Laminar Distribution of Cannabinoid Receptor 1 in the Prefrontal Cortex of Nonhuman Primates.

Cannabis is an annual herb of the genus Cannabis, with a history of medical use going back thousands of years. However, its abuse causes many side-effects, including confusion of consciousness, alienation, and mental disorders such as schizophrenia and depression. Research conducted on rodents suggests that there are two types of cannabinoid receptors-cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R). CB1R is found mostly in the central nervous system, particularly in the prefrontal cortex (PFC), and alterations in its expression in the PFC have been strongly linked to mental disorders. Within the layers of the PFC, Brodmann area 46 is associated with the processing of complex cognitive information. However, it remains unclear whether CB1R is expressed in the PFC 46 area of non-human primate. In this work, we applied western blotting along with immunofluorescent histochemical staining to investigate the distribution pattern of CB1R in the PFC of nonhuman primate, Our findings reveal that CB1R is highly expressed in the monkey PFC, especially in area 46. Furthermore, CB1R exhibits a layered distribution pattern within area 46 of the PFC, with the inner granular layer displaying the highest expression levels. Additionally, CB1R+PV+ cells are widely distributed in lay II-VI of area 46, with layer IV showing notable prevalence. In conclusion, CB1R is distributed in the PV interneurons in area 46 of the prefrontal cortex, particularly in layer IV, suggesting that cannabis may modulate PFC activities via regulating interneuron in the PFC. And cannabis-induced side effects may be caused by abnormal expression of CB1R.

A Bayesian Spatio-temporal Model to Optimize Allocation of Buprenorphine in North Carolina.

The opioid epidemic is an ongoing public health crisis. In North Carolina, overdose deaths due to illicit opioid overdose have sharply increased over the last 5-7 years. Buprenorphine is a U.S. Food and Drug Administration approved medication for treatment of opioid use disorder and is obtained by prescription. Prior to January 2023, providers had to obtain a waiver and were limited in the number of patients that they could prescribe buprenorphine. Thus, identifying counties where increasing buprenorphine would yield the greatest overall reduction in overdose death can help policymakers target certain geographical regions to inform an effective public health response. We propose a Bayesian spatiotemporal model that relates yearly, county-level changes in illicit opioid overdose death rates to changes in buprenorphine prescriptions. We use our model to forecast the statewide count and rate of illicit opioid overdose deaths in future years, and we use nonlinear constrained optimization to identify the optimal buprenorphine increase in each county under a set of constraints on available resources. Our model estimates a negative relationship between death rate and increasing buprenorphine after accounting for other covariates, and our identified optimal single-year allocation strategy is estimated to reduce opioid overdose deaths by over 5.

A Descriptive Study on Opioid Misuse Prevalence and Office-Based Buprenorphine Access in Ohio Prior to the Removal of the Drug Addiction Treatment Act of 2000 Waiver.

