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Journal of Translational Medicine May 2024Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior....
BACKGROUND
Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression. FDX1, a crucial protein in cellular redox reactions and energy metabolism, has been linked to several cancers. However, its exact role in the development of LUAD is not yet fully understood.
METHODS
We investigated the role of ferredoxin 1 (FDX1) in LUAD progression through analysis of its expression in LUAD tissues and its impact on patient survival. Functional assays were performed to assess the effects of FDX1 overexpression on LUAD cell proliferation, migration, and invasion. A xenograft model was employed to evaluate the tumorigenesis potential of LUAD cells with FDX1 overexpression. Mechanistic insights into FDX1 regulation were gained through depletion experiments targeting the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2)/PI3K signaling pathway.
RESULTS
FDX1 expression was down-regulated in LUAD tissues, correlating with shorter patient survival. Overexpression of FDX1 suppressed LUAD cell proliferation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Mechanistically, the GPRIN2/PI3K signaling pathway was implicated in FDX1 regulation, as depletion of GPRIN2 reversed the effects of FDX1 overexpression on cellular functions.
CONCLUSIONS
Our findings highlight FDX1 as a potential tumor suppressor in LUAD, acting through modulation of the GPRIN2/PI3K signaling pathway. These results suggest FDX1 as a promising therapeutic target for LUAD treatment, warranting further investigation into its clinical relevance.
Topics: Animals; Female; Humans; Male; Mice; Adenocarcinoma of Lung; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Ferredoxins; Gene Expression Regulation, Neoplastic; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinases; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 38802900
DOI: 10.1186/s12967-024-05277-6 -
World Journal of Surgical Oncology May 2024In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence...
BACKGROUND
In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1).
CASE PRESENTATION
After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases.
CONCLUSION
To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual.
Topics: Humans; Female; Multiple Endocrine Neoplasia Type 2a; Siblings; Succinate Dehydrogenase; Adult; Proto-Oncogene Proteins c-ret; Prognosis; Thyroidectomy; Mutation; Genetic Testing; Pedigree; Paraganglioma; High-Throughput Nucleotide Sequencing
PubMed: 38802890
DOI: 10.1186/s12957-024-03418-1 -
BMC Genomics May 2024The filamentous temperature-sensitive H protease (ftsH) gene family belongs to the ATP-dependent zinc metalloproteins, and ftsH genes play critical roles in plant...
BACKGROUND
The filamentous temperature-sensitive H protease (ftsH) gene family belongs to the ATP-dependent zinc metalloproteins, and ftsH genes play critical roles in plant chloroplast development and photosynthesis.
RESULTS
In this study, we performed genome-wide identification and a systematic analysis of soybean ftsH genes. A total of 18 GmftsH genes were identified. The subcellular localization was predicted to be mainly in cell membranes and chloroplasts, and the gene structures, conserved motifs, evolutionary relationships, and expression patterns were comprehensively analyzed. Phylogenetic analysis of the ftsH gene family from soybean and various other species revealed six distinct clades, all of which showed a close relationship to Arabidopsis thaliana. The members of the GmftsH gene family were distributed on 13 soybean chromosomes, with intron numbers ranging from 3 to 15, 13 pairs of repetitive segment. The covariance between these genes and related genes in different species of Oryza sativa, Zea mays, and Arabidopsis thaliana was further investigated. The transcript expression data revealed that the genes of this family showed different expression patterns in three parts, the root, stem, and leaf, and most of the genes were highly expressed in the leaves of the soybean plants. Fluorescence-based real-time quantitative PCR (qRT-PCR) showed that the expression level of GmftsH genes varied under different stress treatments. Specifically, the genes within this family exhibited various induction levels in response to stress conditions of 4℃, 20% PEG-6000, and 100 mmol/L NaCl. These findings suggest that the GmftsH gene family may play a crucial role in the abiotic stress response in soybeans. It was also found that the GmftsH7 gene was localized on the cell membrane, and its expression was significantly upregulated under 4 ℃ treatment. In summary, by conducting a genome-wide analysis of the GmftsH gene family, a strong theoretical basis is established for future studies on the functionality of GmftsH genes.
CONCLUSIONS
This research can potentially serve as a guide for enhancing the stress tolerance characteristics of soybean.
