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1.
BMJ Open ; 14(6): e079139, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851231

ABSTRACT

BACKGROUND AND AIMS: Frailty is widespread in the elderly, while there is a bi-directional relationship between frailty and malnutrition. The objectives of this study were to investigate the prevalence and correlation of frailty and nutritional risk in older adult patients and to analyse the factors associated with fatigue which is one indicator of frailty. METHODS: This cross-sectional multicentre survey study was conducted in five hospitals in the same city from 01 January 2021 to 01 December 2021. We collected information on gender, age, diseases, medication and dietary status. Frailty status was diagnosed using the FRAIL scale, and Nutritional Risk Screening-2002 was used to screen the nutritional risk. Spearman rank correlation was used to analyse the correlation between frailty and nutritional risk. Univariate and multivariate logistic regression analyses were used to analyse the risk factors related to fatigue in all patients and inpatients. RESULTS: Among 2016 older adult patients, the prevalence of frailty was 15.1% (305/2016), the prevalence of nutritional risk was 16.2% (327/2016) and the overlap prevalence of frailty and nutritional risk was 7.3% (147/2016). Multivariate analysis showed that nutritional risk (OR 3.109, 95% CI 2.384 to 4.056, p<0.001) was an independent risk factor for fatigue in all patients; similar results were found for nutritional risk (OR 2.717, 95% CI 2.068 to 3.571, p<0.001) in hospitalised patients. CONCLUSIONS: Frailty and nutritional risk are prevalent among older adult patients, and nutritional risk is associated with the occurrence of fatigue in older adult patients and older adult inpatients. TRIAL REGISTRATION NUMBER: China Clinical Trial Registry (Registered No. ChiCTR-EPC-14005253).


Subject(s)
Fatigue , Frail Elderly , Frailty , Geriatric Assessment , Malnutrition , Nutritional Status , Humans , Cross-Sectional Studies , Male , Fatigue/epidemiology , Female , Aged , Frailty/epidemiology , Malnutrition/epidemiology , Risk Factors , Geriatric Assessment/methods , Aged, 80 and over , Frail Elderly/statistics & numerical data , Prevalence , China/epidemiology , Middle Aged , Nutrition Assessment
2.
Int J Biol Macromol ; 270(Pt 2): 132454, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38763255

ABSTRACT

The multifaceted role of hyaluronic acid (HA) across diverse biomedical disciplines underscores its versatility in tissue regeneration and repair. HA hydrogels employ different crosslinking including chemical (chitosan, collagen), photo- initiation (riboflavin, LAP), enzymatic (HRP/H2O2), and physical interactions (hydrogen bonds, metal coordination). In biophysics and biochemistry, HA's signaling pathways, primarily through CD44 and RHAMM receptors, modulate cell behavior (cell migration; internalization of HA), inflammation, and wound healing. Particularly, smaller HA fragments stimulate inflammatory responses through toll-like receptors, impacting macrophages and cytokine expression. HA's implications in oncology highlight its involvement in tumor progression, metastasis, and treatment. Elevated HA in tumor stroma impacts apoptosis resistance and promotes tumor growth, presenting potential therapeutic targets to halt tumor progression. In orthopedics, HA's presence in synovial fluid aids in osteoarthritis management, as its supplementation alleviates pain, enhances synovial fluid's viscoelastic properties, and promotes cartilage integrity. In ophthalmology, HA's application in dry eye syndrome addresses symptoms by moisturizing the eyes, replenishing tear film deficiencies, and facilitating wound healing. Intravitreal injections and hydrogel-based systems offer versatile approaches for drug delivery and vitreous humor replacement. For skin regeneration and wound healing, HA hydrogel dressings exhibit exceptional properties by promoting moist wound healing and facilitating tissue repair. Integration of advanced regenerative tools like stem cells and solubilized amnion membranes into HA-based systems accelerates wound closure and tissue recovery. Overall, HA's unique properties and interactions render it a promising candidate across diverse biomedical domains, showcasing immense potentials in tissue regeneration and therapeutic interventions. Nevertheless, many detailed cellular and molecular mechanisms of HA and its applications remain unexplored and warrant further investigation.


