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International Journal of Molecular... Mar 2024Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence...
Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence (PIVKA-II) is a protein increased in various cancers (particularly in hepatocellular carcinoma), and it has recently exhibited superior diagnostic performance in PDAC detection compared to other biomarkers. The aim of our research was to identify an in vitro model to study PIVKA-II production, distribution, and release in PDAC. We examined the presence of PIVKA-II protein in a panel of stabilized pancreatic cancer cell lines by Western blot analysis and indirect immunofluorescence (IFA). After quantitative evaluation of PIVKA-II in PaCa 44, H-Paf II, Capan-1, and PANC-1, we adopted the latter as a reference model. Subsequently, we analyzed the effect of glucose addiction on PIVKA-II production in a PANC-1 cell line in vitro; PIVKA-II production seems to be directly related to an increase in glucose concentration in the culture medium. Finally, we evaluated if PIVKA-II released in the presence of increasing doses of glucose is concomitant with the expression of two well-acknowledged epithelial-mesenchymal transition (EMT) markers (Vimentin and Snail). According to our experimental model, we can speculate that PIVKA-II release by PANC-1 cells is glucose-dependent and occurs jointly with EMT activation.
Topics: Humans; Vitamin K; Vitamins; Biomarkers; Protein Precursors; Prothrombin; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Models, Theoretical; Glucose; Biomarkers, Tumor
PubMed: 38542466
DOI: 10.3390/ijms25063498 -
Scientific Reports Mar 2024Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the...
Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.
Topics: Cyperus; Plant Extracts; Tandem Mass Spectrometry; Antioxidants; Phytochemicals; Plant Leaves
PubMed: 38538715
DOI: 10.1038/s41598-024-58041-7 -
Antonie Van Leeuwenhoek Mar 2024A new member of the family Flavobacteriaceae (termed Hal144) was isolated from the marine breadcrumb sponge Halichondria panicea. Sponge material was collected in 2018...
A new member of the family Flavobacteriaceae (termed Hal144) was isolated from the marine breadcrumb sponge Halichondria panicea. Sponge material was collected in 2018 at Schilksee which is located in the Kiel Fjord (Baltic Sea, Germany). Phylogenetic analysis of the full-length Hal144 16S rRNA gene sequence revealed similarities from 94.3 to 96.6% to the nearest type strains of the genus Maribacter. The phylogenetic tree of the 16S rRNA gene sequences depicted a cluster of strain Hal144 with its closest relatives Maribacter aestuarii GY20 (96.6%) and Maribacter thermophilus HT7-2 (96.3%). Genome phylogeny showed that Maribacter halichondriae Hal144 branched from a cluster consisting of Maribacter arenosus, Maribacter luteus, and Maribacter polysiphoniae. Genome comparisons of strain Maribacter halichondriae Hal144 with Maribacter sp. type strains exhibited average nucleotide identities in the range of 75-76% and digital DNA-DNA hybridisation values in the range of 13.1-13.4%. Compared to the next related type strains, strain Hal144 revealed unique genomic features such as phosphoenolpyruvate-dependent phosphotransferase system pathway, serine-glyoxylate cycle, lipid A 3-O-deacylase, 3-hexulose-6-phosphate synthase, enrichment of pseudogenes and of genes involved in cell wall and envelope biogenesis, indicating an adaptation to the host. Strain Hal144 was determined to be Gram-negative, mesophilic, strictly aerobic, flexirubin positive, resistant to aminoglycoside antibiotics, and able to utilize N-acetyl-β-D-glucosamine. Optimal growth occurred at 25-30 °C, within a salinity range of 2-6% sea salt, and a pH range between 5 and 8. The major fatty acids identified were C 3-OH, iso-C, and iso-C G. The DNA G + C content of strain Hal144 was 41.4 mol%. Based on the polyphasic approach, strain Hal144 represents a novel species of the genus Maribacter, and we propose the name Maribacter halichondriae sp. nov. The type strain is Hal144 (= DSM 114563 = LMG 32744).
