Investigating the causal relationship between immune cell and Alzheimer's disease: a mendelian randomization analysis.

BACKGROUND: Complex interactions between the immune system and the brain may affect neural development, survival, and function, with etiological and therapeutic implications for neurodegenerative diseases. However, previous studies investigating the association between immune inflammation and Alzheimer's disease (AD) have yielded inconsistent results. METHODS: We applied Mendelian randomization (MR) to examine the causal relationship between immune cell traits and AD risk using genetic variants as instrumental variables. MR is an epidemiological study design based on genetic information that reduces the effects of confounding and reverse causation. We analyzed the causal associations between 731 immune cell traits and AD risk based on publicly available genetic data. RESULTS: We observed that 5 immune cell traits conferred protection against AD, while 7 immune cell traits increased the risk of AD. These immune cell traits mainly involved T cell regulation, monocyte activation and B cell differentiation. Our findings suggest that immune regulation may influence the development of AD and provide new insights into potential targets for AD prevention and treatment. We also conducted various sensitivity analyses to test the validity and robustness of our results, which revealed no evidence of pleiotropy or heterogeneity. CONCLUSION: Our research shows that immune regulation is important for AD and provides new information on potential targets for AD prevention and treatment. However, this study has limitations, including the possibility of reverse causality, lack of validation in independent cohorts, and potential confounding by population stratification. Further research is needed to validate and amplify these results and to elucidate the potential mechanisms of the immune cell-AD association.

Repetitive transcranial magnetic stimulation as a therapy for post-stroke dysphagia: An overview of systematic reviews and meta-analysis.

OBJECTIVE: Post-stroke dysphagia is a common swallowing disorder that occurs after a stroke, leading to an increased risk of aspiration pneumonia and malnutrition. There is a pressing need for effective and safe interventions for its rehabilitation. This review aims to answer two key scientific questions: (1) What is the efficacy of repetitive transcranial magnetic stimulation in the rehabilitation of post-stroke dysphagia? (2) Is repetitive transcranial magnetic stimulation a safe intervention for post-stroke dysphagia? DATA SOURCES: A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Web of Science, and Embase. The search aimed to identify relevant studies concerning our topic of interest and was completed on 28 May 2024. REVIEW METHODS: In accordance with the PRISMA checklist, a comprehensive search of four databases was conducted, which identified 13 relevant systematic reviews. The inclusion criteria were systematic reviews that evaluated the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Exclusion criteria were reviews that did not focus on post-stroke dysphagia or did not evaluate repetitive transcranial magnetic stimulation as a therapeutic intervention. The quality, bias, reporting, and overall evidence quality of these reviews were assessed using validated tools, including the AMSTAR 2 tool for assessing the methodological quality of systematic reviews, the ROBIS tool for assessing the risk of bias, and the GRADE approach for evaluating the overall quality of evidence. This rigorous approach ensures that our review provides a comprehensive and reliable overview of the current state of knowledge on the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia. RESULTS: The sample sizes for the individual studies included in the systematic reviews/meta-analyses ranged from 66 to 555. The total number of participants across all studies included in the overall analyses was 752. The evidence was limited by the methodological flaws and heterogeneity of the systematic reviews. The quality of the evidence varied from high to low, with most outcomes having moderate quality. Future research should adopt more rigorous, standardized, and comprehensive designs to confirm the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. The main reason for downgrading the evidence quality was the small sample size and high heterogeneity of the primary studies. CONCLUSION: This overview synthesized research on repetitive transcranial magnetic stimulation for dysphagia, aiming to inform clinical and policy decisions. However, the current evidence does not conclusively establish the safety and efficacy of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The studies reviewed varied in quality, and many were of poor quality. Therefore, while some studies suggest potential benefits of repetitive transcranial magnetic stimulation, these findings should be interpreted with caution. There is a pressing need for more rigorous, high-quality research to validate the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The implications of these findings for clinical practice and policy will be clearer once we have more robust, evidence-based recommendations.

SbCASP-LP1C1 improves salt exclusion by enhancing the root apoplastic barrier.

