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Preventive Medicine Jun 2024This study aimed to describe the variability in estimates of the association of daily steps and all-cause mortality in systematic reviews with meta-analyses, to identify... (Review)
Review
OBJECTIVE
This study aimed to describe the variability in estimates of the association of daily steps and all-cause mortality in systematic reviews with meta-analyses, to identify the factors potentially responsible for it, and to provide an updated estimate.
METHODS
Five databases were systematically searched up to May 2024 to identify systematic reviews with meta-analyses and prospective cohort studies. A qualitative synthesis of previous reviews and an updated meta-analysis of cohort studies were performed. Pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated using a random-effects model.
RESULTS
Eleven systematic reviews with meta-analyses and 14 cohort studies were included, revealing considerable variability in result presentation. Our updated meta-analysis showed a nonlinear association, indicating a lower risk of all-cause mortality with increased daily steps, with a protective threshold at 3143 steps/day, and a pooled HR of 0.91 (95% CI: 0.87, 0.95) per 1000 steps/day increment. Physical activity categories consistently indicated progressively reduced mortality risk, with the highly active category (>12,500 steps/day) exhibiting the lowest risk (0.35 (95% CI: 0.29, 0.42)).
CONCLUSION
Systematic reviews and meta-analyses showed considerable variability in effect estimates due to different methods of quantifying exposure. Despite it, our study underscores the importance of increased daily steps in reducing all-cause mortality, with a minimum protective dose of 3000 steps/day, although the optimal dose differed according to age and sex. It is recommended that future studies categorise daily steps by physical activity category, perform dose-response analyses, and use increments of 1000 steps/day.
PubMed: 38901742
DOI: 10.1016/j.ypmed.2024.108047 -
Journal of Affective Disorders Jun 2024Transgender and non-binary (TNB) individuals are at greater risk of mental health concerns relative to their cisgender peers due to experiences of minority stress. Thus,...
BACKGROUND
Transgender and non-binary (TNB) individuals are at greater risk of mental health concerns relative to their cisgender peers due to experiences of minority stress. Thus, it is critically important to identify factors that may be protective and buffer the effects of minority stress. This study examined whether romantic relationship involvement and quality buffered effects of TNB minority stress on depressive symptoms and suicidal ideation.
METHODS
A large international sample (n = 1156) of TNB adults (n = 654 partnered; n = 502 single) reported on minority stress experiences, relationship status and quality, and mental health outcomes (i.e., depressive symptoms and suicidal ideation).
RESULTS
The effects of victimization and rejection on depressive symptoms and suicidal ideation were attenuated among partnered individuals. However, once relationship quality was considered, the buffering effects of relationship involvement applied only to those in more satisfying relationships; the stress-buffering effects were not observed among those in distressed relationships. Of particular importance, general interpersonal satisfaction did not act as a minority stress buffer, suggesting there may be unique stress-buffering effects of being in a satisfying romantic relationship on depressive symptoms and suicidal ideation.
LIMITATIONS
The cross-sectional nature of the current study precludes definitive conclusions regarding causation.
CONCLUSIONS
These findings suggest that romantic involvement may serve a stress-buffering role for TNB adults, but only when these relationships are satisfying. Our results have important theoretical and clinical implications, and further research is needed to investigate the utility of relationship interventions to buffer the effects of TNB minority stress on depressive symptoms and suicidality.
PubMed: 38901693
DOI: 10.1016/j.jad.2024.06.062 -
The Journal of Nutrition Jun 2024Childbearing increases the risk of weight gain and cardiometabolic disease. The reset hypothesis suggests that lactation has protective cardiometabolic effects in the...
Effects of breastfeeding promotion intervention and dietary treatment in postpartum women with overweight and obesity: Results from a randomized controlled trial on weight and cardiometabolic risk factors.
BACKGROUND
Childbearing increases the risk of weight gain and cardiometabolic disease. The reset hypothesis suggests that lactation has protective cardiometabolic effects in the mother. The hypothesis is based on observational studies and the possible interacting role of weight loss needs to be elucidated.
