Polydopamine-mediated immobilization of BMP-2 onto electrospun nanofibers enhances bone regeneration.

Dealing with bone defects is a significant challenge to global health. Electrospinning in bone tissue engineering has emerged as a solution to this problem. In this study, we designed a PVDF-b-PTFE block copolymer by incorporating TFE, which induced a phase shift in PVDF fromαtoß, thereby enhancing the piezoelectric effect. Utilizing the electrospinning process, we not only converted the material into a film with a significant surface area and high porosity but also intensified the piezoelectric effect. Then we used polydopamine to immobilize BMP-2 onto PVDF-b-PTFE electrospun nanofibrous membranes, achieving a controlled release of BMP-2. The scaffold's characters were examined using SEM and XRD. To assess its osteogenic effectsin vitro, we monitored the proliferation of MC3T3-E1 cells on the fibers, conducted ARS staining, and measured the expression of osteogenic genes.In vivo, bone regeneration effects were analyzed through micro-CT scanning and HE staining. ELISA assays confirmed that the sustained release of BMP-2 can be maintained for at least 28 d. SEM images and CCK-8 results demonstrated enhanced cell viability and improved adhesion in the experimental group. Furthermore, the experimental group exhibited more calcium nodules and higher expression levels of osteogenic genes, including COL-I, OCN, and RUNX2. HE staining and micro-CT scans revealed enhanced bone tissue regeneration in the defective area of the PDB group. Through extensive experimentation, we evaluated the scaffold's effectiveness in augmenting osteoblast proliferation and differentiation. This study emphasized the potential of piezoelectric PVDF-b-PTFE nanofibrous membranes with controlled BMP-2 release as a promising approach for bone tissue engineering, providing a viable solution for addressing bone defects.

Associations between adipokines gene polymorphisms and knee osteoarthritis: a meta-analysis.

BACKGROUND: Adipokines gene polymorphisms are speculated to be associated with the risk of knee osteoarthritis (OA), but evidence remains conflicting. This study therefore aimed to examine whether associations exist between adipokines gene polymorphisms and knee OA by considering the evidence collected from eligible studies through a meta-analysis. METHODS: A systematic search was performed on PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang up to March 31, 2020. Meta-analysis was carried out by focusing on the associations between adipokines gene polymorphisms and knee OA with the allele model, dominant model, and recessive model. RESULTS: The present meta-analysis included 5 eligible studies for ADIPOQ rs1501299 with 1,021 cases and 1,097 controls, 3 eligible studies for ADIPOQ rs2241766 with 549 cases and 544 controls, 3 eligible studies for LEPR rs1137101 with 808 cases and 856 controls, 2 eligible studies for VISFATIN rs4730153 with 339 cases and 680 controls and 2 eligible studies for VISFATIN rs16872158 with 339 cases and 680 controls. Significant association was observed between LEPR rs1137101 and knee OA in the overall population (recessive: OR = 0.40, 95% CI 0.21-0.79). Limited data revealed that associations may exist between ADIPOQ rs2241766 and knee OA in Asians (dominant: OR = 1.35, 95% CI 1.03-1.78), between VISFATIN rs4730153 and knee OA in Asians (allele: OR = 0.58, 95% CI 0.41-0.83; dominant: OR = 0.57, 95% CI 0.39-0.83), and between VISFATIN rs16872158 and knee OA in Asians (allele: OR = 1.84, 95% CI 1.26-2.68; dominant: OR = 1.94, 95% CI 1.31-2.89). CONCLUSIONS: Adipokines gene polymorphisms may be associated with knee OA. The association was observed in LEPR rs1137101 in the present study. In addition, limited data revealed that associations may also exist in ADIPOQ rs2241766, VISFATIN rs4730153 and VISFATIN rs16872158. PROSPERO REGISTRATION: CRD42020187664.

