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2.
Heliyon ; 10(11): e32303, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38912505

ABSTRACT

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN). Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA). Results: The mean ΔeGFR of low NK-low memory CD4+ T-high naive CD4+ T group (31.01 mL/min/1.73 m2) was significantly greater than that of high NK-high memory CD4+ T-low naive CD4+ T group (11.83 mL/min/1.73 m2; P = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4+ T-low naive CD4+ T group and approximately 5 years for low NK-low memory CD4+ T-high naive CD4+ T group (log-rank test P = 0.0294). Conclusions: Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function.

3.
Psychophysiology ; : e14598, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691392

ABSTRACT

Numerous studies have established a correlation between social anxiety and poor cognitive control. However, little is known about the cognitive control pattern of individuals with high social anxiety (HSAs) and the underlying mechanisms. Based on the Dual Mechanisms of Control framework and the Expected Value of Control theory, this study explored whether HSAs have an impaired cognitive control pattern (Experiment 1) and whether motivational deficiencies underlie the impaired control pattern (Experiment 2). In Experiment 1, 21 individuals with low social anxiety (LSAs) and 21 HSAs completed an AX-Continuous Performance Task. Results showed that HSAs had a smaller P3b amplitude than LSAs, indicating their weakened proactive control in the cue processing stage, but a larger contingent negative variation (CNV) on cue B as compensation for the negative effects of anxiety in the response preparation stage. No group difference was found in N2 and P3a amplitude on probes, suggesting that reactive control in HSAs was not affected compared to LSAs. In Experiment 2, 21 LSAs and 21 HSAs completed a cued-flanker task, where the likelihood of proactive control engagement was manipulated. The results revealed that HSAs exhibited motivation deficiencies in engaging in proactive control, as evidenced by P3b, CNV amplitude, and response times. These findings shed light on the impaired cognitive control pattern of HSAs and suggest that motivational deficiencies may be the crucial underlying factor.

4.
JBMR Plus ; 8(5): ziae039, 2024 May.
Article in English | MEDLINE | ID: mdl-38644977

ABSTRACT

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8 years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1 g/cm2, the T-score was -1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.

5.
Medicine (Baltimore) ; 103(16): e37868, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640291

ABSTRACT

RATIONALE: The conventional treatment of giant cell tumors is intralesional curettage with local adjuvant therapy. Because hand tumors have a high local recurrence, the primary goal for treating tumors of the hand is to eradicate the lesion. PATIENT CONCERNS: To preserve the metacarpophalangeal (MCP) joint function as well as avoid further recurrence after surgery. DIAGNOSES: The giant cell tumor invades the patient's MCP joint in an index proximal phalanx. INTERVENTIONS: Using computer-aided design and three-dimensional printing techniques, we reformed the original shapes of the MCP joint and its peripheral bone to replica models. The surgeon then performed an en bloc resection and proximal phalanx with MCP joint reconstruction by fabricating the patient's costal osteochondral graft during the operation. OUTCOMES: After 6 months of rehabilitation, the patient's finger functions could pinch and grasp objects naturally. At the 1-year follow-up, the range of motion of the MCP, proximal interphalangeal, and distal interphalangeal joints improved from flexion of 35° to 60°, 75° to 85°, and 60° to 80°, respectively. The hand function achieved the mean performance of non-preferred hands for young females at the postoperative 3-year follow-up. LESSONS: The customized prototyping technique has the potential to replica the original patient's bony graft to reach the goal of minimizing the defects at the donor site and maximizing the function of the reconstructed MCP joint.


