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Microbiology Spectrum Dec 2023In this study, whole-blood RNAs (prolactin and toll-like receptor 3) involved in the prognosis of patients with COVID-19 were identified. The RNA endotypes classified by...
In this study, whole-blood RNAs (prolactin and toll-like receptor 3) involved in the prognosis of patients with COVID-19 were identified. The RNA endotypes classified by these important RNAs highlight the possibility of stratifying the COVID-19 patient population and the need for targeted therapy based on these phenotypes.
Topics: Humans; COVID-19; RNA; Prospective Studies; Phenotype; Prognosis
PubMed: 37966347
DOI: 10.1128/spectrum.02645-23 -
Medicine Nov 2023Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colonic mucosa. Esculetin is a type of natural coumarin that has many pharmacological activities...
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of the colonic mucosa. Esculetin is a type of natural coumarin that has many pharmacological activities such as antioxidant, anticancer, anti-inflammatory, etc. A previous study showed that esculetin improved intestinal inflammation and reduced serum proinflammatory cytokines in UC. The present study aimed to utilize network pharmacology and molecular docking to explore the potential mechanism of esculetin against UC. The potential gene targets of esculetin were predicted through SwissTargetPrediction and Super-PRED web servers. UC-related genes were obtained from DisGeNet, OMIM, and GeneCards databases. The overlap between gene targets of esculetin and UC-related genes were identified as the potential targets of esculetin against UC. The interaction between these overlapping genes was analyzed by the STRING database and the core genes were identified by Cytoscape platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the core genes were then performed. And the results of these analyses were further confirmed through molecular docking. A total of 50 overlapping genes were identified as the potential action targets of esculetin against UC. Among them, 10 genes (AKT1, STAT1, CCND1, SRC, PTGS2, EGFR, NFKB1, ESR1, MMP9, SERPINE1) were finally identified as the core genes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results showed that the top signaling pathway associated with the core genes of esculetin against UC was the prolactin (PRL) signaling pathway. Molecular docking results showed that esculetin has a strong binding affinity to the core genes, as well as PRL and prolactin receptor. This study suggests that esculetin may have a crucial impact on UC through the PRL signaling pathway and provides insights into the potential mechanism of esculetin in the treatment of UC, which may shed light on the mechanism and treatment of UC.
Topics: Humans; Colitis, Ulcerative; Molecular Docking Simulation; Network Pharmacology; Umbelliferones
PubMed: 37960728
DOI: 10.1097/MD.0000000000035852 -
Heliyon Nov 2023The pathogenesis of hyperplasia of mammary glands (HMG) is a complex process, involving multiple links and systems within the body. Current clinical research indicates... (Review)
Review
BACKGROUND
The pathogenesis of hyperplasia of mammary glands (HMG) is a complex process, involving multiple links and systems within the body. Current clinical research indicates that traditional Chinese medicine (TCM) demonstrates a significant therapeutic effect in treating HMG. Single herbs or herbal pairs (two herbs) are the basic units of preventing and treating HMG. It is of great significance to explore the mechanism of single herbs or herbal pairs in treating HMG for clarifying the mechanism of preventing HMG with TCM.
PURPOSE
This study aimed to review the literature, summarize the known mechanisms of single herbs and herbal pair therapy for treating hyperplasia of mammary glands (HMG), and elucidate the relevant substances involved within and outside the body during these treatments.
STUDY DESIGN
In this study, the action mechanism of single herbs or herbal pairs in treating HMG was selected as the research object. English articles were mainly selected and Chinese articles were supplemented. We conducted a literature search in PubMed, CNKI, WanFang Database, etc,including full-text studies published between January 1992 and December 31, 2022. The primary literature was carefully screened, and the mechanism of action was explored by logical analysis.
METHODS
We conducted a literature review focusing on basic studies that explored the mechanisms underlying the effects of herbal treatments for mammary gland hyperplasia. The literature search was performed in PubMed, CNKI, and WanFang Database, covering full-text articles published from January 1992 to 31 December 2022, using various keywords (e.g., hyperplasia of mammary glands, single herb, herbal pair, effect, mechanism, inclusion criteria). Exclusion criteria were also set. We employed methods such as literature measurement, literature research, and content analysis to logically analyze, induce, and deduce the findings of the collected literature.
