Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

Mitochondria: fundamental characteristics, challenges, and impact on aging.

As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism's lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.

Exercise for myocardial ischemia-reperfusion injury: A systematic review and meta-analysis based on preclinical studies.

The main pathological manifestation of coronary artery disease is myocardial injury caused by ischemia-reperfusion (IR) injury. Regular exercise reduces the risk of death during myocardial IR injury. The aim of this study was to describe the effects of various types of exercise on myocardial IR injury. Four electronic databases PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched from inception until February 2022, to identify studies relevant to the current review, using the method of combining subject and free words. Finally, 16 articles were included in the meta-analysis. Results showed that exercise training decreases the Myocardial infarct size compared to the control group (SMD = -2.6, 95 % CI [-3.53 to -1.67], P < 0.01); increasing the coronary blood flow (MD = 2.93, 95 % CI [2.41 to 3.44], P < 0.01), left ventricular developed pressure (SMD = 2.28, 95 % CI [0.12 to 4.43], P < 0.05), cardiac output (SMD = 1.22, 95 % CI [0.61 to 1.83], P < 0.01) compared to the control group. According to the descriptive analysis results also showed that exercise training increases the left ventricular ejection fraction, superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase, copper-zinc superoxide dismutase, glutathione peroxidase, and decrease the creatine kinase, creatine kinase-MB, lactate dehydrogenase, Malondialdehyde, cardiac troponins T. Exercise can improve myocardial function after myocardial IR injury; however, further research is needed in combination with specific issues such as exercise mode, intensity, duration, and model issues.

Extended characterization of IL-33/ST2 as a predictor for wound age determination in skin wound tissue samples of humans and mice.

Interleukin (IL)-33, an important inflammatory cytokine, is highly expressed in skin wound tissue and serum of humans and mice, and plays an essential role in the process of skin wound healing (SWH) dependent on the IL-33/suppression of tumorigenicity 2 (ST2) pathway. However, whether IL-33 and ST2 themselves, as well as their interaction, can be applied for skin wound age determination in forensic practice remains incompletely characterized. Human skin samples with injured intervals of a few minutes to 24 hours (hs) and mouse skin samples with injured intervals of 1 h to 14 days (ds) were collected. Herein, the results demonstrated that IL-33 and ST2 are increased in the human skin wounds, and that in mice skin wounds, there is an increase over time, with IL-33 expression peaking at 24 hs and 10 ds, and ST2 expression peaking at 12 hs and 7 ds. Notably, the relative quantity of IL-33 and ST2 proteins < 0.35 suggested a wound age of 3 hs; their relative quantity > 1.0 suggested a wound age of 24 hs post-mouse skin wounds. In addition, immunofluorescent staining results showed that IL-33 and ST2 were consistently expressed in the cytoplasm of F4/80-positive macrophages and CD31-positive vascular endothelial cells with or without skin wounds, whereas nuclear localization of IL-33 was absent in α-SMA-positive myofibroblasts with skin wounds. Interestingly, IL-33 administration facilitated the wound area closure by increasing the proliferation of cytokeratin (K) 14 -positive keratinocytes and vimentin-positive fibroblasts. In contrast, treating with its antagonist (i.e., anti-IL-33) or receptor antagonist (e.g., anti-ST2) exacerbated the aforementioned pathological changes. Moreover, treatment with IL-33 combined with anti-IL-33 or anti-ST2 reversed the effect of IL-33 on facilitating skin wound closure, suggesting that IL-33 administration facilitated skin wound closure through the IL-33/ST2 signaling pathway. Collectively, these findings indicate that the detection of IL-33/ST2 might be a reliable biomarker for the determination of skin wound age in forensic practice.

Electroacupuncture Reduces Cerebral Hemorrhage Injury in Rats by Improving Cerebral Iron Metabolism.

