Network meta-analysis of the effects of different cognitive trainings on the cognitive function of patients with mild cognitive impairment.

OBJECTIVE: Examining the relationship between the responses of a number of different cognitive trainings on cognitive functioning in middle-aged and elderly patients with mild cognitive impairment. METHODS: Randomized controlled experimental studies published publicly from the time of inception to October 30, 2023 were searched through Web of Science, PubMed, Embase, and Cochrane library databases. Traditional and network meta-analyses were performed using Stata 17.0 software. RESULTS: Fifty papers on 4 types of cognitive training were included. Traditional meta-analysis showed that virtual reality training (SMD = 0.53, 95%CI: [0.36,0.70], P = 0.00), neuropsychological training (SMD = 0.44, 95%CI: [0.18,0.70], P = 0.00), cognitive strategy training (SMD = 0.26, 95%CI: [0.16,0.36], P = 0.00), and cognitive behavioral therapy (SMD = 0.25, 95%CI: [0.08,0.41], P = 0.00) all had significant improvement effects on the cognitive function of middle-aged and elderly patients with mild cognitive impairment. Network meta-analysis revealed neuropsychological training as the best cognitive training, and subgroup analysis of cognitive function subdimensions showed that neuropsychological training had the best effects on working memory, lobal cognitive function, memory, and cognitive flexibility improvement. Meanwhile, virtual reality training had the best effects on processing speed, verbal ability, overall executive function, spatial cognitive ability, and attention improvement. CONCLUSION: Cognitive training can significantly improve the cognitive function of middle-aged and elderly patients with mild cognitive impairment, and neuropsychological training is the best intervention, most effective in interventions lasting more than 8 weeks.

Gold-Catalyzed C(sp3)-C(sp2) Suzuki-Miyaura Coupling Reaction.

A gold-catalyzed C(sp3)-C(sp2) Suzuki-Miyaura coupling reaction facilitated by ligand-enabled Au(I)/Au(III) redox catalysis was developed. The cross-coupling of alkyl organometallics was first realized in the redox catalytic cycle in gold chemistry, without the use of external oxidants. This gold-catalyzed C(sp3)-C(sp2) coupling reaction allows a variety of alkyl chain and useful methyl trifluoroborates to react with aryl and vinyl iodides under very mild conditions, which provides a new reactivity pattern for challenging couplings with alkyl organometallics.

Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation.

BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

The Role of Nicotinamide Mononucleotide Supplementation in Psoriasis Treatment.

Psoriasis is one of several chronic inflammatory skin diseases with a high rate of recurrence, and its pathogenesis remains unclear. Nicotinamide mononucleotide (NMN), as an important precursor of nicotinamide adenine dinucleotide (NAD+), has been reported to be a promising agent in treating various diseases, its positive effects including those induced via its anti-inflammatory and antioxidant properties. For this reason, we have aimed to explore the possible role of NMN in the treatment of psoriasis. Psoriasis models were constructed with imiquimod (IMQ) stimulation for 5 days in vivo and with M5 treatment in keratinocyte cell lines in vitro. NMN treatment during the IMQ application period markedly attenuated excess epidermal proliferation, splenomegaly, and inflammatory responses. According to GEO databases, Sirtuin1 (SIRT1) levels significantly decreased in psoriasis patients' lesion tissues; this was also the case in the IMQ-treated mice, while NMN treatment reversed the SIRT1 decline in the mouse model. Moreover, NMN supplementation also improved the prognoses of the mice after IMQ stimulation, compared to the untreated group with elevated SIRT1 levels. In HEKa and HaCaT cells, the co-culturing of NMN and M5 significantly decreased the expression levels of proinflammation factors, the phosphorylation of NF-κB, stimulator of interferon genes (STING) levels, and reactive oxygen species levels. NMN treatment also recovered the decrease in mitochondrial membrane potential and respiration ability and reduced mtDNA in the cytoplasm, leading to the inhibition of autoimmune inflammation. The knockdown of SIRT1 in vitro eliminated the protective and therapeutic effects of NMN against M5. To conclude, our results indicate that NMN protects against IMQ-induced psoriatic inflammation, oxidative stress, and mitochondrial dysfunction by activating the SIRT1 pathway.

