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JAMA Network Open Jun 2024Daily supplementation with the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) vs placebo has previously been demonstrated to reduce bone loss in an... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Daily supplementation with the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) vs placebo has previously been demonstrated to reduce bone loss in an estrogen deficiency mice model and older women, although the magnitude of the effect was small. We hypothesized that long-term treatment with L reuteri could result in clinically relevant skeletal benefits in postmenopausal osteoporosis.
OBJECTIVE
To evaluate whether daily supplementation with L reuteri vs placebo could reduce early postmenopausal bone loss and whether the effects remained or increased over time during 2 years of treatment.
DESIGN, SETTING, AND PARTICIPANTS
A double-blind, randomized, placebo-controlled clinical trial was conducted between December 4, 2019, and October 6, 2022, at a single center in Gothenburg, southwestern Sweden. Participants were recruited by online advertisements, and letters were sent to 10 062 women aged 50 to 60 years. Responding women (n = 752) underwent telephone screening, resulting in 292 women being invited to a screening visit. Of those who were screened, 239 women met all inclusion criteria and had no exclusion criteria.
INTERVENTIONS
Capsules with L reuteri in 2 doses, 5 × 108 (low dose) or 5 × 109 (high dose) colony-forming units, taken twice daily or placebo were administered. All capsules also included cholecalciferol, 200 IU.
MAIN OUTCOMES AND MEASURES
The primary outcome was the relative change in tibia total volumetric bone mineral density (vBMD) over 2 years. Secondary outcomes included relative change in areal BMD of the lumbar spine and total hip, bone turnover markers C-terminal telopeptide cross-links of collagen type I and type I procollagen intact N-terminal propeptide, as well as tibia trabecular bone volume fraction and cortical vBMD. Both intention-to-treat and per-protocol analyses were conducted.
RESULTS
A total of 239 postmenopausal women (median age, 55 [IQR, 53-56] years) were included. Tibia vBMD (primary outcome), hip and spine vBMD, and tibia cortical area and BMD decreased significantly in all groups, with no group-to-group differences (percent change tibia vBMD high dose vs placebo least-squares means, -0.08 [95 CI, -0.85 to 0.69] and low dose vs placebo least-squares means, -0.22 [95% CI, -0.99 to 0.55]). There were no significant treatment effects on any other predefined outcomes. A prespecified sensitivity analysis found a significant interaction between body mass index (BMI) and treatment effect at 2 years. No significant adverse effects were observed.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of 239 early postmenopausal women, supplementation with L reuteri had no effect on bone loss or bone turnover over 2 years. The observed interaction between BMI and treatment effect warrants further investigation.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04169789.
Topics: Humans; Female; Limosilactobacillus reuteri; Middle Aged; Double-Blind Method; Osteoporosis, Postmenopausal; Bone Density; Probiotics; Sweden
PubMed: 38865129
DOI: 10.1001/jamanetworkopen.2024.15455 -
Nutrition Research and Practice Jun 2024This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
BACKGROUND/OBJECTIVES
This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
MATERIALS/METHODS
MC3T3-E1 osteoblastic cells and RAW 264.7 osteoclastic cells were treated with FJH-UBS. The alkaline phosphatase (ALP) activity, mineralization, collagen synthesis, osteocalcin content, and Runt-related transcription factor 2 (RUNX2) and Osterix expression were measured in MC3T3-E1 cells. The actin ring structures, tartrate-resistant acid phosphatase (TRAP) activity, and the nuclear factor of activator T-cells, cytoplasm 1 (NFATc1) expression were evaluated in RAW 264.7 cells. Ovariectomized ICR mice were orally administered FJH-UBS for eight weeks. The bone mineral density (BMD) and the serum levels of osteocalcin, procollagen 1 N-terminal propeptide (P1NP), osteoprotegerin, and TRAP 5b were analyzed.
