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Current Pharmaceutical Design Jun 2024Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated in diverse physiological processes, spanning metabolic regulation,...
Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated in diverse physiological processes, spanning metabolic regulation, inflammation, and cardiovascular health. This studyprovides a comprehensive exploration of GDF15's multifaceted role, primarily focusing on its association with obesity-related complications and therapeutic potential. GDF15's involvement in energy homeostasis, specifically its regulation of body weight and appetite through hindbrain neuron activation and the GFRAL-RET signaling pathway, underscores its significance as an appetite-regulating hormone. GDF15's intricate modulation within adipose tissue dynamics in response to dietary changes and obesity, coupled with its influence on insulin sensitivity, highlights its critical role in metabolic health. The manuscript delves into the intricate crosstalk between GDF15 and pathways related to insulin sensitivity, macrophage polarization, and adipose tissue function, elucidating its potential as a therapeutic target for metabolic disorders associated with obesity. GDF15's association with chronic low-grade inflammation and its impact on cardiovascular health, particularly during hyperlipidemia and ischemic events, are explored. The intricate relationship between GDF15 and cardiovascular diseases, including its effects on endothelial function, cardiac hypertrophy, and heart failure, emphasizes its multifaceted nature in maintaining overall cardiovascular well-being. Challenges regarding the therapeutic application of GDF15, such as long-term safety concerns and ongoing clinical investigations, are discussed. Lastly, future research directions exploring GDF15's potential in addressing obesity-related complications and cardiovascular risks are proposed, highlighting its promising role as a therapeutic target in reshaping treatment strategies for obesity and associated health conditions.
PubMed: 38934286
DOI: 10.2174/0113816128318741240611114448 -
Frontiers in Genetics 2024Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is...
BACKGROUND
Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration.
METHODS
The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures.
RESULTS
The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome.
CONCLUSION
WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.
PubMed: 38933926
DOI: 10.3389/fgene.2024.1364441 -
Oncology Letters Aug 2024Adjuvant chemotherapy is usually not considered for pT1a pN0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer due to its low recurrence rate. The...
Multiple metastases of human epidermal growth factor receptor 2‑positive, hormone receptor‑positive, pT1a pN0 breast cancer within 1 year after surgery: A case report.
Adjuvant chemotherapy is usually not considered for pT1a pN0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer due to its low recurrence rate. The present report describes a case of pT1a hormone receptor-positive HER2-positive breast cancer with multiple recurrences in the axillary lymph nodes and liver within 1 year after radical surgery. A 58-year-old woman underwent left total mastectomy and sentinel lymph node biopsy for left breast cancer with pathological stage IA (pT1a pN0). The subtype corresponded to luminal B-like breast cancer with a nuclear grade of 3 and a Ki-67 labeling index of 37%. An aromatase inhibitor (letrozole) was planned to be administered for 5 years after surgery, but the patient was diagnosed with multiple liver and axillary lymph node metastases 11 months after surgery. After 1 year of chemotherapy (paclitaxel) in combination with anti-HER2 therapy (pertuzumab and trastuzumab), liver metastases resolved. A complete response of the liver lesion has been maintained 4 years after the anti-HER2 therapy initiation. The present case exhibited two poor prognostic factors: High Ki-67 labeling index and nuclear grade 3. Based on the 'Predict' tool, the present case would be expected to have a cancer-related mortality rate of 6% 10 years after surgery with adjuvant endocrine therapy. Although this value may be controversial for postoperative anti-HER2 therapy, the present case should not be considered to be a low-risk case. When the identification of high-risk pT1a pN0 HER2-positive breast cancer is possible, postoperative anti-HER2 therapy plus chemotherapy would be effective in decreasing the rate of recurrence.
PubMed: 38933808
DOI: 10.3892/ol.2024.14498 -
Nutrients Jun 2024Previous studies have reported that TT genotype carriers of the adenosine A2a receptor () gene rs5751876 polymorphism have better ergogenic and anti-inflammatory... (Randomized Controlled Trial)
Randomized Controlled Trial
Previous studies have reported that TT genotype carriers of the adenosine A2a receptor () gene rs5751876 polymorphism have better ergogenic and anti-inflammatory responses to caffeine intake compared to C allele carriers. The aim of the present study was twofold: (1) to investigate the association of the rs5751876 polymorphism with acute caffeine supplementation on hormonal (growth hormone and testosterone) response to resistance exercise (RE); (2) to examine the relationship between the rs5751876 polymorphism and the resting levels of growth hormone and testosterone in athletes who are light caffeine consumers. A double-blind, crossover, placebo-controlled study involving 30 resistance-trained men (age 21.7 ± 4.1) was conducted to assess the impact of caffeine supplementation on serum growth hormone (GH) and testosterone (TS) levels before, immediately after, and 15 min post-RE. One hour before engaging in resistance exercise, subjects were randomly administered 6 mg of caffeine per kg of body mass or a placebo (maltodextrin). After a 7-day washout period, the same protocol was repeated. Resting testosterone and growth hormone levels were examined in the sera of 94 elite athletes (31 females, age 21.4 ± 2.8; 63 males, age 22.9 ± 3.8). Caffeine consumption led to significantly greater increases in GH and TS in men with the TT genotype compared to C allele carriers. Furthermore, in the group of athletes, carriers of the TT genotype had significantly higher testosterone ( = 0.0125) and growth hormone ( = 0.0365) levels compared to C allele carriers. In conclusion, the gene rs5751876 polymorphism may modify the effect of caffeine intake on the hormonal response to exercise.
