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1.
Clin Immunol ; 264: 110255, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38763433

RESUMO

Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

3.
Commun Biol ; 7(1): 16, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177279

RESUMO

In mammals, females undergo reproductive cessation with age, whereas male fertility gradually declines but persists almost throughout life. However, the detailed effects of ageing on germ cells during and after spermatogenesis, in the testis and epididymis, respectively, remain unclear. Here we comprehensively examined the in vivo male fertility and the overall organization of the testis and epididymis with age, focusing on spermatogenesis, and sperm function and fertility, in mice. We first found that in vivo male fertility decreased with age, which is independent of mating behaviors and testosterone levels. Second, overall sperm production in aged testes was decreased; about 20% of seminiferous tubules showed abnormalities such as germ cell depletion, sperm release failure, and perturbed germ cell associations, and the remaining 80% of tubules contained lower number of germ cells because of decreased proliferation of spermatogonia. Further, the spermatozoa in aged epididymides exhibited decreased total cell numbers, abnormal morphology/structure, decreased motility, and DNA damage, resulting in low fertilizing and developmental rates. We conclude that these multiple ageing effects on germ cells lead to decreased in vivo male fertility. Our present findings are useful to better understand the basic mechanism behind the ageing effect on male fertility in mammals including humans.


Assuntos
Epididimo , Testículo , Animais , Masculino , Camundongos , Envelhecimento , Fertilidade , Mamíferos , Sêmen , Espermatogônias
4.
J Neurosurg Spine ; 40(5): 642-652, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38277664

RESUMO

OBJECTIVE: This study aimed to investigate the effect of surgery within 8 hours on perioperative complications and neurological prognosis in older patients with cervical spinal cord injury by using a propensity score-matched analysis. METHODS: The authors included 87 consecutive patients older than 70 years who had cervical spinal cord injury and who had undergone posterior decompression and fusion surgery within 24 hours of injury. The patients were divided into two groups based on the time from injury to surgery: surgery within 8 hours (group 8 hours) and between 8 and 24 hours (group 8-24 hours). Following the preliminary study, the authors established a 1:1 matched model using propensity scores to adjust for baseline characteristics and neurological status on admission. Perioperative complication rates and neurological outcomes at discharge were compared between the two groups. RESULTS: Preliminary analysis of 87 prematched patients (39 in group 8 hours and 48 in group 8-24 hours) revealed that the motor index score (MIS) on admission was lower for lower extremities (12.3 ± 15.5 vs 20.0 ± 18.6, respectively; p = 0.048), and total extremities (26.7 ± 27.1 vs 40.2 ± 30.6, respectively; p = 0.035) in group 8 hours. In terms of perioperative complications, group 8 hours had significantly higher rates of cardiopulmonary dysfunction (46.2% vs 25.0%, respectively; p = 0.039). MIS improvement (the difference in scores between admission and discharge) was greater in group 8 hours for lower extremities (15.8 ± 12.6 vs 9.0 ± 10.5, respectively; p = 0.009) and total extremities (29.4 ± 21.7 vs 18.7 ± 17.7, respectively; p = 0.016). Using a 1:1 propensity score-matched analysis, 29 patient pairs from group 8 hours and group 8-24 hours were selected. There were no significant differences in baseline characteristics, neurological status on admission, and perioperative complications between the two groups, including cardiopulmonary dysfunction. Even after matching, MIS improvement was significantly greater in group 8 hours for upper extremities (13.0 ± 10.9 vs 7.8 ± 8.3, respectively; p = 0.045), lower extremities (14.8 ± 12.7 vs 8.3 ± 11.0, respectively; p = 0.044) and total extremities (27.8 ± 21.0 vs 16.0 ± 17.5, respectively; p = 0.026). CONCLUSIONS: Results of the comparison after matching demonstrated that urgent surgery within 8 hours did not increase the perioperative complication rate and significantly improved the MIS, suggesting that surgery within 8 hours may be efficient, even in older patients.


Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Complicações Pós-Operatórias , Pontuação de Propensão , Traumatismos da Medula Espinal , Humanos , Masculino , Feminino , Idoso , Traumatismos da Medula Espinal/cirurgia , Descompressão Cirúrgica/métodos , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Vértebras Cervicais/cirurgia , Idoso de 80 Anos ou mais , Fatores de Tempo , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos , Tempo para o Tratamento
5.
Intern Med ; 63(1): 93-96, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37197960

RESUMO

A 62-year-old male was transferred to our hospital complaining of palpitations. His heart rate was 185/min. Electrocardiogram showed a narrow QRS regular tachycardia and the tachycardia changed spontaneously to another narrow QRS tachycardia with two alternating cycle lengths. The arrhythmia was stopped by the administration of adenosine triphosphate. Findings from electrophysiological study suggested that there was an accessory pathway (AP) and dual atrioventricular (AV) nodal pathways. After AP ablation, any other tachyarrythmias were not induced. We supposed that the tachycardia was paroxysmal supraventricular tachycardia involving AP and anterograde conduction alternating between slow and fast AV nodal pathways.


Assuntos
Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Taquicardia Ventricular , Masculino , Humanos , Pessoa de Meia-Idade , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Nó Atrioventricular/cirurgia , Eletrocardiografia
6.
iScience ; 26(12): 108456, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38077127

RESUMO

Male fertility decreases with aging, with spermatogenic decline being one of its causes. Altered testis environment is suggested as a cause of the phenotype; however, the associated mechanisms remain unclear. Herein, we investigated the age-related changes in testicular somatic cells on spermatogenic activity. The number and proliferation of spermatogonia significantly reduced with aging in mice. Interestingly, senescence-associated ß-galactosidase-positive cells appeared in testicular endothelial cell (EC) populations, but not in germ cell populations, with aging. Transcriptome analysis of ECs indicated that senescence occurred in the ECs of aged mice. Furthermore, the support capacity of ECs for spermatogonial proliferation significantly decreased with aging; however, the senolytic-induced removal of senescent cells from aged ECs restored their supporting capacity to a comparable level as that of young ECs. Our results suggest that the accumulation of senescent ECs in the testis is a potential factor contributing to the age-related decline in spermatogenic activity.

7.
J Reprod Dev ; 69(6): 328-336, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-37926520

RESUMO

Senescent cells play a detrimental role in age-associated pathogenesis by producing factors involved in senescence-associated secretory phenotype (SASP). The present study was conducted to examine the possibility that senescent cells are present in aged ovaries and, if so, to determine the tissue region where senescent cells accumulate using a mouse model. Female mice at 2-4 and 8-10 months were used as reproductively young and aged models, respectively; the latter included mice with and without reproductive experience. Cells positive for senescence-associated ß-galactosidase (SA-ß-Gal) staining, one of the markers of cellular senescence, were detected in the stromal region of aged, but not young, ovaries regardless of reproductive experience. Likewise, the localization of cells expressing CDKN2A (cyclin dependent kinase inhibitor 2A), another senescence marker, in the stromal region of aged ovaries was detected with immunohistochemistry. CDKN2A expression detected by western blotting was significantly higher in the ovaries of aged mice with reproductive experience than in those without the experience. Moreover, cells positive for both γH2AX (a senescence marker) and fluorescent SA-ß-Gal staining were present in those isolated from aged ovaries. In addition, the transcript levels of several SASP factors were significantly increased in aged ovaries. These results suggest that senescent cells accumulate in the ovarian stroma and may affect ovarian function in aged mice. Additionally, reproductive experience may promote accumulation.


Assuntos
Senescência Celular , Ovário , Feminino , Animais , Senescência Celular/genética , Imuno-Histoquímica , Células Cultivadas
8.
Artigo em Inglês | MEDLINE | ID: mdl-37793047

RESUMO

Central venous obstruction following pacemaker implantation is not uncommon and can prove challenging in the case of a system upgrade to a cardiac resynchronization therapy pacemaker (CRT-P). We describe the case of a patient who underwent a successful upgrading procedure of a pacemaker to a CRT-P in the presence of an occluded left subclavian vein and superior vena cava, using collateral veins that drained into right atrium.

