disease

DPH Diabetes & Heart Disease Prevention & Control Program Sponsors 20th Annual Diabetes Wellness Expo

DOVER, DE (MAY 9, 2022) – The Delaware Division of Public Health’s (DPH) Diabetes & Heart Disease Prevention & Control Program (DHDPC) and the Delaware Diabetes Coalition are co-sponsoring the 20th Annual Diabetes Wellness Expo on May 10, 2022, at the Delaware State Fairgrounds in Harrington, Delaware. The event is free to the public and will be […]




disease

Delaware Contributes Youth Overdose Death Data for Centers for Disease Control and Prevention’s Report

DOVER, DE (Jan. 3, 2023) – Through the Centers for Disease Control and Prevention’s State Unintentional Drug Overdose Reporting System (SUDORS), Delaware was recently among 47 states to contribute data to the CDC’s Dec. 16, 2022, Morbidity and Mortality Weekly Report, titled “Drug Overdose Deaths Among Persons Aged 10-19 Years – United States, July 2019-December 2021.” The Division of Public Health (DPH) utilizes SUDORS to track available trends and characteristics of […]




disease

DPH Recognizes May as Lyme Disease Awareness Month

As warmer weather brings people outdoors and potentially in contact with ticks, the Delaware Division of Public Health (DPH) is recognizing Lyme Disease Awareness Month this May. According to DPH’s Office of Infectious Disease Epidemiology, Lyme disease is the most common tick-borne disease in Delaware, with over 300 cases reported each year. Lyme disease is spread […]



  • Delaware Health and Social Services
  • Division of Public Health
  • News
  • Delaware Division of Public Health
  • Lyme Disease Awareness Month
  • Office of Infectious Disease Epidemiology
  • Steven Blessing

disease

Delaware Rare Disease Advisory Council Hosts First Meeting

DOVER, Del. — The Delaware Rare Disease Advisory Council held its inaugural meeting on Tuesday, taking its first steps to address innovation and research, patient care, and affordable and accessible treatment therapies.     Delaware is one of 27 states with a Rare Disease Advisory Council. Established by Senate Bill 55, sponsored by Sen. Nicole Poore […]



  • Lt. Governor Bethany Hall-Long
  • News
  • Office of the Lieutenant Governor

disease

DPH Releases 2024 Burden of Chronic Disease Report

The Delaware Division of Public Health’s (DPH) Physical Activity, Nutrition, and Obesity Prevention (PANO) Program released The Burden of Chronic Disease in Delaware 2024 report on June 28, 2024. The report summarizes the current state of chronic diseases and related risk factors in Delaware. It is an update to, and expansion of, Chronic Disease in Delaware: Facts and Figures, published in 2019 by DPH’s […]



  • Delaware Health and Social Services
  • Division of Public Health
  • Annual Report
  • chronic disease
  • DE Division of Public Health
  • Delaware Department of Health and Social Services

disease

24% Deaths In Delhi Caused Due To Infectious, Parasitic Diseases: Report

A Delhi government report has attributed nearly 24 per cent of the total about 89,000 deaths registered in the national capital in 2023 to infectious and parasitic diseases like cholera, diarrhoea, tuberculosis and hepatitis B, among others.




disease

Kazakhstan works to shake free from the ‘Dutch disease’

Kazakhstan is about to unveil a plan that aims to diversify its exports by fostering industrial development and to make the country a base for export-oriented manufacturers connected to global value chains. Jacopo Dettoni reports. 




disease

East-West Center Disease Specialist Warns Hawaiʻi Residents: ‘This is Not the Time to Take Chances’

East-West Center Disease Specialist Warns Hawaiʻi Residents: ‘This is Not the Time to Take Chances’ East-West Center Disease Specialist Warns Hawaiʻi Residents: ‘This is Not the Time to Take Chances’
telleid

News Release

Explore

News Release

Explore




disease

New Findings on Links between Urban Expansion and Viral Disease in Vietnam Offer Lessons for COVID-19

New Findings on Links between Urban Expansion and Viral Disease in Vietnam Offer Lessons for COVID-19 New Findings on Links between Urban Expansion and Viral Disease in Vietnam Offer Lessons for COVID-19
Anonymous (not verified) Mon, 03/30/2020 - 14:07

East-West Wire

Tagline
News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

Explore

East-West Wire

Tagline
News, Commentary, and Analysis
East-West Wire

The East-West Wire is a news, commentary, and analysis service provided by the East-West Center in Honolulu. Any part or all of the Wire content may be used by media with attribution to the East-West Center or the person quoted. To receive East-West Center Wire media releases via email, subscribe here.

