Diversity, Equity, and Inclusion in Headache Care and Research.

ABSTRACT: This article reviews the disparities faced by individuals who experience headache disorders and discusses potential solutions to deliver equitable care. Disparities exist in the diagnosis and treatment of headache disorders with regard to race, ethnicity, sex, gender, sexual orientation, geography, and socioeconomic status. Furthermore, research in the realm of headache disparities is inadequate, and the clinical trial representation of patients from underserved communities is poor. Many barriers exist to optimizing care for underserved communities and this article addresses these barriers and presents ways to combat them.

Tuneable quantised conductance memory states in TiO2 based resistive switching devices in crossbar geometry for high density memory applications.

The tunability and controllability of conductance quantization mediated multilevel resistive switching (RS) memory devices, fabricated in crossbar geometry can be a promising alternative for boosting storage density. Here, we report fabrication of Cu/TiO2/Pt based RS devices in 8×8 crossbar geometry, which showed reliable bipolar RS operations. The crossbar devices showed excellent spatial and temporal variability, time retention and low switching voltage (<1 V) and current (~100 µA). Furthermore, during the reset switching, highly repeatable and reliable integral and half-integral quantized conductance (QC) was observed. The observed QC phenomenon was attributed to the two dimensional confinement of electrons as lateral width of the conducting filament (CF) matches the fermi wavelength. The magnitude and number of the QC steps were found to increase from ~2.5- 12.5 and from 5- 18, respectively by increasing the compliance current (IC) from 50 to 800µA which also increased the diameter of the CF from 1.2 to 3.3 nm. The enhancement in both number and magnitude of QC states was explained using electrochemical dissolution mechanism of CF of varying diameter. A thicker CF, formed at higher IC,undergoes a gradual rupture during reset process yielding a greater number of QC steps compared to a thinner CF. The realisation of QC states in the crossbar Cu/TiO2/Pt device as well as IC mediated tunability of their magnitude and number may find applications in high-density resistive memory storage devices and neuromorphic computing. .

Hyponatremia-induced worsening of trigeminal neuralgia- When the sodium plays the game.

A 78-year-old elderly male who was on treatment for trigeminal neuralgia and hypertension was brought to the emergency with altered sensorium. His vital parameters were within normal limits; however, the arterial blood gas analysis showed severe hyponatremia. He was admitted to the ward, where further workup was carried out and hyponatremia correction started. He had a sudden worsening in his facial pain before he landed in encephalopathy. His medications (oxcarbazepine and chlorthalidone) that could cause hyponatremia were stopped, and judicious correction of hyponatremia was done. His baseline investigations, including a chest roentgenogram and electrocardiogram, were normal. After he regained consciousness, it was noted that the facial pain had regressed significantly despite stopping his first-line drugs. This case of worsening trigeminal neuralgic pain due to hyponatremia responded well to judicious sodium correction.

Comparative efficacy, quality of life, safety, and tolerability of atogepant and rimegepant in migraine prevention: A matching-adjusted indirect comparison analysis.

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1-12. RESULTS: There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1-12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: -1.65 [-2.49, -0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. CONCLUSION: In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

Lead-free alternative cation (Ethylammonium) in organometallic perovskites for thermoelectric applications.

CONTEXT: Hybrid halide perovskites are gaining prominence as a promising option in the advancement of photovoltaic devices. Ethylammonium-based hybrid halide perovskites have demonstrated impressive characteristics, such as a reduced band gap, enhanced stability, and non-toxic properties. In this study, we have explored the structural, electronic, optical, and thermoelectric characteristics of Ethylammonium tin chloride. We have found that Ethylammonium tin chloride (EASnCl3) is a direct wide band gap semiconductor. Additionally, we conducted calculations for various optical parameters, including the dielectric function, absorption coefficient, and refractive index, across a photon energy spectrum ranging from 0 to 7 eV. The research highlights the exceptional qualities of EASnCl3, which exhibits a high absorption coefficient and an elevated Seeback coefficient, among other favorable attributes. These findings position it as a promising material for cost-effective photovoltaic device applications, addressing concerns related to environmental stability. METHODS: Fundamental properties based on the full-potential linearized augmented plane wave (FP-LAPW) method, this computation was performed using the WIEN2k simulation code. We utilized the exchange-correlation potentials PBE-GGA and KTB-mBJ to compute the optimized structure, density of states, and band structure of the material. In order to calculate the thermoelectric properties of the material, the Boltztrap simulation tool has been used. There are several critical absorbance parameters, including the Seeback coefficient, figure of merit, power factor, electrical conductivity, and thermal conductivity, concerning their carrier concentration and chemical potential, that have been taken into consideration.