Subject(s)
Joint Prosthesis , Neoplasms , Female , Humans , Fingers , Ribs/transplantation , Metacarpophalangeal Joint/surgery , Range of Motion, Articular , Finger Joint/surgery
6.
Heliyon ; 10(5): e26926, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38449597

ABSTRACT

Patients with stroke often use ankle-foot orthoses (AFOs) for gait improvement. 3D printing technology has become a popular tool in recent years for the production of AFOs due to its strengths on customization and rapid manufacturing. However, the porosity of the 3D printed materials affects the kinetic features of these orthoses, leading to its lower-strength than solid ones. The effective elastic modulus of 3D printed material was measured following standard test method to obtain the kinetic features precisely in a finite element simulation. This study demonstrated that the porosity of 3D printed samples using 100% fill density was 11% for PLA and 16% for Nylon. As a result, their effective elastic modulus was reduced to 1/3 and 1/12 of fully solid objects, respectively, leading to a lower stiffness of 3D printed orthoses. A fatigue testing platform was built to verify our finite element model, and the findings of the fatigue test were consistent with the analysis of the finite element model. Further, our AFO has been proven to have a lifespan exceeding 200 thousand steps. Our study highlights the significance of determining the actual porosity of 3D printed samples by calculating the effective elastic modulus, which leads to a more precise finite element simulation and enables reliable prediction of the kinetic features of the AFO. Overall, this study provides valuable insights into the production and optimization of 3D printed AFOs for patients with stroke.

7.
Sci Adv ; 10(11): eadd9342, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38478609

ABSTRACT

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth patterns as well as numerous undescribed behaviors such as abortive colonization. Paired analysis of primary and secondary sites revealed fitness as major contributor to dissemination. From the analysis of pro- and nonmetastatic isogenic subclones, we identified a transcriptomic signature able to identify metastatic cells in human tumors and predict patients' survival.


Subject(s)
Ecosystem , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Gene Expression Profiling , Transcriptome
8.
Front Bioeng Biotechnol ; 12: 1351485, 2024.
Article in English | MEDLINE | ID: mdl-38486865

ABSTRACT

Diabetes mellitus and chronic kidney disease represent escalating global epidemics with comorbidities akin to neuropathies, resulting in various neuromuscular symptoms that impede daily performance. Interestingly, previous studies indicated differing sensorimotor functions within these conditions. If assessing sensorimotor features can effectively distinguish between diabetes mellitus and chronic kidney disease, it could serve as a valuable and non-invasive indicator for early detection, swift screening, and ongoing monitoring, aiding in the differentiation between these diseases. This study classified diverse diagnoses based on motor performance using a novel pinch-holding-up-activity test and machine learning models based on deep learning. Dataset from 271 participants, encompassing 3263 hand samples across three cohorts (healthy adults, diabetes mellitus, and chronic kidney disease), formed the basis of analysis. Leveraging convolutional neural networks, three deep learning models were employed to classify healthy adults, diabetes mellitus, and chronic kidney disease based on pinch-holding-up-activity data. Notably, the testing set displayed accuracies of 95.3% and 89.8% for the intra- and inter-participant comparisons, respectively. The weighted F1 scores for these conditions reached 0.897 and 0.953, respectively. The study findings underscore the adeptness of the dilation convolutional neural networks model in distinguishing sensorimotor performance among individuals with diabetes mellitus, chronic kidney disease, and healthy adults. These outcomes suggest discernible differences in sensorimotor performance across the diabetes mellitus, chronic kidney disease, and healthy cohorts, pointing towards the potential of rapid screening based on these parameters as an innovative clinical approach.

