Exosome-Based Macromolecular neurotherapeutic drug delivery approaches in overcoming the Blood-Brain barrier for treating brain disorders.

Delivering drugs to the brain is a complex challenge in medical research, particularly for disorders like Alzheimer's and Parkinson's. The blood-brain barrier restricts the entry of many therapeutic molecules, hindering their effectiveness. Nanoparticles, a potential solution, face issues like toxicity and limited approvals. A new avenue explores the use of small extracellular vesicles (sEVs), i.e., exosomes, as natural carriers for drug delivery. sEVs, tiny structures below 150 nm, show promise due to their minimal immune response and ability to precisely deliver drugs. This review focuses on the potential of sEVs-based drug delivery systems for treating neurological disorders, brain cancers, and other brain-related issues. Notably, bioengineered sEVs-carrying therapeutic compounds exhibit promise in early studies. The unique features of sEVs, such as their small size and natural properties, position them as candidates to overcome challenges in drug delivery to the brain. Ongoing clinical trials and research into sEVs behavior within the body further highlight their potential for revolutionizing drug delivery and addressing complex brain conditions.

Biomedical applications of nanomaterials in the advancement of nucleic acid therapy: Mechanistic challenges, delivery strategies, and therapeutic applications.

In the past few decades, substantial advancement has been made in nucleic acid (NA)-based therapies. Promising treatments include mRNA, siRNA, miRNA, and anti-sense DNA for treating various clinical disorders by modifying the expression of DNA or RNA. However, their effectiveness is limited due to their concentrated negative charge, instability, large size, and host barriers, which make widespread application difficult. The effective delivery of these medicines requires safe vectors that are efficient & selective while having non-pathogenic qualities; thus, nanomaterials have become an attractive option with promising possibilities despite some potential setbacks. Nanomaterials possess ideal characteristics, allowing them to be tuned into functional bio-entity capable of targeted delivery. In this review, current breakthroughs in the non-viral strategy of delivering NAs are discussed with the goal of overcoming challenges that would otherwise be experienced by therapeutics. It offers insight into a wide variety of existing NA-based therapeutic modalities and techniques. In addition to this, it provides a rationale for the use of non-viral vectors and a variety of nanomaterials to accomplish efficient gene therapy. Further, it discusses the potential for biomedical application of nanomaterials-based gene therapy in various conditions, such as cancer therapy, tissue engineering, neurological disorders, and infections.

Exploring the Potential Effect of Methanolic Extract of Salvia officinalis Against UV Exposed Skin Aging: In vivo and In vitro Model.

BACKGROUND: The medicinal plants have enormous pharmacological properties with fewer side effects. Today, there is an increasing demand of medicinal plants as an anti-aging and anti-wrinkle agent. ; Objective: The aim of this study is to evaluate the antioxidant, anti-aging and anti-wrinkle potential of Salvia officinalis. ; Materials and Methods: Salvia officinalis (Lamiaceae) is folk medicine of Asia and Latin America. Powdered crude drug 100 g was successively extracted in a soxhlet apparatus with petroleum ether (60-80ºC), chloroform and methanol. After successive solvents, extraction methanolic extract was used for testing of antioxidant potential using DPPH assay. Further, the antiaging potential of the extract was investigated by the inhibitory effect of various enzymatic estimations i.e. Col-I, Ela- I and Hya-I inhibitory assays on early aging human skin fibroblasts. The antiwrinkle potential of plant Salvia officinalis was done by using a UV light-induced photoaging model. ; Results: Phytochemical analysis showed the presence of glycosides, alkaloids flavonoids, and triterpenoids, saponins and Phenolic Compounds at high level. The extract showed inhibitory concentration (IC50: 24.65) and ascorbic acid. The standard antioxidant showed inhibitory concentration (IC50: 20.10). In enzymatic estimations assay, the Col-I, Ela-I and Hya-I of extract were assessed showing inhibitory concentration as Col-I (IC50:21.36), Ela-I (IC50:35.05) and Hya-I (IC50:23.44), respectively. Thus, MeOH extract of Salvia officinalis can inhibit 50% of the activity of aging-related enzymes Col-I, Ela-I and Hya-I. The wrinkle score of negative control i.e. UV treated group was 2.83 ± 0.408, and MeOH extract of Salvia officinalis treated group is 1.83 ± 0.753. ; Conclusion: This study concluded that MeOH extract of Salvia officinalis has confirmed the high antioxidant potential and in vitro and in vivo inhibitory potential of antiaging enzymes assessed, thus they could be used for further development of cosmetic products and nutraceuticals.

Barriers to antiretroviral therapy initiation for HIV-positive children aged 2-18 months in Swaziland.

Although early antiretroviral therapy (ART) reduces HIV-related mortality in children by up to 75%, almost half of HIV-positive children younger than 1 year old in Swaziland do not initiate ART. This study was conducted to identify barriers to early ART initiation among HIV-positive infants. This was a case-control study among HIV-positive infants, aged 2 to 18 months, who either did not initiate ART (cases), or initiated ART (controls), during 18 months after testing. Multivariable logistic regression showed that infants who visited the clinic every month, or every 2 months, were 5.78 and 6.20 times more likely to initiate ART than those who visited less often (OR 5.78, 95% CI 1.82-18.33 and OR 6.20, 95% CI 1.30-29.60 respectively). Children who lived ≤30 and 31-60 minutes from the nearest clinic were 84% and 79% less likely respectively to initiate ART (OR 0.16, 95% CI 0.03-0.78 and OR 0.21, 95% CI 0.04-0.98) compared with those who lived more than 60 minutes away. Children who received immunisation after 6 months were 22.59 times more likely to initiate ART (OR 22.59, 95% CI 7.00-21.72) than those who did not. Infants of caregivers who had excellent or good relationships with their healthcare provider were 4.32 times more likely to initiate ART (OR 4.32, 95% CI 1.01-18.59) than those of caregivers who had average or poor relationships with healthcare providers. The significant predictors of ART initiation identified in this study should be regarded as priority areas for intervention among HIV-positive women in Swaziland.

Disparities in the prevalence of comorbidities among US adults by state Medicaid expansion status.

INTRODUCTION: About 92% of US older adults have at least one chronic disease or medical condition and 77% have at least two. Low-income and uninsured adults in particular experience a higher burden of comorbidities, and the Medicaid expansion provision of the Affordable Care Act was designed to improve access to healthcare in this population group. However, a significant number of US states have declined expansion. The purpose of this study is to determine the distribution of low-income and uninsured adults in expanded versus non-expanded states, and evaluate the prevalence of comorbidities in both groups. METHODS: Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) dataset was analyzed, and Medicaid expansion status was assessed from the Center for Medicare and Medicaid Services report on State Medicaid and CHIP Income Eligibility Standards. Next, age adjusted mean number of comorbidities between expanded and non-expanded states was compared, with adjustment for socio-demographic differences. RESULTS: Expanded states had a higher proportion of adults with income of at least $50,000 per year (39.6% vs. 35.5%, p<0.01) and a lower proportion of individuals with no health insurance coverage (15.2% vs. 20.3%, p<0.01) compared with non-expanded states. Among the uninsured, there was a higher proportion of obese (31.6% vs. 26.9%, p<001), and higher average number of comorbidities (1.62 vs. 1.52, p<0.01) in non-expanded states compared to expanded states. Overall, the prevalence of comorbidities was higher among BRFSS participants in states that did not expand Medicaid compared with those in expanded states. CONCLUSION: States without Medicaid expansion have a greater proportion of poor, uninsured adults with more chronic diseases and conditions.

Temporal Variation and Association of Aflatoxin B1 Albumin-Adduct Levels with Socio-Economic and Food Consumption Factors in HIV Positive Adults.

The association between aflatoxin exposure and alteration in immune responses observed in humans suggest that aflatoxin could suppress the immune system and work synergistically with HIV to increase disease severity and progression to AIDS. No longitudinal study has been conducted to assess exposure to aflatoxin (AF) among HIV positive individuals. We examined temporal variation in AFB1 albumin adducts (AF-ALB) in HIV positive Ghanaians, and assessed the association with socioeconomic and food consumption factors. We collected socioeconomic and food consumption data for 307 HIV positive antiretroviral naive adults and examined AF-ALB levels at recruitment (baseline) and at six (follow-up 1) and 12 (follow-up 2) months post-recruitment, by age, gender, socioeconomic status (SES) and food consumption patterns. Generalized linear models were used to examine the influence of socioeconomic and food consumption factors on changes in AF-ALB levels over the study period, adjusting for other covariates. AF-ALB levels (pg/mg albumin) were lower at baseline (mean AF-ALB: 14.9, SD: 15.9), higher at six months (mean AF-ALB: 23.3, SD: 26.6), and lower at 12 months (mean AF-ALB: 15.3, SD: 15.4). Participants with the lowest SES had the highest AF-ALB levels at baseline and follow up-2 compared with those with higher SES. Participants who bought less than 20% of their food and who stored maize for less than two months had lower AF-ALB levels. In the adjusted models, there was a statistically significant association between follow up time and season (dry or rainy season) on AF-ALB levels over time (p = 0.04). Asymptomatic HIV-positive Ghanaians had high plasma AF-ALB levels that varied according to season, socioeconomic status, and food consumption patterns. Steps need to be taken to ensure the safety and security of the food supply for the population, but in particular for the most vulnerable groups such as HIV positive people.