For links to all East-West Center media programs, fellowships and services, see www.eastwestcenter.org/journalists.

Explore




disease

Lahore’s Dangerous Smog: Where Disease and Death Stalk

“It’s been horrible; I’ve been sick on and off for the last 10 days,” said 29-year-old asthmatic Natasha Sohail, who teaches A-Level students at three private schools in Lahore. Last week, her condition worsened with a vertigo attack and fever. “It’s criminal what is happening here,” said an incensed Sohail, referring to the “band-aid measures” […]




disease

Ants change the way they build nests to stop diseases spreading

When worker ants are exposed to a pathogenic fungus, they build nests that are more compartmentalised to reduce the risk of an epidemic




disease

New anti-ageing vaccines promise to prevent diseases like Alzheimer's

It may soon be possible to vaccinate ourselves against the diseases of old age, keeping our body and brain healthier for longer




disease

Dazzling images illuminate research on cardiovascular disease

The British Heart Foundation’s Reflections of Research competition showcases beautiful images captured by researchers studying heart and circulatory disease




disease

Is Graves’ Disease the Same as Thyrotoxicosis?

Title: Is Graves’ Disease the Same as Thyrotoxicosis?
Category: Diseases and Conditions
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM




disease

Early COPD Treatment Slows Disease

Title: Early COPD Treatment Slows Disease
Category: Health News
Created: 8/28/2009 12:00:00 AM
Last Editorial Review: 8/28/2009 12:00:00 AM




disease

Study Links Gene to Serious Eye Disease

Title: Study Links Gene to Serious Eye Disease
Category: Health News
Created: 8/25/2010 6:10:00 PM
Last Editorial Review: 8/26/2010 12:00:00 AM




disease

Not Enough Data to Support Kidney Disease Screening, Task Force Says

Title: Not Enough Data to Support Kidney Disease Screening, Task Force Says
Category: Health News
Created: 8/27/2012 6:05:00 PM
Last Editorial Review: 8/28/2012 12:00:00 AM




disease

Teen Smokers Show Early Signs of Heart Disease

Title: Teen Smokers Show Early Signs of Heart Disease
Category: Health News
Created: 8/29/2012 11:00:00 AM
Last Editorial Review: 8/29/2012 12:00:00 AM




disease

New Tick-Borne Disease: 'Heartland Virus'

Title: New Tick-Borne Disease: 'Heartland Virus'
Category: Health News
Created: 8/30/2012 11:00:00 AM
Last Editorial Review: 8/30/2012 12:00:00 AM




disease

Spinal Fluid Test May Aid Early Detection of Parkinson's Disease

Title: Spinal Fluid Test May Aid Early Detection of Parkinson's Disease
Category: Health News
Created: 8/27/2013 9:35:00 AM
Last Editorial Review: 8/27/2013 12:00:00 AM




disease

Gene May Raise Diabetics' Chances of Heart Disease

Title: Gene May Raise Diabetics' Chances of Heart Disease
Category: Health News
Created: 8/27/2013 4:35:00 PM
Last Editorial Review: 8/28/2013 12:00:00 AM




disease

Scientists Spot Genetic Clues to Crohn's Disease

Title: Scientists Spot Genetic Clues to Crohn's Disease
Category: Health News
Created: 8/27/2014 9:35:00 AM
Last Editorial Review: 8/27/2014 12:00:00 AM




disease

Progress Slows Against Heart Disease Deaths for Adults Under 55, Study Shows

Title: Progress Slows Against Heart Disease Deaths for Adults Under 55, Study Shows
Category: Health News
Created: 8/24/2015 12:00:00 AM
Last Editorial Review: 8/25/2015 12:00:00 AM