9.
J Neuroeng Rehabil ; 21(1): 5, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38173006

ABSTRACT

BACKGROUND: The original version of the Tenodesis-Induced-Grip Exoskeleton Robot (TIGER) significantly improved the motor and functional performance of the affected upper extremity of chronic stroke patients. The assist-as-needed (AAN) technique in robot-involved therapy is widely favored for promoting patient active involvement, thereby fostering motor recovery. However, the TIGER lacked an AAN control strategy, which limited its use in different clinical applications. The present study aimed to develop and analyze the training effects of an AAN control mode to be integrated into the TIGER, to analyze the impact of baseline patient characteristics and training paradigms on outcomes for individuals with chronic stroke and to compare training effects on the upper limb function between using the AAN-equipped TIGER and using the original prototype. METHODS: This was a single-arm prospective interventional study which was conducted at a university hospital. In addition to 20 min of regular task-specific motor training, each participant completed a 20-min robotic training program consisting of 10 min in the AAN control mode and 10 min in the functional mode. The training sessions took place twice a week for 9 weeks. The primary outcome was the change score of the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), and the secondary outcomes were the change score of the Box and Blocks Test (BBT), the amount of use (AOU) and quality of movement (QOM) scales of the Motor Activity Log (MAL), the Semmes-Weinstein Monofilament (SWM) test, and the Modified Ashworth Scale (MAS) for fingers and wrist joints. The Generalized Estimating Equations (GEE) and stepwise regression model were used as the statistical analysis methods. RESULTS: Sixteen chronic stroke patients completed all steps of the study. The time from stroke onset to entry into the trial was 21.7 ± 18.9 months. After completing the training with the AAN-equipped TIGER, they exhibited significant improvements in movement reflected in their total score (pre/post values were 34.6 ± 11.5/38.5 ± 13.4) and all their sub-scores (pre/post values were 21.5 ± 6.0/23.3 ± 6.5, 9.5 ± 6.2/11.3 ± 7.2, and 3.6 ± 1.0/3.9 ± 1.0 for the shoulder, elbow, and forearm sub-category, the wrist and hand sub-category, and the coordination sub-category, respectively) on the FMA-UE (GEE, p < 0.05), as well as their scores on the BBT (pre/post values were 5.9 ± 6.5/9.5 ± 10.1; GEE, p = 0.004) and the AOU (pre/post values were 0.35 ± 0.50/0.48 ± 0.65; GEE, p = 0.02). However, the original TIGER exhibited greater improvements in their performance on the FMA-UE than the participants training with the AAN-equipped TIGER (GEE, p = 0.008). The baseline score for the wrist and hand sub-category of the FMA-UE was clearly the best predictor of TIGER-mediated improvements in hand function during the post-treatment assessment (adjusted R2 = 0.282, p = 0.001). CONCLUSIONS: This study developed an AAN-equipped TIGER system and demonstrated its potential effects on improving both the function and activity level of the affected upper extremity of patients with stroke. Nevertheless, its training effects were not found to be advantageous to the original prototype. The baseline score for the FMA-UE sub-category of wrist and hand was the best predictor of improvements in hand function after TIGER rehabilitation. Clinical trial registration ClinicalTrials.gov, identifier NCT03713476; date of registration: October19, 2018. https://clinicaltrials.gov/ct2/show/NCT03713476.


Subject(s)
Exoskeleton Device , Robotics , Stroke Rehabilitation , Stroke , Tenodesis , Humans , Hand Strength , Prospective Studies , Recovery of Function , Robotics/methods , Stroke Rehabilitation/methods , Treatment Outcome , Upper Extremity
10.
Clin Biomech (Bristol, Avon) ; 111: 106154, 2024 01.
Article in English | MEDLINE | ID: mdl-38029478

ABSTRACT

BACKGROUND: Children with developmental coordination disorder show difficulties in making rapid online corrections, and this has been demonstrated in experiments where reaching/pointing movements were employed. However, typical hand movements in real-life contexts involve subsequent movements, such as grasping and manipulating objects after reaching. This study aimed to reinvestigate online correction of reaching movements that were connected with grasping and object manipulation and to explore its impact on the coordination of subsequent hand movements in children with developmental coordination disorder. METHODS: Five children with developmental coordination disorder and five children with typical development were recruited. Their reach-to-manipulate movements in a double-step task were recorded using motion analysis. The manipulative movements included simple and complex forms of pencil rotation. Movement time, movement velocity, and correlation coefficients between finger joints were derived to quantify their motor performances. FINDINGS: Children with developmental coordination disorder showed longer movement time and deceleration phases during online correction of reaching movement than children without developmental coordination disorder. In subsequent grasping and manipulation movements after online correction, they also exhibited lower correlation coefficients in four to five finger joint couplings that are essential for movement completion, compared to children without developmental coordination disorder. INTERPRETATION: Our findings from the current pilot study suggest that children with developmental coordination disorder have impairments in online correction when reaching for objects and may also have reduced coordination of some finger movements that are important for subsequent grasping and object manipulation. Future studies with larger sample sizes are warranted to confirm these findings.


