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Medicine Jun 2024Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor...
BACKGROUND
Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR's prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers.
METHODS
A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR's relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR's association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628).
RESULTS
Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility.
CONCLUSION
suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR's role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.
Topics: Humans; Pancreatitis; Receptors, Urokinase Plasminogen Activator; Prognosis; Biomarkers; Systematic Reviews as Topic; Severity of Illness Index; Length of Stay; Acute Disease
PubMed: 38941433
DOI: 10.1097/MD.0000000000037064 -
MBio Jun 2024Conjugative type 4 secretion systems (T4SSs) are the main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. To deliver the DNA...
Conjugative type 4 secretion systems (T4SSs) are the main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. To deliver the DNA substrate to recipient cells, it must cross the cell envelopes of both donor and recipient bacteria. In the T4SS from the enterococcal conjugative plasmid pCF10, PrgK is known to be the active cell wall degrading enzyme. It has three predicted extracellular hydrolase domains: metallo-peptidase (LytM), soluble lytic transglycosylase (SLT), and cysteine, histidine-dependent amidohydrolases/peptidases (CHAP). Here, we report the structure of the LytM domain and show that its active site is degenerate and lacks the active site metal. Furthermore, we show that only the predicted SLT domain is functional and that it unexpectedly has a muramidase instead of a lytic transglycosylase activity. While we did not observe any peptidoglycan hydrolytic activity for the LytM or CHAP domain, we found that these domains downregulated the SLT muramidase activity. The CHAP domain was also found to be involved in PrgK dimer formation. Furthermore, we show that PrgK interacts with PrgL, which likely targets PrgK to the rest of the T4SS. The presented data provides important information for understanding the function of Gram-positive T4SSs.IMPORTANCEAntibiotic resistance is a large threat to human health and is getting more prevalent. One of the major contributors to the spread of antibiotic resistance among different bacteria is type 4 secretion systems (T4SS). However, mainly T4SSs from Gram-negative bacteria have been studied in detail. T4SSs from Gram-positive bacteria, which stand for more than half of all hospital-acquired infections, are much less understood. The significance of our research is in identifying the function and regulation of a cell wall hydrolase, a key component of the pCF10 T4SS from . This system is one of the best-studied Gram-positive T4SSs, and this added knowledge aids in our understanding of horizontal gene transfer in as well as other medically relevant Gram-positive bacteria.
PubMed: 38940556
DOI: 10.1128/mbio.00488-24 -
Frontiers in Bioscience (Landmark... Jun 2024This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated...
BACKGROUND
This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth.
METHODS
The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between expression and its downstream genes was analyzed in a melanoma tissue array.
RESULTS
TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between expression and the expression of , , and . Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth.
CONCLUSIONS
TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.
Topics: Humans; Endoplasmic Reticulum Stress; Melanoma; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Neoplastic; Cell Death; Apoptosis; Cell Proliferation; Membrane Proteins
PubMed: 38940043
DOI: 10.31083/j.fbl2906233 -
Frontiers in Bioscience (Landmark... Jun 2024This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal...
BACKGROUND
This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation.
METHODS
We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis.
RESULTS
Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes and . However, Sal A does not affect the Chk1-Cdc25C pathway.
CONCLUSIONS
Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation.
Topics: Humans; Checkpoint Kinase 2; cdc25 Phosphatases; Melanoma; Cell Line, Tumor; Cell Proliferation; Lactates; Caffeic Acids; Signal Transduction; Phosphorylation; Cell Survival
PubMed: 38940031
DOI: 10.31083/j.fbl2906213 -
Frontiers in Bioscience (Elite Edition) Jun 2024Dextran is an exopolysaccharide synthesized in reactions catalyzed by enzymes obtained from microbial agents of specific species and strains. Products of dextran... (Review)
Review
Dextran is an exopolysaccharide synthesized in reactions catalyzed by enzymes obtained from microbial agents of specific species and strains. Products of dextran polysaccharides with different molecular weights are suitable for diverse pharmaceutical and clinical uses. Dextran solutions have multiple characteristics, including viscosity, solubility, rheological, and thermal properties; hence, dextran has been studied for its commercial applications in several sectors. Certain bacteria can produce extracellular polysaccharide dextran of different molecular weights and configurations. Dextran products of diverse molecular weights have been used in several industries, including medicine, cosmetics, and food. This article aims to provide an overview of the reports on dextran applications in blood transfusion and clinical studies and its biosynthesis. Information has been summarized on enzyme-catalyzed reactions for dextran biosynthesis from sucrose and on the bio-transformation process of high molecular weight dextran molecules to obtain preparations of diverse molecular weights and configurations.
Topics: Dextrans; Humans; Blood Transfusion; Molecular Weight
PubMed: 38939916
DOI: 10.31083/j.fbe1602017 -
Frontiers in Microbiology 2024Exploring the bacterial community in the rhizosphere was of great value for understanding how this species adapted to the saline-alkali environment and for the rational...