Subject(s)
Hyaluronic Acid , Wound Healing , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Humans , Wound Healing/drug effects , Animals , Regeneration/drug effects , Hydrogels/chemistry , Bioengineering/methods , Tissue Engineering/methods
3.
Heliyon ; 10(8): e29734, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38681582

ABSTRACT

Objective: The Asian Working Group for Sarcopenia 2019 consensus emphasized nutritional assessment and intervention for community-dwelling older people with sarcopenia status. This study aimed to examine the association of serum albumin and dietary protein intake (DPI) with all-cause mortality among older adults at risk of sarcopenia. Methods: We enrolled 1763 older adults at risk of sarcopenia in the Chinese Longitudinal Healthy Longevity Survey (2012-2018) using calf circumference and handgrip strength. Serum albumin concentrations were measured using bromocresol green methods, and DPI frequency was evaluated using a semi-quantitative questionnaire at baseline. Cox proportional hazards models were used to explore the association of serum albumin and DPI with all-cause mortality. Results: During 5606.3 person-years of follow-up (median: 3.28 years), 802 older people died. After adjusting for socio-demographics, health behaviors, and clinical characteristics, we observed an inverse linear association between serum albumin and all-cause mortality (Pnon-linear = 0.429). Participants with low albumin levels (<40.0 g/L) had a 43 % higher risk of mortality than their counterparts (hazard ratio (HR) = 1.43, 95 % confidence interval (CI) = 1.22-1.66). There was no significant association between DPI and mortality (Ps > 0.05). Moreover, the association between low albumin and all-cause mortality remained significant in the lower DPI subgroup (HR = 1.47, 95 % CI = 1.18-1.85), but was not significant in the high DPI subgroup (HR = 1.15, 95 % CI = 0.92-1.39). Conclusions: Serum albumin levels are inversely associated with all-cause mortality in community-based older adults at risk of sarcopenia. Sufficient dietary protein consumption may attenuate the effect of low serum albumin on increased mortality and potential mechanisms for the interaction warrant further exploration.

4.
JCI Insight ; 9(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38016036

ABSTRACT

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Animals , Mice , AMP-Activated Protein Kinases/metabolism , Autophagy/genetics , Macrophages/metabolism
5.
Psychol Res Behav Manag ; 16: 2085-2101, 2023.
Article in English | MEDLINE | ID: mdl-37309511

ABSTRACT

Purpose: Transactional distance remains an important issue in online education, which is an important indicator to evaluate the quality of teaching and learning in online courses and is closely related to the success of learners' online learning. The purpose of this study is to evaluate the potential mechanism of transactional distance and its three modes of interaction on the impact of learning engagement of college students. Participants and Methods: Online Education Student Interaction Scale, Online Social Presence Questionnaire, Academic Self-Regulation Questionnaire and Utrecht Work Engagement Scale-Student scales were used, revised questionnaire for cluster sampling of college students, 827 valid samples. SPSS 24.0 and AMOS 24.0 were used for analysis, and Bootstrap method was used to test the significance level of the mediating effect. Results: Transactional distance (including the three interaction modes) was significantly and positively related to college students' learning engagement. Autonomous motivation played a chain mediating role between transactional distance and learning engagement. In addition, social presence and autonomous motivation mediated the chain between student-student and student-teacher interaction on learning engagement. In addition, however, student-content interactions did not significantly impact social presence, and the chain mediating effect of social presence and autonomous motivation between student-content interaction and learning engagement was not supported. Conclusion: Based on transactional distance theory, this study reveals the role of transactional distance on college students' learning engagement and the mediating effect of social presence and autonomous motivation in the relationship between transactional distance (and three interaction modes of transactional distance) on college students' learning engagement. This study supports the findings of additional online learning research frameworks and empirical studies to enhance our understanding of how online learning affects college students' learning engagement and the important role of online learning in college student's academic development.

6.
Front Oncol ; 13: 1153319, 2023.
Article in English | MEDLINE | ID: mdl-37182180

ABSTRACT

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment.

