Bio-Inspired Superhydrophilic Self-Assembled Coronavirus-Like Pt-WC/CNT for Hydrogen Evolution Reaction.

This study presents a novel approach to enhance the catalytic activity of composite materials by promoting active surface exposure and improving hydrogen transfer performance. Through a self-assembly route involving tailored gas-solid and galvanic replacement reactions, Pt-WC/CNT catalysts with superhydrophilicity and coronavirus-like structure are synthesized. These unique structural features contribute to a remarkable enhancement in the electrocatalytic performance of the hydrogen evolution reaction (HER). Notably, the Pt-WC/CNT catalyst exhibits an outstanding intrinsic activity and efficient bubble transfer properties, leading to a high turnover frequency of 34.97 H2 ·s-1 at an overpotential of 100 mV. This value is 4.8 times higher than that achieved by commercial Pt/C catalysts (7.30 H2 ·s-1 ), establishing Pt-WC/CNT as one of the most active catalysts reported to date. Moreover, the combination of gas-solid and galvanic replacement reactions in the synthesis process offers a scalable route for the production of Pt-loading controllable composite catalysts, thus challenging the dominance of commercial Pt/C catalysts.

Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma.

The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.

A novel circular RNA, circSQSTM1, protects the endothelial function in atherosclerosis.

A novel circRNA named circSQSTM1 (hsa_circRNA_075320) was screened out in atorvastatin (ATV) stimulated endothelial cells (ECs) by our group. Considering the anti-atherosclerotic function of ATV, we hypothesized the circSQSTM1 could protect ECs functions in AS progression. The effects of circSQSTM1 on ECs inflammation, oxidative stress and autophagy were measured by qRT-PCR, Western blotting, monocyte-endothelial adhesion assay, dichloro-dihydro-fluorescein diacetate and mCherry-GFP-LC3 labeling. A luciferase reporter assay, RNA immunoprecipitation, MS2-tagging system and fluorescence in situ hybridization were performed to identify the biological functions of circSQSTM1. The partial left carotid artery ligation model and atherosclerosis model were established to analyze the effects of circSQSTM1 on atherosclerosis progression in vivo. Our results revealed that ATV induced the accumulation of circSQSTM1 in ECs via suppressing m6A modified degradation. In the cytoplasm, circSQSTM1 could relieve Sirt1 by competitively sponging miR-23b-3p. In the nucleus, circSQSTM1 directly interacts with eIF4A3 and promoting the efficient nuclear export of FOXO1 mRNA, which encodes FOXO1 transcription factor to directly activate Sirt1 promoter activity. Hence, circSQSTM1 reduced inflammation, inhibited oxidative stress and promoted autophagy by upregulating Sirt1 in ECs. Moreover, circSQSTM1 overexpression in ECs attenuated the progression of atherosclerosis in ApoE-/- mice. Taken together, the unique noncoding RNA known as circSQSTM1 took a protective role to the ECs in atherosclerosis.

Intestinal Microbes and Hematological Malignancies.

Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematological tumors through direct and indirect mechanisms. Thus, we summarize the correlation between intestinal microbes and hematological malignancies' onset, progression, and therapeutic effect in order to better understand how intestinal microbes affect their initiation and progression, especially in leukemia, lymphoma, and multiple myeloma, which may provide potential therapeutic targets for improving the survival of patients with hematological malignancies.

Excessive serine from the bone marrow microenvironment impairs megakaryopoiesis and thrombopoiesis in Multiple Myeloma.

Thrombocytopenia is a major complication in a subset of patients with multiple myeloma (MM). However, little is known about its development and significance during MM. Here, we show thrombocytopenia is linked to poor prognosis in MM. In addition, we identify serine, which is released from MM cells into the bone marrow microenvironment, as a key metabolic factor that suppresses megakaryopoiesis and thrombopoiesis. The impact of excessive serine on thrombocytopenia is mainly mediated through the suppression of megakaryocyte (MK) differentiation. Extrinsic serine is transported into MKs through SLC38A1 and downregulates SVIL via SAM-mediated tri-methylation of H3K9, ultimately leading to the impairment of megakaryopoiesis. Inhibition of serine utilization or treatment with TPO enhances megakaryopoiesis and thrombopoiesis and suppresses MM progression. Together, we identify serine as a key metabolic regulator of thrombocytopenia, unveil molecular mechanisms governing MM progression, and provide potential therapeutic strategies for treating MM patients by targeting thrombocytopenia.

