Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial.

OBJECTIVE: The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). DESIGN AND METHODS: In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. RESULTS: Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p = .058) and LCQ Psychological domain (p = .026) and Physical domain (p = .045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p = .037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p = .094). There was weak evidence of a greater reduction in cough severity in the CDT group (p = .103). DISCUSSION: Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. TRIAL REGISTRATION: This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.

Drug–Target Interaction Deep Learning-Based Model Identifies the Flavonoid Troxerutin as a Candidate TRPV1 Antagonist

Based on the advances made by artificial intelligence (AI) technologies in drug discovery, including target identification, hit molecule identification, and lead optimization, this study investigated natural compounds that could act as transient receptor potential vanilloid 1 (TRPV1) channel protein antagonists. Using a molecular transformer drug–target interaction (MT-DTI) model, troxerutin was predicted to be a TRPV1 antagonist at IC50 582.73 nM. In a TRPV1-overexpressing HEK293T cell line, we found that troxerutin antagonized the calcium influx induced by the TRPV1 agonist capsaicin in vitro. A structural modeling and docking experiment of troxerutin and human TRPV1 confirmed that troxerutin could be a TRPV1 antagonist. A small-scale clinical trial consisting of 29 participants was performed to examine the efficacy of troxerutin in humans. Compared to a vehicle lotion, both 1% and 10% w/v troxerutin lotions reduced skin irritation, as measured by skin redness induced by capsaicin, suggesting that troxerutin could ameliorate skin sensitivity in clinical practice. We concluded that troxerutin is a potential TRPV1 antagonist based on the deep learning MT-DTI model prediction. The present study provides a useful reference for target-based drug discovery using AI technology and may provide useful information for the integrated research field of AI technology and biology.

The need for sensory nutrition research in individuals with smell loss

Millions of people will now suffer from long-term smell loss as a result of infection with the SARS-CoV-2 virus. Smell is an integral component of the flavor of foods, which is one of the primary drivers of ingestive behavior. When individuals lose their sense of smell, they find food to be less flavorful and less enjoyable, which negatively impacts their quality of life. To compensate, many individuals alter their diet by focusing on tastes, chemesthesis (e.g., chili pepper heat, menthol cooling), and the texture of foods to make it more palatable. Some diet alterations, such as increasing salt use, can result in a lower diet quality, and an increased risk for chronic disease. Sensory nutrition is an area of research that focuses on how the chemical senses (e.g. taste, smell, chemesthesis) and oral somatosensation) affect dietary choices and health. Sensory nutrition strategies designed for individuals with smell loss may help improve the flavor and liking of foods while improving diet quality, and are a necessary area of future research to help improve health and quality of life in the growing population with smell loss.Copyright © 2022 The Author(s)

Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward.

Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.

Unboxing herpes zoster ophthalmicus and the recombinant shingles vaccine

Reactivation of the varicella zoster virus as herpes zoster (shingles) typically affects the peripheral nerves, resulting in a painful rash, most often on the torso. However, it can also manifest ophthalmologically, affecting the ophthalmic division of the trigeminal nerve. This manifestation is associated with a particularly high level of morbidity and may result in blindness. A new recombinant shingles herpes zoster vaccine protects patients against this virus and post-infection sequelae, improving medical and psychosocial outcomes. © 2021 Medicine Today Pty Ltd. All rights reserved.

C apsicum fruits as functional ingredients with antimicrobial activity: an emphasis on mechanisms of action.