RESULTS
FJH-UBS increased the ALP activity, collagen, osteocalcin, mineralization, and RUNX2 and osterix expression in MC3T3-E1 osteoblastic cells, whereas it decreased the TRAP activity, actin ring structures, and NFATc1 expression in RAW 264.7 osteoclastic cells. In ovariectomy-induced osteoporosis mice, FJH-UBS positively restored all of the changes in the bone metabolism biomarkers (BMD, osteocalcin, P1NP, osteoprotegerin, and TRAP 5b) caused by the ovariectomy.
CONCLUSION
FJH-UBS has anti-osteoporotic activity by promoting osteoblast activity and inhibiting osteoclast activity and , suggesting that FJH-UBS is a potential functional food ingredient for osteoporosis.
PubMed: 38854466
DOI: 10.4162/nrp.2024.18.3.309 -
Medicine Jun 2024In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic... (Observational Study)
Observational Study
In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH) and liver fibrosis. The observation and control groups comprised 133 patients with CHB complicated by NASH and 50 healthy patients from our hospital, respectively. Liver function indices, including alanine aminotransferase, glutamic aminotransferase, γ-glutamyltransferase, total bilirubin, total protein, and total cholesterol, were determined using an automatic biochemical analyzer. Hyaluronic acid, type III procollagen, type IV collagen, laminin, and CK18-M65 and M30 levels were detected using ELISA. Serum CK18-M65 and M30 levels in patients with CHB complicated by NASH were positively correlated with the liver fibrosis stage (P < .05). While serum CK18-M65 demonstrated a low diagnostic value for liver fibrosis in the S0-1 stage, it exhibited good diagnostic value for S2-3 stage liver fibrosis. Serum CK18-M30 displayed good diagnostic value for S0-1 and S2-3 hepatic fibrosis, particularly for S2-3 hepatic fibrosis. Elevated serum CK18-M65 and CK18-M30 levels in patients with CHB complicated with NASH suggest their potential utility in evaluating the progression of liver fibrosis in this population. In particular, CK18-M30 exhibits superior diagnostic efficiency.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Hepatitis B, Chronic; Male; Female; Keratin-18; Liver Cirrhosis; Adult; Middle Aged; Biomarkers; Peptide Fragments; Liver Function Tests; Case-Control Studies; Clinical Relevance
PubMed: 38847670
DOI: 10.1097/MD.0000000000038342 -
Biomolecules & Biomedicine Jun 2024Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an...
Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.
PubMed: 38843496
DOI: 10.17305/bb.2024.10500 -
Cellular and Molecular Biology... Jun 2024This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in... (Randomized Controlled Trial)
Randomized Controlled Trial
This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), β-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased β-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.
Topics: Humans; Male; Female; Adult; External Fixators; Osteocalcin; Middle Aged; Bone and Bones; C-Reactive Protein; Quality of Life; Fractures, Open; Interleukin-6; Procollagen; Double-Blind Method; Collagen Type I; Adrenocorticotropic Hormone; Peptide Fragments; Extremities; Peptides; Hydrocortisone
PubMed: 38836683
DOI: 10.14715/cmb/2024.70.6.10 -
Molecular Medicine Reports Aug 2024C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate...
C1q/tumor necrosis factor‑related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)‑induced mice via the AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2‑related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3‑E1 cells were used to construct and models of osteoporosis, respectively. The left femurs of mice were examined using micro‑computed tomography scans and bone‑related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate‑resistant acid phosphatase (TRAP) staining. Runt‑related transcription factor‑2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C‑telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N‑terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3‑E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, , and expression levels were detected using reverse transcription‑quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX‑induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3‑E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3‑E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX‑induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.
Topics: Animals; Sirtuin 1; Female; Mice; Signal Transduction; Osteoporosis; NF-E2-Related Factor 2; Ovariectomy; AMP-Activated Protein Kinases; Mice, Inbred C57BL; Osteoblasts; Cell Line; Osteoclasts; Disease Models, Animal; Femur; Osteogenesis
PubMed: 38818814
DOI: 10.3892/mmr.2024.13257 -
Chemosphere Aug 2024This study aimed to evaluate the adverse effects of particulate matter (PM) exposure on endometrial cells and fertility and to identify possible underlying mechanisms....
