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1.
Scand J Immunol ; 100(2): e13390, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38769661

ABSTRACT

Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.g. diabetes), autoimmune diseases, nervous system-related diseases, digestive system-related diseases, and even tumours. Aldo-keto reductase 1B10 (AKR1B10) is an important player in the development and progression of multiple diseases, such as tumours and inflammatory diseases. AKR1B10 is upregulated in solid tumours, such as hepatocellular carcinoma (HCC), non-small cell lung carcinoma, and breast cancer, and is a reliable serum marker. However, information on the role of AKR1B10 in inflammation is limited. In this study, we summarized the role of AKR1B10 in inflammatory diseases, including its expression, functional contribution to inflammatory responses, and regulation of signalling pathways related to inflammation. We also discussed the role of AKR1B10 in glucose and lipid metabolism and oxidative stress. This study provides novel information and increases the understanding of clinical inflammatory diseases.


Subject(s)
Aldo-Keto Reductases , Inflammation , Humans , Inflammation/immunology , Aldo-Keto Reductases/metabolism , Animals , Oxidative Stress , Signal Transduction , Lipid Metabolism , Glucose/metabolism
2.
Int J Mol Sci ; 25(16)2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39201313

ABSTRACT

This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases.


Subject(s)
Mitochondria , Oxidative Stress , Retinal Ganglion Cells , Humans , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Mitochondria/metabolism , Animals , Reactive Oxygen Species/metabolism , Glaucoma/metabolism , Glaucoma/pathology
3.
Aging Ment Health ; 27(8): 1627-1635, 2023.
Article in English | MEDLINE | ID: mdl-36724006

ABSTRACT

OBJECTIVE: The present study explores how and when lifetime discriminatory experience moderates the mediation effect of early life adversities and social activity on loneliness among older European adults over eight years. METHOD: The study analyzed 13,699 respondents aged 50 years and over who were interviewed in 2009 and re-interviewed in 2017 in the European Survey of Health, Ageing, Retirement. Conditional process analysis using the PROCESS model 15 was applied to examine the moderated mediation effect of lifetime discriminatory experience in 2009 (W) on early life adversities in 2009 (X) and social activity at 2017 (M) to loneliness in 2017 (Y). RESULTS: Our moderated mediation models found that early life adversities (X) are associated with loneliness (Y) (Coeff X→Y=-0.0501, p<.001), but social activity (M) reduces its effect on loneliness (Y) (Coeff X→M→Y=-1.6391, p<.001). However, lifetime discriminatory experience (W) hampers social activity (Coeff M*W→Y = 0.0955, p<.05) and increases loneliness (Coeff X*M→Y = 0.6069, p<.05). CONCLUSION: Older adults experiencing early life adversities may not necessarily develop later life loneliness. However, lifetime discriminatory experience due to political beliefs, religion, ethnicity, sexual orientation/background etc. may reverse the positive effect of social engagement on the relationship between early life adversities and loneliness. Early interventions should address discrimination and social inequalities and increase social participation across the life course to prevent the development of later-life loneliness among older adults.


Subject(s)
Loneliness , Mediation Analysis , Humans , Male , Female , Middle Aged , Aged , Aging , Europe , Social Discrimination
4.
J Biol Chem ; 295(41): 13965-13980, 2020 10 09.
Article in English | MEDLINE | ID: mdl-32763976

ABSTRACT

In addition to acting as a transcriptional co-activator, YAP1 directly mediates translocalization of the pro-oncogenic phosphatase SHP2 from the cytoplasm to nucleus. In the cytoplasm, SHP2 potentiates RAS-ERK signaling, which promotes cell proliferation and cell motility, whereas in the nucleus, it mediates gene regulation. As a result, elucidating the details of SHP2 trafficking is important for understanding its biological roles, including in cancer. YAP1 comprises multiple splicing isoforms defined in part by the presence (as in YAP1-2γ) or absence (as in YAP1-2α) of a γ-segment encoded by exon 6 that disrupts a critical leucine zipper. Although the disruptive segment is known to reduce co-activator function, it is unclear how this element impacts the physical and functional relationships between YAP1 and SHP2. To explore this question, we first demonstrated that YAP1-2γ cannot bind SHP2. Nevertheless, YAP1-2γ exhibits stronger mitogenic and motogenic activities than does YAP1-2α because the YAP1-2α-mediated delivery of SHP2 to the nucleus weakens cytoplasmic RAS-ERK signaling. However, YAP1-2γ confers less in vivo tumorigenicity than does YA1-2α by recruiting tumor-inhibitory macrophages. Mechanistically, YAP1-2γ transactivates and the YAP1-2α-SHP2 complex transrepresses the monocyte/macrophage chemoattractant CCL2 Thus, cell-intrinsic and cell-extrinsic pro-oncogenic YAP1 activities are inversely regulated by alternative splicing of exon 6. Notably, oncogenic KRAS down-regulates the SRSF3 splicing factor that prevents exon 6 skipping, thereby creating a YAP1-2α-dominant situation that supports a "cold" immune microenvironment.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Alternative Splicing , Carcinogenesis/metabolism , Cell Cycle Proteins/metabolism , Oncogene Proteins/metabolism , Signal Transduction , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Cycle Proteins/genetics , Humans , Mice , NIH 3T3 Cells , Oncogene Proteins/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism , Transcription Factors/genetics , YAP-Signaling Proteins
5.
Org Biomol Chem ; 19(39): 8507-8515, 2021 10 14.
Article in English | MEDLINE | ID: mdl-34542126

