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Alternative Therapies in Health and... Jun 2024Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone...
Study on the Mechanism of Xianling Gubao Capsule Regulating Runt-Related Transcription Factor 2 (RUNX2) and Promoting Osteoblast Differentiation by N6-Methyladenosine (m6A) Methyltransferase-Like 3 (METTL3).
BACKGROUND
Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and a higher risk of fractures. It is a significant public health concern, particularly among postmenopausal women and older adults. The imbalance between bone formation and resorption is the fundamental cause of OP. Current clinical drugs for OP have limited efficacy and can cause side effects. Therefore, there is a need to explore alternative treatments and investigate their mechanisms to improve OP management. The Xianling Gubao capsule, a traditional Chinese medicine, is commonly used to treat OP by tonifying the kidney. However, the specific mechanism of action of the Xianling Gubao capsule in improving OP remains unclear, necessitating further research in this area.
METHODS
The N6-methyladenosine (m6A) content was evaluated by dot blot and m6A ribonucleic acid (RNA) methylation assay kit. The contents of methyltransferase-like 3 (METTL3), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and bone gamma-carboxyglutamate protein (BGLAP) were appraised by quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) and western blot. The bilateral ovariectomy (OVX) method was used to establish an animal model of OP. OP bone marrow mesenchymal stem cells (OP-BMSCs) were extracted from mice in the OVX group by the whole bone marrow method. METTL3 overexpression and control vectors were transfected to OP-BMSCs using X-tremeGENE HP DNA Transfection Reagent. The ALP activity in OP-BMSCs was assessed by ALP staining. The calcium nodules in OP-BMSCs were detected by Alizarin Red S (ARS) assay. The Xianling Gubao capsule solution was employed to gavage mice, and the drug-containing serum was used to treat OP-BMSCs. Dot blot allows for the assessment of relative levels of m6A modification. The m6A RNA methylation assay kit is a specialized kit designed to quantitatively measure m6A levels in RNA samples. qRT-PCR allows for the measurement of mRNA levels of target genes. Western blot is used to detect and quantify specific proteins in a sample, and provides information about protein expression levels. OVX mimics the hormonal changes occurring in postmenopausal women and leads to bone loss and osteoporotic conditions in animals. This model allows for the investigation of the effects of the Xianling Gubao capsule on OP in a controlled experimental setting.
RESULTS
The m6A modification and METTL3, RUNX2, ALP, and BGLAP levels were reduced in bone samples of patients with OP and OVX mice compared with the corresponding control groups. Upregulated METTL3 enhanced the osteogenic ability of OP-BMSCs. METTL3 overexpression obviously increased m6A modification and METTL3, RUNX2, ALP, and BGLAP levels in OP-BMSCs. Xianling Gubao capsule treatment could weaken the impact of OP in mice by regulating the m6A modification and METTL3, RUNX2, ALP, and BGLAP levels. Serum containing Xianling Gubao capsule could enhance the osteogenic capability of OP-BMSCs and boost METTL3, RUNX2, ALP, and BGLAP levels. Treatment with the Xianling Gubao capsule shows promising effects in attenuating the impact of OP. The capsule is found to regulate m6A modification and increase the levels of METTL3, RUNX2, ALP, and BGLAP in OP-BMSCs. This indicates that the Xianling Gubao capsule may rescue the diminished osteogenic capability of OP-BMSCs by modulating METTL3. These findings suggest that the Xianling Gubao capsule has the potential to be an effective drug for the treatment of OP.
CONCLUSION
Taken together, the m6A modification and contents of osteogenic-related factors were reduced in OP. Upregulated METTL3 improved the osteogenic ability, m6A modification, and osteogenic-related factor abundances in OP-BMSCs. Xianling Gubao capsule rescued the diminished osteogenic capability of OP-BMSCs by modulating METTL3 and might serve as an effective drug for OP. The Xianling Gubao capsule, as a traditional Chinese medicine, could potentially complement existing therapeutic approaches for OP. By targeting the m6A modification pathway and promoting osteogenic differentiation, the capsule may help to expedite bone formation and repair, which are critical for managing OP and reducing the risk of fractures.