Graphene materials in pollution trace detection and environmental improvement.

Water scarcity is a pressing issue experienced in numerous countries and is expected to become increasingly critical in the future. Anthropogenic activities such as mining, agriculture, industries, and domestic waste discharge toxic contaminants into natural water bodies, causing pollution. Addressing these environmental crises requires tackling the challenge of removing pollutants from water. Graphene oxide (GO), a form of graphene functionalized with oxygen-containing chemical groups, has recently garnered renewed interest due to its exceptional properties. These properties include a large surface area, mechanical stability, and adjustable electrical and optical characteristics. Additionally, surface functional groups like hydroxyl, epoxy, and carboxyl groups make GO an outstanding candidate for interacting with other materials or molecules. Because of its expanded structural diversity and enhanced overall properties, GO and its composites hold significant promise for a wide range of applications in energy storage, conversion, and environmental protection. These applications encompass hydrogen storage materials, photocatalysts for water splitting, the removal of air pollutants, and water purification. Serving as electrode materials for various lithium batteries and supercapacitors. Graphene-based materials, including graphene, graphene oxide, reduced graphene oxide, graphene polymer nanocomposites, and graphene nanoparticle metal hybrids, have emerged as valuable tools in energy and environmental remediation technologies. This review article provides an overview of the significant impact of graphene-based materials in various areas. Regarding energy-related topics, this article explores the applications of graphene-based materials in supercapacitors, lithium-ion batteries, and catalysts for fuel cells. Additionally, the article investigates recent advancements in detecting and treating persistent organic pollutants (POPs) and heavy metals using nanomaterials. The article also discusses recent developments in creating innovative nanomaterials, nanostructures, and treatment methods for addressing POPs and heavy metals in water. It aims to present the field's current state and will be a valuable resource for individuals interested in nanomaterials and related materials.

Blocking µ-opioid receptor by naltrexone exaggerates oxidative stress and airway inflammation via the MAPkinase pathway in a murine model of asthma.

Opioids regulate various physiological and pathophysiological functions, including cell proliferation, immune function, obesity, and neurodegenerative disorders. They have been used for centuries as a treatment for severe pain, binding to opioid receptors a specific G protein-coupled receptor. Common opioids, like ß-endorphin, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), and dynorphins, have analgesic effects. The use of a potent antagonist, like naltrexone hydrochloride, to block the effects of mu Opioid Receptor (µOR) may result in the withdrawal of physiological effects and could potentially impact immune responses in many diseases including respiratory disease. Asthma is a respiratory disease characterized by airway hyperresponsiveness, inflammation, bronchoconstriction, chest tightness, stress generation and release of various cytokines. Airway inflammation leads recruitment and activation of immune cells releasing mediators, including opioids, which may modulate inflammatory response by binding to their respective receptors. The study aims to explore the role of µOR antagonist (naltrexone) in regulating asthma pathophysiology, as the regulation of immune and inflammatory responses in asthma remains unclear. Balb/c mice were sensitized intranasally by 1% TDI and challenged with 2.5% TDI. Naltrexone hydrochloride (1 mg/kg body weight) was administered through intraperitoneal route 1 h before TDI induction. Blocking µOR by naltrexone exacerbates airway inflammation by recruiting inflammatory cells (lymphocytes and neutrophils), enhancing intracellular Reactive oxygen species in bronchoalveolar lavage fluid (BALF), and inflammatory mediator (histamine, Eosinophil peroxidase and neutrophil elastase) in lungs. Naltrexone administration modulated inflammatory cytokines (TNF-α, IL-4, IL-5, IL-6, IL-10, and IL-17A), and enhanced IgE and CRP levels. Naltrexone administration also increased the expression of NF-κB, and phosphorylated p-P38, p-Erk, p-JNK and NF-κB by inhibiting the µOR. Docking study revealed good binding affinity of naltrexone with µOR compared to δ and κ receptors. In future it might elucidate potential therapeutic against many respiratory pathological disorders. In conclusion, µOR blocking by naltrexone regulates and implicates inflammation, bronchoconstriction, and lung physiology.