Topics: Glycine max; Phylogeny; Multigene Family; Gene Expression Regulation, Plant; Plant Proteins; Genome, Plant; Gene Expression Profiling; Arabidopsis; Stress, Physiological; Genome-Wide Association Study; Chromosomes, Plant
PubMed: 38802777
DOI: 10.1186/s12864-024-10389-w -
Narra J Apr 2024Studies have suggested associations between inflammatory markers with the severity of coronavirus disease 2019 (COVID-19). Therefore, exercises that could reduce the...
Studies have suggested associations between inflammatory markers with the severity of coronavirus disease 2019 (COVID-19). Therefore, exercises that could reduce the level of inflammatory markers might be beneficial. The aim of this study was to determine the effect of upper arm and breathing exercises on inflammatory markers such as ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) in severe COVID-19 patients. A quasi-experimental with pre-test and post-test control group design was conducted among severe COVID-19 aged 18-70 years old, with or without comorbidities. Baseline data of inflammatory markers (ferritin, LDH, and CRP) were measured before the exercises and repeated post-exercise. The upper arm and breathing exercises were performed for ten days, twice a day (morning and evening) for ten minutes. A paired Student t-test was used to assess the changes in the inflammatory markers' levels. Our data indicated that levels of ferritin and CRP were not significantly different between pre- and post-exercise. However, the level of LDH decreased significantly from 481.35 U/L to 331.80 U/L (=0.001). This study highlights that pulmonary rehabilitation exercises might be beneficial to enhance the recovery process in severe COVID-19 patients.
Topics: Humans; COVID-19; Middle Aged; Male; Adult; Female; C-Reactive Protein; Biomarkers; Aged; Ferritins; Breathing Exercises; L-Lactate Dehydrogenase; Arm; Adolescent; Inflammation; Severity of Illness Index; Young Adult; Exercise Therapy; SARS-CoV-2
PubMed: 38798834
DOI: 10.52225/narra.v4i1.417 -
Nutrients May 2024As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and...
As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and metabolic disturbances, culminating in reduced fertility rates among older individuals. Ferredoxin (FDX) represents a highly conserved iron-sulfur (Fe-S) protein essential for electron transport across multiple metabolic pathways. Mammalian mitochondria house two distinct ferredoxins, FDX1 and FDX2, which share structural similarities and yet perform unique functions. In our investigation into the regulatory mechanisms governing ovarian aging, we employed a comprehensive multi-omics analysis approach, integrating spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy data. Previous studies have highlighted intricate interactions involving excessive lipid peroxide accumulation, redox-induced metal ion buildup, and alterations in cellular energy metabolism observed in aging cells. Through a multi-omics analysis, we observed a notable decline in the expression of the critical gene FDX1 as ovarian age progressed. This observation prompted speculation regarding FDX1's potential as a promising biomarker for ovarian aging. Following this, we initiated a clinical trial involving 70 patients with aging ovaries. These patients were administered oral nutritional supplements consisting of DHEA, ubiquinol CoQ10, and Cleo-20 T3 for a period of two months to evaluate alterations in energy metabolism regulated by FDX1. Our results demonstrated a significant elevation in FDX1 levels among participants receiving nutritional supplementation. We hypothesize that these nutrients potentiate mitochondrial tricarboxylic acid cycle (TCA) activity or electron transport chain (ETC) efficiency, thereby augmenting FDX1 expression, an essential electron carrier in metabolic pathways, while concurrently mitigating lipid peroxide accumulation and cellular apoptosis. In summary, our findings underscore the potential of nutritional intervention to enhance in vitro fertilization outcomes in senescent cells by bolstering electron transport proteins, thus optimizing energy metabolism and improving oocyte quality in aging women.
Topics: Female; Humans; Ovary; Aging; Ferredoxins; Mitochondria; Adult; Ubiquinone; Dietary Supplements; Metabolic Networks and Pathways; Energy Metabolism; Middle Aged
PubMed: 38794708
DOI: 10.3390/nu16101470 -
Nutrients May 2024Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication,...
Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probiotic -pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate that -pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found that -pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed that -pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination of and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.
Topics: Animals; Probiotics; Gastrointestinal Microbiome; Escherichia coli; Metallothionein; Mice, Inbred C57BL; Cadmium; Mice; Chemical and Drug Induced Liver Injury; Dysbiosis; Male; Liver; Signal Transduction
PubMed: 38794706
DOI: 10.3390/nu16101468 -
Nutrients May 2024Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human...