The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma.

Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota-host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.

Enhanced anaerobic oxidation of methane with the coexistence of iron oxides and sulfate fertilizer in paddy soil.

Iron oxides and sulfate are usually abundant in paddy soil, but their role in reducing methane emissions is little known. In this work, paddy soil was anaerobically cultivated with ferrihydrite and sulfate for 380 days. An activity assay, inhibition experiment, and microbial analysis were conducted to evaluate the microbial activity, possible pathways, and community structure, respectively. The results showed that anaerobic oxidation of methane (AOM) was active in the paddy soil. The AOM activity was much higher with ferrihydrite than sulfate, and an extra 10% of AOM activity was stimulated when ferrihydrite and sulfate coexisted. The microbial community was highly similar to the duplicates but totally different with different electron acceptors. The microbial abundance and diversity decreased due to the oligotrophic condition, but mcrA-carrying archaea increased 2-3 times after 380 days. Both the microbial community and the inhibition experiment implied that there was an intersection between iron and sulfur cycles. A "cryptic sulfur cycle" might link the two cycles, in which sulfate was quickly regenerated by iron oxides, and it might contribute 33% of AOM in the tested paddy soil. Complex links between methane, iron, and sulfur geochemical cycles occur in paddy soil, which may be significant in reducing methane emissions from rice fields.

Nano-Silicon@Exfoliated Graphite/Pyrolytic Polyaniline Composite of a High-Performance Cathode for Lithium Storage.

In this paper, a Si@EG composite was prepared by liquid phase mixing and the elevated temperature solid phase method, while polyaniline was synthesized by the in situ chemical polymerization of aniline monomer to coat the surface of nano-silicon and exfoliated graphite composites (Si@EG). Pyrolytic polyaniline (p-PANI) coating prevents the agglomeration of silicon nanoparticles, forming a good conductive network that effectively alleviates the volume expansion effect of silicon electrodes. SEM, TEM, XRD, Raman, TGA and BET were used to observe the morphology and analyze the structure of the samples. The electrochemical properties of the materials were tested by the constant current charge discharge and cyclic voltammetry (CV) methods. The results show that Si@EG@p-PANI not only inhibits the agglomeration between silicon nanoparticles and forms a good conductive network but also uses the outermost layer of p-PANI carbon coating to effectively alleviate the volume expansion of silicon nanoparticles during cycling. Si@EG@p-PANI had a high initial specific capacity of 1491 mAh g-1 and still maintains 752 mAh g-1 after 100 cycles at 100 mA g-1, which shows that it possesses excellent electrochemical stability and reversibility.

Modulating Dominant Facets of Pt through Multistep Selective Anchored on WC for Enhanced Hydrogen Evolution Catalysis.

Facilitating the exposure of the active crystal facets on the surfaces of composite catalysts is a representative route to promote catalytic activity. Based on a tailored galvanic replacement reaction, herein, a self-assembly route is reported to prepare Pt-WC/CNT with Pt (200) preferential orientation and well-dispersed structure, which are capable of substantially boosting electrocatalysis in hydrogen evolution reaction (HER). Formation mechanism reveals that the (200)-dominated Pt-based catalysts form in galvanic replacement reaction through selective anchored on WC, and the multistep galvanic replacement process plays a critical role to realize the Pt (200)-dominated growth in higher Pt loading catalyst. These unique structural features endow the Pt-WC/CNT with a high turnover frequency of 94.18 H2·s-1 at 100 mV overpotential, 7-fold higher than that of commercial Pt/C (13.55 H2·s-1), ranking it among the most active catalysts. In addition, this method, which combines with gas-solid reaction and galvanic replacement reaction, paves the way to scalable synthesis as Pt facets-controllable composite catalysts to challenge commercial Pt/C.

XCR1+ conventional dendritic cell-induced CD4+ T helper 1 cell activation exacerbates cardiac remodeling after ischemic myocardial injury.

