Nasal Instillation Research Articles

Management of Spinocerebellar Ataxia through Ayurveda—A Case Report

ABSTRACT Spinocerebellar ataxias (SCA) are neurodegenerative disorders marked by progressive cerebellar ataxia, impacting balance, motor coordination, and ocular function due to degeneration. This study evaluated Shodhana Chikitsa and Shaman Chikitsa (purification and symptomatic treatments) for SCA. A 27-year-old man with SCA, showing symptoms like swaying, poor balance, and slurred speech, was referred to the Panchakarma OPD at Ayurveda Hospital, Salod, Wardha. He underwent a comprehensive regimen, including full-body massage with herbal poultices (Patrapottali and Shashtishali Swedana), nasal instillation with medicated oil (Marsha Nasya), and a medicated enema with decoctions and oil, along with oral medications, such as Yogaraja Guggulu, Rasnasaptaka Qwath, Cap Neuron Plus, Agnitundi Vati, and Mahavatavidhwansa Rasa, for two months. Panchtikta Ksheer Vasti (medicated milk enema) was given for eight days. Significant improvements in symptoms and the Scale for Assessment and Rating of Ataxia (SARA) score were observed, suggesting that Ayurvedic treatments may be effective for SCA, warranting further research.

Scope of Ayurvedic Nasal Instillation Therapy (Nasya Karma) in Cosmetology: A Review

Cosmetics has become an important & influential part of human’s daily life in today’s world due to one’s tendency for self-care & regard as it boost their confidence and self-esteem. The increase in daily use of these various cosmetics has also garnered a lot of increased demand in pharmaceutical industry; resulting into various harmful & chemical drug practices for monetary gain also leading to lots of side effects of such cosmetics on human skin. The beauty ailments that commonly affect people are hair fall, greying of hairs, dandruff, acne, melasma, minor skin and oral disorders. These problems are not only difficult to treat but also requires a lot of expenses too. Ayurveda has mentioned various methods to tackle these problems as Ayurvedic scholars has put heavy weightage on importance of beauty; external as well as internal in both male and female and has described treatments for these ailments in ancient texts such as Nasya Karma [Ayurvedic Nasal Instillation Therapy]. Nasya is one of famous Panchakarma procedure used for management of above mention cosmetic ailments. It is a procedure in which herbal drug [oil/decoction/extract/powder] is instilled through nasal route and is highly appreciated for its therapeutic value in diseases related to Urdhava-Jatrugata [above clavicle region]. In this article, we have discussed various types and probable action of Nasya Karma [Ayurvedic Nasal Instillation Therapy] in these disorders and how this single Ayurvedic procedure can be a one stop solution for multiple beauty ailment and can be helpful in reaching the goal of enhancement of beauty with assurance of safety and prevention from any harmful effect.

Tongsai Granules inhibit autophagy and macrophage-mediated inflammatory response to improve acute exacerbations of chronic obstructive pulmonary disease in rats

To investigate the inhibitory effect of Tongsai Granules (TSG) on macrophage-mediated inflammatory response to alleviate acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in rats and explore the underlying mechanism. Twenty-four rats were divided into control group, AECOPD model group, TSG treatment group, and moxifloxacin+salbutamol (MXF+STL) treatment group. In the rat models of COPD, AECOPD was induced by nasal instillation of Klebsiella pneumoniae on day 3 of week 9 after modeling, and saline, TSG or MXF+STL were administered via gavage on days 1 and 2 and days 4 to 7 of week 9. After the treatments, lung tissues were collected for examining for pathologies and expressions of inflammatory markers, MMP2, and MMP9. In cultured macrophage MH-S cells with LPS stimulation, the effect of TSG-medicated serum on IL-1β, IL-6, TNF-α, COX-2, and iNOS expressions and phosphorylation levels of p38, p-p62, LC3, FoxO3a, and mTOR were evaluated. TSG significantly improved lung pathologies and lung function in AECOPD rats by reducing bronchial wall thickness and mean alveolar linear intercept, increasing alveolar numbers, and reducing pulmonary expression of IL-1β, IL-6, TNF- α, MMP2 and MMP9. In MH-S cells, TSG significantly suppressed LPS-induced expressions of inflammatory cytokines, COX-2 and iNOS. Serum pharmacology coupled with network pharmacology identified 10 chemical components in TSG-medicated serum, and functional analysis of their 466 targets suggested that the therapeutic effect of TSG on AECOPD was mediated primarily by luteolin and quercetin, which regulate the MAPK, mTOR, FoxO, and autophagy pathways. In MH-S cells, luteolin significantly inhibited LPS-induced inflammatory responses and expressions of p-p38, FoxO3a, mTOR, p-p62 and LC3. TSG reduces macrophage-mediated inflammatory responses to alleviate AECOPD in rats possibly by modulating p38, mTOR, and FoxO3a pathways and inhibiting autophagy.