Intra-Articular Magnesium Plus Bupivacaine Is the Most Effective and Safe Postoperative Analgesic Option Following Knee Arthroscopy: A Network Meta-analysis.

PURPOSE: To evaluate the comparative efficacy and safety of single-dose intra-articular injection of commonly used analgesics after knee arthroscopy. METHODS: A systematic literature review was done to search for randomized controlled trials (RCTs) published from database inception to October 1, 2020, that compared analgesics (i.e., morphine, bupivacaine, ropivacaine, and magnesium alone or in combination) with placebo or each other after knee arthroscopy. The primary outcomes were postoperative pain intensity at 2 hours and 24 hours. Secondary outcomes included the time to first analgesic request, number of patients requiring supplementary analgesics and side effects. We estimated summary standardized mean differences (SMDs) or odds ratios with 95% credible intervals (95% CrIs) using Bayesian network meta-analysis with random effects. RESULTS: In total, 78 randomized controlled trials comprising 4,425 participants were included. Compared with placebo, magnesium plus bupivacaine was most likely to be effective in relieving pain at both 2-hour (SMD = -3.81, 95% CrI -5.28 to -2.35) and 24-hour after surgery (SMD = -2.81, 95% CrI: -4.29 to -1.30). Following was morphine plus bupivacaine (2-hour: SMD = -2.19, 95% CrI -3.05 to -1.31; 24-hour: SMD = -1.44, 95% CrI -2.14 to -0.73) and bupivacaine alone (2-hour: SMD = -1.66, 95% CrI -2.33 to -0.98; 24-hour: SMD = -0.67, 95% CrI -1.22 to -0.07); ropivacaine alone and magnesium alone were not effective on pain relief. The interval time to first analgesic request was significantly extended compared with placebo except for ropivacaine alone and magnesium alone. The number of patients requiring supplementary analgesics was reduced in all groups except ropivacaine alone. No statistically significant difference was found between any studied analgesics or placebo with regard to side effects. CONCLUSIONS: Of 6 common postoperative intra-articular analgesics, magnesium plus bupivacaine provides the most effective pain relief without increasing short-term side effects after knee arthroscopy. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Association between serum zinc and copper concentrations and copper/zinc ratio with the prevalence of knee chondrocalcinosis: a cross-sectional study.

BACKGROUND: Patients with chondrocalcinosis may suffer from a series of symptoms resembling acute gouty arthritis or septic arthritis, but the aetiology and pathogenesis of chondrocalcinosis have not been fully elucidated yet. This study was aimed to assess serum zinc and copper concentrations, as well as the ratio of serum copper to zinc concentrations (Cu/Zn ratio), in relation to the prevalence of knee chondrocalcinosis. METHODS: Data included in this analysis were retrieved from a large population-based cross-sectional study. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was diagnosed if definite linear cartilage calcification was detected. Serum zinc and copper concentrations were measured using the spectrophotometric flow injection methods by Roche modular P800. The relations of serum zinc and copper concentrations and Cu/Zn ratio to the prevalence of knee chondrocalcinosis were examined using generalized estimating equations, respectively. RESULTS: The prevalence of knee chondrocalcinosis was 1.2% in the sample of this study (n = 12,362). In comparison with the lowest tertile, the odds ratios (ORs) of knee chondrocalcinosis adjusted by age, sex and body mass index were 0.74 (95% CI 0.50-1.09) in the second and 0.56 (95% CI 0.36-0.86) in the third tertiles of serum zinc concentrations (P for trend = 0.009), were 1.26 (95% CI 0.77-2.05) in the second and 2.01 (95% CI 1.25-3.24) in the third tertile of serum copper concentrations (P for trend = 0.003), and were 1.02 (95% CI 0.61-1.69) in the second and 2.23 (95% CI 1.38-3.59) in the third tertile of Cu/Zn ratio (P for trend < 0.001) respectively. These findings were not materially altered by adjustment for potential confounders. CONCLUSIONS: The present study observed that higher serum zinc concentrations, lower serum copper concentrations or lower Cu/Zn ratio are associated with a lower prevalence of knee chondrocalcinosis in a dose-response relationship manner.

