.879. The in vitro evaluation of enteric-coated pellets revealed that a coating level of 15% weight gain is needed in order to impart lag time of 5 h (transit time to reach colon). The results of the study demonstrate that the developed BDS-NLCs could be used as a promising tool for the treatment of inflammatory bowel disease.

Regulatory components of carbon concentrating mechanisms in aquatic unicellular photosynthetic organisms.

This review provides an insight into the regulation of the carbon concentrating mechanisms (CCMs) in lower organisms like cyanobacteria, proteobacteria, and algae. CCMs evolved as a mechanism to concentrate CO2 at the site of primary carboxylating enzyme Ribulose-1, 5-bisphosphate carboxylase oxygenase (Rubisco), so that the enzyme could overcome its affinity towards O2 which leads to wasteful processes like photorespiration. A diverse set of CCMs exist in nature, i.e., carboxysomes in cyanobacteria and proteobacteria; pyrenoids in algae and diatoms, the C4 system, and Crassulacean acid metabolism in higher plants. Prime regulators of CCM in most of the photosynthetic autotrophs belong to the LysR family of transcriptional regulators, which regulate the activity of the components of CCM depending upon the ambient CO2 concentrations. Major targets of these regulators are carbonic anhydrase and inorganic carbon uptake systems (CO2 and HCO3- transporters) whose activities are modulated either at transcriptional level or by changes in the levels of their co-regulatory metabolites. The article provides information on the localization of the CCM components as well as their function and participation in the development of an efficient CCM. Signal transduction cascades leading to activation/inactivation of inducible CCM components on perception of low/high CO2 stimuli have also been brought into picture. A detailed study of the regulatory components can aid in identifying the unraveled aspects of these mechanisms and hence provide information on key molecules that need to be explored to further provide a clear understanding of the mechanism under study.