In vivo edited eosinophils reconcile antigen specific Th2 response and mitigate airway allergy

BackgroundImprovement is needed in the remedies used to control Th2 polarization. Bioengineering approaches have modified immune cells that have immunosuppressive functions. This study aims to generate modified eosinophils (Meos) in vivo and use Meos to balance Th2 polarization and reduce airway allergy.MethodsA cell editor was constructed. The editor contained a peptide carrier, an anti-siglec F antibody, MHC II, ovalbumin, and LgDNA (DNA extracted from a probiotic, Lactobacillus rhamnosus GG). Which was designated as Cedit. Meos are eosinophils modified using Cedits. An airway Th2 polarization mouse model was established used to test the effect of Meos on suppressing airway allergy.ResultsThe Cedits remained physically and chemically stable in solution (pH7.2) for at least 96 h. Cedits specifically bound to eosinophils, which are designated as Meos. Meos produced programmed death ligand-1 (PD-L1); the latter induced antigen specific CD4+ T cell apoptosis. Administration of Cedits through nasal instillations generated Meos in vivo, which significantly reduced the frequency of antigen specific CD4+ T cells in the airways, and mitigated airway Th2 polarization.ConclusionsWe constructed Cedit, which could edit eosinophils into Meos in vivo. Meos could induce antigen specific CD4+ T cell apoptosis, and reconcile airway Th2 polarization.

Abstract PR-15: Identifying synergistic combinations with KRAS inhibition in PDAC

Abstract Background: To date, targeted therapies have largely failed in eliciting sustained responses in advanced pancreatic ductal adenocarcinoma (PDAC). KRAS-targeted therapies have the potential to drastically transform clinical management. Emerging data indicate that only a subset of patients respond, and that acquired resistance is common. Here, we used a combination of in vivo CRISPR activation (CRISPRa) screening and in vitro/preclinical models to identify synergistic combinations with KRAS inhibition (KRASi) in pancreatic and lung cancer. Material and Methods: We used our CRISPRa-competent PPKS (P53(F/F), Kras(LSL-G12D/+), R26(LSL-SAM)) model of adenocarcinoma to conduct targeted screening for drivers of resistance to MRTX133. Our library consisted of ∼450 frequently mutated and amplified putative oncogenes across human adenocarcinoma based on TCGA data. Mice were treated with 1e8 TU of lentiviral library through nasal instillation. After 6 weeks, treatment was initiated with 3 mg/kg MRTX1133 daily, 5 days/week (i.p.). Mice were sacrificed after 4 weeks of treatment and the guide distribution determined through bioinformatic analysis. Genes statistically significantly enriched (FDR<0.05) in the treatment group were determined. Cell lines with acquired resistance to MRTX1133 derived from the KPC PDAC model and the KPP lung adenocarcinoma (LUAD) model were generated using long-term, low-dose treatment. Resistance was confirmed with MTT drug response assays. In vitro combinatorial drug response was determined using a 72h, 96-well MTT assay, and clonogenic response using a 2 week, 384-well FACS assay. Mice were treated with 20 mg/kg MRTX1133 and/or 20mg/kg Temuterkib once daily, 7 days/week (i.p.) for 2 weeks. Results: We performed targeted in vivo CRISPRa screening for drivers of resistance to KRASi in an autochthons model of lung adenocarcinoma (LUAD) using a library targeting 452 genes commonly amplified or mutated in cancer. We identified a set of genes that were specifically enriched in at least 50% of tumors treated with MRTX1133, including MAPK1/ERK2. We also generated 16 cell lines with acquired resistance to MRTX1133, derived from KPC PDAC or KPP LUAD tumors. Transcriptomic analysis identified a large set of genes differentially expressed in cell with acquired resistance relative to controls. GSEA indicated that reactivation of the MAPK cascade as a common trait in resistant cells. To test if ERK inhibition synergizes with KRASi, we quantified the combinatorial response to MRTX1133 and Temuterkib, a specific inhibitor of ERK1 and ERK2, in a set of KPC and KPP derived cell lines, revealing significant synergy and reduced clonogenic potential in a majority of cell lines. A majority of cell lines with acquired resistance to MRTX1133 remained sensitive to Temuterkib. Finally, we tested combinatorial treatment of MRTX1133 and Temuterkib in a syngenetic subcutaneous model of PDAC, which showed at minimum additive effect. In conclusion we have identified ERK inhibition as a promising combination with KRAS inhibition in KRAS-mutant PDAC and LUAD. Citation Format: Fredrik I Thege, Amber Hoskins, Sonja M Woermann, Anirban Maitra. Identifying synergistic combinations with KRAS inhibition in PDAC [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-15.