Topics: Humans; Caffeine; Male; Double-Blind Method; Cross-Over Studies; Resistance Training; Receptor, Adenosine A2A; Young Adult; Testosterone; Adult; Female; Dietary Supplements; Athletes; Polymorphism, Single Nucleotide; Genotype; Human Growth Hormone; Polymorphism, Genetic; Exercise
PubMed: 38931158
DOI: 10.3390/nu16121803 -
Plants (Basel, Switzerland) Jun 2024Enhancing root development is pivotal for boosting crop yield and augmenting stress resilience. In this study, we explored the regulatory effects of xylooligosaccharides...
Enhancing root development is pivotal for boosting crop yield and augmenting stress resilience. In this study, we explored the regulatory effects of xylooligosaccharides (XOSs) on lettuce root growth, comparing their impact with that of indole-3-butyric acid potassium salt (IBAP). Treatment with XOS led to a substantial increase in root dry weight (30.77%), total root length (29.40%), volume (21.58%), and surface area (25.44%) compared to the water-treated control. These enhancements were on par with those induced by IBAP. Comprehensive phytohormone profiling disclosed marked increases in indole-3-acetic acid (IAA), zeatin riboside (ZR), methyl jasmonate (JA-ME), and brassinosteroids (BRs) following XOS application. Through RNA sequencing, we identified 3807 differentially expressed genes (DEGs) in the roots of XOS-treated plants, which were significantly enriched in pathways associated with manganese ion homeostasis, microtubule motor activity, and carbohydrate metabolism. Intriguingly, approximately 62.7% of the DEGs responsive to XOS also responded to IBAP, underscoring common regulatory mechanisms. However, XOS uniquely influenced genes related to cutin, suberine, and wax biosynthesis, as well as plant hormone signal transduction, hinting at novel mechanisms of stress tolerance. Prominent up-regulation of genes encoding beta-glucosidase and beta-fructofuranosidase highlights enhanced carbohydrate metabolism as a key driver of XOS-induced root enhancement. Collectively, these results position XOS as a promising, sustainable option for agricultural biostimulation.
PubMed: 38931130
DOI: 10.3390/plants13121699 -
Plants (Basel, Switzerland) Jun 2024The holly K. Yao & M. B. Deng, a tree endemic to the Dabieshan Mountains region in China, is a commonly used landscaping plant. Like other crops, its growth is affected...
The holly K. Yao & M. B. Deng, a tree endemic to the Dabieshan Mountains region in China, is a commonly used landscaping plant. Like other crops, its growth is affected by salt stress. The molecular mechanism underlying salt tolerance in holly is still unclear. In this study, we used NaCl treatment and RNA sequencing (RNA-seq) at different times to identify the salt stress response genes of holly. A total of 4775 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs obtained at different salt treatment times (3, 6, 9, 12, and 24 h), as compared to control (ck, 0 h), showed that plant hormone signal transduction and carotenoid biosynthesis were highly enriched. The mechanism by which holly responds to salt stress involves many plant hormones, among which the accumulation of abscisic acid (ABA) and its signal transduction may play an important role. In addition, ion homeostasis, osmotic metabolism, accumulation of antioxidant enzymes and nonenzymatic antioxidant compounds, and transcription factors jointly regulate the physiological balance in holly, providing important guarantees for its growth and development under conditions of salt stress. These results lay the foundation for studying the molecular mechanisms of salt tolerance in holly and for the selection of salt-tolerant varieties.
PubMed: 38931069
DOI: 10.3390/plants13121638 -
Plants (Basel, Switzerland) Jun 2024Aluminum (Al) toxicity in acidic soils can significantly reduce peanut yield. The physiological response of peanut leaves to Al poisoning stress still has not been fully...
Aluminum (Al) toxicity in acidic soils can significantly reduce peanut yield. The physiological response of peanut leaves to Al poisoning stress still has not been fully explored. This research examined the influences of Al toxicity on peanut leaves by observing the leaf phenotype, scanning the leaf area and perimeter, and by measuring photosynthetic pigment content, physiological response indices, leaf hormone levels, and mineral element accumulation. Fluorescence quantitative RT-PCR (qPCR) was utilized to determine the relative transcript level of specific genes. The results indicated that Al toxicity hindered peanut leaf development, reducing their biomass, surface area, and perimeter, although the decrease in photosynthetic pigment content was minimal. Al toxicity notably affected the activity of antioxidative enzymes, proline content, and MDA (malondialdehyde) levels in the leaves. Additionally, Al poisoning resulted in the increased accumulation of iron (Fe), potassium (K), and Al in peanut leaves but reduced the levels of calcium (Ca), manganese (Mn), copper (Cu), zinc (Zn), and magnesium (Mg). There were significant changes in the content of hormones and the expression level of genes connected with hormones in peanut leaves. High Al concentrations may activate cellular defense mechanisms, enhancing antioxidative activity to mitigate excess reactive oxygen species (ROS) and affecting hormone-related gene expression, which may impede leaf biomass and development. This research aimed to elucidate the physiological response mechanisms of peanut leaves to Al poisoning stress, providing insights for breeding new varieties resistant to Al poisoning.
PubMed: 38931038
DOI: 10.3390/plants13121606 -
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