disease

Sharp Spike Seen in Statin Use in Elderly Without Heart Disease

Title: Sharp Spike Seen in Statin Use in Elderly Without Heart Disease
Category: Health News
Created: 8/24/2015 12:00:00 AM
Last Editorial Review: 8/25/2015 12:00:00 AM




disease

Impotence Drug Aids Treatment of Rare Lung Disease: Study

Title: Impotence Drug Aids Treatment of Rare Lung Disease: Study
Category: Health News
Created: 8/26/2015 12:00:00 AM
Last Editorial Review: 8/27/2015 12:00:00 AM




disease

Drug May Fight Heart Disease in Whole New Way

Title: Drug May Fight Heart Disease in Whole New Way
Category: Health News
Created: 8/28/2017 12:00:00 AM
Last Editorial Review: 8/29/2017 12:00:00 AM




disease

Pediatric Treatment Approved for 'Kissing Bug' Disease

Title: Pediatric Treatment Approved for 'Kissing Bug' Disease
Category: Health News
Created: 8/30/2017 12:00:00 AM
Last Editorial Review: 8/31/2017 12:00:00 AM




disease

AHA News: Understanding Connection Between Poverty, Childhood Trauma and Heart Disease

Title: AHA News: Understanding Connection Between Poverty, Childhood Trauma and Heart Disease
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




disease

Rising Obesity Rates Undermining Strides Made Against Heart Disease

Title: Rising Obesity Rates Undermining Strides Made Against Heart Disease
Category: Health News
Created: 8/27/2019 12:00:00 AM
Last Editorial Review: 8/28/2019 12:00:00 AM




disease

Nourianz Approved to Treat 'Off' Episodes in Parkinson Disease

Title: Nourianz Approved to Treat 'Off' Episodes in Parkinson Disease
Category: Health News
Created: 8/28/2019 12:00:00 AM
Last Editorial Review: 8/29/2019 12:00:00 AM




disease

COVID Vaccine Protection Against Severe Disease

Title: COVID Vaccine Protection Against Severe Disease
Category: Health News
Created: 8/25/2021 12:00:00 AM
Last Editorial Review: 8/25/2021 12:00:00 AM




disease

More Evidence Ties Gum Disease With Heart Disease

Title: More Evidence Ties Gum Disease With Heart Disease
Category: Health News
Created: 8/27/2021 12:00:00 AM
Last Editorial Review: 8/27/2021 12:00:00 AM




disease

'Stepped' Approach to Treating Diabetic Eye Disease May Be Best

Title: 'Stepped' Approach to Treating Diabetic Eye Disease May Be Best
Category: Health News
Created: 7/15/2022 12:00:00 AM
Last Editorial Review: 7/15/2022 12:00:00 AM




disease

Having Ideal Heart Health May Lessen the Risk for Brain Vessel Disease

Title: Having Ideal Heart Health May Lessen the Risk for Brain Vessel Disease
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM




disease

AHA News: New Report Details What to Know About Cardiovascular Disease Symptoms

Title: AHA News: New Report Details What to Know About Cardiovascular Disease Symptoms
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM




disease

Noninvasive diagnostic modalities and prediction models for detecting pulmonary hypertension associated with interstitial lung disease: a narrative review

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis.




disease

Dynamic dysregulation of retrotransposons in neurodegenerative diseases at the single-cell level [RESOURCES]

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ~42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. Machine learning algorithms for predicting cell disease stage using a combination of RTE and gene expression features suggests dynamic regulation of RTEs in AD. Furthermore, we construct a single-cell atlas of retrotransposable elements in neurodegenerative disease (scARE) using these data sets and features. scARE has six feature analysis modules to explore RTE dynamics in a user-defined condition. To our knowledge, scARE represents the first systematic investigation of RTE dynamics at the single-cell level within the context of neurodegenerative diseases.




disease

PWAS Hub for exploring gene-based associations of common complex diseases [RESOURCES]