Investigating the Effect of Microwave Induction on the Polymerization Rate of Polycarboxylate Superplasticizers.

As a transmission medium and heating energy, microwave is widely favored due to its high efficiency, strong selectivity, and easy control. Here, the effects of different heating methods (conventional thermal induction (CI) and microwave induction (MI)) on the polymerization rate of polycarboxylate superplasticizer (PCE) were investigated. Compared with CI, MI significantly boosted the polymerization rate (by approximately 51 times) and markedly decreased the activation energy (Ea), from 46.83 kJ mol-1 to 35.07 kJ mol-1. The polar of the monomers and initiators in the PCE synthesis contributes to varying permittivities and loss factors under the microwave field, which are influenced by their concentration and reaction temperature. The insights gained from the microwave thermal effects and the micro-kinetics of the PCE polymerization system are able to propose theoretical underpinnings for the industrial-scale application of microwave induction polymerization, potentially steering the synthesis of polymer materials towards a more efficient and cleaner process.

TAZ acting as a potential pathogenic biomarker to promote the development of lichen planus.

BACKGROUND: Lichen planus is a chronic inflammatory disorder. Transcriptional coactivator with PDZ-binding motif (TAZ/WWTR1) is an important downstream effector of the Hippo pathway which regulates organ size and tissue homeostasis. But little is known about the role of TAZ in lichen planus so far. OBJECTIVE: To explore the expression of TAZ in lichen planus and normal skin, and to discover the relationship between TAZ expression and the clinical characteristics of lichen planus patients. METHODS: The method of immunohistochemistry was performed to quantify the expression of TAZ in 262 patients with lichen planus and 90 control tissues. Western blot and quantitative real-time reverse transcriptase-PCR (qRT-PCR) analysis were performed to examine and compare TAZ expression in 4 cases of fresh lichen planus lesions and normal skin tissues. RESULTS: TAZ was weakly expressed in the basal layers of the epidermis in normal skin tissues with a positive rate of 52.22% (47/90). But in lichen planus, TAZ was strongly expressed in almost the entire epidermis with a positive rate of 81.30% (213/262), and the difference between the two groups was statistically significant (p<0.05). Additionally, TAZ expression was significantly related to the location of the lichen planus, clinical phenotype, smoking, and alcohol preference (p<0.05). Western blot and qRT-PCR showed that the expression of TAZ in protein and mRNA levels in four cases of lichen planus lesions was significantly higher than that in normal skin tissues. CONCLUSION: TAZ may play a regulatory role in the occurrence and development of lichen planus, which might provide a new perspective for studying pathogenesis and theoretical treatment targets.

Oral administration of punicalagin attenuates imiquimod-induced psoriasis by reducing ROS generation and inflammation via MAPK/ERK and NF-κB signaling pathways.

Psoriasis, an immune-mediated chronic inflammatory skin disease, imposes a huge mental and physical burden on patients and severely affects their quality of life. Punicalagin (PU), the most abundant ellagitannin in pomegranates, has become a research hotspot owing to its diverse biological activities. However, its effects on psoriasis remain unclear. We explored the impact and molecular mechanism of PU on M5-stimulated keratinocyte cell lines and imiquimod (IMQ)-induced psoriasis-like skin inflammation in BABL/c mice using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin and eosin (H&E) stain, immunohistochemistry, and immunofluorescent. Administration of PU-enriched pomegranate extract at dosages of 150 and 250 mg/kg/day markedly attenuated psoriatic severity, abrogated splenomegaly, and reduced IMQ-induced abnormal epidermal proliferation, CD4+ T-cell infiltration, and inflammatory factor expression. Moreover, PU could decrease expression levels of pro-inflammatory cytokines, such as IL-1ß, IL-1α, IL-6, IL-8, TNF-α, IL-17A, IL-22, IL-23A, and reactive oxygen species (ROS), followed by keratinocyte proliferation inhibition in the M5-stimulated cell line model of inflammation through inhibition of mitogen-activated protein kinases/extracellular regulated protein kinases (MAPK/ERK) and nuclear factor kappaB (NF-κB) signaling pathways. Our results indicate that PU may serve as a promising nutritional intervention for psoriasis by ameliorating cellular oxidative stress and inflammation.