Yinqin Qingfei granules alleviate Mycoplasma pneumoniae pneumonia via inhibiting NLRP3 inflammasome-mediated macrophage pyroptosis.

Mycoplasma pneumoniae pneumonia (MPP) is a prevalent respiratory infectious disease in children. Given the increasing resistance of M. pneumoniae (MP) to macrolide antibiotics, the identification of new therapeutic agents is critical. Yinqin Qingfei granules (YQQFG), a Chinese patent medicine formulated specifically for pediatric MPP, lacks a clear explanation of its mechanism. The primary components of YQQFG were identified using LC-MS/MS. In vitro, RAW264.7 cells infected with MP underwent morphological examination via scanning electron microscopy. Drug-containing serum was prepared, and its intervention concentration was determined using the CCK-8 assay. The active components of YQQFG were molecularly docked with NLRP3 protein using Autodock Vina software. A RAW264.7 cell line overexpressing NLRP3 was created using lentivirus to pinpoint the target of YQQFG. In vivo, MPP model mice were established via nasal instillation of MP. Lung damage was assessed by lung index and H&E staining. Pyroptosis-associated protein levels in cells and lung tissue were measured by western blot, while interleukin (IL)-1β and IL-18 levels in cell supernatants and mouse serum were quantified using ELISA. Immunofluorescence double staining of lung tissue sections was conducted to assess the correlation between NLRP3 protein expression and macrophages. The expression of the community-acquired respiratory distress syndrome toxin (CARDS TX) was evaluated by qPCR. 25 effective components with favorable oral bioavailability were identified in YQQFG. Both in vitro and in vivo studies demonstrated that YQQFG substantially reduced the expression of the NLRP3/Caspase-1/GSDMD pathway, decreasing the release of IL-1β and IL-18, and inhibited MP exotoxin. Molecular docking indicated strong affinity between most YQQFG components and NLRP3 protein. Lentivirus transfection and immunofluorescence double staining confirmed that YQQFG significantly suppressed NLRP3 expression in macrophages, outperforming azithromycin (AZM). The combination of YQQFG and AZM yielded the optimal therapeutic effect for MPP. YQQFG mitigates inflammatory responses by suppressing NLRP3 inflammasome-mediated macrophage pyroptosis, thereby ameliorating MP-induced acute lung injury. YQQFG serves as an effective adjunct and alternative medication for pediatric MPP treatment.

Enolase inhibitors as therapeutic leads for Naegleria fowleri infection.

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used systemically. Here, we describe findings that demonstrate these agents are potent inhibitors of N. fowleri ENO (NfENO) and are lethal to amoebae. In particular, (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) was a potent enzyme inhibitor (IC50 = 0.14 ± 0.04 μM) that was toxic to trophozoites (EC50 = 0.21 ± 0.02 μM) while the reported CC50 was >300 μM. Molecular docking simulation revealed that HEX binds strongly to the active site of NfENO with a binding affinity of -8.6 kcal/mol. Metabolomic studies of parasites treated with HEX revealed a 4.5 to 78-fold accumulation of glycolytic intermediates upstream of NfENO. Last, nasal instillation of HEX increased longevity of amoebae-infected rodents. Two days after infection, animals were treated for 10 days with 3 mg/kg HEX, followed by one week of observation. At the end of the one-week observation, eight of 12 HEX-treated animals remained alive (resulting in an indeterminable median survival time) while one of 12 vehicle-treated rodents remained, yielding a median survival time of 10.9 days. However, intranasal HEX delivery was not curative as brains of six of the eight survivors were positive for amoebae. These findings suggest that HEX requires further evaluation to develop as a lead for treatment of PAM.