PubMed: 38940781
DOI: No ID Found -
Translational Vision Science &... Jun 2024To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PURPOSE
To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated low-level red light (RLRL) and 0.01% atropine exposure in premyopic schoolchildren.
METHODS
Prospective randomized trial. Sixty-nine schoolchildren with cycloplegic refraction >-0.75 D and ≤0.50 D were randomly assigned to RLRL and 0.01% atropine groups. SRVD, DRVD, and RT were measured using swept-source optical coherence tomography at baseline and six months. The macular zone was divided into three concentric rings (fovea, parafovea, and perifovea) using the Early Treatment Diabetic Retinopathy Study.
RESULTS
After six months, the whole, parafoveal, and perifoveal SRVD significantly increased in the two groups (all P < 0.05). Multivariate regression analyses showed that none of these changes varied significantly between the two groups (all P > 0.05), whereas foveal SRVD remained stable in both groups (all P > 0.05). In the RLRL group, the whole and perifoveal DRVD increased significantly (all P < 0.05), whereas no statistical difference was observed in the foveal and parafoveal DRVD. DRVD remained stable in the 0.01% atropine group (all P > 0.05). No significant differences were observed in RT changes between the two groups (all P > 0.05). In comparison, there were no significant changes in SRVD, DRVD, or RT after six months in the placebo group in our previous study.
CONCLUSIONS
SRVD increased similarly in the RLRL and 0.01% atropine groups, whereas DRVD increased only in the former group. There were no significant RT changes in either group after six months of treatment in premyopic schoolchildren.
TRANSLATIONAL RELEVANCE
This research observed the effects of low-level red light and 0.01% atropine on retinal vasculature, offering valuable insights into myopia progression prevention.
Topics: Humans; Atropine; Male; Female; Child; Prospective Studies; Retinal Vessels; Mydriatics; Tomography, Optical Coherence; Myopia; Ophthalmic Solutions; Phototherapy; Microvascular Density; Red Light
PubMed: 38940757
DOI: 10.1167/tvst.13.6.23 -
Journal of Radiation Research Jun 2024The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and...
The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.
PubMed: 38940734
DOI: 10.1093/jrr/rrae050 -
Multimedia Manual of Cardiothoracic... Jun 2024Donor organ recovery techniques have improved with novel preservation solutions, implementation of advanced preservation systems and machine perfusion. However, surgical...
Donor organ recovery techniques have improved with novel preservation solutions, implementation of advanced preservation systems and machine perfusion. However, surgical techniques for organ procurement have not changed. In this video tutorial, we have outlined key steps in double lung en bloc organ recovery, including introduction of pulmonoplegia, pulmonectomy en bloc and separation of the two single-lung blocks.
Topics: Humans; Lung Transplantation; Tissue and Organ Procurement; Tissue and Organ Harvesting; Lung; Organ Preservation; Tissue Donors; Pneumonectomy
PubMed: 38940725
DOI: 10.1510/mmcts.2024.050 -
Medeniyet Medical Journal Jun 2024The aim of this study was to investigate the effect of various astaxanthin (ATX) doses on oxidative damage and autophagy in renal ischemia-reperfusion (I/R)...
OBJECTIVE
The aim of this study was to investigate the effect of various astaxanthin (ATX) doses on oxidative damage and autophagy in renal ischemia-reperfusion (I/R) injury-modeled rats.
METHODS
The rats were divided into five groups: sham group (n=8), I/R (n=8), I/R + 5 mg/kg ATX (n=8), I/R + 10 mg/kg ATX (n=8), and I/R + 25 mg/kg ATX (n=8) groups. ATX was dissolved in 5 mg/kg, 10 mg/kg, and 25 mg/kg olive oil for 7 days and administered to the rats in the experimental group. Sham and I/R groups were also administered ATX solution (olive oil) via oral gavage for 7 days. Renal ischemia reperfusion was induced in all rats except the sham group after the last dose was administered on the 7 day. Reperfusion was conducted for 24 hours after 45 minutes of ischemia.