ABSTRACT

Quinoliziniums, cationic aromatic heterocycles bearing a quaternary bridgehead nitrogen, have been widely used as fluorescent dyes, DNA intercalators, ionic liquids etc. A library of new quinolizinium compounds was synthesized from quinolines and internal alkyne substrates in up to 65% isolated yields. Systematic studies of their photophysical properties were conducted. The quinoliziniums have been used in three visible-light-induced photocatalysis reactions with good yields.


Subject(s)
Intercalating Agents
6.
Fa Yi Xue Za Zhi ; 30(2): 122-5, 2014 Apr.
Article in Zh | MEDLINE | ID: mdl-25073321

ABSTRACT

Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown etiology, found mostly in central or northwestern mountain area (with altitude between 1,815 and 2,225 meters) of Yunnan province from June to September every year. It occurs mostly in young female adults, with high incidences in Lisu, Yi and Miao ethnics and high familial aggregation. The clinical manifestation of YSDS is changeful and the pathological characteristic is lack of specificity. The pathogenesis may be attributed to several factors including poor hygiene and lower socioeconomic conditions, lack of Selenium or Chromium, infection of Coxsackie B virus, mushroom consumption and special geological conditions. This article reviews the epidemiologic features, clinical manifestations, pathological features, etiology and hypothesis in order to provide clues for the research of YSDS.


Subject(s)
Death, Sudden , Adult , China , Death, Sudden/epidemiology , Death, Sudden/etiology , Death, Sudden/pathology , Female , Humans , Syndrome
7.
Trials ; 25(1): 251, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605374

ABSTRACT

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.


Subject(s)
Anterior Cruciate Ligament Reconstruction , Quadriceps Muscle , Humans , Anterior Cruciate Ligament Reconstruction/adverse effects , Anterior Cruciate Ligament Reconstruction/methods , Knee Joint/diagnostic imaging , Knee Joint/surgery , Muscle Strength , Randomized Controlled Trials as Topic , Vitamin D , Vitamins , Adolescent , Young Adult , Adult , Middle Aged
8.
Int J Med Robot ; 20(3): e2655, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38922786

ABSTRACT

BACKGROUND: Up to 20% of patients remain unsatisfied after total knee arthroplasty (TKA), prompting the development of new implants. Bi-Cruciate Retaining (BCR) TKA preserves both the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL), with the ACL beneficial for its proprioceptive qualities. The Bi-Cruciate Stabilised (BCS) TKA substitutes the ACL and PCL with a unique dual cam-post mechanism. Robotics improve accuracy and facilitate technically demanding TKA. METHODS: This was a retrospective case-control study recruited from two centres. Measured outcomes included kinematic analysis, proprioception, and functional outcomes. RESULTS: There was a significantly larger maximum flexion angle and range of flexion to extension in sit-to-stand and stairs in BCR when compared to BCS. Further analysis revealed more similarities between BCR and normal native knees. Proprioception and functional scores did not have any statistical difference. CONCLUSION: BCR TKA demonstrated better knee flexion in weight-bearing active range of motion and showed similarities with normal knee kinematics.