Physical Distancing Measures and Walking Activity in Middle-aged and Older Residents in Changsha, China, During the COVID-19 Epidemic Period: Longitudinal Observational Study.

BACKGROUND: Physical distancing measures taken to contain COVID-19 transmission may substantially reduce physical activity levels and cause individuals to adopt a more sedentary lifestyle. OBJECTIVE: The objective of this study is to determine if there was any change in daily steps, an important component of daily physical activity, and examine risk factors for frequent low daily steps during the COVID-19 epidemic. METHODS: We used data collected from the Step Study, a population-based longitudinal study of walking activity among residents aged ≥40 years in Changsha, China. Daily steps were collected via a smartphone linked to WeChat, a social networking platform. We plotted mean daily steps and the prevalence of low daily steps (≤1500 steps/day) 30 days before (reference period) and 30 days after (epidemic period) January 21, 2020 (date of the first COVID-19 case diagnosed in Changsha), and compared it with the same corresponding period from 2019. We examined the association of risk factors with the prevalence of frequent low daily steps (≤1500 steps/day for ≥14 days) using logistic regression. RESULTS: Among 3544 participants (mean age 51.6 years; n=1226 females, 34.6%), mean daily steps dropped from 8097 to 5440 and the prevalence of low daily steps increased from 3% (2287/76,136 person-day) to 18.5% (12,951/70,183 person-day) during the reference and epidemic periods, respectively. No such phenomenon was observed during the corresponding period in 2019. Older age (P for interaction=.001) and female sex (P for interaction<.001) were both associated with a higher prevalence of frequent low daily steps and were more pronounced during the epidemic period. More education was associated with a lower prevalence of frequent low daily steps during the reference period but not the epidemic period (P for interaction=.34). Body mass index or comorbidity were not associated with frequent low daily steps during either period. CONCLUSIONS: Daily steps of Changsha residents aged ≥40 years dropped significantly during the COVID-19 period, especially among older adults and females. Although successful physical distancing, measured by the rapid downward trend in daily step counts of residents, played a critical role in the containment of the COVID-19 epidemic, our findings of an increase in the prevalence of frequent low daily steps raise concerns about unintended effects on physical activity.

Comparative Risk-Benefit Profiles of Individual Devices for Graft Fixation in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Network Meta-analysis.

PURPOSE: To compare the efficacy and safety of individual devices for femoral and/or tibial graft fixation in anterior cruciate ligament (ACL) reconstruction. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to December 12, 2018. Randomized controlled trials comparing individual devices for ACL graft fixation were included. Bayesian network meta-analysis was performed to assess the efficacy profile using the following outcomes: Lysholm score, International Knee Documentation Committee (IKDC) category, laxity, range of motion, and Tegner score. The incidence of infection, effusion, and graft rupture for each device was reported. RESULTS: We included 57 randomized controlled trials involving 4,304 patients aged 23.8 to 40.9 years. The female proportion ranged from 0% to 100%. The length of follow-up ranged from 6 to 144 months. Of the 13 studied femoral fixation devices, none was significantly different from the others regarding the Lysholm score, IKDC category, range of motion, and Tegner score. Bioabsorbable interference screws (standardized mean difference, 1.3; 95% credible interval, 0.0-2.5) showed higher laxity than the EndoPearl at a borderline level of statistical significance, but the difference varied substantially within multiple sensitivity analyses. Infection (2.0%) was most commonly seen with the EndoPearl, whereas the bone mulch screw had the highest incidence of effusion (5.5%) and graft rupture (5.5%). For the 9 studied tibial fixation devices, no significant difference was observed in the aforementioned efficacy measurements. Bioabsorbable interference screws with staples had the highest incidence of infection (11.1%) and effusion (15.6%), whereas graft rupture was most commonly seen with the bone plug (4.0%). CONCLUSIONS: Graft fixation devices in ACL reconstruction share a similar efficacy profile in terms of the Lysholm score, IKDC category, range of motion, and Tegner score but not laxity. On the other hand, safety profiles seem to vary among different devices. These findings can support surgeons, alongside their experience and preference, as well as the relative cost of each device, in delivering an individualized plan for an optimal operation. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and II studies.