FOXE1 Contributes to the Development of Psoriasis by Regulating WNT5A.

Psoriasis is a common, chronic, and relapsing inflammatory skin disease characterized by hyperproliferation of keratinocytes (KCs) and infiltration of immune cells. The pathogenesis of psoriasis is complex, and the exact mechanism remains partially understood. In this study, we showed that the forkhead box family protein, FOXE1, had increased expression in lesional skins compared with nonlesional skin from patients with psoriasis. FOXE1 expression was also increased in an imiquimod-induced psoriatic mouse model as well as in M5-stimulated KCs. Using combinational approaches of knockdown and overexpression of FOXE1, we demonstrated that FOXE1 may promote the proliferation of KCs by facilitating G1/S transition and activating extracellular signal-regulated kinase 1/2 signaling pathway. In addition, knockdown of FOXE1 reduced the production of IL-1ß, IL-6, and TNF-α by KCs. RNA-sequencing profiling identified WNT5A as a potential downstream effector of FOXE1. Knockdown of WNT5A inhibited the proliferation of KCs; reduced the production of IL-1ß, IL-6, and TNF-α by KCs; and mitigated the growth-promoting effect of FOXE1 in FOXE1-overexpressed KCs. Finally, depletion of FOXE1 by lentiviral delivery of small hairpin RNAs or genetic approach ameliorated dermatitis symptoms in imiquimod-induced psoriasis-like mouse models. Taken together, our results indicated that FOXE1 participates in the pathogenesis of psoriasis and can serve as a target of psoriasis treatment.

Exploration of the underlying comorbidity mechanism in psoriasis and periodontitis: a bioinformatics analysis.

BACKGROUND: Increasing evidence indicates that psoriasis (PSO) and periodontitis (PD) are likely to occur together, however, the underlying mechanism remains unclear. MATERIALS AND METHODS: The expression profiles of PSO (lesion vs non-lesion, GSE30999, GSE14905) and PD (affected vs unaffected gingival tissue, GSE16134, GSE10334) were downloaded from the GEO database. First, we investigated the common differentially expressed genes (DEGs) of PSO and PD. Then, GO and KEGG enrichment analysis, protein interaction network (PPI) construction, and hub gene identification analysis were carried out. Finally, GO and KEGG enrichment analysis, miRNA interaction analysis, and transcription factors (TFs) interaction analysis for hub genes were performed. RESULTS: Eighteen DEGs were identified for further analysis, including 15 up-regulated genes and 3 down-regulated genes. 9 hub genes were then identified via Cytohubba, including IL1B, CXCL1, CXCL8, MMP12, CCL18, SELL, CXCL13, FCGR3B, and SELE. Their functions are mainly enriched in two aspects: neutrophil chemotaxis and migration, chemokine activation and interaction. The enriched signaling pathways includes three categories: host defense, inflammation-related signaling pathways, and disease-related pathways. 9 common miRNAs based on experimental evidence and 10 common TFs were further identified in both PSO and PD. CONCLUSION: Our study revealed possible comorbidity mechanisms in PSO and PD from the perspective of bioinformatics tentatively. The data can present new insight for joint prevention and treatment of in PSO and PD, as well as provide data support for further prospective studies.

MAPK Cascade Signaling Is Involved in α-MMC Induced Growth Inhibition of Multiple Myeloma MM.1S Cells via G2 Arrest and Mitochondrial-Pathway-Dependent Apoptosis In Vitro.