This study aimed to evaluate the adverse effects of particulate matter (PM) exposure on endometrial cells and fertility and to identify possible underlying mechanisms. Thirteen women (aged 15-52 years) were included in this study. Enrolled patients underwent laparoscopic surgery at Gangnam Severance Hospital between 1 January and 31 December 2021. For in vivo experiments, 36 female and nine male C57BL/6 mice were randomly divided into control(vehicle), low-dose(10 mg/kg/d), and high-dose exposure groups(20 mg/kg/d). PM was inhaled nasally for four weeks and natural mating was performed. NIST® SRM® 1648a was used for PM exposure. qRT-PCR, western blotting and Masson's trichrome staining were performed. PM treatment in human endometrial stromal cells induced inflammation with significant upregulation of IL-1β, p-NF-kB, and p-c-Jun compared to those of controls. Additionally, PM treatment significantly increased apoptosis in human endometrial stromal cells by downregulating p-AKT and upregulating p-p53/p53, Cas-3, BAX/Bcl-2, p-AMPK, and p-ERK. After PM treatment, the relative expression of IL-1β, IL-6, TNF-α, p-NF-κB, p-c-Jun, and p-Nrf2/Nrf2 significantly increased in murine endometrium compared to those of the controls. Expression of apoptotic proteins p53, p27, and Cas-3, was also significantly elevated in murine endometrium of the PM exposure group compared to that of the controls. A significant increase in expression of procollagen Ⅰ, and Masson's trichrome staining scores in the murine endometrium was noted after PM treatment. PM treatment significantly decreased ERα expression. After natural mating, all 3 female mice in the control group gave birth to 25 offspring (mean 8.1), whereas in the low-dose PM treatment group, two of three female mice gave birth to nine offspring (mean 4.5). No pregnant mice or offspring was present in the high-dose PM treatment group. PM exposure induces adverse effects on the endometrium through aberrant activation of inflammatory and apoptotic pathways and is associated with detrimental effects on murine fertility.
Topics: Particulate Matter; Female; Animals; Humans; Apoptosis; Mice; Adult; Endometrium; Male; Mice, Inbred C57BL; Adolescent; Young Adult; Inflammation; Middle Aged; Fertility; Air Pollutants; Stromal Cells
PubMed: 38810796
DOI: 10.1016/j.chemosphere.2024.142466 -
Scientific Reports May 2024Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and...
Prolyl 4-hydroxylases (P4Hs) are a family of key modifying enzymes in collagen synthesis. P4Hs have been confirmed to be closely associated with tumor occurrence and development. However, the expression of P4Hs in head and neck cancer (HNSC) as well as its relationship with prognosis and tumor immunity infiltration has not yet been analyzed. We investigated the transcriptional expression, survival data, and immune infiltration of P4Hs in patients with HNSC from multiple databases. P4H1-3 expression was significantly higher in HNSC tumor tissues than in normal tissues. Moreover, P4HA1 and P4HA2 were associated with tumor stage, patient prognosis, and immune cell infiltration. P4HA3 was related to patient prognosis and immune cell infiltration. Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.
Topics: Humans; Biomarkers, Tumor; Prognosis; Head and Neck Neoplasms; Immunotherapy; Procollagen-Proline Dioxygenase; Gene Expression Regulation, Neoplastic; Female; Male; Nasopharyngeal Carcinoma
PubMed: 38806556
DOI: 10.1038/s41598-024-62678-9 -
Narra J Apr 2024Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure,...
Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-β1 (TGF-β1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-β1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (=0.345 and =0.333, respectively; both had <0.05). PICP and TGF-β1 biomarkers did not significantly correlate with Cn (>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.
Topics: Humans; Mitral Valve Stenosis; Rheumatic Heart Disease; Biomarkers; Male; Female; Cross-Sectional Studies; Fibrosis; Adult; Atrial Function, Left; Heart Atria; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1; Middle Aged; Matrix Metalloproteinase 1; Procollagen; Indonesia; Peptide Fragments; Echocardiography
PubMed: 38798862
DOI: 10.52225/narra.v4i1.293