9.
J Clin Med ; 12(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37685817

RESUMO

Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden.

10.
BMC Musculoskelet Disord ; 24(1): 724, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700275

RESUMO

BACKGROUND: There are few studies about sexual function in the patient with posterior lumbar spinal fusion for degenerative lumbar disease. The aim of this study is to investigate sexual activities in patients with lumbar degenerative disease before and after lumbar fusion surgery. METHODS: We recruited 35 patients who underwent lumbar spinal fusion at the age of 55 years or younger. They were 17 men and 18 women with a mean age of 47.4 years. After informed consent, the patients were asked to complete anonymous questionnaire concerning sexual desire, activity, and satisfaction before and after surgery. RESULTS: In the presick period, 69% of the patients had sexual desire, and 79% achieved satisfaction during sexual activity. Lumbar degenerative disease decreased sexual desire and frequency of sexual activity in 40%, and 74% respectively. Before surgery, satisfaction in sexual activities decreased in 53%, and 55% of the patients felt discomfort during sexual activity. Adjustment in sexual position was required in 44% of man and 54% of woman. After surgery, Sexual desire, frequency of sexual activity and satisfaction did not regain after surgery in 94%, 93% and 92%, respectively. Those who did not feel discomfort after surgery was significantly lower VAS in both low back pain and leg pain than the patients felt discomfort (low back pain; p = 0.024, leg pain; p = 0.046). CONCLUSION: This study demonstrated that lumbar degenerative diseases decreased sexual desire, frequency of sexual activity and satisfaction, and little of the patients regained their sexual activities after posterior lumbar fusion surgery in the middle-aged patients.


Assuntos
Dor Lombar , Fusão Vertebral , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Dor Lombar/cirurgia , Comportamento Sexual , Região Lombossacral , Emoções , Fusão Vertebral/efeitos adversos
11.
BMC Musculoskelet Disord ; 24(1): 626, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37533001

RESUMO

BACKGROUND: Under the restriction of social activities during the coronavirus disease 2019 (COVID-19) pandemic, there was concern about the loss of muscle mass due to a decrease in physical activity for the elderly. The purpose of this study was to investigate the characteristics of older patients with postmenopausal osteoporosis who developed loss of muscle mass during the COVID-19 pandemic in Japan. METHODS: A total of 54 patients with postmenopausal osteoporosis were evaluated in this study. Whole-body dual-energy X-ray absorptiometry was performed pre- and post-COVID-19 pandemic to measure trunk and lower limb muscle mass. At the time of the post-COVID-19 pandemic, we conducted a survey to compare lifestyle before pandemic (the frequency of going out, the frequency of meeting acquaintances or families living apart, regular exercise habits, walking time, family structure), and comorbidities between the muscle mass loss (ML) group and the muscle mass maintenance (MM) group. The ML group consisted of patients with at least a 5% decrease in lower limb muscle mass or trunk muscle mass. RESULTS: A significant difference was found only for the family structure (P = 0.0279); in the ML group, those living alone were the largest group, while in the MM group they were the smallest group. CONCLUSIONS: The ML group was significantly more likely to live alone than the MM group. The current study showed that loss of muscle mass was more common in patients living alone.


Assuntos
COVID-19 , Osteoporose Pós-Menopausa , Feminino , Humanos , Idoso , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/epidemiologia , Pandemias , Estudos de Casos e Controles , COVID-19/epidemiologia , Músculo Esquelético/diagnóstico por imagem
12.
Reprod Med Biol ; 22(1): e12538, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638351