Association of brain-derived neurotrophic factor levels and depressive symptoms in young adults with acne vulgaris.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the proteins that contributes to the survival, growth, maintenance of neurons, and plays important roles in the pathophysiology of depression. It has been reported that depression is closely associated with the pathogenesis of acne vulgaris disease. But, there is no report of serum BDNF levels in patients with acne vulgaris. The study aimed to determine the potential association between BDNF and depressive symptoms in young adults with acne vulgaris. METHODS: In this analytical cross-sectional study, the serum BDNF levels were measured in peripheral blood samples of 20 consecutive acne vulgaris patients with depression and 98 consecutive acne vulgaris patients without depression and also compared it with a 59 healthy control group by using a ELISA. The potential correlation between the BDNF levels, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and depressive symptoms such as nine-item patient health questionnaire (PHQ-9) and Athens insomnia scale (AIS) were evaluated with multivariate logistic regression analysis. RESULTS: Our results showed that levels of BDNF expression were lower in consecutive acne vulgaris patients when compared with healthy control (P < 0.05). There was a negative correlation between levels of BDNF and the PHQ-9 scores (r = - 0.486, P < 0.001). Furthermore, acne vulgaris patients with depression showed lower serum BDNF levels (10.96 ± 2.12 ng/ml) compared with acne vulgaris patients without depression (13.85 ± 2.47 ng/ml), as well as with healthy control (14.35 ± 2.70 ng/mg; both P < 0.05). No difference was found in serum BDNF levels between healthy control and acne vulgaris patients without depressive symptoms (z = 0.964, P > 0.05). Similarly, the overall area under the curve of receiver operating characteristic was 0.82, indicating the highly conserving of serum BDNF levels as an biomarker for screening of depression in young adults with acne vulgaris (72% sensitivity and 85% specificity). CONCLUSION: Serum BDNF levels were decreased and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris.

The role of different SIRT1-mediated signaling pathways in toxic injury.

Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction of apoptosis, and inhibition of energy metabolism. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is a member of the evolutionarily highly conserved Sir2 (silent information regulator 2) superprotein family, which is located in the nucleus and cytoplasm. It can deacetylate protein substrates in various signal transduction pathways to regulate gene expression, cell apoptosis and senescence, participate in the process of neuroprotection, energy metabolism, inflammation and the oxidative stress response in living organisms, and plays an important role in toxic damage caused by toxicants and in the process of SIRT1 activator/inhibitor antagonized toxic damage. This review summarizes the role that SIRT1 plays in toxic damage caused by toxicants via its interactions with protein substrates in certain signaling pathways.

Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study.

OBJECTIVE: To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China. METHODS: Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression. RESULTS: This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55-0.94), 0.72 (95% CI 0.51-1.01) and 0.47 (95% CI 0.31-0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results. CONCLUSIONS: In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

[Cross-sectional association between dietary zinc intake and phalangeal osteoporosis].