Multiple myeloma is a hematological malignancy characterized by the unrestricted proliferation of plasma cells that secrete monoclonal immunoglobulins in the bone marrow. Alpha-momorcharin (α-MMC) is a type I ribosome-inactivating protein extracted from the seeds of the edible plant Momordica charantia L., which has a variety of biological activities. This study aimed to investigate the inhibitory effect of α-MMC on the proliferation of multiple myeloma MM.1S cells and the molecular mechanism of MM.1S cell death induced through the activation of cell signal transduction pathways. The cell counting kit-8 (CCK-8) assay was used to determine the inhibitory effect of α-MMC on the proliferation of MM.1S cells and its toxic effect on normal human peripheral blood mononuclear cells (PBMCs). The effect of α-MMC on the MM.1S cells' morphology was observed via inverted microscope imaging. The effects of α-MMC on the MM.1S cell cycle, mitochondrial membrane potential (MMP), and apoptosis were explored using propidium iodide, JC-1, annexin V- fluorescein isothiocyanate/propidium iodide fluorescence staining, and flow cytometry (FCM) analysis. Western blot was used to detect the expressions levels of apoptosis-related proteins and MAPK-signaling-pathway-related proteins in MM.1S cells induced by α-MMC. The results of the CCK-8 showed that in the concentration range of no significant toxicity to PBMCs, α-MMC inhibited the proliferation of MM.1S cells in a time-dependent and concentration-dependent manner, and the IC50 value was 13.04 and 7.518 µg/mL for 24 and 48 h, respectively. Through inverted microscope imaging, it was observed that α-MMC induced a typical apoptotic morphology in MM.1S cells. The results of the FCM detection and analysis showed that α-MMC could arrest the MM.1S cells cycle at the G2 phase, decrease the MMP, and induce cell apoptosis. Western blot analysis found that α-MMC upregulated the expression levels of Bax, Bid, cleaved caspase-3, and cleaved PARP, and downregulated the expression levels of Mcl-1. At the same time, α-MMC decreased the expression levels of p-c-Raf, p-MEK1/2, p-ERK1/2, p-MSK1, and p-P90RSK, and increased the expression levels of p-p38, p-SPAK/JNK, p-c-Jun, and p-ATF2. The above results suggest that α-MMC can inhibit the proliferation of multiple myeloma MM.1S cells. MAPK cascade signaling is involved in the growth inhibition effect of α-MMC on MM.1S cells via cycle arrest and mitochondrial-pathway-dependent apoptosis.

Storage Stability of Blood Samples for miRNAs in Glycosylated Extracellular Vesicles.

Extracellular vesicle (EV) miRNAs are promising biomarkers for clinical diagnosis. However, their stability is a crucial concern affecting reliability and accuracy. Factors such as sample collection, processing, storage conditions, and experimental procedures impact EV miRNA stability. Studying EV miRNA stability aims to find optimal handling and storage methods, ensuring integrity and functionality throughout research. In this study, we used RT-qPCR and GlyExo-Capture technology, which can specifically capture glycosylated EVs by lectin, to assess the stability of glycosylated EV miRNAs. We found that slow acceleration centrifugation and two-step centrifugation methods were suitable for subsequent experiments. To ensure uniformity, we recommend using the two-step centrifugation method. We also studied blood storage before serum separation and recommend separation within 2 h at 4 °C or 25 °C. For separated serum samples, higher temperatures accelerated miRNA degradation, and the storage duration should be adjusted based on laboratory conditions. Short-term storage at -20 °C is acceptable for up to 3 months while avoiding repeated freeze-thaw cycles. We developed protective agents to extend the storage time at 25 °C, meeting clinical requirements. Additionally, Lakebio's cfRNA storage tubes effectively preserved the stability of miRNAs in plasma glycosylated EVs. Understanding EV miRNA stability provides insights into optimizing sample handling, storage strategies, and enhancing reliability in clinical applications.

Gold(I)-Catalyzed Tandem Cyclization/Hydroarylation of o-Alkynylphenols with Haloalkynes.

A convenient and mild protocol for the gold-catalyzed intermolecular coupling of o-alkynylphenols with haloalkynes to give vinyl benzofurans is reported. In this work, the gold catalyst SIPrAuCl and the co-catalyst NaBARF would corporately promote the intramolecular cyclization of the o-alkynylphenol to benzofuran, and then a selective hydroarylation of benzofuran to haloalkyne was catalyzed by the same catalysts. Computational studies suggest that the hydroarylation process takes place via a concerted nucleophilic attack pathway of the benzofuran to the C2 carbon of the activated haloalkyne, and reveal the original driving force of this hydroarylation process.

Cdc25C/cdc2/cyclin B, raf/MEK/ERK and PERK/eIF2α/CHOP pathways are involved in forskolin-induced growth inhibition of MM.1S cells by G2/M arrest and mitochondrion-dependent apoptosis.

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM.