Summary
The associations between body fatness at a young age (childhood, adolescence and young adulthood; age ≤ 30 years) and diffuse large B‐cell lymphoma (DLBCL), oesophageal adenocarcinoma, ...gastric cardia cancer, hepatocellular carcinoma, multiple myeloma, pancreatic cancer, renal cell cancer and thyroid cancer remain inconclusive. We performed a comprehensive systematic literature review and meta‐analysis of observational studies to clarify the associations between body fatness at a young age and the risks of these cancers. PubMed and Web of Science databases were searched for relevant observational studies. Fifty‐six articles yielded data on 27,559 cancer cases, including 3,170 DLBCL, 1,491 oesophageal adenocarcinoma, 1,103 gastric cardia cancer, 1,067 hepatocellular carcinoma, 3,090 multiple myeloma, 7,220 pancreatic cancer, 6,212 renal cell cancer and 4,206 thyroid cancer cases. Each 5 kg m−2 increase in body mass index at a young age was positively associated with DLBCL (relative risk RR 1.21, 95% confidence interval CI 1.09, 1.35), oesophageal adenocarcinoma (RR 1.88, 95% CI 1.37, 2.57), gastric cardia cancer (RR 1.59, 95% CI 1.15, 2.21), hepatocellular carcinoma (RR 1.31, 95% CI 1.13, 1.51), multiple myeloma (RR 1.23, 95% CI 1.15, 1.30), pancreatic cancer (RR 1.17, 95% CI 1.11, 1.24), renal cell cancer (RR 1.22, 95% CI 1.16, 1.28) and thyroid cancer (RR 1.12, 95% CI 1.07, 1.17). In summary, higher body fatness at a young age increases the risks of developing various types of cancer later in life. Prevention of overweight and obesity in children, adolescents and young adults should therefore be emphasized to reverse the obesity epidemic and thereby avoid further increases in the burden of cancer attributed to excess body fatness.
Summary
In the present meta-analysis, reductions in the risk of hip fracture with milk consumption were only observed among American adults, but not among Scandinavian adults, possibly because milk ...products are more commonly fortified with vitamin D in the former population than in Scandinavian countries. The reduction in the risk of hip fracture was also observed with yogurt consumption, which is often associated with healthy lifestyles and dietary patterns that contribute to improved bone health.
Introduction
Although dairy products contain bone-beneficial nutrients, the association between dairy consumption and the risk of hip fracture remains equivocal. Fueling this uncertainty, the elevated risk of hip fracture in association with milk consumption was observed in a cohort of Swedish women. A systematic review and meta-analysis of prospective cohort studies was performed to critically evaluate the association, or lack thereof, between dairy consumption (milk, yogurt, and cheese) and the risk of hip fracture.
Methods
A random effects model was used to generate the summary relative risks (RRs) with their 95% confidence intervals (CIs) for the associations of interest.
Results
In the meta-analysis of the highest versus lowest category of consumption, higher consumption of yogurt (RR 0.78, 95% CI 0.68, 0.90), but not milk (RR 0.86, 95% CI 0.73, 1.02) or cheese (RR 0.85, 95% CI 0.66, 1.08), was associated with a lower risk of hip fracture. For milk, the reduced risk of fracture with higher milk consumption was observed in the USA (RR 0.75, 95% CI 0.65, 0.87), but not in Scandinavian countries (RR 1.00, 95% CI 0.85, 1.17). These findings were further supported by the fact that American studies (RR 0.93, 95% CI 0.88, 0.98; per 1 glass/day), but not Scandinavian studies (RR 1.01, 95% CI 0.95, 1.07; per 1 glass/day), demonstrated a linear association between milk consumption and the risk of hip fracture.
Conclusions
The cumulative evidence from prospective cohort studies reassuringly suggests that the risk of hip fracture may not be elevated among people who consume milk, yogurt, and cheese, and that a greater consumption of milk or yogurt may even be associated with a lower risk of hip fracture depending on the factors that may differ across the population of interest.
Summary
In the present meta-analysis based on real-world data, the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1ra), or sodium-glucose ...cotransporter-2 inhibitors (SGLT2i) was not associated with the risk of fracture.
Introduction
Cumulative evidence from randomized control trials (RCTs) with limited fracture events showed that the use of DPP-4i, GLP-1ra, or SGLT2i may not affect the risk of fracture. However, additional insights from large population-based studies with routinely collected data on fracture events and an adequate amount of fracture events are necessary to draw firm conclusions. To refine and complement the results from RCTs, a systematic review and meta-analysis of observational studies were performed to investigate the association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture in real-world settings.
Methods
The PubMed and Web of Science databases were searched to identify relevant observational studies. A random-effect model was used to estimate the summary relative risks (RRs).
Results
The use of DPP-4i (RR 0.83, 95% CI confidence interval 0.60, 1.14;
n
= 11), GLP-1ra (RR 0.65, 95% CI 0.24, 1.74;
n
= 4), or SGLT2i (RR 1.02, 95% CI 0.91, 1.16;
n
= 4) was not associated with the risk of fracture. In general, there was a consistent lack of association between the use of DPP-4i or GLP-1ra and the risk of fracture across nearly all subgroups, except for a significantly reduced risk of hip fracture with the use of GLP-1ra (RR 0.21, 95% CI 0.04, 0.98).
Conclusions
Cumulative real-world evidence does not support an association between the use of DPP-4i, GLP-1ra, or SGLT2i and the risk of fracture. Our findings, together with the cumulative evidence from RCTs, should reassure policy makers and medical practitioners that the use of these medications is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients in general. Further studies need to investigate the long-term impact of these drugs on the fracture risk, particularly in high-risk populations.
Individuals with diabetes mellitus (DM) have an increased risk of fracture. Glycemic control is crucial to the management of DM, but there are concerns pertaining to hypoglycemia development in the ...course of glycemic control target achievement. The extent to which glycemic control may affect the risk of fracture remains less defined. Hypoglycemia-induced falls have been suggested to contribute to an elevated risk of fracture in DM patients. In this meta-analysis of observational studies, we aimed to investigate the relative contribution of glycemic control, as measured by glycated hemoglobin (HbA1c), and hypoglycemia to the risk of fracture in DM. The PubMed and Web of Science databases were searched for relevant studies. A random-effects model was used to generate summary relative risks (RRs) and 95% confidence intervals (CIs). Both increased HbA1c levels (RR
per 1% increase
1.08, 95% CI 1.03, 1.14;
n
studies
= 10) and hypoglycemia (RR 1.52, 95% CI 1.23, 1.88;
n
studies
= 8) were associated with an increased risk of fracture. The association between HbA1c levels and the risk of fracture was somewhat nonlinear, with a noticeably increased risk observed at an HbA1c level ≥ 8%. The positive associations of HbA1c levels and hypoglycemia with the risk of fracture did not reach statistical significance in the studies that adjusted for insulin use, hypoglycemia, or falls for the former and in those that adjusted for falls for the latter. In summary, both increased HbA1c levels and hypoglycemia may increase the risk of fracture in patients with DM. The positive association between HbA1c levels and the risk of fracture appears to be, in part, explained by hypoglycemia-induced falls, possibly due to insulin use. The avoidance of hypoglycemia in the course of achieving good glycemic control through the careful selection of glucose-lowering medications may contribute to fracture prevention by reducing the risk of falls related to treatment-induced hypoglycemia.
Background
IL‐25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the association of IL‐25 with the ...Th2‐biased inflammatory profiles in CRSwNP.
Methods
Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL‐25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT‐qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL‐25high and IL‐25low) were evaluated, and the effects of IL‐25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro.
Results
The mRNA and protein levels of IL‐25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL‐25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL‐25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro.
Conclusions
Local IL‐25 plays a crucial role in promoting Th2‐biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRSwNP patients.
Summary
We conducted a meta-analysis of observational study to clarify the association between sex hormone-binding globulin (SHBG) levels and the risk of fracture in older adults. We found that ...higher SHBG levels were associated with an increased risk of fracture in older adults.
Introduction
The association between SHBG levels and the risk of fracture in older adults remains elusive. We aim to clarify this association by conducting a meta-analysis of observational studies.
Methods
PubMed and Web of Science databases were searched for relevant observational studies investigating the association between SHBG levels and the risk of fracture in older adults. The relative risks (RRs) with 95% confidence intervals (CIs) from each study were transformed into a continuous variable for each 1 μg/dL increase in SHBG and were pooled under a random-effects model.