Subject(s)
Anterior Cruciate Ligament , Arthroplasty, Replacement, Knee , Knee Joint , Posterior Cruciate Ligament , Range of Motion, Articular , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Knee/methods , Robotic Surgical Procedures/methods , Biomechanical Phenomena , Male , Female , Retrospective Studies , Middle Aged , Aged , Posterior Cruciate Ligament/surgery , Case-Control Studies , Knee Joint/surgery , Knee Joint/physiopathology , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament/physiopathology , Knee Prosthesis , Treatment Outcome , Proprioception
9.
Front Cell Dev Biol ; 12: 1406830, 2024.
Article in English | MEDLINE | ID: mdl-38946798

ABSTRACT

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

10.
BMJ Nutr Prev Health ; 6(1): 21-27, 2023.
Article in English | MEDLINE | ID: mdl-37559968

ABSTRACT

Objectives: Even though disinfectants are commonly used in clinical practice and daily life, there are few studies on their antibacterial ability and cytotoxicity, which are closely related to the safety and effectiveness of their use. To provide a basis for the use of disinfectants, the cytotoxicity and antibacterial activity of three most commonly used disinfectants, povidone-iodine, chlorhexidine acetate and polyhexamethylene biguanide (PHMB), were investigated. Design: A CCK-8 assay was used to measure the activities of human fibroblasts (HF) and keratinocytes (HaCat), the two most important cells in wound healing, following their exposure to disinfectants. The effects of different times and concentrations were included. The antibacterial activity of disinfectants against Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae was reflected by their minimum inhibitory concentration and minimum bactericidal concentration. Results: All three disinfectants showed strong cytotoxicity in direct contact with HF and HaCat cells. Cytotoxicity increased with increasing exposure time and concentration. S. aureus, A. baumannii and K. pneumoniae comprised 70%, 55% and 85% of the strains sensitive to povidone iodine; 50%, 45% and 80% of the strains sensitive to chlorhexidine acetate; and 60%, 45% and 80% of the strains sensitive to PHMB, respectively. Conclusions: All three disinfectants were cytotoxic; therefore, it is necessary to pay attention to the use time and concentration in the clinical setting. All three disinfectants were cytotoxic, with povidone-iodine being the most cytotoxic even at low concentrations. PHMB had better antibacterial efficacy against S. aureus and is suitable for the treatment of shallow wounds primarily. All three tested bacteria were significantly more sensitive to PHMB than to the other disinfectants.

11.
Medicine (Baltimore) ; 102(15): e33502, 2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37058074

ABSTRACT

To investigate the clinical phenotype-genotype correlations of a family with Kennedy disease (KD) and improve our understanding of the disease. KD was confirmed after clinical phenotypic analyses, laboratory tests, polymerase chain reaction assays for cytosine-adenine-guanine (CAG) repeats, and neuro-electrophysiological tests. The disease was assessed using the KD1234 scale and the spinal and bulbar muscular atrophy functional rating scale. The average age of disease onset was 30.8 ± 2.85 years. Clinically diagnosed members had 48 CAG repeats (≥35 is abnormal) in the androgen receptor gene. The patients exhibited gynecomastia and testicular dysfunction. The lesions mainly involved the medulla oblongata and spinal cord. Progesterone and serum creatine kinase levels were significantly high. Electromyography showed chronic neurogenic damage and abnormal sensory and motor conduction in family members who did not participate in sports, exercise, or physical hobbies. Our study showed that this family had a stable inheritance of CAG repeats, and the genotype was consistent with the clinical phenotype. Gynecomastia was the first symptom, with progressive androgen resistance resulting in testicular atrophy, infertility, and sexual dysfunction. Changes in serum creatine kinase may indicate the progression or relief of symptoms, and rehabilitation may delay the progression of muscle atrophy.


Subject(s)
Bulbo-Spinal Atrophy, X-Linked , Gynecomastia , Muscular Atrophy, Spinal , Humans , Male , Bulbo-Spinal Atrophy, X-Linked/genetics , Bulbo-Spinal Atrophy, X-Linked/diagnosis , Genotype , Phenotype , Muscular Atrophy , Creatine Kinase , Receptors, Androgen/genetics , Muscular Atrophy, Spinal/genetics
12.
MedComm (2020) ; 4(2): e207, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36818016

ABSTRACT

Anti-obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti-obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti-obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high-fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet-induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.

13.
Nat Commun ; 14(1): 2241, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37193694

ABSTRACT

The "death cap", Amanita phalloides, is the world's most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.


