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1.
Protein phosphorylation and kinases: Potential therapeutic targets in necroptosis.
Shi, Y, Wu, C, Shi, J, Gao, T, Ma, H, Li, L, Zhao, Y
European journal of pharmacology. 2024;:176508
Abstract
Necroptosis is a pivotal contributor to the pathogenesis of various human diseases, including those affecting the nervous system, cardiovascular system, pulmonary system, and kidneys. Extensive investigations have elucidated the mechanisms and physiological ramifications of necroptosis. Among these, protein phosphorylation emerges as a paramount regulatory process, facilitating the activation or inhibition of specific proteins through the addition of phosphate groups to their corresponding amino acid residues. Currently, the targeting of kinases has gained recognition as a firmly established and efficacious therapeutic approach for diverse diseases, notably cancer. In this comprehensive review, we elucidate the intricate role of phosphorylation in governing key molecular players in the necroptotic pathway. Moreover, we provide an in-depth analysis of recent advancements in the development of kinase inhibitors aimed at modulating necroptosis. Lastly, we deliberate on the prospects and challenges associated with the utilization of kinase inhibitors to modulate necroptotic processes.
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2.
Targeted intervention of natural medicinal active ingredients and traditional Chinese medicine on epigenetic modification: Possible strategies for prevention and treatment of atherosclerosis.
Wang, W, Li, H, Shi, Y, Zhou, J, Khan, GJ, Zhu, J, Liu, F, Duan, H, Li, L, Zhai, K
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155139
Abstract
BACKGROUND Atherosclerosis is a deadly consequence of cardiovascular disease and has very high mortality rate worldwide. The epigenetic modifications can regulate the pervasiveness and progression of atherosclerosis through its involvement in regulation of inflammation, oxidative stress, lipid metabolism and several other factors. Specific non-coding RNAs, DNA methylation, and histone modifications are key regulatory factors of atherosclerosis. Natural products from traditional Chinese medicine have shown promising therapeutic potential against atherosclerosis by means of regulating the expression of specific genes, stabilizing arterial plaques and protecting vascular endothelial cells. OBJECTIVE Our study is focusing to explore the pathophysiology and probability of traditional Chinese medicine and natural medicinal active ingredients to treat atherosclerosis. METHODS Comprehensive literature review was conducted using PubMed, Web of Science, Google Scholar and China National Knowledge Infrastructure with a core focus on natural medicinal active ingredients and traditional Chinese medicine prying in epigenetic modification related to atherosclerosis. RESULTS Accumulated evidence demonstrated that natural medicinal active ingredients and traditional Chinese medicine have been widely studied as substances that can regulate epigenetic modification. They can participate in the occurrence and development of atherosclerosis through inflammation, oxidative stress, lipid metabolism, cell proliferation and migration, macrophage polarization and autophagy respectively. CONCLUSION The function of natural medicinal active ingredients and traditional Chinese medicine in regulating epigenetic modification may provide a new potential strategy for the prevention and treatment of atherosclerosis. However, more extensive research is essential to determine the potential of these natural medicinal active ingredients to treat atherosclerosis because of least clinical data.
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3.
The extraction, purification, structural features, bioactivities, and applications of Schisandra chinensis polysaccharides: A review.
Luan, F, Zou, J, Zhang, X, Zeng, J, Peng, X, Li, R, Shi, Y, Zeng, N
International journal of biological macromolecules. 2024;(Pt 2):130030
Abstract
Schisandra chinensis, as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo, including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields.
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4.
Recent advances in Platycodon grandiflorum polysaccharides: Preparation techniques, structural features, and bioactivities.
Feng, L, Shi, Y, Zou, J, Zhang, X, Zhai, B, Guo, D, Sun, J, Wang, M, Luan, F
International journal of biological macromolecules. 2024;(Pt 1):129047
Abstract
Platycodon grandiflorum, a globally recognized medicinal and edible plant, possesses significant nutritional value and pharmacological value. In traditional Chinese medicine, it has the effects of tonifying the spleen and replenishing the Qi, moistening the lung and relieving the cough, clearing the heat and detoxifying, and relieving the pain. Accumulating evidence has revealed that the polysaccharides from P. grandiflorum (PGPs) are one of the major and representative biologically active macromolecules and have diverse biological activities, such as immunomodulatory activity, anti-inflammatory activity, anti-tumor activity, regulation of the gut microbiota, anti-oxidant activity, anti-apoptosis activity, anti-angiogenesis activity, hypoglycemic activity, anti-microbial activity, and so on. Although the polysaccharides extracted from P. grandiflorum have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge of their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. The main purpose of the present review is to provide comprehensively and systematically reorganized information on extraction and purification, structure characterizations, and biological functions as well as toxicities of PGPs to support their therapeutic potentials and sanitarian functions. New valuable insights for future research regarding PGPs were also proposed in the fields of therapeutic agents and functional foods.