RESULTS
Blood samples were collected, and kidney tissue were incised for biochemical and histological analyses. Superoxide dismutase (SOD) and total antioxidant status (TAS) were significantly lower in the I/R group than in the sham group (p<0.05), whereas malondialdehyde (MDA) and total oxidant status (TOS) values were higher (p<0.05). It was determined that SOD and TAS increased and MDA and TOS decreased in the ATX-administration groups compared with the I/R group, independent of the dose (p<0.05). In the 25 mg/kg ATX + I/R group, Beclin-1 and LC3β immunoreactivities were significantly higher than those in the other groups (p<0.05). The lowest p62 immunoreactivity was observed in the 25 mg/kg ATX + I/R group.
CONCLUSIONS
ATX had a protective effect on kidney function and against oxidative damage. Furthermore, high-dose ATX administration protected kidney tissue via autophagy induction in this study.
PubMed: 38940481
DOI: 10.4274/MMJ.galenos.2024.27243 -
Journal of Global Health Jun 2024Diarrhoeal disease disproportionately affects children <5 years in low- and middle-income countries (LMICs). The pathogens responsible for diarrhoea are commonly... (Meta-Analysis)
Meta-Analysis
Lifestraw Family water filters in low- and middle-income countries: a systematic review and meta-analysis to define longer-term public health impact against childhood diarrhoea and inform scale-up.
BACKGROUND
Diarrhoeal disease disproportionately affects children <5 years in low- and middle-income countries (LMICs). The pathogens responsible for diarrhoea are commonly transmitted through faecally-contaminated drinking water. Lifestraw Family point-of-use water filters have been the subject of intervention studies for over a decade and were the first filters evaluated by the World Health Organization in its water treatment evaluation scheme to provide comprehensive protection against many diarrhoea-causing pathogens. This systematic review aimed to: 1) report on aspects related to physical environment and implementation and 2) conduct an updated meta-analysis on Lifestraw Family filter effectiveness against childhood diarrhoea based on studies with ≥12 months of follow-up.
METHODS
We conducted a literature search in November 2022 using MEDLINE, Embase, Cochrane, and CINAHL databases. Inclusion criteria were: 1) RCTs, cluster-RCTs, quasi-experimental, or matched cohort studies on 2) Lifestraw Family 1.0 or 2.0 filters 3) conducted in LMICs 4) that evaluated filter effectiveness against diarrhoea in children <5 and 5) analysed ≥12 months of follow-up data on clinical effectiveness against diarrhoea and were 6) published from 2010 with 7) full-text availability in English. A modified Newcastle-Ottawa Scale was used to assess risk of bias. Relative risk (RR) and 95% confidence intervals (CIs) were extracted and analysed using a random-effects meta-analysis.
RESULTS
We included 6 studies in LMICs involving 4740 children <5. Of the four clinically-effective interventions, common characteristics were access to improved water sources (75%), the 2.0 version of the filter or the 1.0 version with additional water storage (100%), use of behaviour change theory, community engagement, and health messaging (75%), local filter repair-and-replace mechanisms (75%), and specially-trained local interventionists (100%). The meta-analysis showed a 30% reduction in diarrhoea risk in the intervention group (RR = 0.69; 95% CI = 0.52-0.91, P = 0.01).
CONCLUSIONS
Lifestraw Family water filters can be effective interventions to reduce diarrhoea in vulnerable paediatric populations for at least one year, though certain aspects related to physical environment and implementation may increase their public health impact. The findings of this study suggest considerations for scale-up that can be applied in settings in need of longer-term interim solutions until universal access to safe drinking water is achieved.
Topics: Humans; Diarrhea; Developing Countries; Water Purification; Public Health; Filtration; Child, Preschool; Drinking Water; Infant
PubMed: 38939952
DOI: 10.7189/jogh.14.04018 -
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 -
JACC. Advances Apr 2024Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown...