7.
Int Immunopharmacol ; 120: 110291, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37182451

ABSTRACT

OBJECTIVE: Tuberculosis is the leading killer among the chronic single-source infectious diseases. Mycobacterium tuberculosis can induce necrotic-dominant multiple modes of cell death in macrophages, which accelerates bacterium dissemination and expands tissue injury in host lungs. Mining drugs to counteract Mycobacterium tuberculosis-induced cell death would be beneficial to tuberculosis patients. METHODS: In this study, the protective drug was screened out from the FDA-approved drug library in Mycobacterium tuberculosis-infected macrophages with CCK-8 assay. The death mode regulated by the drug was identified using transcriptomic sequencing, cytomorphological observation, and in the experimental mouse Mycobacterium tuberculosis-infection model. The functional mechanism was explored using western blot, co-immunoprecipitation, and DARTS assay. The intracellular bacterial survival was detected using colony forming unit assays. RESULTS: Cisatracurium besylate was identified to be highly protective for the viability of macrophages during Mycobacterium tuberculosis infection via inhibiting necroptosis. Cisatracurium besylate prevented RIPK3 to be associated with the executive molecule MLKL for forming the necroptotic complex, resulting in the inhibition of MLKL phosphorylation and pore formation on cell membrane. However, Cisatracurium besylate did not interfere with the association between RIPK3 with its upstream kinase RIPK1 or ZBP1 but regulated RIPK3 autophosphorylation. Moreover, Cisatracurium besylate significantly inhibited the expansion of intracellular Mycobacterium tuberculosis both in vitro and in vivo, which also displayed a strong auxiliary bacteriostatic effect to support the therapeutic efficacy of isoniazid and rifampicin, the first-line anti-tubercular drugs. CONCLUSION: Cisatracurium besylate performs anti-Mycobacterium tuberculosis and anti-necroptotic roles, which potentiates its application to be an adjuvant drug for antituberculosis therapy to assist the battle against drug-resistant tuberculosis.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Mice , Animals , Apoptosis , Mycobacterium tuberculosis/metabolism , Isoniazid/pharmacology , Isoniazid/therapeutic use , Necroptosis , Protein Kinases/metabolism , Tuberculosis/drug therapy , Tuberculosis/metabolism , Anti-Bacterial Agents/pharmacology , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Macrophages/metabolism
8.
Int J Mol Sci ; 24(6)2023 Mar 18.
Article in English | MEDLINE | ID: mdl-36982891

ABSTRACT

Osteoporosis resulting from an imbalance of bone turnover between resorption and formation is a critical health issue worldwide. Estrogen deficiency following a nature aging process is the leading cause of hormone-related osteoporosis for postmenopausal women, while glucocorticoid-induced osteoporosis remains the most common in drug-induced osteoporosis. Other medications and medical conditions related to secondary osteoporosis include proton pump inhibitors, hypogonadism, selective serotonin receptor inhibitors, chemotherapies, and medroxyprogesterone acetate. This review is a summary of the cellular and molecular mechanisms of bone turnover, the pathophysiology of osteoporosis, and their treatment. Nuclear factor-κß ligand (RANKL) appears to be the critical uncoupling factor that enhances osteoclastogenesis. In contrast, osteoprotegerin (OPG) is a RANKL antagonist secreted by osteoblast lineage cells. Estrogen promotes apoptosis of osteoclasts and inhibits osteoclastogenesis by stimulating the production of OPG and reducing osteoclast differentiation after suppression of IL-1 and TNF, and subsequent M-CSF, RANKL, and IL-6 release. It can also activate the Wnt signaling pathway to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts rather than adipocytes. Estrogen deficiency leads to the uncoupling of bone resorption and formation; therefore, resulting in greater bone loss. Excessive glucocorticoids increase PPAR-2 production, upregulate the expression of Dickkopf-1 (DKK1) in osteoblasts, and inhibit the Wnt signaling pathway, thus decreasing osteoblast differentiation. They promote osteoclast survival by enhancing RANKL expression and inhibiting OPG expression. Appropriate estrogen supplement and avoiding excessive glucocorticoid use are deemed the primary treatment for hormone-related and glucocorticoid-induced osteoporosis. Additionally, current pharmacological treatment includes bisphosphonates, teriparatide (PTH), and RANKL inhibitors (such as denosumab). However, many detailed cellular and molecular mechanisms underlying osteoporosis seem complicated and unexplored and warrant further investigation.


