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Journal of Clinical Medicine Jun 2024Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment... (Review)
Review
Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment option for hormone receptor (HR)-positive BC either in the early or in advanced setting, including different strategies, such as the suppression of estrogen production or directly blocking the ER pathway through SERMs-selective estrogen receptor modulators-or SERDs-selective estrogen receptor degraders. Nevertheless, the development of de novo or acquired endocrine resistance still remains challenging for oncologists. The use of novel ET combined with targeted drugs, such as cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, has significantly improved long-term outcome rates, thus changing the therapeutic algorithm for metastatic BC (MBC) and recently the therapeutic strategy in the adjuvant setting for early high-risk BC. Eluding the resistance to CDK4/6 inhibitors combined with ET is currently an unmet medical need, and there is disagreement concerning the best course of action for patients who continue to progress after this combination approach. Genetic changes in the tumor along its growth uncovered by genomic profiling of recurrent and/or metastatic lesions through tumor and/or liquid biopsies may predict the response or resistance to specific agents, suggesting the best therapeutic strategy for each patient by targeting the altered ER-dependent pathway (novel oral SERDs and a new generation of anti-estrogen agents) or alternative ER-independent signaling pathways such as PI3K/AKT/mTOR or tyrosine kinase receptors ( mutations or HER2 low status) or by inhibiting pathways weakened through germline mutations. These agents are being investigated as single molecules and in combination with other target therapies, offering promising weapons to overcome or avoid treatment failure and propose increasingly more personalized treatment approaches. This review presents novel insights into ET and other targeted therapies for managing metastatic HR/HER2 BC by exploring potential strategies based on clinical evidence and genomic profiling following the failure of the CDK4/6i and ET combination.
PubMed: 38930141
DOI: 10.3390/jcm13123611 -
Medicina (Kaunas, Lithuania) Jun 2024Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo...
Combining Endocrine Therapy with Trastuzumab Emtansine Improves Progression-Free Survival and Overall Survival in HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer.
Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; = 0.00004) and median OS (35.0 vs. 23.1 months; = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; = 0.049). The safety profiles were consistent with previous T-DM1 studies. The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy.
Topics: Humans; Breast Neoplasms; Female; Middle Aged; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Aged; Progression-Free Survival; Adult; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents, Immunological; Neoplasm Metastasis; Aged, 80 and over; Trastuzumab; Receptors, Estrogen
PubMed: 38929568
DOI: 10.3390/medicina60060951 -
Antioxidants (Basel, Switzerland) May 2024Horticultural crops play a vital role in global food production, nutrition, and the economy. Horticultural crops are highly vulnerable to abiotic stresses. These abiotic... (Review)
Review
Horticultural crops play a vital role in global food production, nutrition, and the economy. Horticultural crops are highly vulnerable to abiotic stresses. These abiotic stresses hinder plant growth and development by affecting seed germination, impairing photosynthetic activity, and damaging root development, thus leading to a decrease in fruit yield, quality, and productivity. Scientists have conducted extensive research to investigate the mechanisms of resilience and the ability to cope with environmental stresses. In contrast, the use of phytohormones to alleviate the detrimental impacts of abiotic stresses on horticulture plants has been generally recognized as an effective method. Among phytohormones, melatonin (MT) is a novel plant hormone that regulates various plants' physiological functions such as seedling development, root system architecture, photosynthetic efficiency, balanced redox homeostasis, secondary metabolites production, accumulation of mineral nutrient uptake, and activated antioxidant defense system. Importantly, MT application significantly restricted heavy metals (HMs) uptake and increased mineral nutrient accumulation by modifying the root architecture system. In addition, MT is a naturally occurring, multifunctional, nontoxic biomolecule having antioxidant properties. Furthermore, this review described the hormonal interaction between MT and other signaling molecules in order to enhance abiotic stress tolerance in horticulture crops. This review focuses on current research advancements and prospective approaches for enhancing crop tolerance to abiotic stress.
PubMed: 38929102
DOI: 10.3390/antiox13060663 -
Foods (Basel, Switzerland) Jun 2024In order to cope with the limited supply of feed for global animal production, there is a pressing need to explore alternative feed resources. Orange pulp, a by-product...
Effects of Fermented Navel Orange Pulp on Growth Performance, Carcass Characteristics, Meat Quality, Meat Nutritional Value, and Serum Biochemical Indicators of Finishing Tibetan Pigs.
In order to cope with the limited supply of feed for global animal production, there is a pressing need to explore alternative feed resources. Orange pulp, a by-product of agriculture and industry, has shown potential to positively or neutrally impact pig productive performance when included in their diet. However, there is a lack of research on the effects of fermented navel orange pulp (FNOP) on pig growth and productive performance. This study aimed to investigate the effects of FNOP as a dry matter substitute on pig's growth performance, carcass characteristics, meat quality, meat nutritional value, and serum biochemical indicators. The experiment involved 128 finishing Tibetan pigs, divided into four feed treatment groups, with varying levels (0%, 5%, 10% and 15%) of FNOP replacing dry matter in the basal diet. The results indicate that substituting 5% to 15% FNOP had no adverse effects on pig growth performance. However, at a 15% substitution rate, there was a decrease in serum growth hormone and IGF-1 levels, along with an increase in the feed-to-gain ratio. A 10% FNOP replacement notably increased the loin-eye muscle area of pigs. Additionally, 5% and 10% FNOP substitutions reduced the drip loss of pork. The study also found that substituting 5% to 15% FNOP increased unsaturated fatty acids and umami nucleotide contents in pork and raised serum total protein and uric acid (nucleotide-metabolism-related product) levels. These findings suggest that moderate FNOP substitution might improve meat quality, nutritional value, and maintain growth and productive performance in Tibetan pigs by improving protein synthesis and nucleotide metabolism, while also reducing feed costs. The optimal substitution ratio identified was 10%.