Subject(s)
Motor Skills Disorders , Psychomotor Performance , Child , Humans , Pilot Projects , Biomechanical Phenomena , Movement , Rotation
11.
BMC Psychiatry ; 23(1): 807, 2023 11 07.
Article in English | MEDLINE | ID: mdl-37936136

ABSTRACT

BACKGROUND: Previous works reported people with schizophrenia experienced inferior hand functions which influence their daily participation and work efficiency. Sensorimotor capability is one of indispensable elements acting in a well-executed feed-forward and feedback control loop to contribute to hand performances. However, rare studies investigated contribution of sensorimotor ability to hand functions for people with schizophrenia. This study aimed to explore hand function in people with schizophrenia based on the perspective of the sensorimotor control capabilities of the hands. METHODS: Twenty-seven people at the chronic stage of schizophrenia were enrolled. The following assessment tools were used: the Purdue Pegboard Test (PPT) and the VALPAR Component Work Sample-8 (VCWS 8) system for hand function; the Self-Reported Graphic version of the Personal and Social Performance (SRG-PSP) scale for functionality; and the Semmes-Weinstein Monofilaments (SWM), the pinch-holding-up-activity (PHUA) test and the Manual Tactile Test (MTT) for the sensory and sensorimotor parameters. The Clinical Global Impression-Severity (CGI-S) scale and the Extrapyramidal Symptom Rating Scale (ESRS) were used to grade the severity of the illness and the side-effects of the drugs. Spearman's rank correlation coefficient was used to analyze associations among hand function, functionality, and sensorimotor capabilities. A multiple linear regression analysis was used to identify the determinants of hand function. RESULTS: The results indicated that both hand function and sensorimotor capability were worse in people with schizophrenia than in healthy people, with the exception of the sensory threshold measured with the SWM. Moreover, the sensorimotor abilities of the hands were associated with hand function. The results of the regression analysis showed that the MTT measure of stereognosis was a determinant of the PPT measure of the dominant hand function and of the performance on the VCWS 8, and that the ESRS and the MTT measure of barognosis were determinants of the performance on the assembly task of the PPT. CONCLUSIONS: The findings suggested that sensorimotor capabilities, especially stereognosis and barognosis, are crucial determinants of hand function in people with schizophrenia. The results also revealed that the side effects of drugs and the duration of the illness directly affect hand function. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov , identifier NCT04941677, 28/06/2021.


Subject(s)
Schizophrenia , Humans , Hand , Pinch Strength , Self Report
12.
ACS Synth Biol ; 12(12): 3743-3753, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37991716

ABSTRACT

Soil microbial communities with reduced complexity are emerging as model systems for studying consortia-scale phenotypes. To establish synthetic biology tools for studying these communities in hard-to-image environmental materials, we evaluated whether a single member of a model soil consortium (MSC) can be programmed to report on gene expression without requiring matrix disruption. For these studies, we targeted a five-membered MSC that includes Dyadobacter fermentans, Ensifer adhaerens, Rhodococcus sp003130705, Streptomyces sp001905665, and Variovorax beijingensis. By coupling the expression of a methyl halide transferase to a constitutive promoter, we show that V. beijingensis can be programmed to synthesize methyl halides that accumulate in the soil headspace at levels that are ≥24-fold higher than all other MSC members across a range of environmentally relevant hydration conditions. We find that methyl halide production can report on an MSC promoter that is activated by changes in water potential, and we demonstrate that a synthetic gas signal can be read out directly using gas chromatography and indirectly using a soil-derived Methylorubrum that is programmed to produce a visual output in response to methyl halides. These tools will be useful for future studies that investigate how MSC responds to dynamic hydration conditions, such as drought and flood events induced by climate change, which can alter soil water potential and induce the release of stored carbon.