Topics: Animals; Seawater; Phosphatidylethanolamines; Phylogeny; RNA, Ribosomal, 16S; Porifera; DNA, Bacterial; Sequence Analysis, DNA; Bacterial Typing Techniques; Vitamin K 2; Fatty Acids; Flavobacteriaceae
PubMed: 38489089
DOI: 10.1007/s10482-024-01950-4 -
BMC Veterinary Research Mar 2024Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin,...
Effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological profiles during transition period in dromedary camels.
BACKGROUND
Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin, especially vitamin A and E and trace elements remained most critical in the animal's ration and affects their productive and reproductive performance adversely. Animals cannot be able to produce these vitamins in their bodies; hence, an exogenous regular supply is needed to fulfil the physiological needs and to maintain high production performance. This study elucidated effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological parameters in dromedary camels during transition period.
RESULTS
At 0 day, there were no appreciable differences in the expression patterns of the metabolic (IGF-I, ACACA, SCD, FASN, LPL, and BTN1A1) genes between the control and treatment groups, despite lower levels. A substantial variation in the mRNA levels of SOD1, SOD3, PRDX2, PRDX3, PRDX4, PRDX6, and AhpC/TSA was observed between the control and treatment groups, according to the antioxidant markers. In comparison to the control group, the treatment group displayed a significant up-regulation at 0 and 21 days. The treatment and control groups exhibited substantial differences in the mRNA values of IL-1α, IL-1β, IL-6, and TNFα, as indicated by immunological markers. In comparison to the control group, there was a noticeable down-regulation in the treatment group at 0 and + 21 days. But IL10 produced the opposite pattern. No significant difference was observed in glucose, cholesterol, triglyceride, HDL, total protein, NEFA, BHBA, cortisol and IGF-1 levels between control and treatment group. The activity of serum GPx, SOD and TAC was significantly affected by time and treatment x time in supplemented groups as compared with control group. IL-1, IL-1, IL-6, and TNF were noticeably greater in the control group and lower in the treatment group. Additionally, in all groups, the concentration of all pro-inflammatory cytokines peaked on the day of delivery and its lowest levels showed on day 21 following calving. The IL-10 level was at its peak 21 days prior to calving and was lowest on calving day.
CONCLUSION
The results demonstrated a beneficial effect of antioxidant vitamins and trace elements on the metabolic, antioxidant and immunological markers in dromedary camels throughout their transition period.
Topics: Animals; Trace Elements; Antioxidants; Vitamins; Camelus; Vitamin A; Interleukin-6; Vitamin K; Zinc; RNA, Messenger; Gene Expression; Interleukin-1
PubMed: 38481237
DOI: 10.1186/s12917-024-03959-3 -
Journal of Thrombosis and Thrombolysis Apr 2024Vitamin K antagonists (VKA) is the primary anticoagulant in most settings of Sub-Saharan Africa. Understanding the quality of anticoagulation services in the continent...
Vitamin K antagonists (VKA) is the primary anticoagulant in most settings of Sub-Saharan Africa. Understanding the quality of anticoagulation services in the continent is vital in optimising the intended benefits. This study assessed the quality of anticoagulation and associated factors among VKA-treated patients in nine SSA countries. We conducted a retrospective cohort study of randomly selected patients on anticoagulation from 20 clinics in Botswana, the Democratic Republic of Congo, Ethiopia, Gambia, Ghana, Mozambique, Nigeria, Tanzania, and South Africa. Eligible participants were those on VKAs for at least three months and with at least four international normalised ratios (INR) results in 2019-2021. We report the proportion of INR values in the therapeutic range, time-in-therapeutic range (TTR) using the Rosendaal method, and the proportion of patients with TTR ≥ 65% (optimal anticoagulation). The mean age was 51.1(16.1) years, and 64.2% were women. The most common indications for VKA included venous thromboembolism (29.6%), prosthetic valves (26.7%) and atrial fibrillation/flutter (30.1%). We analysed 6743 INR tests from 1011 participants, and of these, 48.5% were sub-therapeutic, 34.1% therapeutic, and 17.4% were supratherapeutic relative to disease-specific reference ranges. TTR was calculated for 660 patients using 4927 INR measurements. The median (interquartile range [IQR]) TTR was 35.8(15.9,57.2) %. Optimal anticoagulation control was evident in 19.2% of participants, varying from 2.7% in Tanzania to 23.1% in Ethiopia. The proportion of patients with TTR ≥ 65% was 15,4% for prosthetic heart valves, 21.1% for venous thromboembolism and 23.7% for atrial fibrillation or flutter. Countries with universal health coverage had higher odds of optimal anticoagulation control (adjusted odds ratio (aOR) 1.79, 95% confidence interval [CI], 1.15- 2.81, p = 0.01). Patients on VKAs for different therapeutic indications in SSA had suboptimal TTR. Universal health coverage increased the odds of achieving TTR by 79%. The evidence calls for more intensive warfarin management strategies in SSA, including providing VKA services without out-of-pocket payments.