RESULTS
This review reveals that several distinct mechanisms contribute to the beneficial effects of single herbs or herbal pairs on the recovery of mammary gland hyperplasia. Regarding hormone levels, Chinese herbs can decrease hormones such as Estradiol(E2) and Prolactin(PRL), increase Progesterone(P) levels, balance the E2/P ratio, reduce the expression of sex hormone receptors, and lessen the self-sensitivity of breast tissue under the influence of E2. Histologically, Chinese herbs can inhibit breast neovascularization and alleviate blood viscosity. At the cellular level, Chinese herbs can modulate the expression of apoptosis genes and proteins, decrease cell proliferation activity, and ultimately inhibit or even reverse breast hyperplasia. From a pharmacological perspective, Chinese herbs exhibit analgesic, anti-inflammatory, antioxidant, and immune-regulating properties.
CONCLUSION
The evidence in this review demonstrates the effectiveness of single herbs or herbal pairs in preventing and treating mammary gland hyperplasia, with precise underlying mechanisms.
PubMed: 37920486
DOI: 10.1016/j.heliyon.2023.e21000 -
Journal of Proteome Research Dec 2023Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the...
Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting ∼5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.
Topics: Humans; Male; Mice; Female; Animals; Alzheimer Disease; Tandem Mass Spectrometry; Proteome; Reproducibility of Results; Chromatography, Reverse-Phase
PubMed: 37910662
DOI: 10.1021/acs.jproteome.3c00496 -
Frontiers in Endocrinology 2023While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with...
PURPOSE
While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.
METHODS
The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.
RESULTS
Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [Lu]Lu-DOTA-TATE dose and peaked within 48 hours.
CONCLUSIONS
[Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Pheochromocytoma; Retrospective Studies; Prolactin; Hydrocortisone; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Follicle Stimulating Hormone; Catecholamines; Thyrotropin
PubMed: 37886645
DOI: 10.3389/fendo.2023.1275813 -
International Journal of Molecular... Sep 2023Breast cancer remains the most frequently diagnosed cancer in women worldwide. Tumors that express hormone receptors account for 75% of all cases. Understanding... (Review)
Review
Breast cancer remains the most frequently diagnosed cancer in women worldwide. Tumors that express hormone receptors account for 75% of all cases. Understanding alternative signaling cascades is important for finding new therapeutic targets for hormone receptor-positive breast cancer patients. JAK-STAT signaling is commonly activated in hormone receptor-positive breast tumors, inducing inflammation, proliferation, migration, and treatment resistance in cancer cells. In hormone receptor-positive breast cancer, the JAK-STAT cascade is stimulated by hormones and cytokines, such as prolactin and IL-6. In normal cells, JAK-STAT is inhibited by the action of the adaptor protein, LNK. However, the role of LNK in breast tumors is not fully understood. This review compiles published reports on the expression and activation of the JAK-STAT pathway by IL-6 and prolactin and potential inhibition of the cascade by LNK in hormone receptor-positive breast cancer. Additionally, it includes analyses of available datasets to determine the level of expression of LNK and various members of the JAK-STAT family for the purpose of establishing associations between expression and clinical outcomes. Together, experimental evidence and in silico studies provide a better understanding of the potential implications of the JAK-STAT-LNK loop in hormone receptor-positive breast cancer progression.
Topics: Humans; Female; Signal Transduction; Janus Kinases; Breast Neoplasms; Prolactin; Interleukin-6; STAT Transcription Factors
PubMed: 37834225
DOI: 10.3390/ijms241914777 -
International Journal of Molecular... Sep 2023High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study...
