-
Frontiers in Cellular and Infection... 2023Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP.
METHOD
In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two.
RESULTS
After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group ( < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin.
CONCLUSION
This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.
Topics: Humans; Gastrointestinal Microbiome; Pyrrolidonecarboxylic Acid; Tamsulosin; RNA, Ribosomal, 16S
PubMed: 37475958
DOI: 10.3389/fcimb.2023.1091083 -
The Clinical Respiratory Journal Nov 2023Our purpose of this study is to evaluate the effect and safety of macitentan in the treatment of pulmonary hypertension (PH). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Our purpose of this study is to evaluate the effect and safety of macitentan in the treatment of pulmonary hypertension (PH).
METHODS
We retrieved the safety and efficacy of macitentan treatment for PH using PubMed, the Cochrane Library, EMBASE databases and clinicaltrials.gov. The Cochrane Risk of Bias Tool was used for literature screening and quality assessment. Data analysis was conducted using RevMan 5.4.1 and Stata/SE 15.1 software. Results are presented as standardization mean differences (SMDs) and odds ratio (OR).
RESULTS
Meta-analysis of seven randomized controlled trial (RCT) studies and four non-RCT studies with 2769 patients was included, involving 723 in the macitentan group and 599 in the placebo group. The results of the study showed that macitentan had effectively decreased pulmonary vascular resistance (PVR) (SMD = -0.53, 95% CI: -0.77--0.29, p < 0.05), cardiac index (CI) (SMD = 0.60, 95% CI: 0.37-0.83, p < 0.05) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = -0.22, 95% CI: -0.40--0.03, p < 0.05). Furthermore, macitentan also significantly reduced PVR (SMD = -0.58, 95% CI: -0.80--0.35, p < 0.05), 6-min walk distance (6WMD) (SMD = 0.33, 95% CI: 0.15-0.50, p < 0.05), CI (SMD = 0.48, 95% CI: 0.28-0.69, p < 0.05), mean pulmonary arterial pressure (mPAP) (SMD = -0.43, 95% CI: -0.64--0.23, p < 0.05) and NT-proBNP (SMD = -0.55, 95% CI: -1.07--0.03, p < 0.05) between baseline and follow-up. The adverse reactions to macitentan were mild, with headache, anaemia and bronchitis. Other efficacy and safety outcomes did not reach statistical differences.
CONCLUSION
Macitentan therapy for PH is effective and safe. The effectiveness on PVR, mPAP, mean right atrial pressure (mRAP), mortality and other indicators still needs to be further confirmed.
Topics: Humans; Hypertension, Pulmonary; Sulfonamides; Pyrimidines; Vascular Resistance
PubMed: 37427711
DOI: 10.1111/crj.13621 -
Nature Microbiology Sep 2023Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct...
Timely detection of outbreaks is needed for poliovirus eradication, but gold standard detection in the Democratic Republic of the Congo takes 30 days (median). Direct molecular detection and nanopore sequencing (DDNS) of poliovirus in stool samples is a promising fast method. Here we report prospective testing of stool samples from suspected polio cases, and their contacts, in the Democratic Republic of the Congo between 10 August 2021 and 4 February 2022. DDNS detected polioviruses in 62/2,339 (2.7%) of samples, while gold standard combination of cell culture, quantitative PCR and Sanger sequencing detected polioviruses in 51/2,339 (2.2%) of the same samples. DDNS provided case confirmation in 7 days (median) in routine surveillance conditions. DDNS enabled confirmation of three serotype 2 circulating vaccine-derived poliovirus outbreaks 23 days (mean) earlier (range 6-30 days) than the gold standard method. The mean sequence similarity between sequences obtained by the two methods was 99.98%. Our data confirm the feasibility of implementing DDNS in a national poliovirus laboratory.
Topics: Poliovirus; Nanopore Sequencing; Polymerase Chain Reaction; Dansyl Compounds
PubMed: 37591995
DOI: 10.1038/s41564-023-01453-4 -
Viruses Nov 2023Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of...
Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.