Topics: Humans; Female; Middle Aged; Male; Atrial Fibrillation; Venous Thromboembolism; Retrospective Studies; Anticoagulants; International Normalized Ratio; Vitamin K; Africa South of the Sahara
PubMed: 38478250
DOI: 10.1007/s11239-023-02928-1 -
Nutrients Feb 2024Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from... (Review)
Review
Vascular calcification (VC) is a consequence of chronic kidney disease (CKD) which is of paramount importance regarding the survival of CKD patients. VC is far from being controlled with actual medication; as a result, in recent years, diet modulation has become more compelling. The concept of medical nutritional therapy points out the idea that food may prevent or treat diseases. The aim of this review was to evaluate the influence of food habits and nutritional intervention in the occurrence and progression of VC in CKD. Evidence reports the harmfulness of ultra-processed food, food additives, and animal-based proteins due to the increased intake of high absorbable phosphorus, the scarcity of fibers, and the increased production of uremic toxins. Available data are more supportive of a plant-dominant diet, especially for the impact on gut microbiota composition, which varies significantly depending on VC presence. Magnesium has been shown to prevent VC but only in experimental and small clinical studies. Vitamin K has drawn considerable attention due to its activation of VC inhibitors. There are positive studies; unfortunately, recent trials failed to prove its efficacy in preventing VC. Future research is needed and should aim to transform food into a medical intervention to eliminate VC danger in CKD.
Topics: Animals; Humans; Renal Insufficiency, Chronic; Vascular Calcification; Phosphorus; Vitamin K; Food
PubMed: 38474744
DOI: 10.3390/nu16050617 -
International Journal of Molecular... Feb 2024Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to... (Review)
Review
Free radicals (FRs) are unstable molecules that cause reactive stress (RS), an imbalance between reactive oxygen and nitrogen species in the body and its ability to neutralize them. These species are generated by both internal and external factors and can damage cellular lipids, proteins, and DNA. Antioxidants prevent or slow down the oxidation process by interrupting the transfer of electrons between substances and reactive agents. This is particularly important at the cellular level because oxidation reactions lead to the formation of FR and contribute to various diseases. As we age, RS accumulates and leads to organ dysfunction and age-related disorders. Polyphenols; vitamins A, C, and E; and selenoproteins possess antioxidant properties and may have a role in preventing and treating certain human diseases associated with RS. In this review, we explore the current evidence on the potential benefits of dietary supplementation and investigate the intricate connection between SIRT1, a crucial regulator of aging and longevity; the transcription factor NRF2; and polyphenols, vitamins, and selenium. Finally, we discuss the positive effects of antioxidant molecules, such as reducing RS, and their potential in slowing down several diseases.
Topics: Humans; Antioxidants; Vitamins; Selenium; Polyphenols; Oxidative Stress; Vitamin A; Vitamin K; Reactive Oxygen Species
PubMed: 38473850
DOI: 10.3390/ijms25052600 -
Arthritis Research & Therapy Mar 2024Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on...