Objective: To study the effects of electroacupuncture at Baihui and Dazhui points on the expression of hepcidin (Hepc), transferrin (Tf), transferrin receptor (TfR), and ferritin (Ft) in rats with cerebral hemorrhage to provide a theoretical basis for the treatment of cerebral hemorrhage with acupuncture. Method: The model of cerebral hemorrhage in rats was established by autologous blood injection method and treated by electroacupuncture (EA) at the acupoints of Baihui and Dazhui. Hepc siRNA was injected into the lateral ventricle 30 min before model preparation to produce the cerebral hemorrhage model. The modified neurological severity score (mNSS) was used to assess the neurological function, and the total iron content in brain tissue was determined using atomic absorption spectrometry; the expression of Hepc, Ft, Tf, and TfR in perihematoma tissue was detected using immunohistochemistry; the interference efficiency of Hepc siRNA was detected using western blot and reverse transcription polymerase chain reaction (RT-PCR). Results: The degree of neurological deficit showed a downward trend at 3 days, 7 days, and 14 days, and electroacupuncture significantly reduced the neurological deficit score at each time point (P < 0.01). Regarding total iron content in brain tissue, on the 3rd day, the 7th day, and the 14th day, the iron content of the hematoma tissue after intracerebral hemorrhage was reduced by electroacupuncture (P < 0.01). Regarding immunohistochemical results. Hepc, Ft, Tf, and TfR protein expressions on day 14 were significantly higher after cerebral hemorrhage (P < 0.01). After electroacupuncture, the expression of Hepc, Ft, Tf, and TfR protein was significantly reduced (P < 0.01). Western blot and RT-PCR revealed that the interference efficiency of Hepc siRNA was statistically significant (P < 0.01). Conclusion: Electroacupuncture can reduce neurological severity scores in rats with cerebral hemorrhage and may exert cerebral protective effects by reducing Hepc protein and gene expression; lowering Ft, Tf, and TfR protein expression; and promoting iron metabolism in the brain of rats with cerebral hemorrhage.

Crosstalk between the Gut and Brain in Ischemic Stroke: Mechanistic Insights and Therapeutic Options.

There has been a significant amount of interest in the past two decades in the study of the evolution of the gut microbiota, its internal and external impacts on the gut, and risk factors for cerebrovascular disorders such as cerebral ischemic stroke. The network of bidirectional communication between gut microorganisms and their host is known as the microbiota-gut-brain axis (MGBA). There is mounting evidence that maintaining gut microbiota homeostasis can frequently enhance the effectiveness of ischemic stroke treatment by modulating immune, metabolic, and inflammatory responses through MGBA. To effectively monitor and cure ischemic stroke, restoring a healthy microbial ecology in the gut may be a critical therapeutic focus. This review highlights mechanistic insights on the MGBA in disease pathophysiology. This review summarizes the role of MGBA signaling in the development of stroke risk factors such as aging, hypertension, obesity, diabetes, and atherosclerosis, as well as changes in the microbiota in experimental or clinical populations. In addition, this review also examines dietary changes, the administration of probiotics and prebiotics, and fecal microbiota transplantation as treatment options for ischemic stroke as potential health benefits. It will become more apparent how the MGBA affects human health and disease with continuing advancements in this emerging field of biomedical sciences.

Exercise Preconditioning Regulates the Toll-Like Receptor 4/Nuclear Factor-κB Signaling Pathway and Reduces Cerebral Ischemia/Reperfusion Inflammatory Injury: A Study in Rats.

OBJECTIVE: To explore the influence of exercise preconditioning (EP) on the activity of the toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway in a rat model of cerebral ischemia/reperfusion (I/R) inflammatory injury. METHODS: Ischemia was induced in rats using transient middle cerebral artery occlusion (tMCAO) after 3 weeks of EP. Fifty-four rats were divided into sham, MCAO, and EP+MCAO groups. Following the induction of cerebral I/R injury, rats were scored for neurological deficits. Various techniques were used to evaluate ischemic infarct volume and explore pathological changes in tissue morphology after cerebral I/R injury, wherein the levels of TLR4 and NF-κB were analyzed. In addition, enzyme-linked immunosorbent assays were used to detect the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in peripheral serum. RESULTS: Twenty-four hours after cerebral I/R injury, the neurological deficit scores decreased and ischemic cortical damage alleviated in EP+MCAO group; the number of TLR4- and NF-κB-positive cells, the expression of TLR4 and NF-κB in the ischemic side, and the concentrations of TNF-α and IL-1ß in the peripheral serum were lower in EP+MCAO group than those in the MCAO group (P <.05). CONCLUSIONS: The present study indicates that EP can improve cerebral I/R-induced neurological deficits in rats, reduce infarct volume, mitigate pathological damage in the ischemic cortex, and exert neuroprotective effects. The mechanism underlying these effects might involve the regulation of the TLR4/NF-κB signaling pathway and the inhibition of central and peripheral inflammatory cascades during cerebral I/R injury.