Urolithin A alleviates respiratory syncytial virus-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling

To observe the therapeutic effects of urolithin A (UA) on respiratory syncytial virus (RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms. Babl/c mice (5-7 days old) were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5, 5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks. Bronchoalveolar lavage fluid (BALF) was then collected for detection of inflammatory cells and mediators, and lung pathology was evaluated with HE staining. RSV-infected BEAS-2B cells were treated with 2.5, 5 or 10 µmol/ L UA. Inflammatory factors, cell viability, apoptosis and autophagy were analyzed using ELISA, CCK-8 assay, TUNEL staining, flow cytometry, Western blotting and immunofluorescence staining. The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR. A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1. In neonatal Babl/c mice, RSV infection caused obvious lung pathologies, promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ, Beclin-1 and miR-136 expressions, and increased the total cell number, inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions. All these changes were alleviated dose-dependently by UA. In BEAS-2B cells, RSV infection significantly increased cell apoptosis, LC3B-positive cells and miR-136 expression and reduced Sirt1 expression (P<0.01), which were dose-dependently attenuated by UA. Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1. In RSV-infected BEAS-2B cells with UA treatment, overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression, and these changes were further enhanced by their combined treatment. UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Nasal instillation of polystyrene nanoplastics induce lung injury via mitochondrial DNA release and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-signaling cascade

Nanoplastics (NPs) are a common type of degraded plastic material associated with adverse health effects such as pulmonary injury. However, the molecular mechanism(s) underlying lung injury as caused by NPs remains uncertain. Thus, we herein investigated the pulmonary toxicity of NPs on RAW264.7 cells and C57BL/6 mice. Our in vitro study indicated that NPs induced oxidative stress, cell death, inflammation, and the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-signaling pathway. Mice in our in vivo study displayed significant pulmonary fibrosis, inflammation, apoptosis, necrosis, and excessive double-stranded DNA release into serum and bronchoalveolar lavage fluid. Our mechanistic exploration uncovered cGAS-STING-signaling activation as the leading cause of NPs-induced pulmonary fibrosis. The current study opens an avenue toward elucidating the role of the cGAS-STING-signaling pathway in NPs-induced pulmonary injury.

Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms

To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.

Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.

We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with low in vivo toxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared to in vivo -JetPEI ® . Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cells in vivo . Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.

Direct exposure to CpG and specific antigens mitigate airway allergy through modulating dendritic cell properties

BackgroundCpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. MethodsDME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. ResultsThe airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. ConclusionsDirect exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.

THE KOSHATAKI VYOSHADI YOGA OF VISHA VAIDYA JYOTSNIKA- AN OVERVIEW

Introduction: Visha Chikitsa is one of the Ashtanga’s (Eight branches) of Ayurveda. That has been explained with names like Gara Chikitsa, Agadatantra, Vishagara Vairodika Prashamana [1]. Besides Samhitas (classical texts), many textbooks deal with Agadatantra (ayurvedic toxicology) and are written in various regional Indian languages. Many of them have been translated into English and Hindi. Kerala, rich in its Ayurveda heritage, has contributed to the Agadatantra. Visha Vaidya Jyotsnika is one of the textbooks that gives knowledge about the practice of Visha Chikitsa. Koshataki Vyoshadi Yoga is one of the vishagna formulations for Sarva Visha Chikitsa mentioned in this textbook. It has eight ingredients and is administered in Nasya (nasal instillation) and Anjana form. This paper is an attempt to analyse the benefits of Koshataki Vyoshadi Yoga. Materials and methods: The comprehensive review of Koshataki Vyoshadi Yoga formulation is done from the literature of Visha Vaidya Jyotsnika. The objective is to analyse Koshataki Vyoshadi Yoga for its benefit in Vi-sha Chikitsa. Observation and results: In this yoga, most of the drugs having Kaphavata Shamaka, Vishaghna, Krimigna, Uttejaka (Stimulant), Vranaropana, Sajnasthapana, Vamaka, Rasayana may be found to be one of the effective anti-poisonous formulations. Conclusion: Based on the properties and effects of Koshataki Vyoshadi Yoga mentioned by Acharya in Sarva-Visha Chikitsa. It is suitable for use in treating poison where fast action is required.