Subject(s)
Glycoproteins , Osteoporosis , Humans , Female , Glycoproteins/metabolism , Glucocorticoids/metabolism , Osteoclasts/metabolism , Osteoprotegerin/metabolism , Osteoblasts/metabolism , Osteoporosis/chemically induced , Osteoporosis/genetics , Osteoporosis/drug therapy , Cell Differentiation , Estrogens/metabolism , RANK Ligand/metabolism
10.
J Interpers Violence ; 38(1-2): NP1842-NP1867, 2023 01.
Article in English | MEDLINE | ID: mdl-35465755

ABSTRACT

A history of child sexual abuse (CSA) is associated with a variety of psychological issues and conduct disorders in adolescents. However, little is known about the association between CSA and its characteristics and murderous behaviors in young adults. The purpose of this study was to examine this relationship and explore the mediating effect of psychological adjustment (PA). A cross-sectional study was conducted with 4034 college students in Anhui Province, China. The participants were invited to complete self-report questionnaires regarding the history of CSA, self-perceived PA and murderous behaviors. PA was evaluated by two of the most important indicators: resilience and emotional release. Mediation analyses were computed via parallel mediation models. Of the participants, 14.1% reported experiencing CSA. After controlling for potential confounders, CSA victimization was robustly and positively associated with murderous ideation (OR: 2.36, 95% CI: 1.77-3.14), murderous plans (OR: 4.02, 95% CI: 2.63-6.12), murderous preparation (OR: 3.87, 95% CI: 2.37-6.31), and murderous attempts (OR: 5.35, 95% CI: 3.11-9.21). CSA victimization that was persistent and of the combined contact or noncontact types greatly increased the risk of murderous behaviors. A dose-response relationship was observed between the duration of experienced CSA and murderous behaviors. Furthermore, the results of the mediation analysis revealed that PA partially mediated the relationship between CSA victimization and murderous behaviors. Therefore, PA protects against the development of murderous behaviors in abused individuals. These findings have important implications for the prevention and intervention of murderous behaviors in adolescents who experienced CSA, highlighting the importance of considering PA as a protective role in this relationship.


Subject(s)
Child Abuse, Sexual , Child Abuse , Crime Victims , Adolescent , Young Adult , Child , Humans , Child Abuse, Sexual/psychology , Cross-Sectional Studies , Emotional Adjustment , Crime Victims/psychology , Students/psychology , China , Surveys and Questionnaires
11.
Ecotoxicol Environ Saf ; 249: 114387, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36508816

ABSTRACT

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.


Subject(s)
Benzhydryl Compounds , Maternal Exposure , Prenatal Exposure Delayed Effects , Animals , Female , Humans , Mice , Pregnancy , Benzhydryl Compounds/toxicity , Benzhydryl Compounds/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Sexual Maturation/drug effects
12.
Asia Pac J Clin Nutr ; 31(3): 543-550, 2022.
Article in English | MEDLINE | ID: mdl-36173226

ABSTRACT

BACKGROUND AND OBJECTIVES: Assess the different nutritional status between admission and discharged in older adult patients using the GLIM criteria. METHODS AND STUDY DESIGN: A retrospective analysis was conducted on a multicenter study which initiated in 34 hospitals in China with 2734 hospitalized older patients. The dynamic changes of malnutrition according to GLIM criteria were performed between at admission and discharge, and their significance was analyzed using the chi-square test. The association between malnutrition and clinical outcomes was analyzed using the chi-square test, t-test, or rank sum test, and divided into different disease types for further analysis. RESULTS: The incidence of nutritional risk in elderly patients was 51.6% at admission and 48.4% at discharge. The prevalence of malnutrition according to the GLIM criteria was 19.6% at admission and increased to 33.4% at discharge, which was significantly different. Different age and disease type were related with nutrition status. Malnutrition is significantly association with adverse clinical outcomes such as increased risk of complications and prolonged length of hospital stay. CONCLUSIONS: The GLIM criteria can be used in elderly patients to assess malnutrition. The prevalence of malnutrition in elderly inpatients is high, and the prevalence of malnutrition at discharge is higher than that observed at admission. Attention should be paid to the dynamic changes of malnutrition in elderly patients during hospitalization.