Capsicum spp. fruits (CFs) are a basic ingredient in the diet and have been used as active ingredients in the pharmaceutical, cosmetic, and food products, due to their antioxidant, anti-inflammatory, antiseptic, and antimicrobial properties. The antimicrobial activity is the most studied property due to its effectiveness against pathogenic species, however, few studies have focused on the mechanisms of action involved. Therefore, this review discusses the effects generated by the CFs compounds on the viability and metabolism of microorganisms, highlighting the mechanisms by which these compounds exert their antimicrobial effects. The information provided shows that CFs are mainly source of capsaicinoids and phenolic compounds responsible for the inhibition of bacteria, yeasts, and fungi, through an increase in the permeabilization of the membrane and cell wall. Also, these compounds show an antiviral effect associated with the inactivation of virus binding proteins, preventing their replication and infection. Despite this, there is still a lack of information about the mechanisms that regulate the interactions between CFs compounds and food-important-microorganisms. Therefore, future research should focus on new antimicrobial compounds from CFs for their subsequent use against novel infectious agents, mainly virus of importance in health such as SARS-CoV-2.

The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.

INTRODUCTION: Chronic cough heavily affects patients' quality of life, and there are no effective licensed therapies available. Cough is a complication of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, asthma, and other diseases. Patients with various diseases have a different profile of tussive responses to diverse cough triggers, thereby suggesting sundry mechanisms of neuronal dysfunctions. Previously, we demonstrated that the small molecule drug XC8 shows a clinical anti-asthmatic effect. The objective of the present study was to investigate the effect of XC8 on cough. METHODS: We studied the antitussive effect of XC8 on cough induced by agonists activating human transient receptor potential (TRP) cation channels TRPA1 or TRPV1 in guinea pigs. We checked the agonistic/antagonistic activity of XC8 on the human cation channels TRPA1, TRPV1, TRPM8, P2X purinoceptor 2 (P2X2), and human acid sensing ion channel 3 (hASIC3) in Fluorescent Imaging Plate Reader (FLIPR) assay. RESULTS: XC8 demonstrated clear antitussive activity and dose-dependently inhibited cough in guinea pigs induced by citric acid alone (up to 67.1%) or in combination with IFN-γ (up to 76.4%). XC8 suppressed cough reflexes induced by the repeated inhalation of citric acid (up to 80%) or by cinnamaldehyde (up to 60%). No activity of XC8 against cough evoked by capsaicin was revealed. No direct agonistic/antagonistic activity of XC8 on human TRPA1, TRPV1, TRPM8, P2X2, or hASIC3 was detected. CONCLUSIONS: XC8 acts against cough evoked by the activation of TRPA1 (citric acid/cinnamaldehyde) but not TRPV1 (capsaicin) channels. XC8 inhibits the cough reflex and suppresses the cough potentiation by IFN-γ. XC8 might be of significant therapeutic value for patients suffering from chronic cough associated with inflammation.

Virtual Screening of Natural Curcumins and Related Compounds Against SARS-CoV-2

The new coronavirus (COVID-19) is a viral disease that was classified as a pandemic situation on a global scale in early 2020. Severe Acute Respiratory Syndrome (SARS-CoV)-2 has the enzyme Mpro, until then, best characterized as an important biological target for intracellular viral replication. To investigate the interactions between curcumins and other compounds derived from cinnamic acid with the SARS-CoV-2 Mpro protease as well as to infer their physicochemical and drug-like properties, four natural curcumins and eight related compounds were selected for in silico screening, of molecular docking with the biological target Mpro, to suggest a therapeutic method associated with antiSARS-CoV-2 drugs, such as anakinra, azithromycin, baricitinib, hydroxychloroquine and remdesivir. All curcumins and related compounds can act as synergistic inhibitors of the main viral protein in SARS-CoV-2. The curcumins and other compound ligands showed similar interactions with the enzyme comparable to the control ligands. The ligands capsaicin, dehydrozingerol, dibenzoylmethane and isoeugenol stand out, due to their strong interactions. Among the compounds tested in this study, capsaicin, an alkaloid that is obtained from the fruits of plants of the genus Capsicum, showed significant activity in terms of its potential to inhibit SARS-CoV-2 viral replication. Controls N3, AZT and BRT has different action sites at COVID-19 Mpro PDB:6LU7. Curcumin and related ligands mostly approximate to the BRT receptor site Curcumin and related compounds associated with AZT and N3 are a promissory strategy