Subject(s)
Hydrocarbons, Brominated , Soil , Soil/chemistry , Water , Signal Transduction
13.
ACS Appl Mater Interfaces ; 15(48): 55244-55257, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37991845

ABSTRACT

In this study, we investigated a novel approach to fabricate multifunctional ionic gel sensors by using deep eutectic solvents (DESs) as replacements for water. When two distinct DESs were combined, customizable mechanical and conductive properties were created, resulting in improved performance compared with traditional hydrogel-based strain sensors. DES ionic gels possess superior mechanical properties, transparency, biocompatibility, and antimicrobial properties, making them suitable for a wide range of applications such as flexible electronics, soft robotics, and healthcare. We conducted a comprehensive evaluation of the DES ionic gels, evaluating their performance under extreme temperature conditions (-70 to 80 °C), impressive optical transparency (94%), and biocompatibility. Furthermore, a series of tests were conducted to evaluate the antibacterial performance (Escherichia coli) of the DES ionic gels. Their wide strain (1-400%) and temperature (15-50 °C)-sensing ranges demonstrate the versatility and adaptability of DES ionic gels for diverse sensing requirements. The resulting DES ionic gels were successfully applied in human activity and vital sign monitoring, demonstrating their potential for biointegrated sensing devices and healthcare applications. This study offers valuable insights into the development and optimization of hydrogel sensors, particularly for applications that require environmental stability, biocompatibility, and antibacterial performance, thereby paving the way for future advancements in this field.


Subject(s)
Anti-Bacterial Agents , Deep Eutectic Solvents , Humans , Solvents , Anti-Bacterial Agents/pharmacology , Hydrogels/pharmacology , Water , Escherichia coli , Ions
14.
J Allergy Clin Immunol Glob ; 2(4): 100161, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37781666

ABSTRACT

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD). Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas. Methods: This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma. Results: Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, -0.021; 95% CI, -0.031 to -0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005). Conclusions: Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

15.
JACS Au ; 3(10): 2918-2929, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37885593

ABSTRACT

The 18 kDa translocator protein (TSPO) has gained considerable attention as a clinical biomarker for neuroinflammation and a potential therapeutic target. However, the mechanisms by which TSPO associates with ligands, particularly the endogenous porphyrin ligand protoporphyrin IX (PpIX), remain poorly understood. In this study, we employed mutagenesis- and spectroscopy-based functional assays to investigate TSPO-mediated photo-oxidative degradation of PpIX and identify key residues involved in the reaction. We provide structural evidence using electron spin resonance, which sheds light on the highly conserved intracellular loop (LP1) connecting transmembrane 1 (TM1) and TM2. Our findings show that LP1 does not act as a lid to regulate ligand binding; instead, it interacts strongly with the TM3-TM4 linker (LP3) to stabilize the local structure of LP3. This LP1-LP3 interaction is crucial for maintaining the binding pocket structure, which is essential for proper ligand binding. Our results also demonstrate that PpIX accesses the pocket through the lipid bilayer without requiring conformational changes in TSPO. This study provides an improved understanding of TSPO-mediated PpIX degradation, highlighting potential therapeutic strategies to regulate the reaction.