Cardiac remodeling has no established therapies targeting inflammation. CD4+ T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI-/-/ApoeR61h/h mice. Flow cytometry analyses throughout the period of progressive cardiac dysfunction revealed that CD4+ T Helper 1 (Th1) cells were predominantly activated in T-cell subsets. Probucol was reported to attenuate cardiac dysfunction after coronary artery ligation model (ligation-MI) in rats. To determine whether probucol suppress cardiac remodeling after HFD-CHD, we treated SR-BI-/-/ApoeR61h/h mice with probucol. We found treatment with probucol in HFD-CHD mice reduced cardiac dysfunction, with attenuated activation of Th1 cells. RNA-seq analyses revealed that probucol suppressed the expression of CXCR3, a Th1-related chemokine receptor, in the heart. XCR1+ cDC1 cells, which highly expresses the CXCR3 ligands CXCL9 and CXCL10, were predominantly activated after HFD-CHD. XCR1+ cDC1 lineage skewing of pre-DC progenitors was observed in bone marrow, with subsequent systemic expansion of XCR1+ cDC1 cells after HFD-CHD. Activation of CXCR3+ Th1 cell and XCR1+ cDC1 cells was also observed in ligation-MI. Notably, post-MI depletion of XCR1+ cDC1 cells suppressed CXCR3+ Th1 cell activation and prevented cardiac dysfunction. In patient autopsy samples, CXCR3+ Th1 and XCR1+ cDC1 cells infiltrated the infarcted area. In this study, we identified a critical role of XCR1+ cDC1-activated CXCR3+ Th1 cells in ischemic cardiac remodeling.

Long-term effects of soluble and insoluble ferric irons on anaerobic oxidation of methane in paddy soil.

Iron-dependent anaerobic oxidation of methane (Fe-AOM) is an important process to reduce methane emissions into the atmosphere. It is well known that iron bioavailability largely influences microbial iron reduction, but the long-term effects of different ferric irons on soil Fe-AOM remain unknown. In this work, paddy soil in the ferruginous zone was collected and inoculated with insoluble ferrihydrite and soluble EDTA-Fe(III) for 420 days. Stable isotope experiments, activity inhibition tests, and molecular biological techniques were performed to reveal the activity, microbial community, and possible mechanism of paddy soil Fe-AOM. The results showed that ferrihydrite was a better electron acceptor for long-term Fe-AOM cultivation. Although EDTA-Fe(III) is highly bioavailable and could stimulate Fe-AOM activity for a short time, it restricted the activity increase in the long term. The abundances of archaea, iron-reducing bacteria (IRB), and gene mcrA largely increased after cultivation, indicating the important roles of mcrA-carrying archaea and IRB. Remarkably, archaeal communities were similar, but bacteria were totally different with different ferric irons. The results of the microbial community and activity inhibition suggested that Fe-AOM was performed likely by the cooperation between archaea (Methanomassiliicoccaceae or pGrfC26) and IRB in the cultures.

A Dietary Oxysterol, 7-Ketocholesterol, Exacerbates Imiquimod-Induced Psoriasis-like Dermatitis in Steatohepatitic Mice.

Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. We previously identified an oxidized derivative of cholesterol, 7-ketocholesterol (7KC), in diet-induced steatohepatitic mice. Here, we investigated whether 7KC exacerbates psoriasis-like dermatitis by accelerating steatohepatitis in mice. A high-fat/high-cholesterol/high-sucrose/bile salt diet (nonalcoholic steatohepatitis (NASH) diet) with or without 0.0125% 7KC was fed to C57BL/6 mice (7KC or control group) for three weeks to induce steatohepatitis. A 5% imiquimod cream was then applied to the ears and dorsal skin for four days to induce psoriasis-like dermatitis. Hepatic lipid accumulation and inflammatory cell infiltration were exacerbated in the 7KC group compared with the control group after three weeks. Serum tumor necrosis factor-α (TNF-α) levels were also elevated in the 7KC group (108.5 ± 9.8 vs. 83.1 ± 13.1 pg/mL, p < 0.005). Imiquimod cream increased the psoriasis area severity index (PASI) score in mice in the 7KC group (9.14 ± 0.75 vs. 5.17 ± 1.17, p < 0.0001). Additionally, Tnfa, Il23a, Il17a, and Il22 mRNA levels in the dorsal lesion were significantly upregulated. Finally, Th17 cell differentiation and the TNF signaling pathway were enhanced in the dorsal lesions and liver of mice in the 7KC group. These data suggest that steatohepatitis and psoriasis are linked by a potent, diet-related factor.

Intestinal Klebsiella pneumoniae Contributes to Pneumonia by Synthesizing Glutamine in Multiple Myeloma.

Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut-lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia.