Sweet sorghum [Sorghum bicolor (L.) Moench], a C4 crop with high biomass and strong resistance to multiple stresses, can grow and reproduce in saline-alkaline soil and is an ideal raw material for biofuels. Under high-salinity conditions, sweet sorghum shows extensive salt exclusion. However, the specific molecular mechanism of the apoplastic barrier in salt exclusion is unknown. In this study, SbCASP-LP1C1 (a CASP-like protein1C1) was localized in the plasma membrane of sweet sorghum root endodermal cells, and its function was further studied by heterologous expression in Arabidopsis (35 S:SbCASP-LP1C1-GFP). When germinated and grown on 50 mM NaCl, the SbCASP-LP1C1-expressing lines had longer roots and a higher salinity threshold compared with wild-type (Col-0) plant and the casp-lp T-DNA insertion mutant in Arabidopsis. The 35 S:SbCASP-LP1C1-GFP lines also suffered less oxidative damage as determined by DAB and NBT staining, and the expression levels of several antioxidant genes were higher in these lines. Moreover, the stele of 35 S:SbCASP-LP1C1-GFP lines was less permeable to propidium iodide, and these plants contained less Na+ in their shoots and roots compared to wild type and casp-lp. In the 35 S:SbCASP-LP1C1-GFP lines, the expression levels of two Casparian strip synthesis genes, MYB36 and ESB1, were increased. These results indicate that SbCASP-LP1C1 may be involved in the polymerization of lignin monomers in the Casparian strip of sweet sorghum, thereby regulating salt tolerance. These results provide a theoretical basis to understand the role of plant roots in salt exclusion and a means by which to improve the salt tolerance of crops.

Arabidopsis ZINC FINGER PROTEIN1 Acts Downstream of GL2 to Repress Root Hair Initiation and Elongation by Directly Suppressing bHLH Genes.

Cys2His2-like fold group (C2H2)-type zinc finger proteins promote root hair growth and development by regulating their target genes. However, little is known about their potential negative roles in root hair initiation and elongation. Here, we show that the C2H2-type zinc finger protein named ZINC FINGER PROTEIN1 (AtZP1), which contains an ERF-associated amphiphilic repression (EAR) motif, negatively regulates Arabidopsis (Arabidopsis thaliana) root hair initiation and elongation. Our results demonstrate that AtZP1 is highly expressed in root hairs and that AtZP1 inhibits transcriptional activity during root hair development. Plants overexpressing AtZP1 lacked root hairs, while loss-of-function mutants had longer and more numerous root hairs than the wild type. Transcriptome analysis indicated that AtZP1 downregulates genes encoding basic helix-loop-helix (bHLH) transcription factors associated with root hair cell differentiation and elongation. Mutation or deletion of the EAR motif substantially reduced the inhibitory activity of AtZP1. Chromatin immunoprecipitation assays, AtZP1:glucocorticoid receptor (GR) induction experiments, electrophoretic mobility shift assays, and yeast one-hybrid assays showed that AtZP1 directly targets the promoters of bHLH transcription factor genes, including the key root hair initiation gene ROOT HAIR DEFECTIVE6 (RHD6) and root hair elongation genes ROOT HAIR DEFECTIVE 6-LIKE 2 (RSL2) and RSL4, and suppresses root hair development. Our findings suggest that AtZP1 functions downstream of GL2 and negatively regulates root hair initiation and elongation, by suppressing RHD6, RSL4, and RSL2 transcription via the GL2/ZP1/RSL pathway.

SbCASP4 improves salt exclusion by enhancing the root apoplastic barrier.