16.
ACS Nano ; 17(14): 13158-13175, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37436002

ABSTRACT

Tumour hypoxia plays an important role in modulating tumorigenesis, angiogenesis, invasion, immunosuppression, resistance to treatment, and even maintenance of the stemness of cancer stem cells (CSCs). Moreover, the targeting and treatment of hypoxic cancer cells and CSCs to reduce the influence of tumor hypoxia on cancer therapy remains an imperative clinical problem that needs to be addressed. Since cancer cells upregulate the expression of glucose transporter 1 (GLUT1) through the Warburg effect, we considered the possibility of GLUT1-mediated transcytosis in cancer cells and developed a tumor hypoxia-targeting nanomedicine. Our experimental results indicate that glucosamine-labeled liposomal ceramide can be efficiently transported between cancer cells by GLUT1 transporters and substantially accumulated in the hypoxic area in in vitro CSC spheroids and in vivo tumor xenografts. We also verified the effects of exogenous ceramide on tumor hypoxia, including important bioactivities such as upregulation of p53 and retinoblastoma protein (RB), downregulation of hypoxia-inducible factor-1 alpha (HIF-1α) expression, disruption of the OCT4-SOX2 network of stemness, and inhibition of CD47 and PD-L1 expression. To achieve an ideal therapeutic outcome, we combined treatment of glucosamine-labeled liposomal ceramide with paclitaxel and carboplatin, and we found an excellent synergistic effect, with tumor clearance being noted in three-fourths of the mice. Overall, our findings provide a potential therapeutic strategy for the treatment of cancer.


Subject(s)
Hypoxia , Neoplasms , Humans , Mice , Animals , Glucose Transporter Type 1/metabolism , Hypoxia/metabolism , Cell Hypoxia , Liposomes/pharmacology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Transcytosis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Cell Line, Tumor , Neoplasms/pathology
17.
Sports Biomech ; : 1-16, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37458569

ABSTRACT

This study aimed to investigate the hamstring onset time and recruitment level during jumping tasks in athletes with chronic hamstring strain injuries. Thirteen hamstring injured athletes and thirteen matched healthy athletes were recruited. Activation onset time and muscle recruitment (median frequency of the EMG) of the lateral hamstring (LH) and medial hamstring (MH) was measured during double leg jumps in vertical and horizontal directions on the force platforms. The peak vertical ground reaction force and loading rate were obtained for all jumps. The injured group showed a delayed onset time (p = 0.029) and a lower recruitment of the LH during the landing (p = 0.018) than the control group. Activation deficits in the injured group led to a higher landing force and loading rate. Additionally, the LH and MH were lesser recruited in the vertical direction than the horizontal directions in the landing. In conclusion, athletes with hamstring injuries show hamstring activation deficits of the injured leg during jumping leading to degrading jump-landing performance. Also, jumping in different directions play a role to modify the recruitment of the hamstrings in the injured athletes. Therefore, movement plane is suggested to be considered in clinical rehabilitation for the hamstring injury.

18.
Sports Biomech ; : 1-19, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37272087

ABSTRACT

It is unclear how hamstring stiffness influences lower limb muscle activation during jump-landing mechanics. The study aimed to investigate the role of the hamstring stiffness on lower limb muscle recruitment during jumping manoeuvres. Thirty male athletes were recruited and allocated into high- and low-stiffness groups. Hamstring stiffness was determined as the average stiffness of bilateral hamstrings using a MyotonPRO. Surface electromyography of the bilateral gluteus maximus, quadriceps, and hamstring muscles was assessed during the takeoff, at ground contact, and at landing, while ground reaction force (GRF) was measured during the squat jump, countermovement jump, and drop vertical jump. The results showed that athletes with greater hamstring stiffness exhibited a higher median frequency of the lateral hamstrings in both limbs and the vastus medialis in the dominant limb than the low-stiffness group during takeoff, adjustment, and landing phases for all vertical jumps. The high stiffness group landed with lower vertical GRF in the drop vertical jump. In conclusion, athletes with high hamstring stiffness showed greater motor unit recruitment during takeoff and landing phases. This recruitment did not influence takeoff performance but aid with absorbing landing force. Therefore, the contribution of the lower limb muscle stiffness should be considered in sports activities.

