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JAMA Network Open Jun 2024
Topics: Humans; Opioid-Related Disorders; Primary Health Care; Health Knowledge, Attitudes, Practice; Female; Male; Adult; Middle Aged; Analgesics, Opioid; Cross-Sectional Studies; Surveys and Questionnaires
PubMed: 38941101
DOI: 10.1001/jamanetworkopen.2024.19094 -
JAMA Network Open Jun 2024Understanding the cost of drug development can help inform the development of policies to reduce costs, encourage innovation, and improve patient access to drugs.
IMPORTANCE
Understanding the cost of drug development can help inform the development of policies to reduce costs, encourage innovation, and improve patient access to drugs.
OBJECTIVE
To estimate the cost of drug development by therapeutic class and trends in pharmaceutical research and development (R&D) intensity over time.
DESIGN, SETTING, AND PARTICIPANTS
In this economic evaluation study, an analytical model of drug development constructed using public and proprietary sources that collectively cover data from 2000 to 2018 was used to estimate the cost of bringing a drug to market, overall and for specific therapeutic classes. The analysis for the study was completed in October 2020.
MAIN OUTCOMES AND MEASURES
Three measures of development cost from nonclinical through postmarketing stages were estimated: mean out-of-pocket cost or cash outlay, mean expected cost, and mean expected capitalized cost. Pharmaceutical R&D intensity, defined as the ratio of R&D spending to total sales, from 2008 to 2019, based on the time frame for available data, was also analyzed.
RESULTS
The estimated mean cost of developing a new drug was approximately $172.7 million (2018 dollars) (range, $72.5 million for genitourinary to $297.2 million for pain and anesthesia), inclusive of postmarketing studies. The cost increased to $515.8 million when cost of failures was included. When the costs of failures and capital were included, the mean expected capitalized cost of drug development increased to $879.3 million (range, $378.7 million for anti-infectives to $1756.2 million for pain and anesthesia); results varied widely by therapeutic class. The pharmaceutical industry as a whole experienced a decline of 15.6% in sales but increased R&D intensity from 11.9% to 17.7% from 2008 to 2019. By contrast, R&D intensity of large pharmaceutical companies increased from 16.6% to 19.3%, whereas sales increased by 10.0% (from $380.0 to $418.0 billion) over the same 2008 to 2019 period, even though the cost of drug development remained relatively stable or may have even decreased.
CONCLUSIONS AND RELEVANCE
In this economic evaluation of new drug development costs, even though the cost of drug development appears to have remained stable, R&D intensity of large pharmaceutical companies remained relatively unchanged, despite substantial growth in revenues during this period. These findings can inform the design of drug-related policies and their potential impacts on innovation and competition.
Topics: Drug Development; United States; Humans; Drug Costs; Drug Industry; Pharmaceutical Research
PubMed: 38941099
DOI: 10.1001/jamanetworkopen.2024.15445 -
JAMA Network Open Jun 2024Air pollution is a recognized risk factor associated with chronic diseases, including respiratory and cardiovascular conditions, which can lead to physical and cognitive...
IMPORTANCE
Air pollution is a recognized risk factor associated with chronic diseases, including respiratory and cardiovascular conditions, which can lead to physical and cognitive impairments in later life. Although these losses of function, individually or in combination, reduce individuals' likelihood of living independently, little is known about the association of air pollution with this critical outcome.
OBJECTIVE
To investigate associations between air pollution and loss of independence in later life.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted as part of the Environmental Predictors Of Cognitive Health and Aging study and used 1998 to 2016 data from the Health and Retirement Study. Participants included respondents from this nationally representative, population-based cohort who were older than 50 years and had not previously reported a loss of independence. Analyses were performed from August 31 to October 15, 2023.