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5.
The anterior chamber of the eye technology and its anatomical, optical, and immunological bases.
Yang, SN, Shi, Y, Berggren, PO
Physiological reviews. 2024;(3):881-929
Abstract
The anterior chamber of the eye (ACE) is distinct in its anatomy, optics, and immunology. This guarantees that the eye perceives visual information in the context of physiology even when encountering adverse incidents like inflammation. In addition, this endows the ACE with the special nursery bed iris enriched in vasculatures and nerves. The ACE constitutes a confined space enclosing an oxygen/nutrient-rich, immune-privileged, and less stressful milieu as well as an optically transparent medium. Therefore, aside from visual perception, the ACE unexpectedly serves as an excellent transplantation site for different body parts and a unique platform for noninvasive, longitudinal, and intravital microimaging of different grafts. On the basis of these merits, the ACE technology has evolved from the prototypical through the conventional to the advanced version. Studies using this technology as a versatile biomedical research platform have led to a diverse range of basic knowledge and in-depth understanding of a variety of cells, tissues, and organs as well as artificial biomaterials, pharmaceuticals, and abiotic substances. Remarkably, the technology turns in vivo dynamic imaging of the morphological characteristics, organotypic features, developmental fates, and specific functions of intracameral grafts into reality under physiological and pathological conditions. Here we review the anatomical, optical, and immunological bases as well as technical details of the ACE technology. Moreover, we discuss major achievements obtained and potential prospective avenues for this technology.
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6.
Treatment of preterm brain injury via gut-microbiota-metabolite-brain axis.
Li, L, Liu, T, Shi, Y
CNS neuroscience & therapeutics. 2024;(1):e14556
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Abstract
BACKGROUND Brain injury in preterm infants potentially disrupts critical structural and functional connective networks in the brain. It is a major cause of neurological sequelae and developmental deficits in preterm infants. Interesting findings suggest that the gut microbiota (GM) and their metabolites contribute to the programming of the central nervous system (CNS) during developmental stages and may exert structural and functional effects throughout the lifespan. AIM: To summarize the existing knowledge of the potential mechanisms related to immune, endocrine, neural, and blood-brain barrier (BBB) mediated by GM and its metabolites in neural development and function. METHODS We review the recent literature and included 150 articles to summarize the mechanisms through which GM and their metabolites work on the nervous system. Potential health benefits and challenges of relevant treatments are also discussed. RESULTS This review discusses the direct and indirect ways through which the GM may act on the nervous system. Treatment of preterm brain injury with GM or related derivatives, including probiotics, prebiotics, synbiotics, dietary interventions, and fecal transplants are also included. CONCLUSION This review summarizes mechanisms underlying microbiota-gut-brain axis and novel therapeutic opportunities for neurological sequelae in preterm infants. Optimizing the initial colonization and microbiota development in preterm infants may represent a novel therapy to promote brain development and reduce long-term sequelae.
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7.
Fraxini cortex: Progresses in phytochemistry, pharmacology and ethnomedicinal uses.