Modeling and simulation of multifaceted properties of X2NaIO6 (X = Ca and Sr) double perovskite oxides for advanced technological applications.

CONTEXT: In this study, the authors have investigated the structural, optoelectronic, thermoelectric, and thermodynamic properties of Ca2NaIO6 and Sr2NaIO6 double perovskite oxides. Both materials exhibit semiconductor behavior with direct band gaps (Eg) of 0.353 eV and 0.263 eV, respectively. Optical parameters like absorption coefficient α(ω), reflectivity R(ω), dielectric constants, and refractive index have been calculated. The most notable absorption peaks are identified at 5.52 eV (equal to 108.33 × 104 cm-1) in the case of Ca2NaIO6 and at 11.16 eV (equivalent to 118.17 × 104 cm-1) for Sr2NaIO6. These findings suggest a promising outlook for applications in optoelectronics. Moreover, their commendably low thermal conductivity and a high figure of merit, particularly at low temperatures (100 K), indicate their effectiveness as thermoelectric materials. This analysis underscores that these materials hold potential as suitable candidates for n-type doping, making them well-suited for use in thermoelectric devices. Studying thermal properties, including thermal expansion, bulk modulus, acoustic Debye temperature, entropy, and heat capacity, contributes to understanding the materials' thermodynamic stability. The titled materials are dynamically stable. The analysis of these double perovskite materials highlights their potential across various technological applications due to their advantageous structural, electronic, optical, and transport properties, offering new possibilities in material science and technology development. METHODS: The study utilized the full potential linearized augmented plane wave (FP-LAPW) method in conjunction with density functional theory within the WIEN2k simulation code. This approach is widely recognized as one of the most dependable methods for evaluating the photovoltaic characteristics of semiconducting perovskites. The thermoelectric properties were ascertained using the rigid band approach and the constant scattering time approximation, both implemented in the BoltzTraP computational code.

Curcumin and PCI-34051 combined treatment ameliorates inflammation and fibrosis by affecting MAP kinase pathway.

OBJECTIVE: Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination. MATERIALS AND METHODS: To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously. RESULTS: Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes. CONCLUSIONS: Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.

A novel approach to environmental pollution management/remediation techniques using derived advanced materials.

The carbon dioxide (CO2) crisis is one of the world's most urgent issues. Meeting the worldwide targets set for CO2 capture and storage (CCS) is crucial. Because it may significantly reduce energy consumption compared to traditional amine-based adsorption capture, adsorption dependant CO2 capture is regarded as one of the most hopeful techniques in this paradigm. The expansion of unique, critical edge adsorbent materials has received most of the research attention to date, with the main objective of improving adsorption capacity and lifespan while lowering the temperature of adsorption, thereby lowering the energy demand of sorbent revival. There are specific materials needed for each step of the carbon cycle, including capture, regeneration, and conversion. The potential and efficiency of metal-organic frameworks (MOFs) in overcoming this obstacle have recently been proven through research. In this study, we pinpoint MOFs' precise structural and chemical characteristics that have contributed to their high capture capacity, effective regeneration and separation processes, and efficient catalytic conversions. As prospective materials for the next generation of energy storage and conversion applications, carbon-based compounds like graphene, carbon nanotubes, and fullerenes are receiving a lot of interest. Their distinctive physicochemical characteristics make them suitable for these popular study topics, including structural stability and flexibility, high porosity, and customizable physicochemical traits. It is possible to precisely design the interior of MOFs to include coordinatively unsaturated metal sites, certain heteroatoms, covalent functionalization, various building unit interactions, and integrated nanoscale metal catalysts. This is essential for the creation of MOFs with improved performance. Utilizing the accuracy of MOF chemistry, more complicated materials must be built to handle selectivity, capacity, and conversion all at once to achieve a comprehensive solution. This review summarizes, the most recent developments in adsorption-based CO2 combustion capture, the CO2 adsorption capacities of various classes of solid sorbents, and the significance of advanced carbon nanomaterials for environmental remediation and energy conversion. This review also addresses the difficulties and potential of developing carbon-based electrodes for energy conversion and storage applications.

Electronic structure, theoretical power conversion efficiency, and thermoelectric properties of bismuth-based alkaline earth antiperovskites.