PWAS (proteome-wide association study) is an innovative genetic association approach that complements widely used methods like GWAS (genome-wide association study). The PWAS approach involves consecutive phases. Initially, machine learning modeling and probabilistic considerations quantify the impact of genetic variants on protein-coding genes’ biochemical functions. Secondly, for each individual, aggregating the variants per gene determines a gene-damaging score. Finally, standard statistical tests are activated in the case-control setting to yield statistically significant genes per phenotype. The PWAS Hub offers a user-friendly interface for an in-depth exploration of gene–disease associations from the UK Biobank (UKB). Results from PWAS cover 99 common diseases and conditions, each with over 10,000 diagnosed individuals per phenotype. Users can explore genes associated with these diseases, with separate analyses conducted for males and females. For each phenotype, the analyses account for sex-based genetic effects, inheritance modes (dominant and recessive), and the pleiotropic nature of associated genes. The PWAS Hub showcases its usefulness for asthma by navigating through proteomic-genetic analyses. Inspecting PWAS asthma-listed genes (a total of 27) provide insights into the underlying cellular and molecular mechanisms. Comparison of PWAS-statistically significant genes for common diseases to the Open Targets benchmark shows partial but significant overlap in gene associations for most phenotypes. Graphical tools facilitate comparing genetic effects between PWAS and coding GWAS results, aiding in understanding the sex-specific genetic impact on common diseases. This adaptable platform is attractive to clinicians, researchers, and individuals interested in delving into gene–disease associations and sex-specific genetic effects.




disease

Potential Drawbacks of Noninvasive Diagnostic Methods for Nonalcoholic Fatty Liver Disease

The rising obesity epidemic is a phenomenon that has gained increasing attention from health providers and health policy makers. This led to recognition of nonalcoholic fatty liver disease (MASLD). The standard for its assessment has been histologic, which is neither practical nor acceptable by patients. Subsequently, a number of noninvasive assessment methods have been developed. However, despite ease of implementation, their confounding variables do hinder their accuracy. Nonetheless, the development of the liver stiffness measurement (LSM) and incorporation of other biological parameters has minimized but not eliminated the need for liver biopsy. Imaging methods are useful in evaluation, estimation, and following the progression of steatosis and fibrosis with particular attention to controlled attenuation parameter (CAP) and MRI–Proton Density Fat Fraction (MRI-PDFF). The choices for the family physician are broad and rely on tests’ availability, cost, and patient acceptance. Great efforts have been undertaken to produce more robust and novel noninvasive markers that indicate fibrinogenesis directly in an implementable and cost-effective way.




disease

Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24–$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005–March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.




disease

Correlations of Long Noncoding RNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism [Articles]

Hepatocyte nuclear factor 4 alpha antisense 1 (HNF4A-AS1) is a long noncoding RNA (lncRNA) gene physically located next to the transcription factor HNF4A gene in the human genome. Its transcription products have been reported to inhibit the progression of hepatocellular carcinoma (HCC) and negatively regulate the expression of cytochrome P450s (CYPs), including CYP1A2, 2B6, 2C9, 2C19, 2E1, and 3A4. By altering CYP expression, lncRNA HNF4A-AS1 also contributes to the susceptibility of drug-induced liver injury. Thus, HNF4A-AS1 lncRNA is a promising target for controlling HCC and modulating drug metabolism. However, HNF4A-AS1 has four annotated alternative transcripts in the human genome browsers, and it is unclear which transcripts the small interfering RNAs or small hairpin RNAs used in the previous studies are silenced and which transcripts should be used as the target. In this study, four annotated and two newly identified transcripts were confirmed. These six transcripts showed different expression levels in different liver disease conditions, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and obesity. The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment. Several HNF4A-AS1 transcripts highly displayed correlations with these situations. In addition, some of the HNF4A-AS1 transcripts also showed a strong correlation with CYP3A4 during HepaRG maturation and rifampicin exposure. Our findings provide valuable insights into the specific roles of HNF4A-AS1 transcripts, paving the way for more targeted therapeutic strategies for liver diseases and drug metabolism.