Blocking glycine utilization inhibits multiple myeloma progression by disrupting glutathione balance.

Metabolites in the tumor microenvironment are a critical factor for tumor progression. However, the lack of knowledge about the metabolic profile in the bone marrow (BM) microenvironment of multiple myeloma (MM) limits our understanding of MM progression. Here, we show that the glycine concentration in the BM microenvironment is elevated due to bone collagen degradation mediated by MM cell-secreted matrix metallopeptidase 13 (MMP13), while the elevated glycine level is linked to MM progression. MM cells utilize the channel protein solute carrier family 6 member 9 (SLC6A9) to absorb extrinsic glycine subsequently involved in the synthesis of glutathione (GSH) and purines. Inhibiting glycine utilization via SLC6A9 knockdown or the treatment with betaine suppresses MM cell proliferation and enhances the effects of bortezomib on MM cells. Together, we identify glycine as a key metabolic regulator of MM, unveil molecular mechanisms governing MM progression, and provide a promising therapeutic strategy for MM treatment.

Comprehensive treatment of pelvic floor muscle training plus biofeedback electrical stimulation for stress urinary incontinence: a clinical study.

OBJECTIVE: To investigate the clinical effect of pelvic floor muscle training (PFMT) plus biofeedback electrical stimulation (BES) on stress urinary incontinence (SUI). METHODS: 110 patients with SUI admitted to our hospital in the Department of Obstetrics and Gynecology from November 2018 to November 2019 were selected and divided into control group (n=55) and study group (n=55). The study group received PFMT plus BES while the control group received PFMT alone. RESULTS: Compared with the control group, the incontinence quality of life (I-QOL) score and the international consultation on incontinence questionnaire-urinary incontinence short form (ICI-Q-SF) score in the study group were significantly better (P<0.05), and the patients had better pelvic floor muscle endurance, strength, and coordination (P<0.05). CONCLUSION: PFMT plus BES could improve the strength, endurance, and coordination of pelvic floor muscles in SUI patients. It can positively influence the improvement of the I-QOL and ICI-Q-SF scores. CLINICAL TRIAL REGISTRATION: The name of the registry: Chinese Registry of Clinical Trials. TRIAL REGISTRATION NUMBER: ChiCTR21000684765. Trial URL: http://www.chictr.org.cn/showproj.aspx?proj=73654424.

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1.

Diabetic cardiomyopathy (DCM) is initially characterized by early diastolic dysfunction, left ventricular remodeling, hypertrophy, and myocardial fibrosis, and it is eventually characterized by clinical heart failure. MicroRNAs (miRNAs), endogenous small noncoding RNAs, play significant roles in diabetes mellitus (DM). However, it is still largely unknown about the mechanism that links miRNAs and the development of DCM. Here, we aimed to elucidate the mechanism underlying the potential role of microRNA-340-5p in DCM in db/db mouse, which is a commonly used model of type 2 DM and diabetic complications that lead to heart failure. We first demonstrated that miR-340-5p expression was dramatically increased in heart tissues of mice and cardiomyocytes under diabetic conditions. Overexpression of miR-340-5p exacerbated DCM, which was reflected by extensive myocardial fibrosis and more serious dysfunction in db/db mice as represented by increased apoptotic cardiomyocytes, elevated ROS production, and impaired mitochondrial function. Inhibition of miR-340-5p by a tough decoy (TUD) vector was beneficial for preventing ROS production and apoptosis, thus rescuing diabetic cardiomyopathy. We identified myeloid cell leukemia 1 (Mcl-1) as a major target gene for miR-340-5p and showed that the inhibition of Mcl-1 was responsible for increased functional loss of mitochondria, oxidative stress, and cardiomyocyte apoptosis, thereby caused cardiac dysfunction in diabetic mice. In conclusion, our results showed that miR-340-5p plays a crucial role in the development of DCM and can be targeted for therapeutic intervention.

Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy.

Although patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1ß, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction.

Genetic Aberrations and Interaction of NEK2 and TP53 Accelerate Aggressiveness of Multiple Myeloma.