BACKGROUND
Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients.
METHODS
In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN.
RESULTS
Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo.
CONCLUSION
In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.
Topics: Humans; Mice; Animals; Lupus Nephritis; Vitamin K 3; Mice, Inbred MRL lpr; Kidney; Lupus Erythematosus, Systemic; Fibrosis; Protein Serine-Threonine Kinases; Tumor Suppressor Proteins
PubMed: 38459604
DOI: 10.1186/s13075-024-03292-y -
PloS One 2024The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and...
BACKGROUND
The European rivaroxaban post-authorization safety study evaluated bleeding risk among patients initiated on rivaroxaban or vitamin K antagonists for the treatment and secondary prevention of venous thromboembolism in routine clinical practice.
METHODS
Cohorts were created using electronic healthcare databases from the UK, the Netherlands, Germany and Sweden. Patients with a first prescription of rivaroxaban or vitamin K antagonist during the period from December 2011 (in the UK, January 2012) to December 2017 (in Germany, December 2016) for venous thromboembolism indication, with no record of atrial fibrillation or recent cancer history, were observed until the occurrence of each safety outcome (hospitalization for intracranial, gastrointestinal, urogenital or other bleeding), death or study end (December 2018; in Germany, December 2017). Crude incidence rates of each outcome per 100 person-years were computed.
RESULTS
Overall, 44 737 rivaroxaban and 45 842 vitamin K antagonist patients were enrolled, mean age, 59.9-63.8 years. Incidence rates were similar between rivaroxaban and vitamin K antagonist users with some exceptions, including higher incidence rates for gastrointestinal bleeding in rivaroxaban users than in vitamin K antagonist users. Among rivaroxaban users, mortality and bleeding risk generally increased with age, renal impairment and diabetes.
CONCLUSIONS
This study provides further data from routine clinical practice that broadly support safety profile of rivaroxaban for VTE indication and complement findings from previous randomized clinical trials.
Topics: Humans; Middle Aged; Rivaroxaban; Venous Thromboembolism; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Fibrinolytic Agents; Vitamin K; Factor Xa Inhibitors
PubMed: 38451960
DOI: 10.1371/journal.pone.0298596 -
Iranian Journal of Pharmaceutical... 2023is one of the plants used in the diet of Iranian people. Previous studies have investigated the antioxidant and antibacterial effects of this plant extract, but no...
BACKGROUND
is one of the plants used in the diet of Iranian people. Previous studies have investigated the antioxidant and antibacterial effects of this plant extract, but no study has been conducted on its anticancer properties.
OBJECTIVES
In this study, we investigated the effect of extract on MCF-7 breast cancer cells.
METHODS
The inhibitory effect of leaf extract was determined on the growth of cancer cells by the MTT test. The ROS (reactive oxygen species) test was used to investigate the impact of the extract on intracellular oxidative stress. Flow cytometry and real-time PCR tests were used to investigate the apoptosis-related molecular processes. The GC-MS analysis was performed to determine the most abundant components.
RESULTS
The GC-MS analysis showed that phytol, mono-ethylhexyl phthalate (MEHP), cinnamaldehyde, and neophytadiene constituted 60% of the extracted content. The MTT assay demonstrated that leaf extract caused 50% lethality at a 400 μg/mL dose in MCF7 cells. The extract at low doses decreased the ROS level for 24 hours in MCF-7, but by increasing the concentration, the ROS levels increased. At the IC dose (inhibitory concentration (IC) associated with 50% impact), the ROS level increased 3.5 times compared to the control group. Examining the effect of N-acetyl cysteine (NAC) showed that this antioxidant agent could prevent the lethal impact of the extract and eliminate the ROS increase in MCF7 cells. Flow cytometry and real-time PCR results showed that the extract specifically induced apoptosis through the internal apoptosis pathway in this cancer cell line.
CONCLUSIONS
The extract induced apoptosis by increasing ROS in MCF-7 cancer cells and can be considered for further studies.
PubMed: 38444704
DOI: 10.5812/ijpr-136643