Results
A total of 16 observational studies were included in the present meta-analysis. The summary RR of fracture risk associated with each 1 μg/dL increase in SHBG was 1.18 (95% CI 1.11, 1.26); no statistically significant heterogeneity was observed across studies (
I
2
= 0%,
P
= 0.67). The positive association was also evident in men (RR 1.22, 95% CI 1.12, 1.33) and women (RR 1.15, 95% CI, 1.05, 1.26). By site of fracture, higher SHBG levels were positively associated with higher risks of hip fracture (RR 1.43, 95% CI 1.23, 1.65), vertebral fracture (RR 1.31, 95% CI 1.12, 1.54), and non-vertebral fracture (RR 1.21, 95% CI 1.06, 1.38).
Conclusions
The present meta-analysis suggests that higher SHBG levels predict an increased risk of fracture in older adults. Further studies should aim to elucidate the complex biological mechanisms by which SHBG may affect fracture risk.
Summary
Higher body fatness in adulthood has been consistently associated with an increased risk of postmenopausal breast cancer, as well as a tendency towards a lower risk of premenopausal breast ...cancer. However, the association between body fatness at a young age (≤30 years), body fatness gain and the risk of breast cancer is less defined. PubMed and Web of Science databases were searched to identify relevant publications. Risk estimates with 95% confidence intervals from each study were transformed into a continuous variable for each 5 kg m−2 increase in body mass index (BMI) and were pooled under a random‐effects model. Each 5 kg m−2 increase in BMI was significantly associated with a 14%, 12% and 17% lower risk of breast cancer later in life among all women, premenopausal women and postmenopausal women, respectively. Significant heterogeneity and publication bias were observed. The results remained unchanged after the trim and fill method was applied to correct the bias. Each 5 kg m−2 increase in BMI from a young age until cohort entry was significantly associated with a 13% and 14% higher risk of breast cancer in all women and postmenopausal women, respectively. In summary, higher body fatness at a young age may have a protective role in the later development of breast cancer in both premenopausal and postmenopausal women. However, this potential benefit should not be overemphasized, as our findings suggest that increased body fatness gain from a young age is positively associated with postmenopausal breast cancer risk. These findings further justify the need to maintain a steady weight throughout life.
The current study investigated the efficacy of a probiotic mixture on ameliorating heat stress-induced impairment of intestinal microflora, morphology, and barrier integrity in broilers. The ...probiotic mixture contained Bacillus licheniformis, Bacillus subtilis, and Lactobacillus plantarum. Three hundred sixty 21-d-old Ross 308 male broilers were allocated in 4 experimental treatments, each of which was replicated 6 times with 15 broilers per replicate. A 2 × 2 factorial design was used in the study, and the main factors were composed of diet (basal diet or addition of 1.5 g/kg of probiotic mixture) and temperature (thermoneutral zone or heat stress). From d 22 to 42, birds were either raised in a thermoneutral zone (22°C) or subjected to cyclic heat stress by exposing them to 33°C for 10 h (from 0800 to 1800) and 22°C from 1800 to 0800. Compared with birds kept in the thermoneutral zone, birds subjected to heat stress had reduced ADG and ADFI; lower viable counts of Lactobacillus and Bifidobacterium and increased viable counts of coliforms and Clostridium in small intestinal contents; shorter jejunal villus height, deeper crypt depth, and lower ratio of villus height to crypt depth; decreased jejunal transepithelial electrical resistance and a higher level of jejunal paracellular permeability of fluorescein isothiocyanate dextran 4 kDa; and downregulated protein levels of occludin and zonula occludens-1 (P < 0.05). Supplemental probiotics increased (P < 0.05) small intestinal Lactobacillus and Bifidobacterium, jejunal villus height, protein level of occludin, and decreased (P < 0.05) feed to gain ratio and small intestinal coliforms. These results indicate that dietary addition of probiotic mixture was effective in partially ameliorating intestinal barrier function. But no temperature × diet interaction was observed in the present study, revealing that the supplemented probiotics had the same effect at both temperatures.