OBJECTIVE: To examine the association between dietary zinc intake and phalangeal osteoporosis.
 Methods: The subjects of this study were members aged over 40 years or above of the general population who had undergone routine health examinations at Xiangya Hospital, Central South University in Changsha, Hunan, China, between October 2013 and December 2015. Dietary zinc intake was measured using the semi-quantitative food frequency questionnaire. Phalangeal osteoporosis was diagnosed according to the WHO criteria based on the assessment of bone mineral density. According to the quartile distribution, serum zinc concentrations were classified into categories: Q1≤15.40 mg/d, Q2 15.41-18.67 mg/d, Q3 18.68-22.76 mg/d, and Q4≥22.77 mg/d. The association between dietary zinc intake with phalangeal osteoporosis was evaluated by conducting multivariable adjusted logistic regression. The dose-response relationship between them was assessed by restricted cubic spline regression.
 Results: A total of 6 267 subjects were included, 602 (9.6%) among them were suffered from phalangeal osteoporosis. The multivariable-adjusted models (i.e. Model 2 and 3) showed that, compared with the lowest quartile, the odds ratios (ORs) for phalangeal osteoporosis were lower in the second, third and fourth quartiles of dietary zinc intake (Model 2: P for trend = 0.045; Model 3: P for trend = 0.031) in the total population; the ORs for phalangeal osteoporosis were lower in the third and fourth quartiles of dietary zinc intake (Model 2 and 3: P for trend = 0.018) in the male population; and the ORs for phalangeal osteoporosis were lower in the second, third and fourth dietary zinc intake quartiles (Model 2: P for trend = 0.227; Model 3: P for trend = 0.217) in the female population. There also existed dose-response relationship between dietary zinc intake and the prevalence of phalangeal osteoporosis (P<0.001).
 Conclusion: Dietary zinc intake is negatively associated with phalangeal osteoporosis in the total population and male subgroup, but not female subgroup.

[Association between serum copper concentration and hypertension in knee osteoarthritis patients].

OBJECTIVE: To examine the association between serum copper concentration and the prevalence of hypertension in patients with knee osteoarthritis (OA).
 Methods: A total of 935 patients who were aged ≥40 years and underwent routine checkups from October 2013 to November 2014 at the Health Management Center of Xiangya Hospital, Central South University were included. They were diagnosed as knee OA by weight-bearing bilateral anteroposterior radiography. Serum copper concentration was measured using the chemiluminescence method. Blood pressure was measured by an electronic sphygmomanometer. The association between serum copper concentration and hypertension was evaluated by conducting multivariable adjusted logistic regression.
 Results: Compared with the lowest quintile, the multivariable-adjusted odds ratio (OR) and related 95% confidence interval (95% CI) of hypertension were 1.46 (95% CI 1.02 to 2.09, P for trend=0.035) and 1.47 (95% CI 0.77 to 2.78, P for trend=0.032) in the total population and female subgroup of the highestest quintile, respectively. There was no significant association between serum copper and hypertension in male subgroup among OA patients (OR=1.21, 95% CI 0.76 to 1.93, P for trend=0.354).
 Conclusion: The serum copper concentration was significantly associated with the prevalence of hypertension in total population and female subgroup, but may not in male subgroup among patients with knee OA.

[Primitive myxoid mesenchymal tumor of infancy: a clinicopathologic study of 3 additional cases].

OBJECTIVE: To study the clinicopathologic characteristics, immunophenotypes and differential diagnosis of primitive myxoid mesenchymal tumor of infancy (PMMTI). METHODS: The clinical data, histological features and immunohistochemic results of 3 cases of PMMTI were reviewed. RESULTS: There were 2 males and 1 female aged 4 years, 2 days and 3 months respectively. The tumor occurred in the head and neck (n = 2), and lumbar regions (n = 1).Histologically, they were composed of ovoid, short spindled to polygonal mesenchymal cells with less eosinophilic cytoplasm, or vacuolated cytoplasm. There was mild nuclear atypia with mitotic activity of 0-2/10 HPF.In most areas, the neoplastic cells showed a diffuse growth pattern, whereas in some areas, they formed a vaguely nodular pattern with peripheral collagenized stroma. They were embedded in a myxoid stroma that contained a rich delicate vascular network. Besides, small cyst-like spaces were also present in one case. The tumor cells expressed vimentin, but not alpha smooth muscle actin, desmin, myogenin, S-100 protein, CD34 and cytokeratin. The patients underwent surgery.One patient had local recurrences twice and died 2 years later. Compared with the primary tumor, the recurrent lesions exhibited increased cellularity, marked cellular atypia and mitotic activity (10/10 HPF). The other two patients remained well with no evidence of disease at last during follow-up. CONCLUSIONS: PMMTI is a rare soft tissue tumor of infancy, composed of primitive mesenchymal cells and myxoid stroma.It occurs mainly in the somatic soft tissues of the trunk, head and neck region, and the extremities, and is characterized by a high rate of local recurrence if incompletely excised. Metastasis and tumor related death may occur, albeit very rarely.Increased awareness of this novel entity will help avoid misinterpreting the lesion as a variety of other infantile mesenchymal neoplasms, including congenital fibrosarcoma and lipoblastoma.