Subject(s)
Hexosyltransferases , Mycotoxins , Humans , Male , Animals , Mice , Alpha-Amanitin/pharmacology , Indocyanine Green/pharmacology , Antidotes , Amanita , Membrane Proteins
14.
Neurosignals ; 20(4): 237-51, 2012.
Article in English | MEDLINE | ID: mdl-23172129

ABSTRACT

Nuclear factor of activated T cells 5 (NFAT5) has been implicated in regulating several genes that are thought to be neuroprotective in ischemic injury. Because of the embryonic lethality of NFAT5 knockout (NFAT5(-/-)) mice, the heterozygous (NFAT5(+/-)) mice were used to study the in vivo role of NFAT5 in hypoxia/ischemia (H/I) condition. The NFAT5(+/-) mice exhibited more severe neurological deficits, larger infarct area and edema formation associated with increased aquaporin 4 expressions in the brain. Under in vitro H/I condition, increased apoptotic cell death was found in NFAT5(-/-) neurons. Moreover, SMIT, a downstream to NFAT5, was upregulated in NFAT5(+/+) neurons, while the SMIT level could not be upregulated in NFAT5(-/-) neurons under H/I condition. The elevation of reactive oxygen species generation in NFAT5(-/-) neurons under H/I condition further confirmed that NFAT5(-/-) neurons were more susceptible to oxidative stress. The present study demonstrated that activation of NFAT5 and its downstream SMIT induction is important in protecting neurons from ischemia-induced oxidative stress.


Subject(s)
Brain Ischemia/genetics , Brain Ischemia/pathology , Cell Death/genetics , Cell Death/physiology , Neurons/pathology , Transcription Factors/deficiency , Animals , Blood-Brain Barrier/physiology , Blotting, Western , Cells, Cultured , Hypertonic Solutions , Immunohistochemistry , In Situ Nick-End Labeling , Infarction, Middle Cerebral Artery/pathology , Ischemic Attack, Transient/pathology , L-Lactate Dehydrogenase/metabolism , Luciferases/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Osmotic Pressure , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction , Symporters/biosynthesis , Symporters/genetics , Transcription Factors/genetics , Transcription Factors/physiology
15.
Comput Intell Neurosci ; 2022: 2440263, 2022.
Article in English | MEDLINE | ID: mdl-35694572

ABSTRACT

With the vigorous development of higher education in China, many universities have made great progress in various indicators in recent years. As the number of college students increases year by year, the effect of instruction in the classroom is especially important. The high quality of teaching directly affects the efficiency of students' listening to lectures, and more and more universities are receiving attention. However, the traditional dance classroom education and the one-to-many education model cannot adapt to the development trend of higher art education under the changes of the times and cannot effectively guarantee the quality of classroom education. The development of wireless sensor networks provides practical and feasible technical solutions for the development of dance education systems. Compared with general detection methods, image sensors can provide more real-time and more intuitive on-site information and wirelessly send image information to user terminals. This article describes the classic feature extraction algorithm and proposes a new feature extraction algorithm based on chart filling. The effectiveness of each algorithm is verified through several data sets. Image recognition is carried out by computer, including from computer to image processing, through the computer to recognize objects and various different modes of the target technology. The identification process usually includes several steps. First, the preprocessing of the image is required, then the segmentation of the image is performed, and then the feature extraction and matching are performed. In layman's terms, image recognition hopes to imitate the human heart to read photos. By applying the image recognition technology to the dance education system, changes in the methods and forms of dance education can be stimulated.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , China , Humans , Image Processing, Computer-Assisted/methods , Students , Teaching , Universities
16.
J Hazard Mater ; 440: 129698, 2022 10 15.
Article in English | MEDLINE | ID: mdl-35952428

ABSTRACT

The health concerns of microplastics (MPs) and nanoplastics (NPs) surge, but the key indicators to evaluate the adverse risks of MPs/NPs are elusive. Recently, MPs/Ps were found to disturb glucose and lipid metabolism in rodents, suggesting that MPs/NPs may play a role in obesity progression. In this study, we firstly demonstrated that the distribution of fluorescent polystyrene nanoplastics (nPS, 60 nm) white adipose tissue (WAT) of mice. Furthermore, nPS could traffic across adipocytes in vitro and reduced lipolysis under ß-adrenergic stimulation in adipocytes in vitro and ex vivo. Consistently, chronic oral exposure to nPS at the dietary exposure relevant concentrations (3 and 223 µg/kg body weight) impaired fasting-induced lipid mobilization in obese mice and subsequently contributed to larger adipocyte size in the subcutaneous WAT. In addition, the chronic exposure of nPS induced macrophage infiltration in the small intestine and increased lipid accumulation in the liver, accelerating the disruption of systemic metabolism. Collectively, our findings highlight the potential obesogenic role of nPS via diminishing lipid mobilization in WAT of obese mice and suggest that lipolysis relevant parameters may be used for evaluating the adverse effect of MPs/NPs in clinics.