Human milk (HM) contains the essential macronutrients and bioactive compounds necessary for the normal growth and development of newborns. The milk collected by human milk banks is stored frozen and pasteurized, reducing its nutritional and biological value. The purpose of this study was to determine the effect of hyperbaric storage at subzero temperatures (HS-ST) on the macronutrients and bioactive proteins in HM. As control samples, HM was stored at the same temperatures under 0.1 MPa. A Miris HM analyzer was used to determine the macronutrients and the energy value. The lactoferrin (LF), lysozyme (LYZ) and lactalbumin (LAC) content was checked using high-performance liquid chromatography, and an ELISA test was used to quantify secretory immunoglobulin A (sIgA). The results showed that the macronutrient content did not change significantly after 90 days of storage at 60 MPa/-5 °C, 78 MPa/-7 °C, 111 MPa/-10 °C or 130 MPa/-12 °C. Retention higher than 90% of LYZ, LAC, LF and sIgA was observed in the HM stored at conditions of up to 111 MPa/-10 °C. However, at 130 MPa/-12 °C, there was a reduction in LYZ and LF, by 39 and 89%, respectively. The storage of HM at subzero temperatures at 0.1 MPa did not affect the content of carbohydrates or crude and true protein. For fat and the energy value, significant decreases were observed at -5 °C after 90 days of storage.
Topics: Humans; Milk, Human; Nutritive Value; Lactoferrin; Food Storage; Muramidase; Lactalbumin; Immunoglobulin A, Secretory; Nutrients; Milk Proteins; Female
PubMed: 38794693
DOI: 10.3390/nu16101455 -
Medicina (Kaunas, Lithuania) May 2024: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of...
: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. : This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. : Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. : This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations.
Topics: Humans; Female; Fumarate Hydratase; Uterine Neoplasms; Succinate Dehydrogenase; Adult; Leiomyoma; Middle Aged
PubMed: 38793008
DOI: 10.3390/medicina60050825 -
Medicina (Kaunas, Lithuania) Apr 2024: The administration of iron to premature newborns is a common intervention aimed at preventing iron deficiency (ID). However, there is no consensus on the optimal...
: The administration of iron to premature newborns is a common intervention aimed at preventing iron deficiency (ID). However, there is no consensus on the optimal timing and dosage for iron supplementation in this population. This study evaluates the effects and potential adverse outcomes of administering iron on the 7th and 21st days of life in premature infants. : This research was conducted on 108 premature neonates at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania. The study population was divided into a control group of 48 newborns who did not receive iron supplementation and an intervention group of 60 newborns who did. The analysis utilized univariate and multivariate regression to examine binary outcomes. : The findings indicate that iron supplementation significantly increased the risk of anemia during the premature period at 21 days of life, as demonstrated by both univariate and multivariate regression analyses, with an odds ratio (OR) of 2.40 (95% CI, 1.01-5.68) and an adjusted odds ratio (AOR) of 2.75 (95% CI, 1.06-7.11), respectively. Contrary to expectations, iron supplementation did not significantly alter the risk of abnormal serum ferritin or iron levels at 21 days of life, according to the univariate analysis ( = 0.380 and = 0.526, respectively). : The observed increase in the risk of anemia without a corresponding improvement in the serum ferritin or iron levels suggests the need for further investigation into alternative strategies for iron supplementation in premature newborns.
Topics: Humans; Infant, Newborn; Prospective Studies; Male; Infant, Premature; Female; Iron; Romania; Anemia, Iron-Deficiency; Cohort Studies; Dietary Supplements; Ferritins
PubMed: 38792868
DOI: 10.3390/medicina60050684 -
Molecules (Basel, Switzerland) May 2024is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and...
BACKGROUND
is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of . The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in .
RESULTS
A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against strains ranged from 64 to 128 μg/mL. Time-kill assays showed that myricetin was a bactericidal agent against . In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by culture on rabbit erythrocytes in a dose-dependent manner.
CONCLUSIONS
Myricetin was newly discovered to be a competitive inhibitor of NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.
Topics: Flavonoids; Staphylococcus aureus; Microbial Sensitivity Tests; Anti-Bacterial Agents; NADH Dehydrogenase; Enzyme Inhibitors; Animals; Bacterial Proteins; Humans; Virulence Factors
PubMed: 38792214
DOI: 10.3390/molecules29102354