SIGNIFICANCE STATEMENT

This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.




disease

Proteomic Analysis of Signaling Pathways Modulated by Fatty Acid Binding Protein 5 (FABP5) in Macrophages [Special Section: Cannabinoid Signaling in Human Health and Disease]

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

SIGNIFICANCE STATEMENT

This research offers a comprehensive analysis of fatty acid binding protein 5 (FABP5) in macrophages during inflammatory response. The authors employed quantitative proteomic and phosphoproteomic approaches to investigate this utilizing bone marrow-derived macrophages that were M1 and M2 polarized using lipopolysaccharide with interferon and interleukin-4, respectively. This revealed multiple pathways related to inflammation that were differentially regulated due to the absence of FABP5. These findings underscore the potential therapeutic significance of macrophage-FABP5 as a candidate for addressing inflammatory-related diseases.




disease

Regulation of Cannabinoid and Opioid Receptor Levels by Endogenous and Pharmacological Chaperones [Special Section: Cannabinoid Signaling in Human Health and Disease]

Cannabinoid and opioid receptor activities can be modulated by a variety of post-translational mechanisms including the formation of interacting complexes. This study examines the involvement of endogenous and exogenous chaperones in modulating the abundance and activity of cannabinoid CB1 receptor (CB1R), opioid receptor (DOR), and CB1R-DOR interacting complexes. Focusing on endogenous protein chaperones, namely receptor transporter proteins (RTPs), we examined relative mRNA expression in the mouse spinal cord and found RTP4 to be expressed at higher levels compared with other RTPs. Next, we assessed the effect of RTP4 on receptor abundance by manipulating RTP4 expression in cell lines. Overexpression of RTP4 causes an increase and knock-down causes a decrease in the levels of CB1R, DOR, and CB1R-DOR interacting complexes; this is accompanied by parallel changes in signaling. The ability of small molecule lipophilic ligands to function as exogenous chaperones was examined using receptor-selective antagonists. Long-term treatment leads to increases in receptor abundance and activity with no changes in mRNA supporting a role as pharmacological chaperones. Finally, the effect of cannabidiol (CBD), a small molecule ligand and a major active component of cannabis, on receptor abundance and activity in mice was examined. We find that CBD administration leads to increases in receptor abundance and activity in mouse spinal cord. Together, these results highlight a role for chaperones (proteins and small molecules) in modulating levels and activity of CB1R, DOR, and their interacting complexes potentially through mechanisms including receptor maturation and trafficking.

SIGNIFICANCE STATEMENT

This study highlights a role for chaperones (endogenous and small membrane-permeable molecules) in modulating levels of cannabinoid CB1 receptor, delta opioid receptor, and their interacting complexes. These chaperones could be developed as therapeutics for pathologies involving these receptors.




disease

Evaluating the Abuse Potential of Lenabasum, a Selective Cannabinoid Receptor 2 Agonist [Special Section: Cannabinoid Signaling in Human Health and Disease]

Endocannabinoids, which are present throughout the central nervous system (CNS), can activate cannabinoid receptors 1 and 2 (CB1 and CB2). CB1 and CB2 agonists exhibit broad anti-inflammatory properties, suggesting their potential to treat inflammatory diseases. However, careful evaluation of abuse potential is necessary. This study evaluated the abuse potential of lenabasum, a selective CB2 receptor agonist in participants (n = 56) endorsing recreational cannabis use. Three doses of lenabasum (20, 60, and 120 mg) were compared with placebo and nabilone (3 and 6 mg). The primary endpoint was the peak effect (Emax) on a bipolar Drug Liking visual analog scale (VAS). Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. Lenabasum was safe and well tolerated. Compared with placebo, a 20-mg dose of lenabasum did not increase ratings of Drug Liking and had no distinguishable effect on other VAS endpoints. Dose-dependent increases in ratings of Drug Liking were observed with 60 and 120 mg lenabasum. Drug Liking and all other VAS outcomes were greatest for nabilone 3 mg and 6 mg, a medication currently approved by the US Food and Drug Administration (FDA). At a target therapeutic dose (20 mg), lenabasum did not elicit subjective ratings of Drug Liking. However, supratherapeutic doses of lenabasum (60 and 120 mg) did elicit subjective ratings of Drug Liking compared with placebo. Although both doses of lenabasum were associated with lower ratings of Drug Liking compared with 3 mg and 6 mg nabilone, lenabasum does have abuse potential and should be used cautiously in clinical settings.