CONTEXT: This research paper investigates the properties and potential applications of antiperovskite materials. Antiperovskites are a class of materials with a unique crystal structure, where the central atom is surrounded by a cage of anions. We review recent research on antiperovskite-based materials for energy storage, photovoltaics, catalysis, and sensors. We discovered that these materials display direct band gap semiconductors, strong absorption in the visible (VIS), ultra-violet (UV), and near infrared regions (NIR) based on their fundamental features, which is the most admirable quality that may be found in many optoelectronic devices. Both mechanical and thermodynamic stability have been confirmed for these materials. We discovered that these materials exhibit high figures of merit through the calculation of transport properties, which makes them a promising candidate for thermoelectric devices. It is anticipated that the proposed material BiPMg3, which has a theoretical efficiency of 11.5%, will make a suitable photovoltaic absorber. This paper highlights the potential of these materials for future technological advancements. METHODS: Herein, we have used most authentic techniques to compute fundamental physical properties of these antiperovskites. Full-potential linear augmented plane wave (FP-LAPW) method has been used to investigate electronic, magnetic, optical properties, and make antiperovskites attractive for a variety of applications. In light of its implementation, we have checked the theoretical power conversion efficiency by first principles spectroscopic screening methodology, and inspect the fundamental physical parameters of antiperovskites, focusing on their potential as functional materials for energy and information technologies.

Harassment in the headache field: a global web-based cross-sectional survey.

BACKGROUND: Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. METHODS: We adopted a cross­sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). RESULTS: Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5-13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0-2.0). CONCLUSIONS: Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.

Temporal analysis of remote electric neuromodulation for the prevention of migraine.

Aim: To evaluate the onset, magnitude and persistence of efficacy of remote electrical neuromodulation (REN) compared with placebo for the preventive treatment of migraine. Materials & methods: Analysis was conducted on data from a prospective, double-blind, placebo-controlled clinical trial, which assessed the efficacy of REN for the prevention of migraine. The number of monthly migraine days (MMD) per group was calculated in 2-week intervals and compared between the groups. Results: Differences between the active (N = 95) and placebo (N = 84) groups reached significance at 2 weeks: therapeutic gain 0.84 MMD; p = 0.036. 4 weeks gain 1.59 MMD; p = 0.025, 6 weeks gain 2.27 MMD; p < 0.001, 8 weeks gain 2.68 MMD; p < 0.001. Conclusion: REN provides rapid and consistent efficacy in preventive treatment of migraine.

Patient-reported migraine-specific quality of life, activity impairment and headache impact with once-daily atogepant for preventive treatment of migraine in a randomized, 52-week trial.

BACKGROUND: Atogepant is an oral, small-molecule, calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. METHODS: In this 52-week, multicenter, randomized, open-label trial, adults with 4-14 monthly migraine days received atogepant 60 mg once-daily or standard care. Health outcome endpoints collected from participants randomized to atogepant included change from baseline in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1) Role Function-Restrictive (RFR), Role Function-Preventive (RFP) and Emotional Function (EF) domain scores, change in Activity Impairment in Migraine-Diary (AIM-D) Performance of Daily Activities (PDA) and Physical Impairment (PI) domain scores, and change in Headache Impact Test-6 (HIT-6) total score. RESULTS: Of 744 randomized participants, 521 received atogepant 60 mg in the modified intent-to-treat population. Least-squares mean changes from baseline in MSQ-RFR score were 30.02 (95% confidence interval = 28.16-31.87) at week 12 and 34.70 (95% confidence interval = 32.74-36.66) at week 52. Improvements were also observed in other MSQ domains, AIM-D PDA, PI and HIT-6 total scores. A ≥5-point improvement from baseline in HIT-6 score was observed in 59.9% of participants at week 4 and 80.8% of participants at week 52. CONCLUSION: Over 52 weeks, atogepant 60 mg once-daily was associated with sustained improvements in quality of life and reductions in activity impairment and headache impact.Trial Registration: NCT03700320.

ß-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model.

Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. ß-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including ß-Endorphin as an anti­inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of ß-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. ß-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of ß-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of ß-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of ß-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, ß-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of ß-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of ß-Endorphin in regulating asthma.

Health-related quality of life (hrQoL) among patients with primary cicatricial alopecia (PCA): A systematic review.