MAIN CONCLUSION: SbCASP4 improves the salt tolerance of sweet sorghum [Sorghum bicolor (L.) Mocnch] by enhancing the root apoplastic barrier and blocking the transport of sodium ions to the shoot. Sweet sorghum [Sorghum bicolor (L.) Mocnch] is a C4 crop with high biomass and tolerance to abiotic stresses such as salt, drought, and waterlogging. Sweet sorghum is widely used in bioenergy production, as a forage crop, and in liquors and beer. Root salt exclusion has been reported to underlie the salt tolerance of sweet sorghum. The Casparian strip has a key role in root salt exclusion, and the membrane domain protein (CASP) family participates in Casparian strip aggregation. However, the function and the regulatory mechanisms of SbCASP in response to salt stress in sweet sorghum are unclear. In the current study, we cloned SbCASP4 and determined that it is induced by salt stress and expressed in the endodermis cells of sweet sorghum. Histochemical staining and physiological indicators showed that heterologous expression of SbCASP4 significantly increased the tolerance to salt stress in transgenic Arabidopsis thaliana. Compared with wild type and casp5 mutants, under 50 mM NaCl treatment, SbCASP4-expression lines had the less leaf Na+, lower PI accumulation in stele, smaller oxidative damage and higher salinity threshold, longer root length and higher expression levels of the genes related to Casparian strip formation.

Adaptation Mechanism of Salt Excluders under Saline Conditions and Its Applications.

Global soil salinization is increasingly a serious threat to agriculture worldwide. Therefore, it is imperative to improve crop salt tolerance as a means of adaptation to saline habitats. Some halophytes and most monocotyledonous crops are salt-excluders. Understanding the regulatory mechanisms of salt exclusion at the molecular level in salt-exclusion plants is critical for improving the salt tolerance of monocotyledonous crops such as maize, wheat, rice, and sorghum. In this review, we summarize recent research into salt-exclusion mechanisms and the genes that underlie them. Findings related to salt exclusion may accelerate the process of breeding tolerant cultivars by using genomic and molecular tools.

Mechanism, Formulation, and Efficacy Evaluation of Natural Products for Skin Pigmentation Treatment.

Skin pigmentation typically arises from the excessive secretion and accumulation of melanin, resulting in a darker complexion compared to normal skin. Currently, the local application of chemical drugs is a first-line strategy for pigmentation disorders, but the safety and efficacy of drugs still cannot meet clinical treatment needs. For long-term and safe medication, researchers have paid attention to natural products with higher biocompatibility. This article begins by examining the pathogenesis and treatment approaches of skin pigmentation diseases and summarizes the research progress and mechanism of natural products with lightening or whitening effects that are clinically common or experimentally proven. Moreover, we outline the novel formulations of natural products in treating pigmentation disorders, including liposomes, nanoparticles, microemulsions, microneedles, and tocosomes. Finally, the pharmacodynamic evaluation methods in the study of pigmentation disorder were first systematically analyzed. In brief, this review aims to collect natural products for skin pigmentation treatment and investigate their formulation design and efficacy evaluation to provide insights for the development of new products for this complex skin disease.

The latest research progress: Active components of Traditional Chinese medicine as promising candidates for ovarian cancer therapy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ovarian cancer ranks the first in the mortality of gynecological tumors. Because there are no obvious symptoms in the early stage of ovarian cancer, most patients are in the advanced stage of the disease at the time of diagnosis. The incidence of ovarian cancer is increasing year by year, and the incidence of ovarian cancer has a trend of younger age. In recent years. Traditional Chinese medicine (TCM) has a significant impact on improving the quality of life of cancer patients, reducing drug toxicity, preventing metastasis and recurrence, enhancing the efficacy of radiotherapy and chemotherapy, and prolonging survival time, so patients have benefited a lot. AIM OF THE STUDY: This review summarizes the mechanisms and molecular pathways through which active ingredients of TCM act in ovarian cancer. It explores the advantages of TCM in treating ovarian cancer. This review provides theoretical support for the use of TCM in the treatment of ovarian cancer, offering new perspectives for its clinical prevention and treatment. MATERIALS AND METHODS: This review conducted a literature search on PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) for relevant studies on TCM active ingredients in preventing ovarian cancer. The search terms included "ovarian cancer" combined with "Chinese herbal medicine," "Herbal medicine," "Traditional Chinese medicine," and "Active ingredients of Chinese medicine". Based on existing experimental and clinical research, the paper systematically summarized and analyzed the mechanisms of TCM in treating ovarian cancer. RESULTS: Active ingredients of TCM inhibit the occurrence and development of ovarian cancer through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, suppressing tumor cell migration and invasion, inducing tumor cell autophagy, promoting epithelial-mesenchymal transition, and enhancing the efficacy of radiotherapy and chemotherapy drugs. Chinese medicine provides a comprehensive treatment option for ovarian cancer patients, synergizing with radiotherapy and chemotherapy drugs to enhance treatment effectiveness and introduce new hope and possibilities in clinical therapy. CONCLUSIONS: Active ingredients of TCM can inhibit the occurrence and development of ovarian cancer, but further clinical research is needed to support their application.