Revealing tumor cells and tissues with high selectivity through folic acid-targeted nanofluorescence probes responsive to acidic microenvironments.

Tumor-specific fluorescent probes must fulfill the dual requirements of targeted accumulation within tumors and high-resolution imaging capabilities. To achieve both tumor-targeted accumulation and high-resolution imaging performance, we developed a composite comprising an acid-responsive bodipy conjugated to amphiphilic PEG-b-PLA polymer, along with folic acid (FA)-modified PEG-b-PLA as a targeting moiety for active tumor-specific accumulation. Finally, a novel assembly of hybrid fluorescent nanoparticles was successfully synthesized by integrating these two components, demonstrating exceptional responsiveness to acidic conditions for fluorescence excitation and remarkable tumor-targeted accumulation capabilities. We conducted comprehensive in vitro and in vivo investigations employing techniques such as analysis of physicochemical properties, fluorescence-based probes detection at varying pH levels, assessment of in vitro cytotoxicity, evaluation of cellular uptake capacity, analysis of lysosomal co-localization imaging, examination of tumor fluorescence images in vivo, and investigation of biological distribution patterns. The results demonstrated that the acid-responsive nanofluorescence probe we designed and synthesized possesses desirable physical and chemical characteristics, including a small particle size and low cytotoxicity. Moreover, it exhibits rapid real-time response to acidic environments and displays enhanced fluorescence intensity, enabling the real-time tracking of probe entry into tumor cells as well as intracellular lysozyme accumulation. We achieved highly specific in vivo tumor visualization by combining nanoprobes targeting folate receptor. Through imaging cervical tumor mice, we demonstrated the precise imaging performance and high targeted accumulation of FA-targeted nanofluorescence probes in tumor tissue. Furthermore, we confirmed the in vivo safety of the FA-targeted nanofluorescence probe through biological distribution analysis. These findings highlight the potential widespread application of FA-targeted acid-responsive nanofluorescence probes for selective imaging of tumor cells and tissues.

Separation of benzene and toluene associated with vapochromic behaviors by hybrid[4]arene-based co-crystals.

The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow. However, when hybrid[4]arene-based co-crystal captures cyclohexane and pyridine, neither structures nor colors change. Interestingly, hybrid[4]arene-based co-crystal can separate benzene from a benzene/cyclohexane equal-volume mixture and allow toluene to be removed from a toluene/ pyridine equal-volume mixture with purities reaching 100%. In addition, the process of adsorptive separation can be visually monitored. The selectivity of benzene from a benzene/cyclohexane equal-volume mixture and toluene from a toluene/ pyridine equal-volume mixture is attributed to the different changes in the charge-transfer interaction between hybrid[4]arene and 1,2,4,5-tetracyanobenzene when hybrid[4]arene-based co-crystal captures different vapors. Moreover, hybrid[4]arene-based co-crystal can be reused without losing selectivity and performance. This work constructs a vapochromic material for hydrocarbon separation.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

The association between selenium and bone health: a meta-analysis.