Exploring the bacterial community in the rhizosphere was of great value for understanding how this species adapted to the saline-alkali environment and for the rational development and use of saline-alkali soils. In this study, high-throughput sequencing technology was used to investigate the diversity characteristics and distribution patterns of soil bacterial communities in the rhizosphere of -dominated communities in the Hetao Irrigation Distract, Inner Mongolia, China. The relationships among bacterial characteristics, soil physicochemical properties and vegetation in four sampling sites were analyzed. The soil bacterial communities in the rhizosphere of -dominated communities were mainly composed of 16 phyla (i.e., and ), and these populations accounted for more than 99% of the total bacterial community. At the genus level, the main bacterial communities comprised and , which accounted for 15.70% of the total bacterial community. An alpha diversity analysis indicated that the richness and diversity of rhizosphere soil bacteria differed significantly among the sampling sites, and the bacterial richness and diversity indices of severe saline-alkali land were higher than those of light and moderate saline-alkali land. The principal component analysis (PCA) and linear discriminant analysis effect size (LEfSe) showed significant differences in the species composition of the rhizosphere soil bacterial community among different sampling sites. A correlation analysis showed that the number of bacterial species exhibited the highest correlation with the soil water content (SWC). The richness and evenness indices were significantly correlated with the SWC and SO , K and Mg concentrations. The electrical conductivity (EC), soluble ions (Na, CO + HCO , K, Ca, Mg, and SO ), SWC and vegetation coverage (VC) were the main drivers affecting the changes in its community structure. The bacterial community in the rhizosphere of enhanced the adaptability of to saline-alkali environment by participating in the cycling process of nutrient elements, the decomposition of organic matter and the production of plant growth regulating substances. These results provided a theoretical reference for further study on the relationship among rhizosphere soil microorganisms and salt tolerance in halophytes.
PubMed: 38939186
DOI: 10.3389/fmicb.2024.1358783 -
Journal of Extracellular Biology Jul 2023Interest in the use of extracellular vesicles (EVs) as biomarkers of disease is rapidly growing. However, one main unsolved issue in the EV field is finding a technique...
Interest in the use of extracellular vesicles (EVs) as biomarkers of disease is rapidly growing. However, one main unsolved issue in the EV field is finding a technique able to eliminate non-EV contaminants present in biofluid samples in a one-step isolation protocol. Due to the expansion and value of size exclusion chromatography (SEC) as one of the best EV isolation methods, we have tested several agarose resins with different agarose percentages, bead sizes and crosslinking features to optimize EV isolation. For this optimization of SEC, we first employed conditioned media from a melanoma cell culture, a simpler sample in comparison to biological fluids, but which also contains abundant contaminants such as soluble protein and lipoproteins (LPPs). The distinct agaroses and the combinations of resins with different agarose percentages in the same column were tested. Soluble protein, EVs and LPPs levels from the different eluted fractions were quantitated by immunodetection or absorbance measurements. Samples were also analysed by NTA and TEM to verify the yield and the LPP contamination. Different percentages of agarose resins (2%, 4% and 6%) yielded samples with increasing LPP contamination respectively, which was not improved in the columns that combined them. Crosslinking of the agarose did not affect EV isolation yield nor the LPP contamination. In contrast, reducing the bead size greatly improved EV purity. We thus selected 4% Rapid Run Fine agarose beads as the resin that more efficiently isolated EVs with almost no contamination of other particles. Using blood plasma samples, this resin also demonstrated an improved capacity in the isolation of EVs from LPPs in comparison to the agaroses most commonly used in the field and differential ultracentrifugation.
PubMed: 38939075
DOI: 10.1002/jex2.100 -
Przeglad Gastroenterologiczny 2024is a common medicinal plant widely cultivated in tropical regions of the world. The outer seed coat of , obtained by cleaning the seeds, contains soluble and insoluble... (Review)
Review
The role and therapeutic effectiveness of seed husk (psyllium husk) in the prevention and non-pharmacological treatment of gastrointestinal diseases. Part 1. Clinical use of psyllium husk in the treatment of irritable bowel syndrome, ulcerative colitis, and colorectal cancer.
is a common medicinal plant widely cultivated in tropical regions of the world. The outer seed coat of , obtained by cleaning the seeds, contains soluble and insoluble fibre in a ratio of 7:3, making products containing husk an ideal source of health-beneficial fibre. The results of clinical trials demonstrate the therapeutic efficacy of psyllium husk for various gastrointestinal disorders. It has also been documented that psyllium ingestion exhibits antioxidant, immunomodulatory, antiproliferative, anticancer, and antiviral effects. Such pleiotropic effects of husk are related to the presence in its composition of arabinoxylan, which forms a gel in an aqueous environment, as well as bioactive compounds and their metabolites. This article presents the evidence available in the literature on the therapeutic potential and possible mechanisms of action of psyllium in the treatment of irritable bowel syndrome and ulcerative colitis, and prevention of colorectal cancer.
PubMed: 38939069
DOI: 10.5114/pg.2024.139209 -
Przeglad Gastroenterologiczny 2024Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this... (Review)
Review
Safety and efficacy of Single-Pass Albumin Dialysis (SPAD), Prometheus, and Molecular Adsorbent Recycling System (MARS) liver haemodialysis vs. Standard Medical Therapy (SMT): meta-analysis and systematic review.
INTRODUCTION
Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned.Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction.
MATERIAL AND METHODS
PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment.
RESULTS
Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; = 0.31, respectively).
CONCLUSIONS
MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events.
PubMed: 38939063
DOI: 10.5114/pg.2024.139297 -
JACS Au Jun 2024Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is approved only for...
Fidaxomicin (Fdx) constitutes a glycosylated natural product with excellent antibacterial activity against various Gram-positive bacteria but is approved only for infections. Poor water solubility and acid lability preclude its use for other infections. Herein, we describe our strategy to overcome the acid lability by introducing acid-stable S-linked glycosides. We describe the direct, diastereoselective modification of unprotected Fdx without the need to avoid air or moisture. Using our newly established approach, Fdx was converted to the single atom exchanged analogue S-Fdx, in which the acid labile O-glycosidic bond to the noviose sugar was replaced by the acid stable S-glycosidic bond. Studies of the antibacterial activity of a structurally diverse set of thioglycoside derivatives revealed high potency of acyl derivatives of S-Fdx against (MIC range: 0.12-4 μg/mL) and excellent potency against (MIC range: 0.06-0.5 μg/mL).
PubMed: 38938792
DOI: 10.1021/jacsau.4c00206