SIGNIFICANCE STATEMENT

This work provides evidence that in people with a history of recreational cannabis use, lenabasum was safe and well tolerated, although it did demonstrate abuse potential. This work supports further development of lenabasum for potential therapeutic indications.




disease

Cannabinoid 2 Receptor Activation Protects against Diabetic Cardiomyopathy through Inhibition of AGE/RAGE-Induced Oxidative Stress, Fibrosis, and Inflammasome Activation [Special Section: Cannabinoid Signaling in Human Health and Disease]

Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)–receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β-caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms.

SIGNIFICANCE STATEMENT

BCP, a CB2R agonist, shows protection against DCM. BCP attenuates oxidative stress, inflammation, and fibrosis in DCM via activating CB2Rs. BCP mediating CB2R activation favorably modulates AGE/RAGE, PI3K/AKT/Nrf2β and TGF-β/Smad and (NLRP3) inflammasome in diabetic cardiomyopathy.




disease

KLS-13019, a Novel Structural Analogue of Cannabidiol and GPR55 Receptor Antagonist, Prevents and Reverses Chemotherapy-Induced Peripheral Neuropathy in Rats [Special Section: Cannabinoid Signaling in Human Health and Disease]

Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential. Thus, neuropathic pain represents an area of critical unmet medical need, and novel classes of therapeutics with improved efficacy and safety profiles are urgently needed. The cannabidiol structural analog and novel antagonist of GPR55, KLS-13019, was screened in rat models of neuropathic pain. Tactile sensitivity associated with chemotherapy exposure was induced in rats with once-daily 1-mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for 1 week. Rats were then administered KLS-13019 or comparator drugs on day 7 in an acute dosing paradigm or days 7–10 in a chronic dosing paradigm, and mechanical or cold allodynia was assessed. Allodynia was reversed in a dose-dependent manner in the rats treated with KLS-13019, with the highest dose reverting the response to prepaclitaxel injection baseline levels with both intraperitoneal and oral administration after acute dosing. In the chronic dosing paradigm, four consecutive doses of KLS-13019 completely reversed allodynia for the duration of the phenotype in control animals. Additionally, coadministration of KLS-13019 with paclitaxel prevented the allodynic phenotype from developing. Together, these data suggest that KLS-13019 represents a potential new drug for the treatment of neuropathic pain.

SIGNIFICANCE STATEMENT

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment with no known cure. The GPR55 antagonist KLS-13019 represents a novel class of drug for this condition that is a potent, durable inhibitor of allodynia associated with CIPN in rats in both prevention and reversal-dosing paradigms. This novel therapeutic approach addresses a critical area of unmet medical need.




disease

The Minor Phytocannabinoid Delta-8-Tetrahydrocannabinol Attenuates Collagen-Induced Arthritic Inflammation and Pain-Depressed Behaviors [Special Section: Cannabinoid Signaling in Human Health and Disease]

Patients with arthritis report using cannabis for pain management, and the major cannabinoid delta-9-tetrahydrocannabinol (9-THC) has anti-inflammatory properties, yet the effects of minor cannabinoids on arthritis are largely unknown. The goal of the present study was to determine the antiarthritic potential of the minor cannabinoid delta-8-tetrahydrocannabinol (8-THC) using the collagen-induced arthritis (CIA) mouse model. Adult male DBA/1J mice were immunized and boosted 21 days later with an emulsion of collagen and complete Freund’s adjuvant. Beginning on the day of the booster, mice were administered twice-daily injections of 8-THC (3 or 30 mg/kg), the steroid dexamethasone (2 mg/kg), or vehicle for two weeks. Dorsal-ventral paw thickness and qualitative measures of arthritis were recorded daily, and latency to fall from an inverted grid was measured on alternating days, to determine arthritis severity and functional impairment. On the final day of testing, spontaneous wire-climbing behavior and temperature preference in a thermal gradient ring were measured to assess CIA-depressed behavior. The 8-THC treatment (30 mg/kg) reduced paw swelling and qualitative signs of arthritis. 8-THC also blocked CIA-depressed climbing and CIA-induced preference for a heated floor without producing locomotor effects but did not affect latency to fall from a wire grid. In alignment with the morphologic and behavioral assessments in vivo, histology revealed that 8-THC reduced synovial inflammation, proteoglycan loss and cartilage and bone erosion in the foot joints in a dose-dependent manner. Together, these findings suggest that 8-THC not only blocked morphologic changes but also prevented functional loss caused by collagen-induced arthritis.

