Alkaloids in Processed Rhizoma Corydalis and Crude Rhizoma Corydalis Analyzed by GC/MS

The alkaloids in the processed Rhizoma Corydalis and the crude Rhizoma Corydalis were qualitatively and semiquantitatively analyzed using gas chromatography-mass spectrometry (GC/MS) method. The processing herb drug procedure was carried out according to the standard method of Chinese Pharmacopoeia. The samples were extracted using Soxhlet extractor with different solvents: methanol and acetone. The extraction effect on different solvents was investigated. The results showed that 11 kinds of alkaloids were identified from the crude Rhizoma Corydalis and only two were from the processed Rhizoma Corydalis. A total of 13 kinds of alkaloids were all based on two backbones. The alkaloids in the processed sample were less than those in the crude Rhizoma Corydalis significantly, while almost the corydaline has been changed in conformation after the sample had undergone processing, which provided support for the conclusion of reducing toxicity when the herbal medicine having been undergone a traditional drugs treatment process

Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms

Abstract Background Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin proteasome system via targeting the 19S proteasome-associated deubiquitinases (UCHL5 and USP14), without effecting on the 20S proteasome. In this present study, we investigated the effect of NiPT, a novel proteasomal deubiquitinase inhibitor, on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Methods Cell viability was examined by MTS assay and trypan blue exclusion staining assay in KBM5, KBM5R, K562, BaF3-p210-WT, BaF3-p210-T315I cells, and CML patients’ bone marrow samples treated with NiPT. Cell apoptosis in CML cells was detected with Annexin V-FITC/PI and rhodamine-123 staining followed by fluorescence microscopy and flow cytometry and with western blot analyses for apoptosis-associated proteins. Expression levels of Bcr-Abl in CML cells were analyzed by using western blotting and real-time PCR. The 20S proteasome peptidase activity was measured using specific fluorogenic substrate. Active-site-directed labeling of proteasomal DUBs, as well as the phosphorylation of USP14 was used for evaluating the inhibition of the DUBs activity by NiPT. Mouse xenograft models of KBM5 and KBM5R cells were analyzed, and Bcr-Abl-related proteins and protein biomarkers related to proliferation, differentiation, and adhesion in tumor tissues were detected by western blots and/or immunohistological analyses. Results NiPT induced apoptosis in CML cells and inhibited the growth of IM-resistant Bcr-Abl-T315I xenografts in nude mice. Mechanistically, NiPT induced decreases in Bcr-Abl proteins, which were associated with downregulation of Bcr-Abl transcription and with the cleavage of Bcr-Abl protein by activated caspases. NiPT-induced ubiquitin proteasome system inhibition induced caspase activation in both IM-resistant and IM-sensitive CML cells, and the caspase activation was required for NiPT-induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings support that NiPT can overcome IM resistance through both Bcr-Abl-dependent and Bcr-Abl-independent mechanisms, providing potentially a new option for CML treatment

CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment

Experiences and lessons learned from mangrove conservation in China

Mangrove forests are recognized as one of the most biologically diverse marine ecosystems on the planet, along with coral reefs and seagrass beds, and are known as the planet's three major marine ecosystems. As China has increased its efforts to protect mangroves on all fronts, the area of mangrove forests has grown steadily since the beginning of this century, and China is now one of the few countries in the world with a net increase in the area of mangrove forests. China's top-level design, legislation and practice, supervision, protection and restoration policies, publicity and education on mangrove protection have achieved noticeable results, and a mangrove protection model with Chinese characteristics has been explored and formed, and mangrove forests, the “guardians of the coast,” are becoming a shining business card of beautiful China. Therefore, China's important experience in striking a balance between mangrove protection and economic development can provide a reference for other mangrove areas worldwide, and is of great significance in solving the global problem of mangrove forests in danger

Delocalization of d-electrons induced by cation coupling in ultrathin Chevrel-phase NiMo₃S₄ nanosheets for efficient electrochemical water splitting

Chevrel-phase metal sulfides are known to be promising materials for energy conversion and storage applications. However, a detailed understanding of the intrinsic kinetic mechanisms of electrocatalytic bifunctional hydrogen and oxygen evolution reactions (HER/OER) on NiMo3S4-based Chevrel-phases is lacking. Herein, novel ultrathin self-assembled nanosheets of NiMo3S4 are coupled with transition metal atoms (M/N-NiMo3S4; where M = Co, Fe, and Cu) were formed by a facile hydrothermal approach. Notably, the Co/N-NiMo3S4 electrocatalyst exhibits excellent performance in terms of ultralow overpotentials of 78, 208, 282, and 307 mV at 10, 100, 500, and 1000 mA cm−2 for the HER; and 186, 204, and 225 mV at 50, 100, and 300 mA cm−2 for the OER, respectively. Experimental and first principle calculations demonstrate that Co atoms coupling with edge Ni atoms results in d‐electron delocalization on Co/N-NiMo3S4, signifying the efficient charge transfer to improve overall water electrolysis. In addition, an upshift in the d‐band center of Co/N-NiMo3S4 can optimize the free energies of a variety of reaction intermediates for water adsorption and dissociation; thereby facilitating the robust alkaline overall water electrolysis at 1.47 V. This work therefore greatly deepens the understanding of the bifunctional hydrogen and oxygen evolution reaction of Chevrel-phase electrocatalysts.</p