Injectable, thermo-sensitive and self-adhesive supramolecular hydrogels built from binary herbal small molecules towards reusable antibacterial coatings.

Herbal hydrogels as a new class of sustainable functional materials have attracted extensive attention. However, the development of herbal hydrogels is significantly hindered due to their poor hydrogel performances and the lack of universal preparation methods. In this study, four herbal hydrogels composed of phytochemical polyphenols and stevioside compounds are prepared through a facile heating-cooling process, where multiple hydrogen bonding interactions between two monomers provide the main driving force for gelation. These herbal hydrogels exhibit thermo-sensitivity and good reversibility (25-90 °C), robust adhesion behaviours on hydrophilic and hydrophobic surfaces (maximum adhesion strength of 591.7 kPa), and outstanding antibacterial properties (100% bacteriostatic ratio). Profiting from these intriguing characteristics, they are demonstrated to show great potential as natural antibacterial coatings by depositing thin hydrogel layers onto diverse substrates. More importantly, the hydrogel coatings could be easily recycled by thermal regelation and reused at least 5 times. This work proposes a simple and universal strategy for preparing functional hydrogels based on binary herbal small molecules, which also sheds light on the development of reusable hydrogel coatings.

Transcranial Magnetic Stimulation as a Therapy for Migraine: An Overview of Systematic Reviews.

Introduction: This overview of systematic reviews (SRs) systematically collected, evaluated, and combined the evidence for migraine treatment with transcranial magnetic stimulation (TMS). Methods: We conducted a systematic literature search in various databases, such as PubMed, The Cochrane Library, Web of Science, Embase, the China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and strength of evidence of the included studies using AMSTAR-2, ROBIS, the PRISMA checklist, and the GRADE system. Results: We performed an overview of 7 relevant SRs, of which 4 were of moderate quality and 3 were of low quality according to AMSTAR 2. All SRs had low risk of bias in Phase 1 (Assessing relevance), Domain 1 (Study eligibility criteria), and Domain 4 (Synthesis and findings) as evaluated by ROBIS. In Domain 2 (Identification and selection of studies), 4 SRs (57.1%) had low risk of bias, while in Domain 3 (data collection and study appraisal) and Risk of Bias in the Review Phase 3, 4 SRs (57.1%) had low risk of bias. The PRISMA reporting standards were generally comprehensive, but some limitations were observed in the assessments, pooled results, evidence reliability, registration and protocols, and funding sources. The GRADE levels ranged from moderate to low, with 10 outcomes of moderate quality and 6 outcomes of low quality. The main reason for the low quality of evidence was the small sample size and high heterogeneity of the available studies. Conclusion: TMS may improve migraine severity and frequency, but the evidence is limited due to methodological flaws and heterogeneity. Future studies should standardize use, assess side effects, and compare with other treatments.

Preparation and Evaluation of Auxiliary Permeable Microneedle Patch Composed of Polyvinyl Alcohol and Eudragit NM30D Aqueous Dispersion.