SIGNIFICANCE STATEMENT

Despite increasing use of cannabis products, the potential effects of minor cannabinoids are largely unknown. Here, the minor cannabinoid delta-8-tetrahydrocannabinol blocked the development of experimentally induced arthritis by preventing both pathophysiological as well as functional effects of the disease model. These data support the development of novel cannabinoid treatments for inflammatory arthritis.




disease

Select Minor Cannabinoids from Cannabis sativa Are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain [Special Section: Cannabinoid Signaling in Human Health and Disease]

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), 8-tetrahydrocannabinol (8-THC), and 9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose 8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose 8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential.

SIGNIFICANCE STATEMENT

Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study, we evaluated five minor cannabinoids (CBN, CBDV, CBG, THCV, and 8-THC) for their cannabimimetic and analgesic effects in mice. We found that four of the five minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.




disease

The Potential of Cannabichromene (CBC) as a Therapeutic Agent [Special Section: Cannabinoid Signaling in Human Health and Disease-Minireview]

There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa. The two most abundant cannabinoids (9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). Although the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials. In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC.

SIGNIFICANCE STATEMENT

Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on 9-tetrahydrocannabinol and cannabidiol. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.




disease

The Intoxication Equivalency of 11-Hydroxy-{Delta}9-Tetrahydrocannabinol Relative to {Delta}9-Tetrahydrocannabinol [Special Section: Cannabinoid Signaling in Human Health and Disease]

9-Tetrahydrocannabinol (THC) is a psychoactive phytocannabinoid found in the Cannabis sativa plant. THC is primarily metabolized into 11-hydroxy-9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-9-tetrahydrocannabinol (COOH-THC), which may themselves be psychoactive. There is very little research-based evidence concerning the pharmacokinetics and pharmacodynamics of 11-OH-THC as an individual compound. Male C57BL/6 mice were treated with THC or 11-OH-THC via intraperitoneal injection, tail vein intravenous injection, or oral gavage, and whole-blood compound levels were measured to determine pharmacokinetic parameters [Cmax, time to Cmax (Tmax), elimination half-life, area under the curve, apparent volume of distribution, systemic clearance, terminal rate constant, and absolute bioavailability] while also monitoring changes in catalepsy, body temperature, and nociception. 11-OH-THC achieved a Tmax at 30 minutes for all routes of administration. The maximum concentration at 30 minutes was not different between intravenous and intraperitoneal routes, but the oral gavage Cmax was significantly lower. THC had a 10-minute time to the maximum concentration, which was the first blood collection time point, for intravenous and intraperitoneal and 60 minutes for oral gavage, with a lower Cmax for intraperitoneal and oral gavage compared with intravenous. When accounting for circulating compound levels and ED50 responses, these data suggest that 11-OH-THC was 153% as active as THC in the tail-flick test of nociception and 78% as active as THC for catalepsy. Therefore, 11-OH-THC displayed equal or greater activity than the parent compound THC, even when accounting for pharmacokinetic differences. Thus, the THC metabolite 11-OH-THC likely plays a critical role in the bioactivity of cannabis; understanding its activity when administered directly will aid in the interpretation of future animal and human studies.

SIGNIFICANCE STATEMENT

This study establishes that the primary metabolite of THC, 11-OH-THC, displays equal or greater activity than THC in a mouse model of cannabinoid activity when directly administered and even when accounting for route of administration, sex, pharmacokinetic, and pharmacodynamic differences. These data provide critical insight into the bioactivity of THC metabolites that will inform the interpretation of future in vivo cannabinoid research and represent a model for how THC consumption and metabolism may affect cannabis use in humans.