PubMed: 38928851
DOI: 10.3390/foods13121910 -
International Journal of Molecular... Jun 2024Melatonin (MEL), a hormone primarily known for its role in regulating sleep and circadian rhythms in animals, has emerged as a multifaceted molecule in plants. Recent... (Review)
Review
Melatonin (MEL), a hormone primarily known for its role in regulating sleep and circadian rhythms in animals, has emerged as a multifaceted molecule in plants. Recent research has shed light on its diverse functions in plant growth and defense mechanisms. This review explores the intricate roles of MEL in plant growth and defense responses. MEL is involved in plant growth owing to its influence on hormone regulation. MEL promotes root elongation and lateral root formation and enhances photosynthesis, thereby promoting overall plant growth and productivity. Additionally, MEL is implicated in regulating the circadian rhythm of plants, affecting key physiological processes that influence plant growth patterns. MEL also exhibits antioxidant properties and scavenges reactive oxygen species, thereby mitigating oxidative stress. Furthermore, it activates defense pathways against various biotic stressors. MEL also enhances the production of secondary metabolites that contribute to plant resistance against environmental changes. MEL's ability to modulate plant response to abiotic stresses has also been extensively studied. It regulates stomatal closure, conserves water, and enhances stress tolerance by activating stress-responsive genes and modulating signaling pathways. Moreover, MEL and nitric oxide cooperate in stress responses, antioxidant defense, and plant growth. Understanding the mechanisms underlying MEL's actions in plants will provide new insights into the development of innovative strategies for enhancing crop productivity, improving stress tolerance, and combating plant diseases. Further research in this area will deepen our knowledge of MEL's intricate functions and its potential applications in sustainable agriculture.
Topics: Melatonin; Plant Development; Antioxidants; Stress, Physiological; Plants; Circadian Rhythm; Plant Growth Regulators; Gene Expression Regulation, Plant
PubMed: 38928504
DOI: 10.3390/ijms25126799 -
International Journal of Molecular... Jun 2024Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and...
Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na decreased by 34.34, K increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress.
Topics: Nicotiana; Seedlings; Antioxidants; Signal Transduction; Eugenol; Gene Expression Regulation, Plant; Salt Stress; Plant Growth Regulators; Salt Tolerance; Reactive Oxygen Species
PubMed: 38928476
DOI: 10.3390/ijms25126771 -
International Journal of Molecular... Jun 2024Cytochrome P450 monooxygenases () play a variety of physiological roles, including pesticide resistance, plant allelochemical detoxification, and hormone metabolism... (Comparative Study)
Comparative Study
Cytochrome P450 monooxygenases () play a variety of physiological roles, including pesticide resistance, plant allelochemical detoxification, and hormone metabolism catalysis. However, limited information is available on the classification and expression profiles of the gene family in aphid species. This is the first study to identify the cytochrome P450 gene family in 19 aphid species at the whole genome level. A total of 1100 genes were identified in 19 aphid species. Three hundred genes belonged to six cereal crop aphid species, which were further classified into four subfamilies according to the phylogenetic relationship. The conserved motifs, exon-intron structures, and genomic organization of the same subfamilies were similar. Predictions of subcellular localization revealed that the endoplasmic reticulum harbored the majority of CYP450 proteins. In and , the increase in the gene was primarily caused by segmental duplication events. However, only tandem duplication occurred in the gene family of , , and . Synteny analysis found three continuous colinear gene pairs among six cereal crop aphid species. Furthermore, we obtained the expression profiles of four cereal crop aphids, including , , and . Differential expression analysis provided growth stage specificity genes, tissue specificity genes, organ specificity genes and some detoxification metabolic genes among these four cereal crop aphids. Meanwhile, their expression patterns were showed. The related functions and pathways of were revealed by GO and KEGG enrichment analysis. Above all, we picked the differentially expressed genes from all of the differentially expressed genes (DEGs). These differentially expressed genes provided some new potential candidates for aphid control and management. This work establishes the foundation for further investigations into the regulatory functions of the gene family in aphid species and beyond.
Topics: Aphids; Animals; Cytochrome P-450 Enzyme System; Phylogeny; Multigene Family; Edible Grain; Genome, Insect; Gene Expression Profiling; Synteny; Insect Proteins
PubMed: 38928374
DOI: 10.3390/ijms25126668 -
International Journal of Molecular... Jun 2024The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that...