Poor transdermal permeability limits the possibility of most drug delivery through the skin. Auxiliary permeable microneedles (AP-MNs) with a three-dimensional network structure can effectively break the skin stratum corneum barrier and assist in the transdermal delivery of active ingredients. Herein, we propose a simple method for preparing AP-MNs using polyvinyl alcohol and Eudragit NM30D for the first time. To optimize the formulation of microneedles, the characteristics of swelling properties, skin insertion, solution viscosity, and needle integrity were systematically examined. Additionally, the morphology, mechanical strength, formation mechanism, skin permeability, swelling performance, biocompatibility, and in vitro transdermal drug delivery of AP-MNs were evaluated. The results indicated that the microneedles exhibited excellent mechanical-strength and hydrogel-forming properties after swelling. Further, it proved that a continuous and unblockable network channel was created based on physical entanglement and encapsulation of two materials. The 24 h cumulative permeation of acidic and alkaline model drugs, azelaic acid and matrine, were 51.73 ± 2.61% and 54.02 ± 2.85%, respectively, significantly enhancing the transdermal permeability of the two drugs. In summary, the novel auxiliary permeable microneedles prepared through a simple blending route of two materials was a promising and valuable way to improve drug permeation efficiency.

Ovarian Cancer Risk Scores Based on Immune-Related Pseudogenes to Predict Overall Survival and Guide Immunotherapy and Chemotherapy.

BACKGROUND: Ovarian cancer (OC) is the top of the aggressive malignancies in females with a poor survival rate. However, the roles of immune-related pseudogenes (irPseus) in the immune infiltration of OC and the impact on overall survival (OS) have not been adequately studied. Therefore, this study aims to identify a novel model constructed by irPseus to predict OS in OC and to determine its significance in immunotherapy and chemotherapy. METHODS: In this study, with the use of The Cancer Genome Atlas (TCGA) combined with Genotype-Tissue Expression (GTEx), 55 differentially expressed irPseus (DEirPseus) were identified. Then, we constructed 10 irPseus pairs with the help of univariate, Lasso, and multivariate Cox regression analysis. The prognostic performance of the model was determined and measured by the Kaplan-Meier curve, a time-dependent receiver operating characteristic (ROC) curve. RESULTS: After dividing OC subjects into high- and low-risk subgroups via the cut-off point, it was revealed that subjects in the high-risk group had a shorter OS. The multivariate Cox regression performed between the model and multiple clinicopathological variables revealed that the model could effectively and independently predict the prognosis of OC. The prognostic model characterized infiltration by various kinds of immune cells and demonstrated the immunotherapy response of subjects with cytotoxic lymphocyte antigen 4 (CTLA4), anti-programmed death-1 (PD-1), and anti-PD-ligand 1 (PD-L1) therapy. A high risk score was related to a higher inhibitory concentration (IC50) for etoposide (P=0.0099) and mitomycin C (P=0.0013). CONCLUSION: It was the first study to identify a novel signature developed by DEirPseus pairs and verify the role in predicting OS, immune infiltrates, immunotherapy, and chemosensitivity. The irPseus are vital factors predicting the prognosis of OC and could act as a novel potential treatment target.

The developmental dynamics of the sweet sorghum root transcriptome elucidate the differentiation of apoplastic barriers.