19.
J Sleep Res ; 32(5): e13918, 2023 10.
Article in English | MEDLINE | ID: mdl-37128654

ABSTRACT

Sleep quality and depression during pregnancy often affect women's adaptation to motherhood and are linked with adverse maternal and neonatal outcomes. Using a prospective cohort study comprising 190 pregnant women in central Taiwan, we investigated the trajectories of sleep quality and depressive symptoms and their associated predictors in perinatal women from pregnancy to postpartum. Sleep and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index and the Edinburgh Postnatal Depression Scale, respectively, from mid-pregnancy to 3 months postpartum. We used group-based trajectory modelling and logistic regression modelling to analyse the data collected from the structured questionnaires. Pregnant women (50.5% primipara) with a mean (standard deviation) age of 32.3 (4.1) years were included. We identified three distinctive classes of sleep quality trajectories during the perinatal period: 'stable good' (18.4%), 'increasing poor' (48.9%), and 'stable poor' (32.6%). We further detected three stable trajectories of depressive symptoms: 'stable low' (36.3%), 'stable mild' (42.1%), and 'stable high' (21.6%). A significant association between sleep quality and depression trajectories was evident (p < 0.001). High fatigue symptoms and low social support predicted the high trajectories of poor sleep and depressive symptoms. Distinctive dynamic sleep quality and stable depression trajectories were characterised. Our findings revealed that both the sleep and depression trajectories were closely associated with one another, with common predictors of fatigue symptoms and social support. The early assessment of maternal sleep and depression status is important for identifying at-risk women and initiating interventions tailored to perinatal women to improve their sleep and mental health.


Subject(s)
Depression, Postpartum , Pregnancy Complications , Infant, Newborn , Female , Pregnancy , Humans , Adult , Depression/psychology , Depression, Postpartum/diagnosis , Sleep Quality , Prospective Studies , Pregnancy Complications/epidemiology , Pregnancy Complications/diagnosis , Postpartum Period/psychology , Fatigue/epidemiology , Fatigue/etiology , Risk Factors
20.
Sci Rep ; 13(1): 6381, 2023 04 19.
Article in English | MEDLINE | ID: mdl-37076662

ABSTRACT

Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated. We aimed to compare the clinical features between nonallergic and allergic childhood asthma and apply microRNA to explore the underlying mechanism of nonallergic childhood asthma. We enrolled 405 asthmatic children (76 nonallergic, 52 allergic with total IgE < 150 IU/mL and 277 allergic with total IgE > 150 IU/mL). Clinical characteristics were compared between groups. Comprehensive miRNA sequencing (RNA-seq) was performed using peripheral blood from 11 nonallergic and 11 allergic patients with elevated IgE, respectively. Differentially expressed miRNA (DEmiRNA) were determined with DESeq2. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed to determine functional pathways involved. Publicly available mRNA expression data was applied to investigate the predicted target mRNA networks via Ingenuity Pathway Analysis (IPA). The average age of nonallergic asthma was significantly younger (5.614 ± 2.743 vs 6.676 ± 3.118 years-old). Higher severity and worse control were more common in nonallergic asthma (two-way ANOVA, P < 0.0001). Long-term severity was higher, and intermittent attacks persisted in nonallergic patients. We identified 140 top DEmiRNAs based on false discovery rate (FDR) q-value < 0.001. Forty predicted target mRNA gene were associated with nonallergic asthma. The enriched pathway based on GO included Wnt signaling pathway. IgE expression was predicted to be downregulated by a network involving simultaneous interaction with IL-4, activation of IL-10 and inhibition of FCER2. Nonallergic childhood asthma were distinct in their younger age, higher long-term severity and more persistent course. Differentially expressed miRNA signatures associate with downregulation of total IgE expression and predicted target mRNA genes related molecular networks contribute to canonical pathways of nonallergic childhood asthma. We demonstrated the negative role of miRNAs involved in regulating IgE expression indicating differences between asthma phenotypes. Identification of biomarkers of miRNAs could contribute to understand the molecular mechanism of endotypes in nonallergic childhood asthma, which can potentially allow delivery of precision medicine to pediatric asthma.


Subject(s)
Asthma , Hypersensitivity , MicroRNAs , Humans , Child , MicroRNAs/genetics , Asthma/complications , Hypersensitivity/complications , Blood Cells , Immunoglobulin E
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