OBJECTIVE
To examine the individual and interaction effects of a breastfeeding promotion intervention (BPI) and dietary intervention for weight loss postpartum (Diet) on body weight and cardiometabolic risk factors at 6 mo postpartum.
METHODS
Pregnant women (n = 156) with a pre-pregnancy BMI of 25-35 kg/m were randomized to 4 groups in a 2x2 factorial design: BPI, Diet, both treatments or no treatment. BPI consisted of individual counseling by a lactation consultant during pregnancy, at childbirth, and thereafter monthly or more frequently based on individual needs. Diet was initiated at 11 wk postpartum. Body weight, body composition, waist- and hip circumference, markers of lipid and glucose metabolism and blood pressure were measured at 2 wk and 6 mo postpartum.We analyzed main and interaction effects using 2-way ANCOVA adjusted for baseline values.
RESULTS
Among the participants attending both visits (n = 108), 99% practiced any breastfeeding at baseline and 97% at follow-up. The BPI did not affect rates of exclusive or partial breastfeeding, age at introduction of complementary foods or have main effects on body weight or cardiometabolic risk factors. There was a main effect of Diet reducing body weight, fat mass, fat-free mass, percent fat mass, waist- and hip circumference, fasting glucose and insulin (all p ≤ 0.03), with no interactions between the treatments.
CONCLUSIONS
There were no effects of BPI on body weight or cardiometabolic risk factors at 6 mo postpartum. Diet caused weight loss and had favorable effects on risk factors for cardiovascular disease and type 2 diabetes.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT03580057).
PubMed: 38901636
DOI: 10.1016/j.tjnut.2024.06.006 -
International Journal of Biological... Jun 2024Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but...
Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1β-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.
PubMed: 38901508
DOI: 10.1016/j.ijbiomac.2024.133137 -
Free Radical Biology & Medicine Jun 2024Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute...
BACKGROUND
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate.
METHODS
The floxed Pten (Pten) and myeloid-specific Pten knockout (Pten) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some Pten mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from Pten and Pten mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3β) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells.
RESULTS
Here, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3β and MST1 binding.
CONCLUSIONS
Our study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI.
PubMed: 38901501
DOI: 10.1016/j.freeradbiomed.2024.06.016 -
American Journal of Veterinary Research Jun 2024Salmonella Typhimurium is a significant zoonotic concern for human food poisoning and a substantial economic burden in the swine industry. We previously reported that...
Nasally delivered chitosan-coated poly(lactide-co-glycolide) encapsulating honeybee venom enhances T helper 1-related immunity against Salmonella Typhimurium infection in pigs.
OBJECTIVE
Salmonella Typhimurium is a significant zoonotic concern for human food poisoning and a substantial economic burden in the swine industry. We previously reported that nasally delivered chitosan-coated poly(lactide-co-glycolide) (PLGA) encapsulating honeybee venom (CP-HBV) could enhance CD4+ T helper 1 (Th1)-related immune responses in healthy pigs. Building upon these findings, the current study aimed to investigate the protective immune enhancement by nasally delivered CP-HBV in pigs challenged with S Typhimurium.
ANIMALS
36 healthy, 4-week-old, female, Landrace X Yorkshire X Duroc pigs.
METHODS
36 pigs were allocated into 3 groups: CP-HBV (n = 16), control (n = 16), and healthy baseline control (n = 4). CP-HBV and control groups were challenged with S Typhimurium 7 days post-treatment. Pigs from the healthy control group were sacrificed at 0 days postinfection (DPI), and 4 pigs from each of the control and CP-HBV groups were sacrificed at 1, 2, 4, and 7 DPI. Salmonella shedding, immune cell frequencies, cytokines, and transcriptional factor expression levels were measured.