Subject(s)
Malnutrition , Nutrition Assessment , Aged , Hospitalization , Humans , Malnutrition/epidemiology , Nutritional Status , Retrospective Studies
13.
J Am Med Dir Assoc ; 23(8): 1431.e1-1431.e19, 2022 08.
Article in English | MEDLINE | ID: mdl-35697124

ABSTRACT

OBJECTIVES: The aim is to inspect the effects of exercise and nutritional intervention on prefrail older adults' physical function. DESIGN: Systematic review and meta-analysis registered with PROSPERO (registration number: CRD42021261197). SETTING AND PARTICIPANTS: Randomized controlled trials involving prefrail older adults who received exercise and/or nutritional interventions. METHODS: Ovid MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials (CENTRAL), Web of Science, Clinical Trials, and PubMed were searched from inception to September 1, 2021. Primary outcomes were physical function, including physical performance, mobility, and grip strength. The short physical performance battery score and chair sit-to-stand test were used to assess the physical performance. Timed up and go and gait speed were applied to assess the mobility. Secondary outcomes were frailty status, weight, body mass index, Barthel index, and quality of life (Euro quality of life 5 dimension index values). RESULTS: We included 16 randomized controlled trials comprising 1199 prefrail older adults (intervention group, n = 593; control group, n = 606). Exercise and nutritional interventions significantly improved the short physical performance battery score [n = 5, mean difference 0.81, 95% confidence interval (CI) 0.21‒1.42, I2 = 62%], handgrip strength (n = 7, mean difference 1.52, 95% CI 0.70‒2.34, I2 = 6%), and gait speed (n = 4, standard weighted mean difference -1.06, 95% CI -1.87 to -0.25, I2 = 89%). There were no significant differences among the chair sit-to-stand test, timed up and go, weight, body mass index, and Barthel index. CONCLUSIONS AND IMPLICATIONS: Our systematic review and meta-analysis shows that the receipt of exercise and nutritional intervention significantly improved physical function in prefrail older adults.


Subject(s)
Frailty , Quality of Life , Aged , Body Mass Index , Exercise , Hand Strength , Humans
14.
Article in English | MEDLINE | ID: mdl-35564864

ABSTRACT

Background: Preterm labor and the following preterm births, which account for most of the perinatal deaths, are an important issue in public health. The study aims to assess the risk of subsequent preterm labor in pregnant females who have prepregnancy polycystic ovary syndrome (PCOS). Methods: This study has enrolled 1,000,000 randomly sampled females retrieved from the Taiwan National Health Insurance Research Database (NHIRD) during 1998−2012. The study excluded prepregnancy PCOS females who were initially diagnosed at age <15 or >45, and those who had inconsistent diagnoses. Moreover, the medical records of blood hormone tests, gynecologic ultrasonography, pelvic examinations, and tocometers were verified to confirm the accuracy of both diagnoses of PCOS and preterm labor. Among the prepregnancy PCOS females who became pregnant (the case group), each was age-matched to four females without prepregnancy PCOS (the control group). Results: Pregnant females in the case group (n = 1959) had a higher incidence of preterm labor than those in the control group (n = 7836) (42.98% vs. 21.99%, p < 0.0001). Analyzed by using logistic regression, the risk of preterm labor was significantly higher in the case group compared with the control group (crude OR: 2.674; 95% CI: 2.410−2.968, p < 0.0001). After adjustment with covariates, further analysis revealed a similar trend (adjusted OR: 2.405; 95% CI: 2.158−2.680, p < 0.0001). Among 1959 PCOS females in the case group, 196 had undergone metformin treatment. Compared with females without metformin treatment (the non-metformin subgroup), the metformin users (metformin subgroup) presented a reduced risk for preterm labor (adjusted OR: 2.238; 95% CI: 1.657−3.023). The risk of subsequent preterm labor was reduced by about 10% for the metformin subgroup compared with the non-metformin subgroup. Conclusions: Prepregnancy PCOS is an independent and significant risk factor of subsequent preterm labor. Among prepregnancy PCOS females, the risk of preterm labor is lowered by about 10% in metformin users compared with non-metformin females.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Premature Birth , Cohort Studies , Female , Humans , Infant, Newborn , Metformin/therapeutic use , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/epidemiology , Pregnancy , Premature Birth/epidemiology , Premature Birth/etiology , Risk Factors
15.
Drug Deliv ; 29(1): 637-651, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35188021