EXPOSURES
Mean 10-year pollutant concentrations (particulate matter less than 2.5 μm in diameter [PM2.5] or ranging from 2.5 μm to 10 μm in diameter [PM10-2.5], nitrogen dioxide [NO2], and ozone [O3]) were estimated at respondent addresses using spatiotemporal models along with PM2.5 levels from 9 emission sources.
MAIN OUTCOMES AND MEASURES
Loss of independence was defined as newly receiving care for at least 1 activity of daily living or instrumental activity of daily living due to health and memory problems or moving to a nursing home. Associations were estimated with generalized estimating equation regression adjusting for potential confounders.
RESULTS
Among 25 314 respondents older than 50 years (mean [SD] baseline age, 61.1 [9.4] years; 11 208 male [44.3%]), 9985 individuals (39.4%) experienced lost independence during a mean (SD) follow-up of 10.2 (5.5) years. Higher exposure levels of mean concentration were associated with increased risks of lost independence for total PM2.5 levels (risk ratio [RR] per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.10), PM2.5 levels from road traffic (RR per 1-IQR of 10-year mean, 1.09; 95% CI, 1.03-1.16) and nonroad traffic (RR per 1-IQR of 10-year mean, 1.13; 95% CI, 1.03-1.24), and NO2 levels (RR per 1-IQR of 10-year mean, 1.05; 95% CI, 1.01-1.08). Compared with other sources, traffic-generated pollutants were most consistently and robustly associated with loss of independence; only road traffic-related PM2.5 levels remained associated with increased risk after adjustment for PM2.5 from other sources (RR per 1-IQR increase in 10-year mean concentration, 1.10; 95% CI, 1.00-1.21). Other pollutant-outcome associations were null, except for O3 levels, which were associated with lower risks of lost independence (RR per 1-IQR increase in 10-year mean concentration, 0.94; 95% CI, 0.92-0.97).
CONCLUSIONS AND RELEVANCE
This study found that long-term exposure to air pollution was associated with the need for help for lost independence in later life, with especially large and consistent increases in risk for pollution generated by traffic-related sources. These findings suggest that controlling air pollution could be associated with diversion or delay of the need for care and prolonged ability to live independently.
Topics: Humans; Male; Aged; Female; Air Pollution; Middle Aged; United States; Particulate Matter; Environmental Exposure; Air Pollutants; Cohort Studies; Ozone; Independent Living; Nitrogen Dioxide; Aged, 80 and over; Risk Factors
PubMed: 38941096
DOI: 10.1001/jamanetworkopen.2024.18460 -
JAMA Network Open Jun 2024While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain.
IMPORTANCE
While adults aged 80 years and older account for 70% of hip fractures in the US, performance of fracture risk assessment tools in this population is uncertain.
OBJECTIVE
To compare performance of the Fracture Risk Assessment Tool (FRAX), Garvan Fracture Risk Calculator, and femoral neck bone mineral density (FNBMD) alone in 5-year hip fracture prediction.
DESIGN, SETTING AND PARTICIPANTS
Prognostic analysis of 3 prospective cohort studies including participants attending an index examination (1997 to 2016) at age 80 years or older. Data were analyzed from March 2023 to April 2024.
MAIN OUTCOMES AND MEASURES
Participants contacted every 4 or 6 months after index examination to ascertain incident hip fractures and vital status. Predicted 5-year hip fracture probabilities calculated using FRAX and Garvan models incorporating FNBMD and FNBMD alone. Model discrimination assessed by area under receiver operating characteristic curve (AUC). Model calibration assessed by comparing observed vs predicted hip fracture probabilities within predicted risk quintiles.