RESULTS
The CP-HBV group exhibited lower bacterial shedding and an enhanced Th1-related immune response characterized by an upregulation of CD4+ T cells and CD4+ Interferon-γ+ T cells, accompanied by increased expression of Th1-related cytokines and reduced expression of regulatory T cells and immunosuppressive cytokines compared to the control group.
CLINICAL RELEVANCE
CP-HBV is a promising strategy for controlling Salmonella infections in pigs and improving public health.
PubMed: 38901460
DOI: 10.2460/ajvr.24.03.0086 -
Biomedicine & Pharmacotherapy =... Jun 2024Reactive oxidative species (ROS) generation triggers pyroptosis and induces development of inflammatory osteolysis. Hecogenin (HG) has anti-inflammatory and...
Reactive oxidative species (ROS) generation triggers pyroptosis and induces development of inflammatory osteolysis. Hecogenin (HG) has anti-inflammatory and antioxidative property, but its effects on inflammatory osteolysis remains unclear. In our study, we investigated the mechanism of HG on pyroptosis and its effect on inflammatory osteolysis in vitro and in vivo. The impact of HG on osteoclastogenesis was evaluated using cytotoxicity, TRAcP staining and bone resorption assays. The RNA-sequencing was employed to identify potential signaling pathways, and then RT-qPCR, western blot, immunofluorescence, and ELISA were used to verify. To determine the protective effect of HG in vivo, Lipopolysaccharide (LPS)-induced animal models were utilized, along with micro-CT and histological examination. HG suppressed RANKL-induced osteoclast differentiation, bone resorption, NFATc1 activity and downstream factors. RNA-sequencing results showed that HG inhibited osteoclastogenesis by modulating the inflammatory response and macrophage polarization. Furthermore, HG inhibited the NF-κB pathway, and deactivated the NLRP3 inflammasome. HG activated the expression of nuclear factor E2-related factor 2 (Nrf2) to eliminate ROS generation. Importantly, the inhibitory effect of HG on NLRP3 inflammasome could be reversed by treatment with the Nrf2 inhibitor ML385. In vivo, HG prevented the mice against LPS-induced osteolysis by suppressing osteoclastogenesis and inflammatory factors. In conclusion, HG could activate Nrf2 to eliminate ROS generation, inactivate NLRP3 inflammasome and inhibit pyroptosis, thereby suppressing osteoclastogenesis in vitro and alleviating inflammatory osteolysis in vivo, which indicating that HG might be a promising candidate to treat inflammatory osteolysis.
PubMed: 38901204
DOI: 10.1016/j.biopha.2024.116933 -
Clinics (Sao Paulo, Brazil) 2024Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic...
INTRODUCTION
Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic aspects. Therefore, this study aimed to evaluate the effect of Physical Training (PT) by swimming on the metabolic parameters of rats subjected to restraint stress.
METHODS
Wistar rats (n = 40) were divided into four groups: Control (C), Trained (T), Stressed (S), and Trained/Stressed (TS). The restraint stress protocol involved confining the animals in PVC pipes for 60 minutes/day for 12 weeks. Concurrently, the swimming PT protocol was performed without additional load in entailed sessions of 60 minutes conducted five days a week for the same duration. The following parameters were analyzed: fitness progression assessed by the physical capacity test, body mass, serum level of glucose, triglyceride, cholesterol and corticosterone, as well as glycemic tolerance test, evaluated after glucose administration (2 g/kg, i.p.).
RESULTS
Trained groups (T and TS) exhibited enhanced physical capacity (169 ± 21 and 162 ± 22% increase, respectively) compared to untrained groups (C: 9 ± 5 and S: 11 ± 13% increase). Corticosterone levels were significantly higher in the S group (335 ± 9 nmoL/L) compared to C (141 ± 3 nmoL/L), T (174 ± 3 nmoL/L) and TS (231 ± 7 nmoL/L), which did not differ from each other. There were no significant changes in serum glucose, cholesterol, and triglyceride levels among the groups. However, the glycemic curve after glucose loading revealed increased glycemia in the S group (area under curve 913 ± 30 AU) but the TS group exhibited values (673 ± 12 AU) similar to the groups C (644 ± 10 AU) and T (649 ± 9 AU).