Inhalation bioaccessibility of imidacloprid in particulate matter: Implications for risk assessment during spraying

Adverse health outcomes due to the inhalation of pesticide residues in atmospheric particulate matter (PM) are gaining global attention. Quantitative health risk assessments of pesticide inhalation exposure highlight the need to understand the bioaccessibility of pesticide residues. Herein, the inhalation bioaccessibility of imidacloprid in PM was determined using three commonly used in vitro lung modeling methods (Artificial Lysosomal Fluid, Gamble Solution, and Simulated Lung Fluid). To validate its feasibility and effectiveness, we evaluated the bioavailability of imidacloprid using a mouse nasal instillation assay. The in vitro inhalation bioaccessibility of imidacloprid was extracted using Gamble Solution with a solid–liquid ratio of 1/1000, an oscillation rate of 150 r/min, and an extraction time of 24 h, showed a strong linear correlation with its in vivo liver-based bioavailability (R2 =0.8928). Moreover, the margin of exposure was incorporated into the inhalation exposure risk assessment, considering both formulations and nozzles. The inhalation unit exposure of imidacloprid for residents was 0.95–4.09 ng/m3. The margin of exposure for imidacloprid was determined to be acceptable when considering inhalation bioaccessibility. Taken together, these results indicate that the inhalation bioaccessibility of pesticides should be incorporated into assessments of human health risks posed by PM particles.

Ayurvedic Management of Vataja Pratishyaya w.s.r to Allergic Rhinitis (AR)- A Single Case Study

Introduction- In Ayurveda it is said that Nasa is the gate way of Shirah. There are 31 and 18 Nasa roga described by Acharya Sushruta and Acharya Vagbhatta respectively. There are 5 types of Pratishyaya described by Acharya Sushruta and Acharya Vagbhatta i.e Vataja, Pittaja, Kaphaja, Raktaja and Sannipataja. The Vataja Pratishyaya can be correlated with Allergic Rhinitis (AR). The management of Vataja Pratishyaya can be done by various treatment methods like Gritapana, Nasya, Dhumapana, Swedana, Internal medication. Aim-To evaluate the effect of Vaspa Swedana(Steam inhalation), Anutaila Marsha Nasya (Nasal instillation) , Chitraka Haritaki Avaleha (Orally) in the management of Vataja Pratishyaya (Allergic Rhinitis). Materials and Methods: The subject approached to Shalakya Tantra ENT OPD of Institute of Teaching and Research in Ayurveda (I.T.R.A), Jamnagar, with the symptoms of Running nose, Excessive Sneezing, Nasal obstruction, Itching of the nasal cavity since 15 days was systemically reviewed and Vaspa Swedana (Steam Inhaltion), Anutaila Marsha Nasya (Nasal Instillation), Chitraka Haritaki Avaleha (Orally) were prescribed. Results: The adopted Ayurvedic treatment showed complete remission in the disease Vataja Pratishyaya (Allergic Rhinitis) within 28 days. Discussion: Allergic Rhinitis is an allergic inflammation of the nasal membrane. It occurs when an allergen like pollen, dust or animal dander is inhaled by a private with a sensitized system. The symptoms of Vata- Kaphaj Pratishaya resembles most of Rhinitis. In Ayurveda the concept of allergy is widely elaborated under the concept of Ama, concept of Asatmya &amp; concept of Viruddha Aahara.Conclusion:.Here the treatment methods which are opted has Vata -Kapha Samana properties and has given a satisfactory result within 28 days.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50µl, 0.667IU) to induce emphysema. Treatment with PNU-282987 (2.0mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1β, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.

Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.

Advancing temporal sepsis biomarking: Covariate vascular endothelial growth factor A and B gene expression profiling in a murine model of SARS-CoV infection