The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that can regulate plant morphogenesis and stress resistance and alter the accumulation of flavonoids in these processes. However, the direct effect of melatonin on citrus flavonoids remains unclear. In this study, nontargeted metabolomics and transcriptomics were utilized to reveal how exogenous melatonin affects flavonoid biosynthesis in "Bingtangcheng" citrus fruits. The melatonin treatment at 0.1 mmol L significantly increased the contents of seven polymethoxylated flavones (PMFs) and up-regulated a series of flavonoid pathway genes, including (4-coumaroyl CoA ligase), (flavone synthase), and (flavonoid hydroxylases). Meanwhile, (chalcone synthase) was down-regulated, causing a decrease in the content of most flavonoid glycosides. Pearson correlation analysis obtained 21 transcription factors co-expressed with differentially accumulated flavonoids, among which the AP2/EREBP members were the most numerous. Additionally, circadian rhythm and photosynthesis pathways were enriched in the DEG (differentially expressed gene) analysis, suggesting that melatonin might also mediate changes in the flavonoid biosynthesis pathway by affecting the fruit's circadian rhythm. These results provide valuable information for further exploration of the molecular mechanisms through which melatonin regulates citrus fruit metabolism.
Topics: Citrus; Melatonin; Flavonoids; Gene Expression Regulation, Plant; Fruit; Metabolomics; Gene Expression Profiling; Transcriptome; Metabolome; Plant Proteins
PubMed: 38928338
DOI: 10.3390/ijms25126632 -
International Journal of Molecular... Jun 2024The morphological architecture of inflorescence influences seed production. The regulatory mechanisms underlying alfalfa () inflorescence elongation remain unclear....
The morphological architecture of inflorescence influences seed production. The regulatory mechanisms underlying alfalfa () inflorescence elongation remain unclear. Therefore, in this study, we conducted a comparative analysis of the transcriptome, proteome, and metabolome of two extreme materials at three developmental stages to explore the mechanisms underlying inflorescence elongation in alfalfa. We observed the developmental processes of long and short inflorescences and found that the elongation capacity of alfalfa with long inflorescence was stronger than that of alfalfa with short inflorescences. Furthermore, integrative analysis of the transcriptome and proteome indicated that the phenylpropanoid biosynthesis pathway was closely correlated with the structural formation of the inflorescence. Additionally, we identified key genes and proteins associated with lignin biosynthesis based on the differential expressed genes and proteins (DEGs and DEPs) involved in phenylpropanoid biosynthesis. Moreover, targeted hormone metabolome analysis revealed that IAA, GA, and CK play an important role in the peduncle elongation of alfalfa inflorescences. Based on omics analysis, we detected key genes and proteins related to plant hormone biosynthesis and signal transduction. From the WGCNA and WPCNA results, we furthermore screened 28 candidate genes and six key proteins that were correlated with lignin biosynthesis, plant hormone biosynthesis, and signaling pathways. In addition, 19 crucial transcription factors were discovered using correlation analysis that might play a role in regulating candidate genes. This study provides insight into the molecular mechanism of inflorescence elongation in alfalfa and establishes a theoretical foundation for improving alfalfa seed production.
Topics: Medicago sativa; Inflorescence; Gene Expression Regulation, Plant; Plant Proteins; Transcriptome; Lignin; Plant Growth Regulators; Proteome; Gene Expression Profiling; Proteomics; Metabolome; Multiomics
PubMed: 38928203
DOI: 10.3390/ijms25126497 -
International Journal of Molecular... Jun 2024The GRAS gene family, responsible for encoding transcription factors, serves pivotal functions in plant development, growth, and responses to stress. The exploration of...
The GRAS gene family, responsible for encoding transcription factors, serves pivotal functions in plant development, growth, and responses to stress. The exploration of the GRAS gene family within the Orchidaceae has been comparatively limited, despite its identification and functional description in various plant species. This study aimed to conduct a thorough examination of the GRAS gene family in , focusing on its physicochemical attributes, phylogenetic associations, gene structure, cis-acting elements, and expression profiles under heat stress. The results show that a total of 54 s were pinpointed from the genome repository and categorized into ten subfamilies via phylogenetic associations. Assessment of gene sequence and structure disclosed the prevalent existence of the VHIID domain in most s, with around 57.41% (31/54) s lacking introns. The Ka/Ks ratios of all s were below one, indicating purifying selection across all . Examination of cis-acting elements unveiled the presence of numerous elements linked to light response, plant hormone signaling, and stress responsiveness. Furthermore, contained the highest quantity of cis-acting elements linked to stress response. Experimental results from RT-qPCR demonstrated notable variations in the expression levels of eight s after heat stress conditions, particularly within the LAS, HAM, and SCL4/7 subfamilies. In conclusion, this study revealed the expression pattern of s under heat stress, providing reference for further exploration into the roles of transcription factors in stress adaptation.
Topics: Heat-Shock Response; Gene Expression Regulation, Plant; Orchidaceae; Plant Proteins; Phylogeny; Multigene Family; Transcription Factors; Genome, Plant; Gene Expression Profiling
PubMed: 38928070
DOI: 10.3390/ijms25126363