The effects of different tensile parameters for the neurodynamic mobilization technique on tricipital muscle wet weight and MuRf-1 expression in rabbits with sciatic nerve injury.

BACKGROUND: After peripheral nerve injury, muscles without innervation begin to undergo atrophy. Research has suggested that MuRf-1 may play a role in muscle atrophy. The neurodynamic mobilization technique (NMT) is a manual therapy method used to elongate a nerve along its long axis, resulting in improved blood flow to the nerve. However, the nerve can be damaged if elongated too much. The purpose of this study is to observe the effect of NMT on muscle wet weight and MuRf-1 expression in rabbits with sciatic nerve injury. METHODS: Six adult rabbits were measured to determine the relationship between the joint angle of the lower limb and percent of sciatic nerve elongation to define the tensile parameters of NMT; Thirty adult rabbits were randomly assigned into a sham, model, NMT-A, NMT-B, or NMT-C groups. Four weeks post-treatment, the wet mass of the tricipital muscles and MuRf-1 expression were observed. RESULTS: The wet mass of the tricipital muscles in the NMT-B group was significantly greater than the NMT-A, NMT-C, and model groups. In addition, MuRf-1 expression was significantly reduced in the NMT-B group compared with the NMT-A, NMT-C, and model groups. CONCLUSIONS: Elongating the nerve by NMT of 9% in rabbits decreased MuRf-1 expression and decelerated muscle atrophy in the subjects with sciatic nerve injury.

Exploring the role of traditional Chinese medicine rehabilitation in stroke based on microRNA-mediated pyroptosis: A review.

Stroke, also known as "cerebrovascular accident," is a disease caused by acute impairment of brain circulation, which has a high rate of disability and mortality. Ischemic stroke (IS) is the most common type of stroke and a major cause of death and disability worldwide. At present, there are still many limitations in the treatment of IS, so it may be urgent to explore more treatments for IS. In recent years, the clinical application of traditional Chinese medicine rehabilitation methods such as traditional Chinese medicine, acupuncture, massage, traditional exercises and modern rehabilitation technology has achieved good results in the treatment of IS. Concurrently, studies have identified microRNA (miRNA), which are intimately associated with traditional Chinese medicine rehabilitation, as regulators of pyroptosis through their influence on microglia activity, inflammatory response, oxidative stress, angiogenesis and other factors, but at present, the mechanism of this direction has not been systematically summarized. Consequently, this article delineates in detail the specific role of miRNA in IS and the related activation pathways of pyroptosis in IS. This article presents a detailed discussion of the role of microRNA-mediated pyroptosis in IS, with a particular focus on the signaling pathways involved. The aim is to provide new insights for the research of traditional Chinese medicine (TCM) rehabilitation in the prevention and treatment of IS. In addition, the article explores the potential of TCM rehabilitation in regulating miRNA-mediated pyroptosis to intervene in IS.

A promising new approach to cancer therapy: Manipulate ferroptosis by hijacking endogenous iron.

Ferroptosis, a form of regulated cell death characterized by iron-dependent phospholipid peroxidation, has emerged as a focal point in the field of cancer therapy. Compared with other cell death modes such as apoptosis and necrosis, ferroptosis exhibits many distinct characteristics in the molecular mechanisms and cell morphology, offering a promising avenue for combating cancers that are resistant to conventional therapeutic modalities. In light of the serious side effects associated with current Fenton-modulating ferroptosis therapies utilizing exogenous iron-based inorganic nanomaterials, hijacking endogenous iron could serve as an effective alternative strategy to trigger ferroptosis through targeting cellular iron regulatory mechanisms. A better understanding of the underlying iron regulatory mechanism in the process of ferroptosis has shed light on the current findings of endogenous ferroptosis-based nanomedicine strategies for cancer therapy. Here in this review article, we provide a comprehensive discussion on the regulatory network of iron metabolism and its pivotal role in ferroptosis, and present recent updates on the application of nanoparticles endowed with the ability to hijack endogenous iron for ferroptosis. We envision that the insights in the study may expedite the development and translation of endogenous ferroptosis-based nanomedicines for effective cancer treatment.