The limited specificity of standard inflammatory biomarkers poses a challenge for the diagnosis and monitoring of sepsis. The differential gene expression patterns of Vascular Endothelial Growth Factor A and B (VEGF-A and B) are promising candidates. This study aimed to elucidate variations in VEGF-A/B gene expression following SARS-CoV MA15 disease initiation. Biomarker tracking was examined in a murine C57BL wild-type (WT) genotype MA15 (SARS-CoV) nasal instillation model. In [GSE40824], the expression of TNF and VEGF-A significantly differed between the groups (p = 1.53e-07, and 0.0043) and over time. In [GSE40827], [GSE51386], [GSE51387], and [GSE40840], the expression of TNF, VEGF-A, and VEGF-B was significantly different between groups, but not over time. In [GSE50878] and [GSE68220], TNF, NF-κB1, and VEGF-B showed significant differences in expression between the groups. The difference in VEGF-A expression was significant between the groups in [GSE68220] but not in [GSE50878]. However, the change over time from day 2 to day 4 was significant. In [GSE49262], TNF, NF-κB1, and VEGF-A significantly differed between the groups, and the changes in NF-κB1 and VEGF-A over time were significant. In [GSE49263], four genes differed significantly between the groups. In [GSE50000], TNF, NF-κB1, VEGF-A, and VEGF-B showed non-significant upregulation in the group with the higher dose. TNF, NF-κB1, and VEGF-A levels decreased from days 1–4 and increased from days 4–7. VEGF-B decreased from days 1–2 and increased from days 2–4 and from days 4–7. In [GSE33266], NF-κB1, VEGF-A, and VEGF-B levels varied between doses and time points. Our findings suggest that VEGF-A exhibits a more consistent and pronounced response to SARS MA15 infection regarding dose dependency and temporal expression changes.

Evaluation of Dinacharya in the Context of Netra

“Sarvaendriynam Nayanam Pradhanam” Chakshurindriya (eye) has been given utmost importance among all the sense organs i.e., nose, ear, eyes, tongue, skin by all the Acharyas. So, it must be protected wisely. Many eye disorders, including refractive errors, dry eye, computer vision syndrome, age-related macular degeneration, cataract, hypertensive retinopathy, diabetic retinopathy, and glaucoma, have been linked to the changing lifestyle of the modern era. This is especially with regard to the busy modern lifestyle and prolonged use of digital screens in our daily lives, from smartphone’s to computers. The daily routine for eye care as explained in Dincharya (daily regimen), involves a combination of preventive measures, therapeutic practices and lifestyle adjustments. These practices aim to balance the Doshas (internal energies) Vata, Pitta, Kapha associated with eye health. Ayurveda aims at prevention and cure of diseases and explains in detail the Rutucharya, Dinacharya, Sadvritta. In, eye care the Dincharya (daily regimen) includes Anjana (collyrium), Abhyanga (massage), Nasya (nasal instillation of drugs), Snana (bathing), Netraprakshalana (eye wash), Padabhyanga (foot massage), Padaprakshalana (cleaning of foot), and Padatra Dharana (use of footwear), Chhatra dharana, Netra Vyayama (eye exercise). Due to hazardous lifestyle, many people are not taking proper care of own self’s in the right way. Here, this review article explores the application of Dinacharya (daily regimen) principles specifically tailored for eye care, emphasizing a holistic approach to maintain ocular health.

Nasal instillation of povidone-iodine ameliorates ongoing mucosal inflammation in a pre-sensitized murine model of Der p1-induced allergic rhinitis.

Interleukin(IL)-33, when cleaved into smaller fragments by proteases, becomes hyperactive, contributing to allergic inflammation. Povidone-iodine (PVP-I) is an iodine-based compound that exhibits antimicrobial properties and inhibits proteases. This study aimed to investigate whether PVP-I treatment inhibits IL-33 cleavage, improves allergic rhinitis (AR) symptoms, and suppresses allergic inflammation in a mouse model. In vitro experiments using full-length recombinant human IL-33 and allergens, including house dust mites or Dermatophagoides pteronyssinus 1, were conducted using western blotting. Fifty BALB/c mice were divided into five groups: control (CON), AR with phosphate-buffered saline treatment (AR), PVP-I treatment (AR+PVP), trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E64) treatment (AR+E64), and dexamethasone treatment (AR+Dexa). Nasal symptom scores, including rubbing and sneezing, were measured. The cytokine levels in the nasal lavage fluid (NLF) and the concentration of immunoglobulins in the blood serum were assessed. Nasal mucosa from each group was used for reverse transcriptase-polymerase chain reaction (RT-PCR) and histological analyses were conducted. PVP-I treatment reduced nasal symptoms, suppressed allergic inflammation, and decreased the levels of IL-33, IL-5, and IL-13 in the NLF and total immunoglobulin E (IgE) and specific IgE in the serum. Histopathological analysis revealed a reduction in the number of eosinophils and goblet cells in the nasal mucosa of the AR+PVP group when compared to the AR group. RT-PCR and immunofluorescence staining confirmed the downregulation of genes and proteins associated with allergic inflammation. These findings suggest that nasal irrigation with PVP-I may be a promising therapeutic option for managing AR by inhibiting IL-33 activation and suppressing allergic inflammation.