Aims: Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture). Methods: PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (ß), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health. Results: From 748 non-duplicate publications, 19 studies were included. We found a significantly positive association between dietary selenium intake (ß = 0.04, 95% confidence interval (CI) 0.00 to 0.07, p = 0.029) as well as serum selenium (ß = 0.13, 95% CI 0.00 to 0.26, p = 0.046) and BMD. Consistently, those with higher selenium intake had a lower risk of OP (OR = 0.47, 95% CI 0.31 to 0.72, p = 0.001), and patients with OP had a significantly lower level of serum selenium than healthy controls (WMD = -2.01, 95% CI -3.91 to -0.12, p = 0.037). High dietary selenium intake was associated with a lower risk of hip fracture (OR = 0.44, 95% CI 0.37 to 0.52, p < 0.001). Conclusion: Selenium was positively associated with BMD and inversely associated with OP; dietary selenium intake was negatively associated with hip fracture. The causality and therapeutic effect of selenium on OP needs to be investigated in future studies.

Genetically Predicted Levels of Serum Metabolites and Risk of Sarcopenia: A Mendelian Randomization Study.

Metabolites' connection to sarcopenia through inflammation and mitochondrial dysfunction is presumed, but their impact remains unclear due to limitations in conventional observational studies caused by confounding bias and reverse causation. We conducted a Mendelian randomization (MR) analysis to elucidate the association of serum metabolites with sarcopenia and its related traits, i.e., appendicular lean mass and grip strength. Genetic instruments to proxy the serum metabolites were extracted from the most comprehensive genome-wide association study on the topic published so far. The corresponding summary statistics for the associations of genetic instruments with outcomes were calculated from the UK Biobank (n = 324,976 participants). The primary analyses were assessed by an inverse-variance weighted (IVW) method. The weighted median and MR-PRESSO methods were used as sensitive analyses. Fourteen genetically predicted serum metabolites were associated with the risk of sarcopenia (PIVW < 0.05). Two metabolites showed the overlapped association with sarcopenia and its related traits, which were isovalerylcarnitine (sarcopenia: odds ratio [OR] = 4.00, 95% confidence interval [CI] = 1.11~14.52, PIVW = 0.034; appendicular lean mass: ß = -0.45 kg, 95% CI = -0.81~-0.09, PIVW = 0.015; grip strength: ß = -1.51 kg, 95% CI = -2.31~-0.71, PIVW = 2.19 × 10-4) and docosapentaenoate (sarcopenia: OR = 0.16, 95% CI = 0.03~0.83, PIVW = 0.029; appendicular lean mass: ß = -0.45 kg, 95% CI = 0.08~0.81, PIVW = 0.016). Twenty-seven metabolites were suggestive associated with appendicular lean mass or grip strength. This MR study provided evidence for the potential effects of metabolites on sarcopenia.

Biosensors integrated 3D organoid/organ-on-a-chip system: A real-time biomechanical, biophysical, and biochemical monitoring and characterization.

As a full-fidelity simulation of human cells, tissues, organs, and even systems at the microscopic scale, Organ-on-a-Chip (OOC) has significant ethical advantages and development potential compared to animal experiments. The need for the design of new drug high-throughput screening platforms and the mechanistic study of human tissues/organs under pathological conditions, the evolving advances in 3D cell biology and engineering, etc., have promoted the updating of technologies in this field, such as the iteration of chip materials and 3D printing, which in turn facilitate the connection of complex multi-organs-on-chips for simulation and the further development of technology-composite new drug high-throughput screening platforms. As the most critical part of organ-on-a-chip design and practical application, verifying the success of organ model modeling, i.e., evaluating various biochemical and physical parameters in OOC devices, is crucial. Therefore, this paper provides a logical and comprehensive review and discussion of the advances in organ-on-a-chip detection and evaluation technologies from a broad perspective, covering the directions of tissue engineering scaffolds, microenvironment, single/multi-organ function, and stimulus-based evaluation, and provides a more comprehensive review of the progress in the significant organ-on-a-chip research areas in the physiological state.

Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing.

Tendon-bone insertion injuries (TBI), such as anterior cruciate ligament (ACL) and rotator cuff injuries, are common degenerative or traumatic pathologies with a negative impact on the patient's daily life, and they cause huge economic losses every year. The healing process after an injury is complex and is dependent on the surrounding environment. Macrophages accumulate during the entire process of tendon and bone healing and their phenotypes progressively transform as they regenerate. As the "sensor and switch of the immune system", mesenchymal stem cells (MSCs) respond to the inflammatory environment and exert immunomodulatory effects during the tendon-bone healing process. When exposed to appropriate stimuli, they can differentiate into different tissues, including chondrocytes, osteocytes, and epithelial cells, promoting reconstruction of the complex transitional structure of the enthesis. It is well known that MSCs and macrophages communicate with each other during tissue repair. In this review, we discuss the roles of macrophages and MSCs in TBI injury and healing. Reciprocal interactions between MSCs and macrophages and some biological processes utilizing their mutual relations in tendon-bone healing are also described. Additionally, we discuss the limitations in our understanding of tendon-bone healing and propose feasible ways to exploit MSC-macrophage interplay to develop an effective therapeutic strategy for TBI injuries. The Translational potential of this article: This paper reviewed the important functions of macrophages and mesenchymal stem cells in tendon-bone healing and described the reciprocal interactions between them during the healing process. By managing macrophage phenotypes, mesenchymal stem cells and the interactions between them, some possible novel therapies for tendon-bone injury may be proposed to promote tendon-bone healing after restoration surgery.

Comparative risk-benefit profiles of weak opioids in the treatment of osteoarthritis: a network meta-analysis of randomized controlled trials.

BACKGROUND: Despite their poor tolerance, weak opioids are still the most commonly-prescribed medicine for osteoarthritis (OA)-related pain. The objective of this network meta-analysis was to comparatively examine the efficacy and safety of weak opioids in OA treatment. METHODS: Databases including PubMed, Embase, Cochrane Library and Web of Science were searched from inception to 4 April 2022 to retrieve randomized controlled trials (RCTs) comparing weak opioids with placebo or between one another in OA patients. Bayesian network meta-analysis was performed on the following outcomes of interest, namely the change-from-baseline score in pain relief, gastrointestinal (GI) adverse events (AEs), central nervous system (CNS) AEs, and total number of AEs (i.e. the number of subjects experiencing any AE for at least once) during follow-up. The surface under the cumulative ranking curve (SUCRA) was used to rank the effectiveness of each treatment and identify the best treatment. RESULTS: A total of 14 RCTs invoving four types of weak opioids were included in this meta-analysis. Compared to placebo, tramadol (standardized mean difference [SMD] = -0.34, 95% credible interval [CrI]: -0.53 to -0.18) and codeine (SMD = -0.39, 95% CrI: -0.79 to -0.04) were effective for pain relief, but involved a higher risk of GI AEs, CNS AEs and total number of AEs. Dextropropoxyphene demonstrated a significantly lower risk of GI AEs (OR = 0.28, 95%CrI: 0.17 to 0.51), CNS AEs (OR = 0.29, 95%CrI: 0.11 to 0.78) and total number of AEs (OR = 0.35, 95%CrI: 0.15 to 0.82) compared to codeine. Dihydrocodeine had a better safety profile in CNS AEs (SUCRA = 64.8%) and total number of AEs (SUCRA = 66.6%). CONCLUSIONS: The results of the present study confirmed that tramadol and codeine were effective drugs for the treatment of OA, but involved considerable safety issues. Dextropropoxyphene and dihydrocodeine exhibited a relatively good safety profile but their efficacy still warrant further investigation.