Topics: Humans; Animals; Mice; Oseltamivir; Influenza, Human; Probenecid; Influenza Vaccines; Antiviral Agents; Enzyme Inhibitors; Virus Replication; Neuraminidase; Drug Resistance, Viral
PubMed: 38140606
DOI: 10.3390/v15122366 -
International Journal of Molecular... Apr 2024The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their... (Review)
Review
The mission of this review is to identify immune-damaging participants involved in antiviral immunoinflammatory lesions. We argue these could be targeted and their activity changed selectively by maneuvers that, at the same time, may not diminish the impact of components that help resolve lesions. Ideally, we need to identify therapeutic approaches that can reverse ongoing lesions that lack unwanted side effects and are affordable to use. By understanding the delicate balance between immune responses that cause tissue damage and those that aid in resolution, novel strategies can be developed to target detrimental immune components while preserving the beneficial ones. Some strategies involve rebalancing the participation of immune components using various approaches, such as removing or blocking proinflammatory T cell products, expanding regulatory cells, restoring lost protective cell function, using monoclonal antibodies (moAb) to counteract inhibitory molecules, and exploiting metabolic differences between inflammatory and immuno-protective responses. These strategies can help reverse ongoing viral infections. We explain various approaches, from model studies and some clinical evidence, that achieve innate and adaptive immune rebalancing, offering insights into potential applications for controlling chronic viral-induced lesions.
Topics: Humans; Antibodies, Monoclonal; Pyrimethamine; Sulfadiazine
PubMed: 38612744
DOI: 10.3390/ijms25073935 -
International Journal of Molecular... Apr 2024Polymers stand out as promising materials extensively employed in biomedicine and biotechnology. Their versatile applications owe much to the field of tissue... (Review)
Review
Polymers stand out as promising materials extensively employed in biomedicine and biotechnology. Their versatile applications owe much to the field of tissue engineering, which seamlessly integrates materials engineering with medical science. In medicine, biomaterials serve as prototypes for organ development and as implants or scaffolds to facilitate body regeneration. With the growing demand for innovative solutions, synthetic and hybrid polymer materials, such as polyethersulfone, are gaining traction. This article offers a concise characterization of polyethersulfone followed by an exploration of its diverse applications in medical and biotechnological realms. It concludes by summarizing the significant roles of polyethersulfone in advancing both medicine and biotechnology, as outlined in the accompanying table.
Topics: Animals; Humans; Biocompatible Materials; Biotechnology; Polymers; Sulfones; Tissue Engineering; Tissue Scaffolds
PubMed: 38673817
DOI: 10.3390/ijms25084233 -
Nature Communications Nov 2023BSEP (ABCB11) is an ATP-binding cassette transporter that is expressed in hepatocytes and extrudes bile salts into the canaliculi of the liver. BSEP dysfunction, caused...
BSEP (ABCB11) is an ATP-binding cassette transporter that is expressed in hepatocytes and extrudes bile salts into the canaliculi of the liver. BSEP dysfunction, caused by mutations or induced by drugs, is frequently associated with severe cholestatic liver disease. We report the cryo-EM structure of glibenclamide-bound human BSEP in nanodiscs, revealing the basis of small-molecule inhibition. Glibenclamide binds the apex of a central binding pocket between the transmembrane domains, preventing BSEP from undergoing conformational changes, and thus rationalizing the reduced uptake of bile salts. We further report two high-resolution structures of BSEP trapped in distinct nucleotide-bound states by using a catalytically inactivated BSEP variant (BSEP) to visualize a pre-hydrolysis state, and wild-type BSEP trapped by vanadate to visualize a post-hydrolysis state. Our studies provide structural and functional insight into the mechanism of bile salt extrusion and into small-molecule inhibition of BSEP, which may rationalize drug-induced liver toxicity.
Topics: Humans; ATP-Binding Cassette Transporters; Bile Acids and Salts; Cholestasis; Glyburide; Liver
PubMed: 37949847
DOI: 10.1038/s41467-023-43109-1 -
Acta Neuropathologica Communications Sep 2023Inflammasomes, primarily responsible for the activation of IL-1β, have emerged as critical regulators of the tumor microenvironment. By using in vivo and in vitro brain...