ABSTRACT

Pulmonary inhalation administration is an ideal approach to locally treat lung disease and to achieve systemic administration for other diseases. However, the complex nature of the structural characteristics of the lungs often results in the difficulty in the development of lung inhalation preparations. Nanocrystals technology provides a potential formulation strategy for the pulmonary delivery of poorly soluble drugs, owing to the decreased particle size of drug, which is a potential approach to overcome the physiological barrier existing in the lungs and significantly increased bioavailability of drugs. The pulmonary inhalation administration has attracted considerable attentions in recent years. This review discusses the barriers for pulmonary drug delivery and the recent advance of the nanocrystals in pulmonary inhalation delivery. The presence of nanocrystals opens up new prospects for the development of novel pulmonary delivery system. The particle size control, physical instability, potential cytotoxicity, and clearance mechanism of inhaled nanocrystals based formulations are the major considerations in formulation development.


Subject(s)
Drug Carriers/pharmacokinetics , Lung/drug effects , Lung/metabolism , Administration, Inhalation , Cell Survival/drug effects , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Drug Liberation , Drug Stability , Freeze Drying/methods , Macrophages, Alveolar/metabolism , Nanoparticles/chemistry , Particle Size , Pulmonary Surfactants/pharmacology , Solubility , Technology, Pharmaceutical/methods
16.
Int J Mol Sci ; 23(3)2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35163300

ABSTRACT

Osteoporosis is a serious health issue among aging postmenopausal women. The majority of postmenopausal women with osteoporosis have bone loss related to estrogen deficiency. The rapid bone loss results from an increase in bone turnover with an imbalance between bone resorption and bone formation. Osteoporosis can also result from excessive glucocorticoid usage, which induces bone demineralization with significant changes of spatial heterogeneities of bone at microscale, indicating potential risk of fracture. This review is a summary of current literature about the molecular mechanisms of actions, the risk factors, and treatment of estrogen deficiency related osteoporosis (EDOP) and glucocorticoid induced osteoporosis (GIOP). Estrogen binds with estrogen receptor to promote the expression of osteoprotegerin (OPG), and to suppress the action of nuclear factor-κß ligand (RANKL), thus inhibiting osteoclast formation and bone resorptive activity. It can also activate Wnt/ß-catenin signaling to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts, rather than adipocytes. The lack of estrogen will alter the expression of estrogen target genes, increasing the secretion of IL-1, IL-6, and tumor necrosis factor (TNF). On the other hand, excessive glucocorticoids interfere the canonical BMP pathway and inhibit Wnt protein production, causing mesenchymal progenitor cells to differentiate toward adipocytes rather than osteoblasts. It can also increase RANKL/OPG ratio to promote bone resorption by enhancing the maturation and activation of osteoclast. Moreover, excess glucocorticoids are associated with osteoblast and osteocyte apoptosis, resulting in declined bone formation. The main focuses of treatment for EDOP and GIOP are somewhat different. Avoiding excessive glucocorticoid use is mandatory in patients with GIOP. In contrast, appropriate estrogen supplement is deemed the primary treatment for females with EDOP of various causes. Other pharmacological treatments include bisphosphonate, teriparatide, and RANKL inhibitors. Nevertheless, more detailed actions of EDOP and GIOP along with the safety and effectiveness of medications for treating osteoporosis warrant further investigation.


Subject(s)
Estrogens/deficiency , Osteoporosis/etiology , Osteoporosis/metabolism , Bone Remodeling/drug effects , Bone Resorption/metabolism , Cell Differentiation/drug effects , Estrogens/metabolism , Female , Glucocorticoids/pharmacology , Humans , Osteoblasts/metabolism , Osteoclasts/metabolism , Osteocytes/metabolism , Osteogenesis/drug effects , Postmenopause/physiology , RANK Ligand/metabolism , Tumor Necrosis Factor-alpha/metabolism
17.
Prev Med ; 154: 106902, 2022 01.
Article in English | MEDLINE | ID: mdl-34863811