Subject(s)
Diet, High-Fat , Lipolysis , Adipose Tissue , Adrenergic Agents , Animals , Dietary Exposure , Fasting , Glucose , Lipids , Mice , Mice, Obese , Microplastics/toxicity , Plastics , Polystyrenes/toxicity
17.
Trials ; 23(1): 771, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36096886

ABSTRACT

BACKGROUND: The ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient's successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention. DISCUSSION: This is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184023. Registered on 5 January 2022.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Adult , Anterior Cruciate Ligament Injuries/diagnosis , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/adverse effects , Anterior Cruciate Ligament Reconstruction/methods , Electromagnetic Fields , Humans , Muscle Strength/physiology , Quadriceps Muscle/physiology
18.
J Neuroinflammation ; 8: 108, 2011 Aug 29.
Article in English | MEDLINE | ID: mdl-21871134

ABSTRACT

BACKGROUND AND PURPOSE: Oligodendrocyte (OL) death is important in focal cerebral ischemia. TIMP-3 promotes apoptosis in ischemic neurons by inhibiting proteolysis of TNF-α superfamily of death receptors. Since OLs undergo apoptosis during ischemia, we hypothesized that TIMP-3 contributes to OL death. METHODS: Middle cerebral artery occlusion (MCAO) was induced in Timp-3 knockout (KO) and wild type (WT) mice with 24 or 72 h of reperfusion. Cell death in white matter was investigated by stereology and TUNEL. Mature or immature OLs were identified using antibodies against glutathione S-transferase-π (GST-π) and galactocerebroside (GalC), respectively. Expression and level of proteins were examined using immunohistochemistry and immunoblotting. Protein activities were determined using a FRET peptide. RESULTS: Loss of OL-like cells was detected at 72 h only in WT ischemic white matter where TUNEL showed greater cell death. TIMP-3 expression was increased in WT reactive astrocytes. GST-π was reduced in ischemic white matter of WT mice compared with WT shams with no difference between KO and WT at 72 h. GalC level was significantly increased in both KO and WT ischemic white matter at 72 h. However, the increase in GalC in KO mice was significantly higher than WT; most TUNEL-positive cells in ischemic white matter expressed GalC, suggesting TIMP-3 deficiency protects the immature OLs from apoptosis. There were significantly higher levels of cleaved caspase-3 at 72 h in WT white matter than in KO. Greater expression of MMP-3 and -9 was seen in reactive astrocytes and/or microglia/macrophages in WT at 72 h. We found more microglia/macrophages in WT than in KO, which were the predominant source of increased TNF-α detected in the ischemic white matter. TACE activity was significantly increased in ischemic WT white matter, which was expressed in active microglia/macrophages and OLs. CONCLUSIONS: Our results suggested that focal ischemia leads to proliferation of immature OLs in white matter and that TIMP-3 contributes to a caspase-3-dependent immature OL death via TNF-α-mediated neuroinflammation. Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type.


Subject(s)
ADAM Proteins/metabolism , Brain Ischemia/physiopathology , Cell Death/physiology , Oligodendroglia/physiology , Tissue Inhibitor of Metalloproteinase-3/metabolism , Tumor Necrosis Factor-alpha/metabolism , ADAM17 Protein , Animals , Brain/cytology , Brain/metabolism , Brain/pathology , Brain Ischemia/pathology , Caspase 3/metabolism , Fluorescence Resonance Energy Transfer , In Situ Nick-End Labeling , Infarction, Middle Cerebral Artery/metabolism , Male , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Knockout , Oligodendroglia/cytology , Oligodendroglia/pathology , Tissue Inhibitor of Metalloproteinase-3/genetics
19.
Burns ; 47(3): 634-642, 2021 05.
Article in English | MEDLINE | ID: mdl-33402311

ABSTRACT

INTRODUCTION: Allogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen. STUDY DESIGN: Prospective self-controlled trial. OBJECTIVE: To evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin. METHODS: This study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing. RESULTS: There were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH. CONCLUSION: During the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.


Subject(s)
Bandages, Hydrocolloid/standards , Burns/therapy , Collagen/pharmacology , Adolescent , Adult , Bandages, Hydrocolloid/statistics & numerical data , China , Female , Humans , Male , Middle Aged , Prospective Studies
20.
RSC Adv ; 11(53): 33294-33299, 2021 Oct 08.
Article in English | MEDLINE | ID: mdl-35497514

ABSTRACT

A novel fluorescent quinolizinium-based turn-off probe has been developed for selective detection of cysteine. The probe showed high selectivity and sensitivity towards cysteine over other amino acids including the similarly structured homocysteine and glutathione with a detection limit of 0.18 µM (S/N = 3). It was successfully applied to cysteine detection in living cells with low cytotoxicity and quantitative analysis of spiked mouse serum samples with moderate to good recovery (96-109%).

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