BACKGROUND
Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown in comparison to those without ACHD.
OBJECTIVES
The purpose of this study was to compare all-cause mortality or cardiopulmonary hospitalizations in self-identified ACHD versus non-ACHD patients receiving high- or low-dose influenza vaccination within the INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure trial.
METHODS
We prospectively included ACHD patients in the INVESTED (INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure) trial. The primary endpoint was all-cause death or hospitalization for cardiovascular or pulmonary causes.
RESULTS
Of the 272 ACHD patients, 132 were randomly assigned to receive high-dose trivalent and 140 to standard-dose quadrivalent influenza vaccine. Compared to the non-ACHD cohort (n = 4,988), ACHD patients were more likely to be younger, women, smokers, have atrial fibrillation, and have a qualifying event of heart failure. The primary outcome was 49.8 events versus 42.8 events per 100 person-years (adjusted HR: 1.17; 95% CI: 0.95-1.45; = 0.144) in the ACHD group and non-ACHD group, respectively. The interaction between ACHD status and randomized treatment effect was not significant for the primary outcome ( = 0.858). Vaccine-related adverse events were similar in both groups.
CONCLUSIONS
Patients who self-identify as being ACHD had similar primary outcome of all-cause death or hospitalization for cardiovascular or pulmonary causes compared to non-ACHD cohort. High-dose influenza vaccination was similar to standard-dose influenza vaccination on the primary outcome in patients who self-identify as ACHD.
PubMed: 38939662
DOI: 10.1016/j.jacadv.2024.100897 -
JACC. Advances Sep 2023
PubMed: 38939485
DOI: 10.1016/j.jacadv.2023.100545 -
Frontiers in Oncology 2024ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and...
PURPOSE/OBJECTIVES
ZAP-X, a novel and dedicated radiosurgery (SRS) system, has recently emerged, while CyberKnife has solidified its position as a versatile solution for SRS and stereotactic body radiation therapy over the past two decades. This study aims to compare the dosimetric performance and delivery efficiency of ZAP-X and CyberKnife in treating brain metastases of varying target sizes, employing circular collimation.
METHODS AND MATERIALS
Twenty-three patients, encompassing a total of 47 brain metastases, were included in the creation of comparative plans of ZAP-X and CyberKnife for analysis. The comparative plans were generated to achieve identical prescription doses for the targets, while adhering to the same dose constraints for organs at risk (OAR). The prescription isodose percentage was optimized within the range of 97-100% for each plan to ensure effective target-volume coverage. To assess plan quality, indices such as conformity, homogeneity, and gradient (CI, HI, and GI) were computed, along with the reporting of total brain volumes receiving 12Gy and 10Gy. Estimated treatment time and monitor units (MUs) were compared between the two modalities in evaluating delivery efficiency.
RESULTS
Overall, CyberKnife achieved better CI and HI, while ZAP-X exhibited better GI and a smaller irradiated volume for the normal brain. The superiority of CyberKnife's plan conformity was more pronounced for target size less than 1 cc and greater than 10 cc. Conversely, the advantage of ZAP-X's plan dose gradient was more notable for target sizes under 10 cc. The homogeneity of ZAP-X plans, employing multiple isocenters, displayed a strong correlation with the target's shape and the planner's experience in placing isocenters. Generally, the estimated treatment time was similar between the two modalities, and the delivery efficiency was significantly impacted by the chosen collimation sizes for both modalities.
CONCLUSION
This study demonstrates that, within the range of target sizes within the patient cohort, plans generated by ZAP-X and CyberKnife exhibit comparable plan quality and delivery efficiency. At present, with the current platform of the two modalities, CyberKnife outperforms ZAP-X in terms of conformity and homogeneity, while ZAP-X tends to produce plans with a more rapid dose falloff.
PubMed: 38939330
DOI: 10.3389/fonc.2024.1333642