CONCLUSION
Swimming-based training attenuated stress-induced corticosterone release and prevented glucose intolerance in rats, reinforcing the importance of exercise as a potential strategy to mitigate the pathophysiological effects of stress.
Topics: Animals; Rats, Wistar; Physical Conditioning, Animal; Male; Restraint, Physical; Corticosterone; Blood Glucose; Swimming; Stress, Psychological; Cholesterol; Rats; Triglycerides; Time Factors; Glucose Tolerance Test; Random Allocation; Metabolome
PubMed: 38901134
DOI: 10.1016/j.clinsp.2024.100411 -
Clinical Psychology Review Jun 2024Perception has been conceptualised as an active and adaptive process, based upon incoming sensory inputs, which are modified by top-down factors such as cognitions.... (Review)
Review
Perception has been conceptualised as an active and adaptive process, based upon incoming sensory inputs, which are modified by top-down factors such as cognitions. Visuospatial perception is thought to be scaled based on threat, with highly threatening objects or contexts visually inflated to promote escape or avoidance behaviours. This meta-analytical systematic review quantified the effect and evidence quality of threat-evoked visuospatial scaling, as well as how visuospatial scaling relates to affordances (perceived action capabilities) and behavioural avoidance/escape outcomes. Databases and grey literature were systematically searched inclusive to 10/04/24. Studies were assessed with a customised Risk of Bias form and meta-analysis was performed using a random-effects model. 12,354 records were identified. Of these, 49 experiments (n = 3027) were included in the review. There was consistent evidence that threat the of height influenced contextual perception (g = 0.66, 95% CI: 0.45, 0.88) and affordances (g = -0.43, 95% CI: -0.84, -0.03). Threatening objects were viewed as larger (g = 0.76, 95% CI: 0.26, 1.26) and as closer (g = 0.30, 95% CI: 0.17, 0.42). Bodily threat (pain) yielded conflicting effects on visuospatial perception/affordances. We conclude that threat may influence visuospatial perception and affordances. However, since behavioural measures were poorly reported, their relationship with visuospatial perception/affordances remains elusive.
PubMed: 38901066
DOI: 10.1016/j.cpr.2024.102449 -
Journal of Cellular and Molecular... Jun 2024Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover...
Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover novel approaches to overcome this. In this study, we investigated the underlying mechanisms contributing to x-ray radioresistance in HPV-negative HNSCC cells under mild hypoxic conditions (1% oxygen) and explored the potential for autophagy modulation as a promising therapeutic strategy. Our findings show that HNSCC cells exposed to mild hypoxic conditions exhibit increased radioresistance, which is largely mediated by the hypoxia-inducible factor (HIF) pathway. We demonstrate that siRNA knockdown of HIF-1α and HIF-1β leads to increased radiosensitivity in HNSCC cells under hypoxia. Hypoxia-induced radioresistance was not attributed to differences in DNA double strand break repair kinetics, as these remain largely unchanged under normoxic and hypoxic conditions. Rather, we identify autophagy as a critical protective mechanism in HNSCC cells following irradiation under mild hypoxia conditions. Targeting key autophagy genes, such as BECLIN1 and BNIP3/3L, using siRNA sensitizes these cells to irradiation. Whilst autophagy's role in hypoxic radioresistance remains controversial, this study highlights the importance of autophagy modulation as a potential therapeutic approach to enhance the effectiveness of radiotherapy in HNSCC.
Topics: Humans; Autophagy; Radiation Tolerance; Cell Line, Tumor; Squamous Cell Carcinoma of Head and Neck; Cell Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Beclin-1; Head and Neck Neoplasms; Membrane Proteins; DNA Repair; RNA, Small Interfering; Proto-Oncogene Proteins; X-Rays; DNA Breaks, Double-Stranded; Tumor Suppressor Proteins
PubMed: 38899556
DOI: 10.1111/jcmm.18482