Macro-autophagy is associated with drug resistance in various cancers and can function as an adaptive response to maintain cell survival under metabolic stresses, including androgen deprivation. ...Androgen deprivation or treatment with androgen receptor (AR) signaling inhibitor (ARSI), Enzalutamide (MDV-3100, ENZA) or bicalutamide induced autophagy in androgen-dependent and in castration-resistant CaP (castration-resistant prostate cancer (CRPC)) cell lines. The autophagic cascade triggered by AR blockage, correlated with the increased light chain 3-II/I ratio and ATG-5 expression. Autophagy was observed in a subpopulation of C4-2B cells that developed insensitivity to ENZA after sustained exposure in culture. Using flow cytometry and clonogenic assays, we showed that inhibiting autophagy with clomipramine (CMI), chloroquine or metformin increased apoptosis and significantly impaired cell viability. This autophagic process was mediated by AMP-dependent protein kinase (AMPK) activation and the suppression of mammalian target of rapamycin (mTOR) through Raptor phosphorylation (Serine 792). Furthermore, small interfering RNA targeting AMPK significantly inhibited autophagy and promoted cell death in CaP cells acutely or chronically exposed to ENZA or androgen deprivation, suggesting that autophagy is an important survival mechanism in CRPC. Lastly, in vivo studies with mice orthotopically implanted with ENZA-resistant cells demonstrated that the combination of ENZA and autophagy modulators, CMI or metformin significantly reduced tumor growth when compared with control groups (P<0.005). In conclusion, autophagy is as an important mechanism of resistance to ARSI in CRPC. Antiandrogen-induced autophagy is mediated through the activation of AMPK pathway and the suppression of mTOR pathway. Blocking autophagy pharmacologically or genetically significantly impairs prostate cancer cell survival in vitro and in vivo, implying the therapeutics potential of autophagy inhibitors in the antiandrogen-resistance setting.
Artemisia ordosica is one of the main shrubby perennials belonging to Artemisia species of Asteraceae and could be used in folk Chinese/Mongolian medicine to treat symptoms of various inflammatory ...ailments. The present study was conducted to investigate the protective effects of dietary Artemisia ordosica polysaccharide (AOP) against lipopolysaccharide (LPS) induced oxidative stress in broilers via Nrf2/Keap1 and TLR4/NF-κB pathway. A total of 192 1-day-old Arbor Acres male broilers were randomly allotted to four treatments with 6 replicates (n = 8): (1) CON group, non-challenged broilers fed basal diet; (2) LPS group, LPS-challenged broilers fed basal diet; (3) AOP group, non-challenged broilers fed basal diet supplemented with 750 mg/kg AOP; (4) LPS+AOP group, LPS-challenged broilers fed basal diet supplemented with 750 mg/kg AOP. The trial included starter phase (d 1–14), stress period Ⅰ (d 15–21), convalescence Ⅰ (d 22–28), stress period Ⅱ (d 29–35) and convalescence Ⅱ (d 36–42). During stress period Ⅰ (on d 15, 17, 19 and 21) and stress period Ⅱ (on d 29, 31, 33 and 35), broilers were injected intra-abdominally either with LPS solution or with an equal amount of sterile saline. The results showed that dietary AOP supplementation alleviated LPS-induced reduction in antioxidant enzyme activity and excessive production of ROS, 8-OHdG and PC in serum of broilers challenged with LPS. Moreover, dietary AOP supplementation alleviated the decrease of T-AOC and activities of SOD, CAT and GPx in liver of broilers challenged with LPS by increasing expression of Nrf2, and inhibiting over-expression of Keap1 both at gene and protein level. Additionally, dietary AOP supplementation decreased the over-production of IL-1β and IL-6 in liver of broilers challenged by LPS through decreasing mRNA expression of TLR4, MyD88, NF-κB P65, IL-1β and IL-6, and alleviating the increase of protein expression of TLR4, IKKβ, NF-κB P65, IL-1β, IL-6, and the decrease of protein expression of IkBα. In conclusion, dietary AOP supplementation could alleviate LPS-induced oxidative stress through Nrf2/Keap1 and TLR4/NF-κB pathway.
•Dietary AOP alleviated LPS-induced liver injure.•Dietary AOP relieved LPS-induced oxidative stress by activating Nrf2/keap1 pathway.•Dietary AOP relieved LPS-induced oxidative stress by suppressing TLR4/NF-κB pathway.
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