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy

Psoriasis is a globally prevalent chronic inflammatory skin disease. This study aimed to scrutinize the hub genes related to inflammation and potential molecular mechanisms in psoriasis. Utilizing mRNA expression profiles from public datasets GSE13355, GSE78097, and GSE14905, we set up a comprehensive analysis. Initially, we selected differentially expressed genes (DEGs) from psoriasis and control samples in GSE13355, followed by calculating inflammatory indices using genomic set variation analysis (GSVA). Weighted gene co-expression network analysis (WGCNA) was then applied to link significant modules with the inflammatory index. This process helped us identify differentially expressed inflammation-related genes (DE-IRGs). A protein-protein interaction (PPI) network was established, with the molecular complex detection (MCODE) plug-in pinpointing six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as central hub genes. These genes demonstrated pronounced immunohistochemical staining in psoriatic tissues compared to normal skin. Notably, the CCR7 gene exhibited the highest potential for m6A modification sites. Furthermore, we constructed transcription factor-microRNA-mRNA networks, identifying 139 microRNAs and 52 transcription factors associated with the hub genes. For the LASSO logistic regression model, the area under the curve (AUC) in the training set was 1, and in the two validation cohorts GSE78097 and GSE14905 were 1 and 0.872, respectively. In conclusion, our study highlights six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as potential biomarkers in psoriasis, providing insights into the immune and inflammatory responses as pivotal instances in disease pathogenesis. These findings pave the way for exploring new therapeutic targets, particularly focusing on chemokine-associated pathways in psoriasis treatment

Delocalization of d-electrons induced by cation coupling in ultrathin Chevrel-phase NiMo₃S₄ nanosheets for efficient electrochemical water splitting

Chevrel-phase metal sulfides are known to be promising materials for energy conversion and storage applications. However, a detailed understanding of the intrinsic kinetic mechanisms of electrocatalytic bifunctional hydrogen and oxygen evolution reactions (HER/OER) on NiMo3S4-based Chevrel-phases is lacking. Herein, novel ultrathin self-assembled nanosheets of NiMo3S4 are coupled with transition metal atoms (M/N-NiMo3S4; where M = Co, Fe, and Cu) were formed by a facile hydrothermal approach. Notably, the Co/N-NiMo3S4 electrocatalyst exhibits excellent performance in terms of ultralow overpotentials of 78, 208, 282, and 307 mV at 10, 100, 500, and 1000 mA cm−2 for the HER; and 186, 204, and 225 mV at 50, 100, and 300 mA cm−2 for the OER, respectively. Experimental and first principle calculations demonstrate that Co atoms coupling with edge Ni atoms results in d‐electron delocalization on Co/N-NiMo3S4, signifying the efficient charge transfer to improve overall water electrolysis. In addition, an upshift in the d‐band center of Co/N-NiMo3S4 can optimize the free energies of a variety of reaction intermediates for water adsorption and dissociation; thereby facilitating the robust alkaline overall water electrolysis at 1.47 V. This work therefore greatly deepens the understanding of the bifunctional hydrogen and oxygen evolution reaction of Chevrel-phase electrocatalysts.</p

A pan-cancer analysis targeting the oncogenic role of ATP-binding cassette transporter A1 in human tumors

ObjectivesABCA1 is involved in the development and progression of a wide range of malignant tumors, so to further clarify the role of ABCA1 expression therein, and to search for new breakthroughs in the treatment of tumors and cancers, we launched a thorough pan-cancer analysis of ABCA1.MethodsBased on the manipulation of TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus), Human Protein Atlas (HPA) datasets and various bioinformatics tools, The oncogenic role of ABCA1 in 33 tumor types was explored from six aspects: gene expression, prognosis, variation, immunohistochemistry, correlation of tumor-associated fibroblastic infiltration, and enriched analysis of related genes. The potential value of ABCA1 was also mined, such as: ABCA1 may be a potential marker of tumor metastasis, play a role in cancer resistance, and its expression may inhibit the spread of tumor cells.ResultsBased on the analysis results, we found that ABCA1 is expressed elevated and mutated in tumor samples of 33 cancer types compared with matched normal tissues, and these mutations may be related to the mechanism of cancer, metastatic ability, and prognosis, etc. Meanwhile, we also investigated the correlation between ABCA1 expression and tumor-associated fibroblast infiltration, and described its association with corresponding miRNAs, which can provide scientific basis for clinical diagnosis.ConclusionsOur study thoroughly illustrates the impact of ABCA1’s systemic presence across various forms of cancer. Given its specificity to tumors, ABCA1 holds promise as a biomarker for cancer diagnosis, monitoring for recurrence, and predicting outcomes. Consequently, our research could significantly bolster the case for utilizing ABCA1 in the therapeutic approach to cancer

Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing technology and application

BACKGROUND: Long-range chromatin interactions play an important role in transcription regulation. Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET) is an emerging technology that has unique advantages in chromatin interaction analysis, and thus provides insight into the study of transcription regulation. RESULTS: This article introduces the experimental protocol and data analysis process of ChIA-PET, as well as discusses some applications using this technology. It also unveils the direction of future studies based on this technology. CONCLUSIONS: Overall we show that ChIA-PET is the cornerstone to explore the three-dimensional (3D) chromatin structure, and certainly will lead the forthcoming wave of 3D genomics studies