RESULTS
A total of 8890 participants were included, with a mean (SD) age at index examination of 82.6 (2.7) years; 4906 participants (55.2%) were women, 866 (9.7%) were Black, 7836 (88.1%) were White, and 188 (2.1%) were other races and ethnicities. During 5-year follow-up, 321 women (6.5%) and 123 men (3.1%) experienced a hip fracture; 818 women (16.7%) and 921 men (23.1%) died before hip fracture. Among women, AUC was 0.69 (95% CI, 0.67-0.72) for FRAX, 0.69 (95% CI, 0.66-0.72) for Garvan, and 0.72 (95% CI, 0.69-0.75) for FNBMD alone (FNBMD superior to FRAX, P = .01; and Garvan, P = .01). Among men, AUC was 0.71 (95% CI, 0.66-0.75) for FRAX, 0.76 (95% CI, 0.72-0.81) for Garvan, and 0.77 (95% CI, 0.72-0.81) for FNBMD alone (P < .001 Garvan and FNBMD alone superior to FRAX). Among both sexes, Garvan greatly overestimated hip fracture risk among individuals in upper quintiles of predicted risk, while FRAX modestly underestimated risk among those in intermediate quintiles of predicted risk.
CONCLUSIONS AND RELEVANCE
In this prognostic study of adults aged 80 years and older, FRAX and Garvan tools incorporating FNBMD compared with FNBMD alone did not improve 5-year hip fracture discrimination. FRAX modestly underpredicted observed hip fracture probability in intermediate-risk individuals. Garvan markedly overpredicted observed hip fracture probability in high-risk individuals. Until better prediction tools are available, clinicians should prioritize consideration of hip BMD, life expectancy, and patient preferences in decision-making regarding drug treatment initiation for hip fracture prevention in late-life adults.
Topics: Humans; Hip Fractures; Male; Female; Risk Assessment; Aged, 80 and over; Prospective Studies; Bone Density; Risk Factors; Femur Neck
PubMed: 38941095
DOI: 10.1001/jamanetworkopen.2024.18612 -
JAMA Network Open Jun 2024Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations....
IMPORTANCE
Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.
OBJECTIVE
To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.
EXPOSURE
Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days' supply overlapping the period from date of conception to childbirth.
MAIN OUTCOMES AND MEASURES
Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.
RESULTS
Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.
CONCLUSIONS AND RELEVANCE
In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.
Topics: Humans; Female; Pregnancy; Smoking Cessation; Adult; Retrospective Studies; Smoking Cessation Agents; Varenicline; Bupropion; New Zealand; Tobacco Use Cessation Devices; Pregnancy Complications; Sweden; New South Wales; Norway; Young Adult; Smoking; Pregnancy Trimester, First
PubMed: 38941092
DOI: 10.1001/jamanetworkopen.2024.19245 -
JAMA Network Open Jun 2024Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of...
IMPORTANCE
Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of nighttime and daytime heat with dementia-related deaths.
OBJECTIVES
To quantitatively assess the risk and burden of dementia-related deaths associated with short-term nighttime and daytime heat exposure and identify potential effect modifications.
DESIGN, SETTING, AND PARTICIPANTS
This case-crossover study analyzed individual death records for dementia across all mainland China counties from January 1, 2013, to December 31, 2019, using a time-stratified case-crossover approach. Statistical analysis was conducted from January 1, 2013, to December 31, 2019.
EXPOSURES
Two novel heat metrics: hot night excess (HNE) and hot day excess (HDE), representing nighttime and daytime heat intensity, respectively.
MAIN OUTCOMES AND MEASURES
Main outcomes were the relative risk and burden of dementia-related deaths associated with HNE and HDE under different definitions. Analysis was conducted with conditional logistic regression integrated with the distributed lag nonlinear model.
RESULTS
The study involved 132 573 dementia-related deaths (mean [SD] age, 82.5 [22.5] years; 73 086 women [55.1%]). For a 95% threshold, the median hot night threshold was 24.5 °C (IQR, 20.1 °C-26.2 °C) with an HNE of 3.7 °C (IQR, 3.1 °C-4.3 °C), and the median hot day threshold was 33.3 °C (IQR, 29.9 °C-34.7 °C) with an HDE of 0.6 °C (IQR, 0.5 °C-0.8 °C). Both nighttime and daytime heat were associated with increased risk of dementia-related deaths. Hot nights' associations with risk of dementia-related deaths persisted for 6 days, while hot days' associations with risk of dementia-related deaths extended over 10 days. Extreme HDE had a higher relative risk of dementia-related deaths, with a greater burden associated with extreme HNE at more stringent thresholds. At a 97.5% threshold, the odds ratio for dementia-related deaths was 1.38 (95% CI, 1.22-1.55) for extreme HNE and 1.46 (95% CI, 1.27-1.68) for extreme HDE, with an attributable fraction of 1.45% (95% empirical confidence interval [95% eCI], 1.43%-1.47%) for extreme HNE and 1.10% (95% eCI, 1.08%-1.11%) for extreme HDE. Subgroup analyses suggested heightened susceptibility among females, individuals older than 75 years of age, and those with lower educational levels. Regional disparities were observed, with individuals in the south exhibiting greater sensitivity to nighttime heat and those in the north to daytime heat.
CONCLUSIONS AND RELEVANCE
Results of this nationwide case-crossover study suggest that both nighttime and daytime heat are associated with increased risk of dementia-related deaths, with a greater burden associated with nighttime heat. These findings underscore the necessity of time-specific interventions to mitigate extreme heat risk.
Topics: Humans; China; Dementia; Female; Male; Aged; Aged, 80 and over; Hot Temperature; Cross-Over Studies; Risk Factors
PubMed: 38941091
DOI: 10.1001/jamanetworkopen.2024.19250 -
JAMA Health Forum Jun 2024Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of...
IMPORTANCE
Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of psychedelics, approximately one-twentieth to one-fifth of a full dose, over prolonged periods). Analyzing Google search queries can provide insights into public interest and help address this gap.
OBJECTIVE
To analyze trends in public interest in microdosing in the US through Google search queries and assess their association with cannabis and psychedelic legislative reforms.
DESIGN, SETTING, AND PARTICIPANTS
In this cross-sectional study, a dynamic event-time difference-in-difference time series analysis was used to assess the impact of cannabis and psychedelic legislation on microdosing search rates from January 1, 2010, to December 31, 2023. Google search rates mentioning "microdosing," "micro dosing," "microdose," or "micro dose" within the US and across US states were measured in aggregate.
EXPOSURE
Enactment of (1) local psychedelic decriminalization laws; (2) legalization of psychedelic-assisted therapy and statewide psychedelic decriminalization; (3) statewide medical cannabis use laws; (4) statewide recreational cannabis use laws; and (5) all cannabis and psychedelic use restricted.
MAIN OUTCOME AND MEASURES
Microdosing searches per 10 million Google queries were measured, examining annual and monthly changes in search rates across the US, including frequency and nature of related searches.
RESULTS
Searches for microdosing in the US remained stable until 2014, then increased annually thereafter, with a cumulative increase by a factor of 13.4 from 2015 to 2023 (7.9 per 10 million to 105.6 per 10 million searches, respectively). In 2023, there were 3.0 million microdosing searches in the US. Analysis at the state level revealed that local psychedelic decriminalization laws were associated with an increase in search rates by 22.4 per 10 million (95% CI, 7.5-37.2), statewide psychedelic therapeutic legalization and decriminalization were associated with an increase in search rates by 28.9 per 10 million (95% CI, 16.5-41.2), statewide recreational cannabis laws were associated with an increase in search rates by 40.9 per 10 million (95% CI, 28.6-53.3), and statewide medical cannabis laws were associated with an increase in search rates by 11.5 per 10 million (95% CI, 6.0-16.9). From August through December 2023, 27.0% of the variation in monthly microdosing search rates between states was explained by differences in cannabis and psychedelics legal status.
CONCLUSION AND RELEVANCE
This cross-sectional study found that state-led legislative reforms on cannabis and psychedelics were associated with increased public interest in microdosing psychedelics.
Topics: Hallucinogens; Humans; United States; Cross-Sectional Studies; Cannabis; Legislation, Drug
PubMed: 38941086
DOI: 10.1001/jamahealthforum.2024.1653 -
Health & Justice Jun 2024The aim of our study was to evaluate the post-release outcomes of incarcerated individuals with opioid use disorder (OUD) treated with extended-release buprenorphine...
BACKGROUND
The aim of our study was to evaluate the post-release outcomes of incarcerated individuals with opioid use disorder (OUD) treated with extended-release buprenorphine (XRB) in a rural county jail. Administrative data were collected from a pilot program within a jail in Maine that introduced XRB treatment in 2022 and a comparable jail utilizing sublingual buprenorphine (SLB) during the same period to compare post-release outcomes. Log-binomial regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) for jail use of XRB vs. SLB on post-release community buprenorphine continuation.
RESULTS
From September 2022 to September 2023, 70 individuals who received XRB were released from the pilot jail and 130 individuals who received SLB were released from the comparison jail. After adjusting for age, sex, and buprenorphine use at entry to jail, individuals released from the pilot jail were almost 3 times (adjusted RR = 2.67, 95% CI 1.84, 3.88) as likely to continue community buprenorphine treatment post-release relative to the comparison jail. In addition, utilization of XRB allowed for expanded access to OUD treatment, was well tolerated, and reduced medication diversion.
CONCLUSIONS
In this pilot program in Maine, XRB treatment during incarceration was associated with higher post-release community buprenorphine continuation when compared to individuals treated with SLB. These findings provide strong evidence for the superiority of XRB vs. SLB for the treatment of OUD in jail settings.
PubMed: 38940853
DOI: 10.1186/s40352-024-00281-w -
Alternative Therapies in Health and... Jun 2024Medicine logistics, particularly cryogenic storage, maintains pharmaceutical efficacy and safety. Ensuring seamless transportation and storage prevents spoilage,...
BACKGROUND
Medicine logistics, particularly cryogenic storage, maintains pharmaceutical efficacy and safety. Ensuring seamless transportation and storage prevents spoilage, degradation, or contamination, safeguarding patient health.
OBJECTIVE
This study aimed to analyze the relationships among the components of the medication cold chain logistics system using grey relational analysis (GRA). Additionally, we utilized GRA to construct an adjacency matrix, facilitating a comprehensive understanding of the interdependencies within the system.
METHODS
Data from pertinent indices spanning 2021 and 2022 were utilized to conduct a quantitative analysis using GRA. This analysis aimed to identify the most influential elements affecting the growth of pharmaceutical cold chain logistics in a specific location. The negative aspects of the medication cold chain logistics system in particular areas were examined by assessing the grey relationship grades between various components and the medicine cold chain logistics system in those regions.
RESULTS
The analysis revealed significant insights into the correlated risk factors impacting medicine logistics operations. Through an examination of the financial status and operational processes of medicine logistics assets, four categories of risks were identified, encompassing transportation, storage, distribution, and quality management. These categories were established by analyzing the most significant risk factors across these operational domains. Additionally, GRA was employed to assess the factors influencing medicine logistics. The study found a strong relationship between key parameters, such as transportation risk and site facilities and equipment, and the growth of the pharmaceutical logistics sector. Operation risk emerged as the least influential factor, while site facilities and equipment, transportation risk, and operation risk demonstrated substantial influence on the region's medical logistics sector growth.
CONCLUSION
This study provides important recommendations to improve medicine logistics, aiming to mitigate adverse effects and elevate inventory management. Implementation can enhance efficiency and safety in the medicine supply chain, benefiting patient care and public health.
PubMed: 38940801
DOI: No ID Found -
Alternative Therapies in Health and... Jun 2024Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone...
Study on the Mechanism of Xianling Gubao Capsule Regulating Runt-Related Transcription Factor 2 (RUNX2) and Promoting Osteoblast Differentiation by N6-Methyladenosine (m6A) Methyltransferase-Like 3 (METTL3).