It has been previously shown that (never in mitosis gene A)-related kinase 2 (NEK2) is upregulated in multiple myeloma (MM) and contributes to drug resistance. However, the mechanisms behind this upregulation remain poorly understood. In this study, it is found that amplification of NEK2 and hypermethylation of distal CpG islands in its promoter correlate strongly with increased NEK2 expression. Patients with NEK2 amplification have a poor rate of survival and often exhibit TP53 deletion, which is an independent prognostic factor in MM. This combination of TP53 knockout and NEK2 overexpression induces asymmetric mitosis, proliferation, drug resistance, and tumorigenic behaviors in MM in vitro and in vivo. In contrast, delivery of wild type p53 and suppression of NEK2 in TP53-/- MM cell lines inhibit tumor formation and enhance the effect of Bortezomib against MM. It is also discovered that inactivating p53 elevates NEK2 expression genetically by inducing NEK2 amplification, transcriptionally by increased activity of cell cycle-related genes like E2F8 and epigenetically by upregulating DNA methyltransferases. Dual defects of TP53 and NEK2 may define patients with the poorest outcomes in MM with p53 inactivation, and NEK2 may serve as a novel therapeutic target in aggressive MM with p53 abnormalities.

The effect of black carbon on the chemical degradability of PCB1 via TENAX desorption technology from the perspective of adsorption states.

Chemical degradation is one of the crucial methods for the remediation of hydrophobic organic compounds (HOCs) in soil/sediment. The sequestration effect of black carbon (BC) can affect the adsorption state of HOCs, thereby affecting their chemical degradability. Our study focused on the chemical degradability of 2-Chlorobiphenyl (PCB1) sequestrated on the typical BC (fly ash (FC), soot (SC), low-temperature biochar (BC400) and high-temperature biochar (BC900)) by iron-nickel bimetallic nanomaterials (nZVI/Ni) based on TENAX desorption technology. The results showed that PCB1 adsorbed in various states were simultaneously dechlorinated by nZVI/Ni. Specifically, rapid-desorption-state PCB1 tended to degrade more easily than resistant-desorption-state PCB1. Moreover, the degradation mechanism varied according to the type of BC. In the case of FC and SC, the degradation rate was lower than the desorption rate for the PCB1 in rapid and slow desorption states, and the degradation rate of PCB1 in the resistant desorption state was negligible. The PCB1 on FC and SC was first desorbed from BC and then degraded. However, in terms of BC400 and BC900, the degradation rate was higher than the desorption rate, and the degradation rate of the resistant-desorption-state PCB1 was 1.4 × 10-2 h-1 and 4.1 × 10-2 h-1, respectively. The graphitized structure of BC900 can directly transfer electrons, so more than 90% of the resistant-desorption-state PCB1 could be degraded. In addition, BC may affect the longevity of nZVI/Ni, thereby affecting its degradability. Therefore, the chemical degradability of BC-adsorbed HOCs should be comprehensively evaluated based on the adsorption state and the properties of BC.

The effect of tibolone treatment on fasting blood sugar, insulin, insulin resistance and endothelial function in postmenopausal women: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The menopause is associated in females with the presence of dysglycemia, insulin resistance and with the development of endothelial dysfunction. Tibolone (TIB) is a synthetic steroid compound with selective oestrogenic and, to a lesser extent, progestogenic and androgenic properties prescribed to postmenopausal women to alleviate the symptoms of the climaterium and to prevent the development of osteoporosis. However, the impact of TIB on fasting blood sugar (FBS), insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index and flow-mediated dilation (FMD) in women has not been evaluated so far. Thus, to investigate this research question, we conducted the present systematic review and meta-analysis. METHODS: Two independent reviewers searched the Scopus, Web of Science, PubMed/Medline and Embase databases up to 20 December 2020. The weighted mean differences (WMDs) and the 95% confidence intervals (CI) were calculated using the DerSimonian and Laird random effects models between the TIB and control groups and included in the forest plot. RESULTS: The overall findings were generated from 12 eligible randomized controlled trials. As compared to controls, TIB administration resulted in a significant reduction of FBS (WMD: -3.06 mg/dL, 95% CI: -5.30 to -0.82, P = 0.007), and of the HOMA-IR index (WMD: -0.61, 95% CI: -1.11 to -0.11, P = 0.01). However, treatment with TIB did not lead to significant changes of the FMD (WMD: 0.78%, 95% CI: -0.20 to 1.77, P = 0.12) or of insulin levels (WMD: -0.10 mIU/L, 95% CI: -2.04 to 1.83, P = 0.91). CONCLUSION: TIB administration can decrease FBS and the HOMA-IR index in postmenopausal women. However, the use of TIB does not influence insulin levels or FMD.