Exploring the rules of related parameters in acupuncture for post-stroke dysphagia based on data mining.

Background: Post-stroke dysphagia (PSD) affects the efficacy and safety of swallowing, causing serious complications. Acupuncture is a promising and cost-effective treatment for PSD; however, as the number of randomized controlled trials increases, scientific analysis of the parameters and acupoint prescription is required. Therefore, this study aimed to explore the effects of acupuncture on parameters related to post-stroke dysphagia (PSD). Methods: We searched the Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature, and Chongqing VIP Database for randomized controlled trials of acupuncture for PSD in the last 15 years and relevant parameters were analyzed using data mining techniques. Results: In total, 3,205 records were identified, of which 3,507 patients with PSD were included in 39 studies. The comprehensive analysis demonstrated that the closest parameter combinations of acupuncture on PSD were 0.25 mm × 40 mm needle size, 30 min retention time, five treatments per week, and a 4-week total course of treatment. Additionally, the gallbladder and nontraditional meridians, crossing points, and head and neck sites are the most commonly used acupoint parameters. The core acupoints identified were GB20, RN23, EX-HN14, Gongxue, MS6, SJ17, EX-HN12, EX-HN13, and the commonly used combination of EX-HN12, EX-HN13, GB20, and RN23. Conclusion: This study analyzed the patterns of PSD-related needling and acupoint parameters to provide evidence-based guidelines for clinical acupuncturists in treating PSD, potentially benefitting affected patients.

Effects of virtual reality-based rehabilitation on cognitive function and mood in multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a disabling neurological disease that causes cognitive impairment and mental problems that occur in all MS phenotypes but are most common in patients with secondary progressive MS. Various degrees of cognitive impairment and mental health concerns are common among patients with MS (PwMS). Virtual reality (VR)-based rehabilitation is an innovative approach aimed at enhancing cognitive function and mood in PwMS. This study aims to perform a meta-analysis to assess the effects of VR-based rehabilitation on cognitive function and mood in PwMS. METHODS: Using PubMed, Embase, the Cochrane Library, Web of Science, and the Physiotherapy Evidence Database (PEDro), a thorough database search was performed to identify randomized controlled trials (RCTs) examining the effects of VR on PwMS. Trials published until October 31, 2023, that satisfied our predetermined inclusion and exclusion criteria were included. Data were extracted, literature was examined, and the methodological quality of the included trials was assessed. StataSE version 16 was used for the meta-analysis. RESULTS: Our meta-analysis included 461 patients from 10 RCTs. PRIMARY OUTCOMES: The Montreal Cognitive Assessment (MoCA) (weighted mean difference [WMD]=1.93, 95 % confidence interval [CI]=0.51-3.36, P = 0.008, I² = 75.4 %) the Spatial Recall Test (SPART) (WMD=3.57, 95 % CI=1.65-5.50, P < 0.001, I² = 0 %), immediate recall (standard mean difference [SMD]=0.37, 95 % CI=0.10-0.64, P = 0.007, I² = 0 %) and delayed recall ([SMD]=0.30, 95 % CI=0.06-0.54, P = 0.013, I² = 35.4 %) showed improvements in comparison to the control group in terms of global cognitive function immediate recall, delayed recall, and visuospatial abilities. SECONDARY OUTCOMES: Compared to the control group, anxiety improved (standard mean difference [SMD]=0.36, 95 % CI=0.10-0.62, P = 0.007, I² = 43.1 %). However, there were no significant differences in processing speed, attention, working memory or depression. CONCLUSIONS: This systematic review provides valuable evidence for improving cognitive function and mood in PwMS through VR-based rehabilitation. In the future, VR-based rehabilitation may be a potential method to treat cognitive function and emotional symptoms of MS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO; identifier: CRD42023474467.

Prevalence, risk factors, and outcomes of dysphagia after stroke: a systematic review and meta-analysis.

Background: Dysphagia is a common complication after stroke, which not only brings adverse outcomes but also greatly affects the quality of life of patients. At present, there is no systematic review or meta-analysis to comprehensively evaluate the epidemiological characteristics of post-stroke dysphagia (PSD). A systematic review of the prevalence, risk factors, and prognosis of PSD is essential. Methods: Through 31 December 2022, a comprehensive literature search was performed for observational studies related to PSD. Five databases were retrieved. Random-effects models were used to estimate the pooled prevalence, odds ratio (OR), and 95% CIs. Results: A total of 34 studies were included, and the results showed that the overall prevalence of PSD was 46.6% (95% CI, 0.405-0.528). The prevalence of dysphagia in ischemic stroke and hemorrhagic stroke was 43.6% (95% CI 0.370-0.501) and 58.8% (95% CI 0.519-0.654), respectively. The prevalence of PSD in Africa was 49.4% (95% CI, 0.196-0.792), in Asia was 40.1% (95% CI, 0.348-0.454), in Europe was 45.8% (95% CI, 0.327-0.590), in North America was 44.3% (95% CI, 0.370-0.517), in South America was 57.5% (95% CI, 0.441-0.708), and in Oceania was 64.1% (95%CI, 0.558, 0.724). In risk factor analysis, hypertension, previous stroke, and atrial fibrillation were significantly associated with the occurrence of PSD, pooled OR = 1.179 [(95% CI, 1.002-1.386), p < 0.05], pooled OR = 1.514 [(95% CI, 1.204-1.905), p < 0.001], and pooled OR = 1.980 [(95% CI, 1.580-2.481), p < 0.001]. In outcome studies, the prevalence of aphasia and dysarthria in PSD was 35.6% (95% CI, 0.213-0.499) and 54.5% (95% CI, 0.293-0.798), respectively. The prevalence of respiratory tract infection was 27.1% (95%CI, -0.038-0.579), and the prevalence of pneumonitis was 32.1% (95% CI, 0.224-0.418). Persistence of dysphagia at discharge and at 1 month was 74.5% (95% CI, 0.621-0.869) and 50.9% (95% CI, 0.142-0.876), respectively. Mortality rates for PSD patients during admission and discharge at 1 month, 3 months, and 1 year were 11.8% (95% CI, 0.083-0.152), 26.5% (95% CI, 0.170-0.359), 25.7% (95% CI, 0.19-0.324), and 31.3% (95% CI, 0.256-0.369), respectively. Conclusion: This study found that the overall prevalence of PSD was 46.6%. Prevalence is most influenced by the diagnosis method. Hypertension, history of stroke, atrial fibrillation, patient age, and stroke severity were risk factors significantly associated with PSD. The prevalence of aphasia, dysarthria, respiratory tract infection, and pneumonitis in PSD patients is 2-4 times that of patients without PSD.Systematic review registration: www.crd.york.ac.uk/PROSPERO, PROSPERO, CRD42021252967.

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies.

Inflammatory pain (IP) is one of the most prevalent and intractable human conditions, and it leads to progressive dysfunction and reduced quality of life. Additionally, IP is incredibly challenging to treat successfully with drugs or surgery. The development of IP is complex and multifactorial, and peripheral and central sensitization may influence chronicity and treatment resistance in IP. Understanding the mechanisms underlying IP is vital for developing novel therapies. Strong evidence suggests that exercise can be a first-line relief for patients with IP during rehabilitation. However, the mechanisms through which exercise improves IP remain unclear. Here, we reviewed the current animal experimental evidence for an exercise intervention in IP and proposed biological mechanisms for the effects of synaptic plasticity in the anterior cingulate cortex, endocannabinoids, spinal dorsal horn excitability balance, immune cell polarization balance, cytokines, and glial cells. This information will contribute to basic science and strengthen the scientific basis for exercise therapy prescriptions for IP in clinical practice.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

Self-Illuminating Nanoagonist Simultaneously Induces Dual Cell Death Pathways via Death Receptor Clustering for Cancer Therapy.

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H2O2-responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment.

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, -7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

Emerging functions and therapeutic targets of IL-38 in central nervous system diseases.

Interleukin (IL)-38 is a newly discovered cytokine of the IL-1 family, which binds various receptors (i.e., IL-36R, IL-1 receptor accessory protein-like 1, and IL-1R1) in the central nervous system (CNS). The hallmark physiological function of IL-38 is competitive binding to IL-36R, as does the IL-36R antagonist. Emerging research has shown that IL-38 is abnormally expressed in the serum and brain tissue of patients with ischemic stroke (IS) and autism spectrum disorder (ASD), suggesting that IL-38 may play an important role in neurological diseases. Important advances include that IL-38 alleviates neuromyelitis optica disorder (NMOD) by inhibiting Th17 expression, improves IS by protecting against atherosclerosis via regulating immune cells and inflammation, and reduces IL-1ß and CXCL8 release through inhibiting human microglial activity post-ASD. In contrast, IL-38 mRNA is markedly increased and is mainly expressed in phagocytes in spinal cord injury (SCI). IL-38 ablation attenuated SCI by reducing immune cell infiltration. However, the effect and underlying mechanism of IL-38 in CNS diseases remain inadequately characterized. In this review, we summarize the biological characteristics, pathophysiological role, and potential mechanisms of IL-38 in CNS diseases (e.g., NMOD, Alzheimer's disease, ASD, IS, TBI, and SCI), aiming to explore the therapeutic potential of IL-38 in the prevention and treatment of CNS diseases.

Meta-analysis of the therapeutic effect of acupuncture on dysphagia in patients with Parkinson disease.

OBJECTIVE: To systematically evaluate the therapeutic effect of acupuncture on dysphagia in patients with Parkinson disease (PD). METHOD: We searched CNKI, WF, VIP, CBM, Cochrane Library, and Web of Chinese Biomedical Literature Randomized controlled trials on the efficacy of acupuncture in the treatment of dysphagia in patients with PD was retrieved from Science, Embase, and PubMed databases from establishment to October 2022. Outcome indicators included clinical efficacy, swallowing function, hemoglobin, and serum albumin. Literature screening and data extraction of included literature were conducted independently by 2 reviewers, and literature quality was evaluated according to the standards of the Cochrane Collaboration network. Data analysis was performed using Review Manager 5.3 and Stata14.0 software. RESULTS: 466 patients were included in 7 literature, 234 in the observation, and 232 in the control groups. The results of the meta-analysis showed the clinical efficacy in the observation group [odd ratio = 0.25, 95% confidence interval (95%CI) (0.15, 0.40), P < .01]. Swallowing function [standardized mean difference (SMD) = -0.96, 95%CI (-1.24, -0.68), P < .01]; hemoglobin index level [SMD = -0.72, 95%CI (-1.25, -0.20), P < .01]; serum albumin index level [SMD = -1.25, 95%CI (-2.19, -0.31), P < .01]. CONCLUSION: Acupuncture has a specific curative effect on dysphagia in patients with PD, and the therapeutic effect is more significant than that in the control group, which can improve the dysphagia function and nutrition level in patients with PD more effectively.

A novel approach to the immediate effects of electroacupuncture on dry eye: A case series.

INTRODUCTION: Dry eye disease (DED) is an inflammatory disorder that shares several features with autoimmune diseases. Research suggests that electroacupuncture (EA) is a promising alternative treatment option for this disorder; however, evidence of its immediate efficacy is limited. CASE PRESENTATION: Three patients were diagnosed with DED, and used artificial tears or anti-inflammatory drugs for long-term relief of eye symptoms. However, the cure rates were low, and the side effects were high. To improve ocular symptoms, quality of life, and physical and mental health, the patients sought alternative complementary therapies and received electroacupuncture therapy. All patients showed significant improvements in fatigue and dryness of the ocular surface after 3-4 days of treatment, and follow-up after 4 weeks showed no tendency for recurrence. No adverse reactions or unexpected events were observed during treatment. CONCLUSION: We propose an innovative electroacupuncture treatment aimed at fewer acupuncture points, shorter periods, and faster healing that improves the symptoms of patients with DED in the short term. Continuous current stimulation by anatomically positioned needles on both sides of the lacrimal gland and the creation of an electric field may improve the endogenous mechanisms of DED.