An approach has been developed for the amidation (halogenation) of tertiary arylamines by electrophilic activation using N‐haloimide/amides. Several control experiments have been performed, and the ...coupling reaction outcomes indicated that the N‐haloimide/amide brings three major functions, including electrophilic activation, aromatic halogenation and nucleophilic nitrogen sources. This cascade reaction features simple manipulation, requires no additional catalyst, oxidant or additives, and is performed under mild conditions.
Aim
Platinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) ...protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer.
Methods
We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature.
Results
Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer.
Conclusions
There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment.
Abstract A metal‐free N‐iodosuccinimde (NIS)/2,2,6,6‐tetramethylpiperidinyloxy (TEMPO)‐promoted protocol was developed for the oxidative cyanation and nitro‐Mannich reaction of tertiary amines via a ...cross‐dehydrogenative coupling reaction under mild conditions. Several control experiments were performed; the coupling reaction outcomes indicated that the C−N coupled intermediate ( N ‐Mannich base) formed from the tertiary amine and NIS had a stabilizing effect on the iminium cation.
Background： Atopic dermatitis （AD） is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic ...diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczemaJAD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods： A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients （12 years and over） with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and-investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results： A total of 2662 valid questionnaires were collected （1369 male and 1293 female）. Of all 2662 patients, 2062 （77.5%） patients had the disease after 12 years old, while only 600 （22.5%） patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine （80.4%） patients had the disease for more than 6 months. One thousand one hundred and forty-four （43.0%） patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight （58.2%） patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion： Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.
Abstract Multiwavelength properties of the nearby supernova (SN)-associated low-luminosity GRB 171205A are investigated in depth to constrain its physical origin synthetically. The pulse width is ...found to be correlated with energy with a power-law index of −0.24 ± 0.07, which is consistent with the indices of other SN-associated gamma-ray bursts (SN/GRBs) but larger than those of long GRBs. By analyzing the overall light curve of its prompt gamma rays and X-ray plateaus simultaneously, we infer that the early X-rays together with the gamma-rays should reflect the activities of the central engine, while the late X-rays may be dominated by the interaction of external shocks with circumburst material. In addition, we find that the host radio flux and offset of GRB 171205A are similar to those of other nearby low-luminosity GRBs. We adopt nine SN/GRBs with measured offset to build a relation between peak luminosity ( L γ , p ) and spectral lag ( τ ) as L γ , p ∝ τ −1.91±0.33 . The peak luminosity and the projected physical offset of 12 SN/GRBs and 10 kilonova-associated GRBs are found to be moderately correlated, suggesting their different progenitors. The multiwavelength afterglow fitted with a top-hat jet model indicates that the jet half-opening angle and the viewing angle of GRB 171205A are ∼34.°4 and 41.°8, respectively, which implies that the off-axis emissions are dominated by the peripheral cocoon rather than the jet core.
•It was the first time to evaluate the possible molecular mechanism of Corbrin capsules for treatment of AKI-COVID-19.•TP53, JAK2, PIK3CA, PTGS2, KEAP1, and MCL1 as the top six core protein ...targets.•Immune infiltration analysis revealed a notable disparity in the expression of quiescent memory CD4 T cells.•This study provided new understanding of the molecular mechanisms based on network pharmacology.
of the study: This study used network pharmacology and the Gene Expression Omnibus (GEO) database to investigate the therapeutic effects of Corbrin capsules on acute kidney injury (AKI)-COVID-19 (coronavirus disease 2019).
The active constituents and specific molecular targets of Corbrin capsules were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. The targets related to AKI and COVID-19 disease were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and GEO databases. A protein–protein interaction (PPI) network was constructed by utilizing Cytoscape. To enhance the analysis of pathways associated with the pathogenesis of AKI-COVID-19, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Furthermore, immune infiltration analysis was performed by using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Molecular docking was used to assess interactions between differentially expressed genes and active ingredients. Verification was performed by utilizing GEO databases and in vivo assays.
This study revealed an overlap of 18 significantly differentially expressed genes between the Corbrin capsules group and the AKI-COVID-19 target group. Analysis of the PPI network identified TP53, JAK2, PIK3CA, PTGS2, KEAP1, and MCL1 as the top six core protein targets with the highest degrees. The results obtained from GO and KEGG analyses demonstrated that the target genes were primarily enriched in the apoptosis and JAK-STAT signaling pathways. Moreover, the analysis of immune infiltration revealed a notable disparity in the percentage of quiescent memory CD4 + T cells. Western blot analyses provided compelling evidence suggesting that the dysregulation of 6 core protein targets could be effectively reversed by Corbrin capsules.
This study revealed the key components, targets, and pathways involved in treating AKI-related COVID-19 using Corbrin capsules. This study also provided a new understanding of the molecular mechanisms underlying this treatment.
Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, ...this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD.
We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression.
In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models.
Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.
PCSK9: A emerging participant in heart failure Xu, Qian; Zhao, Yi-meng; He, Nai-qi ...
Biomedicine & pharmacotherapy,
February 2023, 2023-Feb, 2023-02-00, 20230201, 2023-02-01, Volume:
158
Journal Article
Peer reviewed
Open access
Heart failure (HF) is a complex clinical syndrome caused by various cardiovascular diseases. Its main pathogenesis includes cardiomyocyte loss, myocardial energy metabolism disorder, and activation ...of cardiac inflammation. Due to the clinically unsatisfactory treatment of heart failure, different mechanisms need to be explored to provide new targets for the treatment of this disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene mainly related to familial hypercholesterolemia, was discovered in 2003. Aside from regulating lipid metabolism, PCSK9 may be involved in other biological processes such as apoptosis, autophagy, pyroptosis, inflammation, and tumor immunity and related to diabetes and neurodegenerative diseases. Recently, clinical data have shown that the circulating PCSK9 level is significantly increased in patients with heart failure, and it is related to the prognosis for heart failure. Furthermore, in animal models and patients with myocardial infarction, PCSK9 in the infarct margin area was also found to be significantly increased, which further suggested that PCSK9 might be closely related to heart failure. However, the specific mechanism of how PCSK9 participates in heart failure remains to be further explored. The purpose of this review is to summarize the potential mechanism of PCSK9’s involvement in heart failure, thereby providing a new treatment strategy for heart failure.
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•HF needs new treatment strategies to ameliorate its present situation.•HF’s pathogenesis involved cell death, energy metabolism, inflammation etc.•PCSK9 contributes to the pathogenesis of HF and may be new target for therapy.•Several PCSK9 inhibitors have been marketed and worked in cardiovascular diseases.
This report describes a method for Ni‐catalyzed intramolecular decarbonylative coupling, which enables the conversion of areneselenol esters to diaryl selenides. The inexpensive and readily available ...catalyst can be employed under mild reaction conditions for the construction of structurally diverse diaryl selenides, including heterocyclic and natural product derivatives.
There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients ...from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow‐up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non‐metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third‐line to the first‐line of treatment for different patient groups with detailed notes are provided.
The Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile the clinical guideline for gastric cancer in 2016 and then renewed it every year. The 2021 CSCO Clinical Practice Guidelines for gastric cancer covered the diagnosis, treatment, follow‐up and screening.
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