Recently, the use of traditional Chinese medicine (TCM) has become more generally accepted, including by the Food and Drug Administration. To expand the use of TCM worldwide, it is important to study the molecular mechanisms by which TCM and its active ingredients produce effects. Gastrodin is an active ingredient from Gastrodia elata Blume. It is reported that gastrodin has neuroprotective function in Parkinson’s disease. But its mechanisms of neuroprotection remain not clear in PD. Here, we build two C. elegans PD model using 6-OHDA and transgenic animal to observe the changes of PD worms treated with or without gastrodin to confirm the function of gastrodin, then utilize mutant worms to investigate DAF-2/DAF-16 signaling pathway, and finally verify the mechanism of gastrodin in PD. Gastrodin attenuates the accumulation of α-synuclein and the injury of dopaminergic neurons, improves chemotaxis behavior in Parkinson’s disease models, then recovers chemotaxis behavior by insulin-like pathway. DAF-2/DAF-16 is required for neuroprotective effect of dopamine neuron in PD. Our study demonstrated that gastrodin rescued dopaminergic neurons and reduced accumulation of α-synuclein protein, and the activity of gastrodin against Parkinson’s disease depended on the insulin-like DAF-2/DAF-16 signaling pathway. Our findings revealed that this insulin-like pathway mediates neuroprotection of gastrodin in a Parkinson’s disease model.

Early, non-invasive identification can generally enhance the survival rate for asymptomatic pancreatic cancer (PC). This systematic review and meta-analysis is conducted to evaluate the precision of diagnosing PC using serum and duodenal fluid exosomes. Following the guidelines of PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses), searches were conducted in the PubMed, Embase, Cochrane Library, and Web of Science databases in April 2024. A study was considered appropriate if it provided diagnostic precision and accuracy for patients with pancreatic cancer. The combined diagnostic impact was assessed by calculating the area beneath the aggregated SROC curve, and the quality of the studies included was evaluated using the QUADAS-2 checklist. All statistical evaluations and graphical representations utilized STATA 14.0. Employing the terms “exosomes” and “pancreatic cancer” along with the search methodology, research was conducted across PubMed, Web of Science, Cochrane, and Embase databases. A total of 1202 studies were extracted from the databases, out of which nine were ultimately selected based on specific inclusion and exclusion standards. Across eight studies, exosomes were isolated from serum, while in a different one, they were taken from duodenal fluid. This document conducts subgroup analyses focusing on various types of exosome biomarkers, their origins, isolation techniques, and methods for analyzing biomarkers. Within the subset of exosome biomarker types, the group with exosomal cell surface proteoglycan exhibited the greatest combined sensitivity (0.96 (95% CI = 0.81–0.99) and specificity (0.90 (95% CI = 0.83–0.95)). Additionally, the set of exosomal cell surface proteoglycans showed the highest aggregated diagnostic ratio (215.92), combined positive likelihood ratio (9.96), area under the curve (0.93), and kombiniertes negative Likelihood-Ratio (0.05). The combined sensitivity of serum-derived exosomes stood at (0.86 (95% CI = 0.77–0.92)), the collective specificity at (0.83 (95% CI = 0.77–0.89)), the aggregate positive likelihood ratio at (5.22), the combined diagnostic ratio at (31.48), the overall area beneath the curve at (0.91), and the combined negative likelihood ratio at (0.17). Within the subgroup examination of exosome isolation techniques, ultracentrifugation emerged as the most sensitive method (0.90 (95% CI = 0.74–0.97)), the most specific method (0.89 (95% CI = 0.83–0.93)), the top positive likelihood ratio (8.35), the highest diagnostic ratio (76.48), the largest combined curve area (0.92), and the smallest negative likelihood ratio (0.11) in the aggregated data. Within the subset of biomarker analysis methods, the aggregate sensitivity via qRT-PCR was (0.84 (95% CI = 0.74–0.90)), the collective specificity (0.78 (95% CI = 0.64–0.87)), the aggregate diagnostic ratio (18.11), the aggregate area under the curve (0.88), the aggregate positive likelihood ratio (3.77), and the combined negative likelihood ratio (0.21). Overall, exosomes are still valuable in the diagnosis of pancreatic cancer. In subgroup analyses, the proteoglycan found on exosomal cell surfaces is highly valuable for diagnosing pancreatic cancer. The more frequent separation method used in the nine included studies was ultracentrifugation, and it did demonstrate good data. Nonetheless, to verify their practicality and usefulness in clinical environments, a significant amount of clinical trials are still necessary.

A significant proportion of children with Autism Spectrum Disorder (ASD) present with immune imbalances. In this study, we sought to alleviate the core symptoms of autism by addressing immune dysregulation, especially T-cell subpopulation imbalances, in BTBR mice through low-dose IL-2 (LdIL-2) treatment. LdIL-2 (30,000 IU) was administered subcutaneously, and changes in autistic behaviors were observed before and after treatment. Behavioral assessments included the three-chamber test, self-grooming test, sniffing test, marble burying test, open field test and Y-maze test. We also examined alterations in peripheral Th/Treg ratios, cytokine levels, and M1/M2 microglia ratios in the central nervous system via flow cytometry. Neuroinflammatory proteins in cerebrospinal fluid were assessed using proteomic analysis. Furthermore, CD25⁺ Treg cells were depleted using PC61, followed by LdIL-2 intervention, to determine the role of Treg cells in LdIL-2-treated BTBR mice. Our results demonstrated that LdIL-2 significantly ameliorated core symptoms of autism in BTBR mice. LdIL-2 treatment increased Treg cell levels, restored Th17/Treg and Tfh/Treg balance, and corrected immune dysregulation. Central nervous system inflammation was reduced in mice. However, the behavioral improvements were diminished when Treg cells were depleted by PC61. This study represents the first attempt to treat ASD using LdIL-2. The treatment proved safe and effective in improving both core symptoms and immune imbalances in autism. Symptom improvement was linked to increased Treg cell levels in peripheral blood. LdIL-2 shows potential as a novel therapy for addressing core symptoms of autism.

Background: Following acute infection, Herpes Simplex virus-1 (HSV-1) establishes lifelong latency and recurrent reactivation in the sensory neurons of trigeminal ganglia (TG). Infected tree shrew differs from mouse and show characteristics similar to human infection. A detailed transcriptomic analysis of the tree shrew model could provide mechanistic insights into HSV-1 infection in humans. Methods: We sequenced the transcriptome of infected TGs from tree shrews and mice, and 4 human donors, then examined viral genes expression up to 58 days in infected TGs from mouse and tree shrew, and compare the latency data with that in human TGs. Results: Here, we found that all HSV-1 genes could be detected in mouse TGs during acute infection, but 22 viral genes necessary for viral transcription, replication and viral maturation were not expressed in tree shrew TGs during this stage. Importantly, during latency, we found that LAT could be detected both in mouse and tree shrew, but the latter also has an ICP0 transcript signal absent in mouse but present in human samples. Importantly, we observed that infected human and tree shrew TGs have a more similar LAT region transcription peak. More importantly, we observed that HSV-1 spontaneously reactivates from latently infected tree shrews with relatively high efficiency. Conclusions: These results represent the first longitudinal transcriptomic characterization of HSV-1 infection in during acute, latency and recurrent phases, and revealed that tree shrew infection has important similar features with human infection.