Cicatricial alopecia may lead to an enormous emotional burden, social distress, and psychological impairment affecting the quality of life. The objective of this review is to systematically describe the health-related quality of life in adults with primary cicatricial alopecia and its subtypes. Studies that (i) reported quality of life in patients with primary cicatricial alopecia or its subtypes; (ii) were original research and not a conference abstract or review (iii) with patients >18 years of age were included in the review. The studies not mentioning quality of life specifically for the cicatricial alopecia cohort were excluded. We searched for literature via OVID in Medline and Embase, in Web of Science, CINAHL, EBSCO (APA PsycArticles, APA PsycInfo, and PSYNDEX Literature), in the Cochrane Library and for grey literature from its inception date till 12 November 2022. The risk of bias was assessed by using the AXIS tool for cross-sectional studies by two independent authors. Thirteen observational cross-sectional and one single-arm study, including 572 patients and eight different instruments, fulfilled the inclusion criteria. Results are descriptively synthesized, and associated factors of quality of life are presented. The data from studies that used the Dermatology Life Quality Index tool (DLQI) showed that more than 70% of the patients have an impaired life quality. While trichodynia and anxiety have a negative effect on the quality of life, disease duration, education, employment, and marital status have no effect. The findings were inconsistent for other factors. Most of these studies failed to justify the sample size. Furthermore, the risk of bias assessment could not surely rule out a non-response bias. Our results suggest that cicatricial alopecia treatments must be integrated with psychosocial intervention and indicate the need for further research with homogenous and more comprehensive tools to identify and address this patient population's unmet mental health needs.

In Vitro Investigation Unveiling New Insights into the Antimalarial Mechanism of Chloroquine: Role in Perturbing Nucleation Events during Heme to ß-Hematin Transformation.

Malaria parasites generate toxic heme during hemoglobin digestion, which is neutralized by crystallizing into inert hemozoin (ß-hematin). Chloroquine blocks this detoxification process, resulting in heme-mediated toxicity in malaria parasites. However, the exact mechanism of chloroquine's action remains unknown. This study investigates the impact of chloroquine on the transformation of heme into ß-hematin. The results show that chloroquine does not completely halt the transformation process but rather slows it down. Additionally, chloroquine complexation with free heme does not affect substrate availability or inhibit ß-hematin formation. Scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) studies indicate that the size of ß-hematin crystal particles and crystallites increases in the presence of chloroquine, suggesting that chloroquine does not impede crystal growth. These findings suggest that chloroquine delays hemozoin production by perturbing the nucleation events of crystals and/or the stability of crystal nuclei. Thus, contrary to prevailing beliefs, this study provides a new perspective on the working mechanism of chloroquine.

An antioxidant ameliorates allergic airway inflammation by inhibiting HDAC 1 via HIF-1α/VEGF axis suppression in mice.

Histone deacetylase inhibitors (HDACi) are novel class of drugs as they are involved in post translational modification of several proteins involved in signaling pathways related to asthma. HDACi have been reported to elicit protective effects on asthma but the signaling pathways associated with it have not been investigated much. Recently, we have demonstrated that intranasal administrations of Pan-HDAC inhibitors, sodium butyrate and curcumin, which have effectively reduced asthma severity via HDAC1 inhibition in Ovalbumin induced mouse model. Present study aimed to investigate possible pathways by which curcumin and sodium butyrate may minimize asthma pathogenesis via HDAC 1 inhibition. Balb/c mice were exposed (sensitized and challenged) with Ovalbumin to establish allergic asthma model followed by pretreatment of curcumin (5 mg/kg) and sodium butyrate (50 mg/kg) through intranasal route. Effects of curcumin and sodium butyrate on HIF-1α/VEGF signaling through activation of PI3K/Akt axis has been investigated using protein expressions followed by chromatin immunoprecipitation of BCL2 and CCL2 against HDAC1. Molecular docking analysis was also performed to investigate effects of curcumin and butyrate on mucus hypersecretion, goblet cell hyperplasia and airway hyperresponsiveness. Augmented expressions of HDAC-1, HIF-1α, VEGF, p-Akt and p-PI3K were observed in asthmatic group which was suppressed in both the treatments. NRF-2 level was significantly restored by curcumin and butyrate treatments. Protein expressions of p-p38, IL-5 and mRNA expressions of GATA-3 were also reduced in curcumin and butyrate treatment groups. Our findings suggest that curcumin and sodium butyrate may attenuate airway inflammation via down regulation of p-Akt/p-PI3K/HIF-1α/VEGF axis.