Zheng, Z, Sun, C, Zhong, Y, Shi, Y, Zhuang, L, Liu, B, Liu, Z
Journal of ethnopharmacology. 2024;:117849
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Fraxini cortex, which has been widely used as a traditional Chinese medicine for 2000 years, is made from the dried bark of four plant species: Fraxinus chinensis subsp. rhynchophylla (Hance) A.E.Murray, Fraxinus chinensis Roxb., Fraxinus chinensis subsp. chinensis and Fraxinus stylosa Lingelsh.. In Chinese traditional medicine, it possesses the properties of heat-clearing and dampness-drying, asthma relief and cough suppression, as well as vision improvement. It is utilized for treating bacterial disorders, enteritis, leukorrhea, chronic bronitis, painful red eyes with swelling, lacrimation due to windward exposure, psoriasis, and other diseases or related symptoms. AIM OF THE STUDY Fraxini cortex is abundant in chemical constituents and has garnered significant attention from plant chemists, particularly regarding coumarins, as evidenced by the recently identified three coumarin compounds. Considering the current dearth of systematic reporting on studies pertaining to Fraxini cortex, herein we provide a comprehensive summary of the advancements in phytochemistry, pharmacology, detection methods, and ethnomedicinal applications of Fraxini cortex. MATERIALS AND METHODS We conducted a comprehensive search across online data sources (Web of Science, Public Medicine (PubMed), China National Knowledge Infrastructure (CNKI), as well as Chinese dissertations) and traditional Chinese medicine classics to gather the necessary literature resources for this review. RESULTS Briefly, The Fraxini cortex yielded a total of 132 phytochemicals, including coumarins, lignans, secoiridoids, phenylethanol glycosides, flavonoids, triterpenoids, and other compounds. Among them, the main active ingredients are coumarins which possess a diverse range of pharmacological activities such as anti-inflammatory effects, anti-tumor properties, prevention of tissue fibrosis and oxidation damage as well as cardioprotective effects. CONCLUSIONS All types of research conducted on Fraxini cortex, particularly in the field of ethnopharmacology, phytochemistry, and pharmacology, have been thoroughly reviewed. However, certain traditional applications and pharmacological activities of Fraxini cortex lack scientific evaluation or convincing evidence due to incomplete methodologies and ambiguous results, as well as a lack of clinical data. To validate its pharmacological activity, clinical efficacy, and safety profile, a systematic and comprehensive research evaluation is imperative. As an important traditional Chinese medicine, Fraxini cortex should be further explored to facilitate the development of novel drugs and therapeutics for various diseases. Greater attention should be given to how it can be better utilized.
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8.
Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial.
Wang, M, Fan, Y, Sun, M, Wang, Y, Zhao, Y, Jin, B, Hu, Y, Han, Z, Song, X, Liu, A, et al
The Lancet. Respiratory medicine. 2024;(3):217-224
Abstract
BACKGROUND Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins. METHODS WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing. FINDINGS Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]). INTERPRETATION In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988). FUNDING Dizal Pharmaceutical.
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9.
Identification and Regulation of Hypoxia-Tolerant and Germination-Related Genes in Rice.
Yuan, H, Zheng, Z, Bao, Y, Zhao, X, Lv, J, Tang, C, Wang, N, Liang, Z, Li, H, Xiang, J, et al
International journal of molecular sciences. 2024;(4)
Abstract
In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory network is critical to the development of hypoxia-tolerant rice varieties and direct seeding of rice. This review summarizes the morphological, physiological, and ecological changes in rice under hypoxia stress, the discovery of hypoxia-tolerant and germination-related genes/QTLs, and the latest research on candidate genes, and explores the linkage of hypoxia tolerance genes and their distribution in indica and japonica rice through population variance analysis and haplotype network analysis. Among the candidate genes, OsMAP1 is a typical gene located on the MAPK cascade reaction for indica-japonica divergence; MHZ6 is involved in both the MAPK signaling and phytohormone transduction pathway. MHZ6 has three major haplotypes and one rare haplotype, with Hap3 being dominated by indica rice varieties, and promotes internode elongation in deep-water rice by activating the SD1 gene. OsAmy3D and Adh1 have similar indica-japonica varietal differentiation, and are mainly present in indica varieties. There are three high-frequency haplotypes of OsTPP7, namely Hap1 (n = 1109), Hap2 (n = 1349), and Hap3 (n = 217); Hap2 is more frequent in japonica, and the genetic background of OsTPP7 was derived from the japonica rice subpopulation. Further artificial selection, natural domestication, and other means to identify more resistance mechanisms of this gene may facilitate future research to breed superior rice cultivars. Finally, this study discusses the application of rice hypoxia-tolerant germplasm in future breeding research.
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10.
Abnormal expression of Krüppel-like transcription factors and their potential values in lung cancer.
Shi, Y, Yao, M, Shen, S, Wang, L, Yao, D
Heliyon. 2024;(7):e28292
Abstract
Lung cancer still is one of the most common malignancy tumors in the world. However, the mechanisms of its occurrence and development have not been fully elucidated. Zinc finger protein family (ZNFs) is the largest transcription factor family in human genome. Recently, the more and more basic and clinical evidences have confirmed that ZNFs/Krüppel-like factors (KLFs) refer to a group of conserved zinc finger-containing transcription factors that are involved in lung cancer progression, with the functions of promotion, inhibition, dual roles and unknown classifications. Based on the recent literature, some of the oncogenic KLFs are promising molecular biomarkers for diagnosis, prognosis or therapeutic targets of lung cancer. Interestingly, a novel computational approach has been proposed by using machine learning on features calculated from primary sequences, the XGBoost-based model with accuracy of 96.4 % is efficient in identifying KLF proteins. This paper reviews the recent some progresses of the oncogenic KLFs with their potential values for diagnosis, prognosis and molecular target in lung cancer.