Apoplastic barriers in the endodermis, such as Casparian strips and suberin lamellae, control the passage of water and minerals into the stele. Apoplastic barriers are thus thought to contribute to salt exclusion in salt-excluding plants such as sweet sorghum (Sorghum bicolor). However, little is known about the genes involved in the development of the apoplastic barrier. Here, we identified candidate genes involved in Casparian strip and suberin lamella development in the roots of a sweet sorghum line (M-81E). Three distinct developmental regions (no differentiation, developing, and mature) were identified based on Casparian strip and suberin lamella staining in root cross sections. Sequencing of RNA extracted from these distinct sections identified key genes participating in the differentiation of the apoplastic barrier. The different sections were structurally distinct, presumably due to differences in gene expression. Genes controlling the phenylpropanoid pathway, fatty acid elongation, and fatty acid ω-hydroxylation appeared to be directly responsible for the formation of the apoplastic barrier. Our dataset elucidates the molecular processes underpinning apoplastic barrier development and provides a basis for future research on molecular mechanisms of apoplastic barrier formation and salt exclusion.Abbreviations: SHR, SHORTROOT; MYB, MYB DOMAIN PROTEIN; CIFs, Casparian strip integrity factors; CASP, Casparian strip domain proteins; PER, peroxidase; ESB1, ENHANCED SUBERIN1; CS, Casparian strip; RPKM, reads per kilobase per million reads; DEGs, differentially expressed genes; FDR, false discovery rate; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; RNA-seq, RNA sequencing; PAL, phenylalanine ammonia-lyase; CYP, cytochrome P450 monooxygenases; 4CL, 4-coumarate-CoA ligase; AAE5, ACYL-ACTIVATING ENZYME5; CCR, cinnamoyl CoA reductase; TKPR, TETRAKETIDE ALPHA-PYRONE REDUCTASE1; CAD, cinnamyl alcohol dehydrogenase; HST, shikimate O-hydroxycinnamoyltransferase; PMAT2, PHENOLIC GLUCOSIDE MALONYLTRANSFERASE2; CCOAOMT, caffeoyl-CoA O-methyltransferase; KCS, ß-ketoacyl-CoA synthase; CUT1, CUTICULAR PROTEIN1; DET2, 5-alpha-reductase; TAX, 3'-N-debenzoyl-2'-deoxytaxol N-benzoyltransferase; CER1, ECERIFERUM1; FAR, fatty acyl reductase; AF-CoA, alcohol-forming fatty acyl-CoA reductase; ABCG, ATP-binding cassette, subfamily G; ERF, ethylene-responsive transcription factor; HSF, heat stress transcription factor; NTF, NUCLEAR TRANSCRIPTION FACTOR Y SUBUNIT B-5; GPAT, glycerol 3-phosphate acyltransferase.

Salt glands of recretohalophyte Tamarix under salinity: Their evolution and adaptation.

Here, we studied the evolution of salt glands in 11 species of Tamarix and determined their role in adaptation to saline environments by measuring the effect of NaCl on plant growth and salt gland characteristics. Cluster analysis divided Tamarix species into three types (types I-III) according to salt-gland characteristics. A phylogenetic tree based on ITS sequences indicated an evolutionary relationship consistent with the geographical distribution of Tamarix. We measured growth under different NaCl conditions (0, 100, 200, and 300 mM) for 40 days in three species (T. gallica, T. ramosissima, and T. laxa) representing the three Tamarix types. With increasing NaCl concentration, the biomass of all species was significantly reduced, especially that of T. gallica. Salt secretion ability and salt-gland density showed similar trends in three types. The order of salt tolerance was type I > type II > type III. We conclude that during Tamarix adaptation to salinity, salt-gland evolution followed two directions: one increasing salt-gland density, and the other increasing salt secretion rate per salt-gland. This study provides a basis for potential mechanisms of recretohalophyte adaptation to salinity.

Evaluation of salt-tolerant germplasm and screening of the salt-tolerance traits of sweet sorghum in the germination stage.

Soil salinity is one of the major abiotic stresses that reduces agricultural productivity and affects large terrestrial areas around the world. Germination is the starting point of the growth and development process of all crops, and it is severely affected by salt stress. Sweet sorghum (Sorghum bicolor (L.) Moench.) is one of the most promising crops that has a relatively high salt tolerance and biomass. However, few studies have evaluated the salt tolerance or screened the reliable evaluation traits of sweet sorghum. In this study, the membership function value of five traits was used as a comprehensive index for the evaluation and selection of salt tolerance in 300 sweet sorghum germplasms. After salt tolerance evaluation, 23 highly salt-tolerant, 38 salt-tolerant, 195 moderately salt-tolerant, 38 salt-sensitive and 6 highly salt-sensitive germplasms during the germination stage were screened. Moreover, the germination index under the 200mM NaCl treatment showed the highest correlation with salt tolerance during the germination stage. This information can be used for effectively evaluating sweet sorghum during the germination stage. These results are important for the evaluation of the salt tolerance of sweet sorghum germplasms during the germination stage.