ABSTRACT

Adverse childhood experiences (ACEs) and adolescent depression are both prevalent social problems that can increase the risk of several negative health consequences throughout life. The original definition of ACEs misdirects the focus of intervention efforts for ACEs to only family dysfunction and parenting practices. We used a broader definition of ACEs and a latent class analysis (LCA) model to examine ACE patterns, aiming to overcome the shortcomings of cumulative and single adversity approaches based on the special social context of China. The data were derived from a middle school in Huaibei City of Anhui Province in 2019 and 2020, which was a prospective study involving 1687 junior high school students. At the initial evaluation (T1), ACEs, psychological resilience, self-esteem, and depressive symptoms were assessed by the students. At Time 2 (T2), the depressive symptoms of students were assessed. LCA and mediation analyses were conducted with Mplus version 8.2. The LCA identified the following three heterogeneous ACE classes: "low adversity" (36.4%), "moderate adversity" (44.2%), and "high adversity" (19.4%). The mediation analysis showed that the ACE patterns affected depressive symptoms through the following two mediation paths only in the moderate but not in the high adversity class: self-esteem alone and a path combining psychological resilience and self-esteem. Psychological resilience separately did not mediate the association between ACE patterns and depressive symptoms. To reduce depressive symptoms, interventions for students with ACEs need to improve self-esteem through many channels.


Subject(s)
Adverse Childhood Experiences , Resilience, Psychological , Adolescent , China , Depression , Humans , Prospective Studies
18.
J Interpers Violence ; 37(7-8): NP5830-NP5840, 2022 04.
Article in English | MEDLINE | ID: mdl-33001763

ABSTRACT

Little is known about the life course prevalence of bullying among university students. The current study examined the prevalence of bullying in different life periods among multi-university students. Our study included 4,034 university students from four types of universities. Participants self-reported four types of bullying (i.e., physical, verbal, relational, and cyber) with bullies and victims, and four periods (i.e., primary school or earlier, middle school, high school, and postsecondary education). Overall, the percentage of university students experiencing at least one type of bullying victimization (BV) and bullying perpetration (BP) during their lifetime was 59.7% and 31.6%, respectively; the percentage of the university students experiencing more than two types of BV and BP was 16.3% and 7.4%, respectively. The prevalence rates of each type of BV and BP were the highest in elementary school or earlier, and these rates decreased from elementary school or earlier to postsecondary education period. Four latent classes were identified for BV: low BV (73.8%), moderate BV (18.6%), secondary school BV (4.4%), and persistent BV (3.2%). Similarly, four classes for BP were identified: low BP (86.6%), primary school BP (8.1%), high school BP (1.5%), and persistent BP (3.8%). These findings may inform school health practice of bullying prevention by taking prevention programs, especially during elementary school or earlier period.


Subject(s)
Bullying , Crime Victims , China/epidemiology , Humans , Life Change Events , Prevalence , Students , Universities
20.
J Affect Disord ; 298(Pt A): 590-598, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34800574

ABSTRACT

BACKGROUND: Adolescence is a life stage with a high risk of depression, sleep disorders and school bullying. The aim of this study is to examine the longitudinal relationships between school bullying (bullying victimization and bullying perpetration), depressive symptoms and sleep problems among adolescents and to consider whether the direct pathways vary by gender. METHODS: The study included 1687 7th grade students (60.4% boys) recruited from a middle school in southeastern China. We collected self-reports of school bullying, depressive symptoms and sleep problems from 2019 (T1) and 2020 (T2) among adolescents. A series of gender-specified cross-lagged paths in a structural equation model was used for the primary analysis. RESULTS: The models revealed evidence for bidirectional associations between school bullying, depressive symptoms and sleep problems. Among girls, higher bullying perpetration at T1 predicted fewer sleep problems and depressive symptoms at T2, while bullying victimization significantly predicted poor quality of sleep and severe depressive symptoms. Furthermore, sleep problems at T1 positively predicted bullying perpetration and victimization at T2 in boys but not in girls. For both boys and girls, severe depressive symptoms significantly predicted more victimization and sleep problems, and sleep problems were positively associated with depressive symptoms. LIMITATIONS: The sample is unrepresentative, as it is from only one middle school. CONCLUSIONS: Our findings highlight that school bullying, depressive symptoms and sleep problems were interrelated across time and that acknowledging gender differences is important.


Subject(s)
Bullying , Crime Victims , Sleep Wake Disorders , Adolescent , Depression/epidemiology , Female , Humans , Longitudinal Studies , Male , Schools , Sleep Wake Disorders/epidemiology
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