Intranasal bacteria transport obesity drugs to the brain
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The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. The integration of novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs, effectively addressing the obstacles associated with their character, such as the rapid clearance and degradation, necessitating subcutaneous injection leading to increasing patient discomfort, and ultimately advancing translational research efforts. Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions, such as diabetes mellitus, weight loss, oncology, and rare diseases, and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines. This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics, delivery platforms, and vaccines. It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs, as well as the recent advancements in screening, design, and delivery technologies. The accelerated advancement in the development of novel peptide-based therapeutics, including peptide-drug complexes, new peptide-based vaccines, and innovative peptide-based diagnostic reagents, has the potential to promote the era of precise customization of disease therapeutic schedule.
Role of pancreatic lipase inhibition in obesity treatment: mechanisms and challenges towards current insights and future directions
The worldwide health emergency of obesity is closely connected to how dietary fats are metabolized, whereas the process is significantly influenced by pancreatic lipase (PL), an enzyme critical for lipid hydrolysis into fatty acids. This narrative review employs a methodological approach utilizing literature searches of PubMed data up to March 2024. The search term criteria encompasses keywords related to the role, mechanism, challenges, and current and future treatments of pancreatic lipase in obesity with an overall references is 106. This paper offers a comprehensive explanation of the role of PL, underlining its significance in the digestive process and lipid imbalances that contribute to obesity and by extension, its impact on obesity development and progression. Additionally, it delves into the dual functionality of the pancreas, emphasizing its impact on metabolism and energy utilization which, when dysregulated, promotes obesity. A focal point of this review is the investigation into the efficacy, challenges, and adverse effects of current pancreatic lipase inhibitors, with orlistat being highlighted as a primary current drug delivery. By discussing advanced obesity treatments, including the exploration of novel anti-obesity medications that target specific biological pathways, this review underscores the complexity of obesity treatment and the necessity for a multifaceted approach. In conclusion, this paper emphasizing the importance of understanding the role of enzymes like pancreatic lipase mechanistic and adopting a multidisciplinary approach to treatment and side effects of current obesity drugs and explore new emerging therapeutic strategies for more effective obesity management.
SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving mutations in the Spike protein to evade humoral immunity. Respiratory tract antiviral IgA antibodies are superior to circulating IgG antibodies in preventing SARS-CoV-2 infection. However, the role of innate immune signals required for the induction of mucosal IgA against SARS-CoV-2 infection is unknown. Here we show that hamsters recovered from ancestral SARS-CoV-2 infection are cross-protected against heterologous SARS-CoV-2 alpha, gamma, delta, and omicron BA.1 variants. Intranasal vaccination with an inactivated whole virus vaccine completely protects hamsters against heterologous SARS-CoV-2 infection. In addition, we show that intranasal boost vaccination of mice recovered from SARS-CoV-2 infection with unadjuvanted Spike protein induces robust levels of respiratory anti-Spike IgA and protects the mice from a heterologous SARS-CoV-2 infection. Furthermore, our findings suggest that MyD88 and MAVS play a role in the induction of the memory IgA response following an intranasal booster with unadjuvanted Spike protein in mice recovered from the SARS-CoV-2 infection. These findings provide a useful basis for the development of cross-protective mucosal vaccines against heterologous SARS-CoV-2 infection.
Bacterial hitchhiking with drug-loaded nanoparticles as a drug delivery strategy for cancer immunotherapy
Select strains of bacteria show significant therapeutic promise in oncology, but there are major limitations for their clinical implementation, including their fast clearance from the circulation and dose-limiting toxicity. To address this challenge, we propose delivering bacteria alongside drug-loaded nanoparticles to reduce the premature clearance of bacteria from the circulation and improve their therapeutic efficacy. We evaluated the ability of the bacterium Magnetospirillum gryphiswaldense, an environmental isolate that holds promise as an anti-cancer immunotherapy, to carry drug-loaded nanoliposomes into melanoma tumors. Using the B16F10 melanoma mouse model, we demonstrated that when injected locally, the bacteria can significantly reduce tumor growth while inducing a strong immune response. Further, we showed that drug-loaded nanoliposomes can be conjugated to the surface of bacteria improving their tumoral delivery and yielding a stronger anticancer response when delivered systemically. These results suggest that bacterial hitchhiking is a promising systemic drug delivery strategy for cancer immunotherapy.
Pediatric obesity and the risk of multiple sclerosis: a nationwide prospective cohort study
Emerging evidence implies a link between high pediatric body mass index (BMI) and an increased risk of multiple sclerosis (MS). However, previous research suggests this association is only present for adolescent obesity and not childhood obesity. The present study aimed to assess the association between pediatric obesity and risk of developing MS, and to investigate if degree of obesity and age at obesity treatment initiation affects the risk. In a subgroup, response to obesity treatment on MS risk was assessed.
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