BACKGROUND
Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and a higher risk of fractures. It is a significant public health concern, particularly among postmenopausal women and older adults. The imbalance between bone formation and resorption is the fundamental cause of OP. Current clinical drugs for OP have limited efficacy and can cause side effects. Therefore, there is a need to explore alternative treatments and investigate their mechanisms to improve OP management. The Xianling Gubao capsule, a traditional Chinese medicine, is commonly used to treat OP by tonifying the kidney. However, the specific mechanism of action of the Xianling Gubao capsule in improving OP remains unclear, necessitating further research in this area.
METHODS
The N6-methyladenosine (m6A) content was evaluated by dot blot and m6A ribonucleic acid (RNA) methylation assay kit. The contents of methyltransferase-like 3 (METTL3), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and bone gamma-carboxyglutamate protein (BGLAP) were appraised by quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) and western blot. The bilateral ovariectomy (OVX) method was used to establish an animal model of OP. OP bone marrow mesenchymal stem cells (OP-BMSCs) were extracted from mice in the OVX group by the whole bone marrow method. METTL3 overexpression and control vectors were transfected to OP-BMSCs using X-tremeGENE HP DNA Transfection Reagent. The ALP activity in OP-BMSCs was assessed by ALP staining. The calcium nodules in OP-BMSCs were detected by Alizarin Red S (ARS) assay. The Xianling Gubao capsule solution was employed to gavage mice, and the drug-containing serum was used to treat OP-BMSCs. Dot blot allows for the assessment of relative levels of m6A modification. The m6A RNA methylation assay kit is a specialized kit designed to quantitatively measure m6A levels in RNA samples. qRT-PCR allows for the measurement of mRNA levels of target genes. Western blot is used to detect and quantify specific proteins in a sample, and provides information about protein expression levels. OVX mimics the hormonal changes occurring in postmenopausal women and leads to bone loss and osteoporotic conditions in animals. This model allows for the investigation of the effects of the Xianling Gubao capsule on OP in a controlled experimental setting.
RESULTS
The m6A modification and METTL3, RUNX2, ALP, and BGLAP levels were reduced in bone samples of patients with OP and OVX mice compared with the corresponding control groups. Upregulated METTL3 enhanced the osteogenic ability of OP-BMSCs. METTL3 overexpression obviously increased m6A modification and METTL3, RUNX2, ALP, and BGLAP levels in OP-BMSCs. Xianling Gubao capsule treatment could weaken the impact of OP in mice by regulating the m6A modification and METTL3, RUNX2, ALP, and BGLAP levels. Serum containing Xianling Gubao capsule could enhance the osteogenic capability of OP-BMSCs and boost METTL3, RUNX2, ALP, and BGLAP levels. Treatment with the Xianling Gubao capsule shows promising effects in attenuating the impact of OP. The capsule is found to regulate m6A modification and increase the levels of METTL3, RUNX2, ALP, and BGLAP in OP-BMSCs. This indicates that the Xianling Gubao capsule may rescue the diminished osteogenic capability of OP-BMSCs by modulating METTL3. These findings suggest that the Xianling Gubao capsule has the potential to be an effective drug for the treatment of OP.
CONCLUSION
Taken together, the m6A modification and contents of osteogenic-related factors were reduced in OP. Upregulated METTL3 improved the osteogenic ability, m6A modification, and osteogenic-related factor abundances in OP-BMSCs. Xianling Gubao capsule rescued the diminished osteogenic capability of OP-BMSCs by modulating METTL3 and might serve as an effective drug for OP. The Xianling Gubao capsule, as a traditional Chinese medicine, could potentially complement existing therapeutic approaches for OP. By targeting the m6A modification pathway and promoting osteogenic differentiation, the capsule may help to expedite bone formation and repair, which are critical for managing OP and reducing the risk of fractures.
PubMed: 38940781
DOI: No ID Found