Inflammasomes, primarily responsible for the activation of IL-1β, have emerged as critical regulators of the tumor microenvironment. By using in vivo and in vitro brain metastasis models, as well as human samples to study the role of the NLRP3 inflammasome in triple-negative breast cancer (TNBC) brain metastases, we found NLRP3 inflammasome components and IL-1β to be highly and specifically expressed in peritumoral astrocytes. Soluble factors from TNBC cells induced upregulation and activation of NLRP3 and IL-1β in astrocytes, while astrocyte-derived mediators augmented the proliferation of metastatic cells. In addition, inhibition of NLRP3 inflammasome activity using MCC950 or dampening the downstream effect of IL-1β prevented the proliferation increase in cancer cells. In vivo, MCC950 reduced IL-1β expression in peritumoral astrocytes, as well as the levels of inflammasome components and active IL-1β. Most importantly, significantly retarded growth of brain metastatic tumors was observed in mice treated with MCC950. Overall, astrocytes contribute to TNBC progression in the brain through activation of the NLRP3 inflammasome and consequent IL-1β release. We conclude that pharmacological targeting of inflammasomes may become a novel strategy in controlling brain metastatic diseases.
Topics: Humans; Animals; Mice; Inflammasomes; Astrocytes; Triple Negative Breast Neoplasms; NLR Family, Pyrin Domain-Containing 3 Protein; Brain Neoplasms; Indenes; Sulfonamides; Tumor Microenvironment
PubMed: 37749707
DOI: 10.1186/s40478-023-01646-2 -
Frontiers in Public Health 2023Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings.
RESULTS
The meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17).
CONCLUSION
We evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.
Topics: Humans; Alkanesulfonates; Fluorocarbons; Hypertension
PubMed: 37655293
DOI: 10.3389/fpubh.2023.1173101 -
PeerJ 2023Sodium dodecyl sulfate (SDS) is an anionic surfactant, which is widely used in various fields in human life. However, SDS discharged into the water environment has a...
Sodium dodecyl sulfate (SDS) is an anionic surfactant, which is widely used in various fields in human life. However, SDS discharged into the water environment has a certain impact on aquatic organisms. In this study, planarian () was used to identify the toxic effects of SDS. A series of SDS solutions with different concentrations were used to treat planarians for the acute toxicity test , and the results showed that the semi-lethal concentration (LC) of SDS to at 24 h, 48 h, 72 h, and 96 h were 4.29 mg/L, 3.76 mg/L, 3.45 mg/L, and 3.20 mg/L respectively. After the planarians were exposed to 0.5 mg/L and 1.0 mg/L SDS solutions for 1, 3, and 5 days, the activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) content were measured to detect the oxidative stress and lipid peroxidation in planarians. Random amplified polymorphic DNA (RAPD) analysis was performed to detect the genotoxicity caused by SDS to planarians. The results showed that the activities of SOD, CAT, and MDA content increased after the treatment, indicating that SDS induced oxidative stress in planarians. RAPD analysis showed that the genomic template stability (GTS) values of planarians treated by 0.5 mg/L and 1.0 mg/L SDS for 1, 3, and 5 days were 67.86%, 64.29%, 58.93%, and 64.29%, 60.71%, 48.21%, respectively. GTS values decreased with the increasing of SDS concentration and exposure time, indicating that SDS had genotoxicity to planarians in a time and dose-related manner. Fluorescent quantitative PCR (qPCR) was used to investigate the effects of SDS on gene expression of planarians. After the planarians were exposed to 1.0 mg/L SDS solution for 1, 3, and 5 days, the expression of was upregulated, and that of , , , , and were downregulated. These results suggested that SDS might induce apoptosis, affect cell proliferation, differentiation, and DNA repair ability of planarian cells and cause toxic effects on planarian .
Topics: Animals; Antioxidants; Planarians; Random Amplified Polymorphic DNA Technique; Sodium Dodecyl Sulfate; Superoxide Dismutase
PubMed: 37456884
DOI: 10.7717/peerj.15660