Background Medications for the treatment of opioid use disorder (MOUD) are effective evidence-based strategies to reduce opioid overdose deaths. Strategies to optimize MOUD availability and uptake are needed. Objective We aim to describe the spatial relationship between the estimated prevalence of opioid misuse and office-based buprenorphine access in the state of Ohio prior to the removal of the Drug Addiction Treatment Act of 2000 (DATA 2000) waiver requirement. Methods We conducted a descriptive ecological study of county-level (N=88) opioid misuse prevalence and office-based buprenorphine prescribing access in Ohio in 2018. Counties were categorized into urban (with and without a major metropolitan area) and rural. The county-level prevalence estimates of opioid misuse per 100,000 were derived from integrated abundance modeling. Utilizing data from the Ohio Department of Mental Health and Addiction Services, as well as the state's Physician Drug Monitoring Program (PDMP), buprenorphine access per 100,000 was estimated by the number of patients in each county that could be served by office-based buprenorphine (prescribing capacity) and the number of patients served by office-based buprenorphine (prescribing frequency) for opioid use disorder. The ratios of opioid misuse prevalence to both prescribing capacity and frequency were calculated by county and mapped. Results Less than half of the 1,828 waivered providers in the state of Ohio in 2018 were prescribing buprenorphine, and 25% of counties had no buprenorphine access. The median estimated opioid misuse prevalence and buprenorphine prescribing capacity per 100,000 were highest in urban counties, particularly those with a major metropolitan area. Although the median estimated opioid misuse prevalence was lower in rural counties, all counties in the highest quartile of estimated misuse prevalence were rural. In addition, the median buprenorphine prescribing frequency was highest in rural counties. While the ratio of opioid misuse prevalence to buprenorphine prescribing capacity was lowest in urban counties, the ratio of opioid misuse prevalence to buprenorphine prescribing frequency was lowest in rural counties. Opioid misuse prevalence and buprenorphine prescribing frequency demonstrated similar spatial patterns, with highest levels in the southern and eastern portions of the state, while office-based buprenorphine prescribing capacity did not. Conclusion Urban counties had higher buprenorphine capacity relative to their burden of opioid misuse; however, access was limited by buprenorphine prescribing frequency. In contrast, in rural counties, a minimal gap was evident between prescribing capacity and frequency, suggesting that buprenorphine prescribing capacity was the major factor limiting access. While the recent deregulation of buprenorphine prescribing should help improve buprenorphine access, future research should investigate whether deregulation similarly impacts buprenorphine prescribing capacity and buprenorphine prescribing frequency.

Astragalus mongholicus Bunge (Fabaceae): Bioactive Compounds and Potential Therapeutic Mechanisms Against Alzheimer's Disease.

Astragalus mongholicus Bunge (Fabaceae) (also known as Astragali radix-AR), a widely used herb by Traditional Chinese Medicine practitioners, possesses a wide range of pharmacological effects, and has been used to treat Alzheimer's disease (AD) historically. Its bioactive compounds are categorized into four families: saponins, flavonoids, polysaccharides, and others. AR's bioactive compounds are effective in managing AD through a variety of mechanisms, including inhibiting Aß production, aggregation and tau hyperphosphorylation, protecting neurons against oxidative stress, neuroinflammation and apoptosis, promoting neural stem cell proliferation and differentiation and ameliorating mitochondrial dysfunction. This review aims to shed light upon the chemical constituents of AR and the mechanisms underlying the therapeutic effect of each compound in manging AD. Also presented are clinical studies which reported successful management of AD with AR and other herbs. These will be helpful for drug development and clinical application of AR to treat AD.

Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms.

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

The Potential Mechanism of Cancer Patients Appearing More Vulnerable to SARS-CoV-2 and Poor Outcomes: A Pan-Cancer Bioinformatics Analysis.

To explore the potential mechanism of cancer patients appearing more vulnerable to SARS-CoV-2 infection and poor COVID-19 outcomes, we conducted an integrative bioinformatics analysis for SARS-CoV-2-required genes and host genes and variants related to SARS-CoV-2 susceptibility and COVID-19 severity. BLCA, HNSC, KIRC, KIRP, LGG, PCPG, PRAD, TGCT, and THCA patients carrying rs10774671-A (OAS1) genotype may be more likely to have poor COVID-19 outcomes relative to those who carry rs10774671-G, because individuals carrying rs10774671-A will have lower expression of OAS1, which serves as a protective factor against SARS-CoV-2 processes and poor COVID-19 outcomes. SARS-CoV-2-required genes were correlated with TME, immune infiltration, overall survival, and anti-cancer drug sensitivity. CHOL patients may have a higher risk of SARS-CoV-2 infection than healthy subjects. SARS-CoV-2-induced ACE2 and NPC1 elevation may have a negative influence on the immune responses of LUSC and CD8+T infiltration of LUAD, and negatively affect the sensitivity of anti-lung cancer drugs. LUSC and LUAD patients may have a varying degree of adverse outcomes if they are infected with SARS-CoV-2. miR-760 may target and inhibit ACE2 expression. Cancer patients appearing vulnerable to SARS-CoV-2 infection and having poor COVID-19 outcomes may be partly due to host genetic factors and dysregulation of SARS-CoV-2-required genes. OAS1, ACE2, and miR-760 could serve as the treatment and intervention targets for SARS-CoV-2.