High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glutathion was determined according to the detected cell proliferation. The results showed that the optimal glutathione concentration was 5 μmol/mL. Trial 2: 500 ng/mL PRL was chosen as the high PRL concentration. The GCs were treated with 0 ng/mL PRL (C group), 500 ng/mL PRL (P group) or 500 ng/mL PRL, and 5 μmol/mL glutathione (P-GSH group). The results indicated that the mitochondrial respiratory chain complex (MRCC) I-V, ATP production, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thioredoxin peroxidase (TPx) in the C group were higher than those in the P group ( < 0.05), while they were lower than those in the P-GSH group ( < 0.05). Compared to the C group, the P group exhibited elevated levels of reactive oxygen species (ROS) and apoptosis ( < 0.05) and increased expression of ATG7 and ATG5 ( < 0.05). However, MRCC I-V, ATP, SOD, A-TOC, TPx, ROS, and apoptosis were decreased after the addition of glutathione ( < 0.05). The knockdown of either or in P group GCs resulted in a significant reduction ( < 0.05) in MRCC I-V, ATP, T-AOC, SOD and TPx, while the overexpression of either receptor showed an opposite trend ( < 0.05). Our findings suggest that high PRL concentrations induce apoptotic cell death in ovine ovarian GCs by downregulating and , activating oxidative stress and autophagic pathways.
Topics: Female; Animals; Sheep; Prolactin; Receptors, Prolactin; Reactive Oxygen Species; Oxidative Stress; Apoptosis; Antioxidants; Granulosa Cells; Glutathione; Superoxide Dismutase; Adenosine Triphosphate
PubMed: 37833858
DOI: 10.3390/ijms241914407 -
Endocrine Apr 2024Sex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the...
PURPOSE
Sex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the expression of estrogen receptors, or have been limited to animal studies. The aim of our study was to explore the relationship between serum sex hormones and the pathological features of PTC in the clinical setting, as further evidence of the role of sex hormones in PTC.
METHODS
Retrospective data analysis of patients who underwent thyroid surgery at the Department of Thyroid Surgery, Nanjing Drum Tower Hospital from January 2022 to September 2022 Correlation between serum sex hormone and pathological features was analyzed in male patients and in menopausal female patients. Serum sex hormones include luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E), total testosterone(TT), progesterone(P), and prolactin(PRL). Tumor pathological characteristics include the number and size of tumor, presence of extrathyroidal extension(ETE), presence of lymph node metastasis(LNM).
RESULTS
Preoperative serum E2 in male patients was positively correlated with tumor size in PTC, LH was negatively correlated with LNM, while TT and P were negatively correlated with ETE. Similar findings were not observed in menopausal female patients.
CONCLUSION
We observed that serum sex hormones correlate with the pathological features of PTC in male patients, for the first time in a clinical study. High serum estrogens may be a risk factor for PTC, while androgens are the opposite. This somewhat corroborates previous research and provides new variables for future PTC prediction models.
Topics: Humans; Male; Female; Thyroid Cancer, Papillary; Thyroid Neoplasms; Retrospective Studies; Carcinoma, Papillary; Gonadal Steroid Hormones; Prolactin
PubMed: 37815746
DOI: 10.1007/s12020-023-03554-w -
Scientific Reports Oct 2023We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with...
We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.
Topics: Rats; Animals; Male; Kisspeptins; Prolactin; Luteinizing Hormone; Receptors, Kisspeptin-1; Semen; Hypothyroidism; Testis; Testosterone
PubMed: 37798396
DOI: 10.1038/s41598-023-44056-z -
Frontiers in Immunology 2023There are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed...
INTRODUCTION
There are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system. Study of common mechanisms of immune dysfunction caused by different viral infections can help develop novel therapeutic strategies to combat infections and associated comorbidities.
METHODS
To identify common mechanisms of immune functions disruption during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we analyzed the corresponding transcription profiles from peripheral blood mononuclear cells (PBMC) using the originally developed pipeline that include transcriptome data collection, processing, normalization, analysis and search for master regulators of several viral infections. The ten datasets containing transcription data from patients infected by nine viruses and healthy people were obtained from Gene Expression Omnibus. The analysis of the data was performed by Genome Enhancer pipeline.
RESULTS
We revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. Using network analysis, we identified PBMC receptors, representing proteins at the top of signaling pathways that may be responsible for the observed transcriptional changes and maintain the current functional state of cells.
DISCUSSION
The identified relationships between some of them and virus-induced alteration of immune functions are new and have not been found earlier, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon. Modulation of the identified receptors can be investigated as one of therapeutic strategies for the treatment of severe viral infections.
Topics: Humans; Leukocytes, Mononuclear; Transcriptome; Antiviral Agents; COVID-19; Viruses; Immunity
PubMed: 37795081
DOI: 10.3389/fimmu.2023.1199482