RESUMO

Background: Development of ovarian follicles is regulated by a complex interaction of intra- and extra-follicular signals. Oocyte-derived paracrine factors (ODPFs) play a central role in this process in cooperation with other signals. Methods: This review provides an overview of the recent advances in our understanding of the paracrine regulation of antral follicle development in mammals. It specifically focuses on the regulation of granulosa cell development by ODPFs, along with other intrafollicular signals. Main Findings: Bi-directional communication between oocytes and surrounding cumulus cells is a fundamental mechanism that determines cumulus cell differentiation. Along with estrogen, ODPFs promote the expression of forkhead box L2, a critical transcription factor required for mural granulosa cells. Follicle-stimulating hormone (FSH) facilitates these processes by stimulating estrogen production in mural granulosa cells. Conclusion: Cooperative interactions among ODPFs, FSH, and estrogen are critical in determining the fate of cumulus and mural granulosa cells, as well as the development of oocytes.

13.
Spine J ; 23(10): 1461-1470, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37437695

RESUMO

BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.


Assuntos
Densidade Óssea , Ossificação do Ligamento Longitudinal Posterior , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Ligamentos Longitudinais , Corpo Humano , Estudos Transversais , Osteogênese , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Vértebras Cervicais/cirurgia , Obesidade/complicações
14.
Elife ; 122023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37461309

RESUMO

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.


Assuntos
Diabetes Mellitus Tipo 2 , Ossificação do Ligamento Longitudinal Posterior , Animais , Camundongos , Osteogênese , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/patologia , Coluna Vertebral/patologia , Ossificação do Ligamento Longitudinal Posterior/genética , Ossificação do Ligamento Longitudinal Posterior/patologia
15.
Spine J ; 23(9): 1287-1295, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160167

RESUMO

BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.


Assuntos
Dislipidemias , Ossificação do Ligamento Longitudinal Posterior , Humanos , Ligamentos Longitudinais/patologia , Osteogênese , Estudos Transversais , LDL-Colesterol , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/epidemiologia , Dislipidemias/epidemiologia , Dislipidemias/complicações , Obesidade/complicações , Obesidade/epidemiologia , Vértebras Cervicais/patologia
16.
Medicina (Kaunas) ; 59(5)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37241092

RESUMO

Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Inteligência Artificial , Discotomia Percutânea/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Endoscopia/métodos , Discotomia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X , Espectroscopia de Ressonância Magnética , Estudos Retrospectivos , Resultado do Tratamento
17.
Nat Commun ; 14(1): 2354, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095084

RESUMO

The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the epididymis. Males lacking Nicol are sterile due to impaired NELL2-mediated lumicrine signalling, leading to defective epididymal differentiation and deficient sperm maturation but can be restored by NICOL expression in testicular germ cells. Our results demonstrate how lumicrine signalling regulates epididymal function for successful sperm maturation and male fertility.


Assuntos
Sêmen , Maturação do Esperma , Masculino , Camundongos , Animais , Testículo/metabolismo , Epididimo/metabolismo , Espermatozoides/metabolismo , Fertilidade , Mamíferos
18.
Arthritis Rheumatol ; 75(8): 1358-1369, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36924130

RESUMO

OBJECTIVE: The severity of osteoarthritis (OA) and cartilage degeneration is highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. We undertook this study to explore the pathologic role of inflammatory macrophage extracellular vesicles (EVs) in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages, and the resulting EVs were harvested for chondrocyte stimulation in vitro and for intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-sequencing analysis and other functional assays. The action of caspase 11 was disrupted in vitro using a specific small interfering RNA or wedelolactone, and in experimental murine OA models by intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-sequencing analyses of stimulated chondrocytes indicated that up-regulated genes were mainly categorized into apoptotic process and tumor necrosis factor signaling pathways, which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase 11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and pathologic changes in collagenase-induced and joint instability-induced OA models. CONCLUSION: Our results provide new insight into the pathologic mechanisms of OA and suggest that noncanonical pyroptosis in chondrocytes represents an attractive therapeutic target for treatment.


Assuntos
Cartilagem Articular , Vesículas Extracelulares , Osteoartrite , Camundongos , Animais , Condrócitos/metabolismo , Piroptose , Cartilagem/metabolismo , Osteoartrite/metabolismo , Macrófagos/metabolismo , RNA Interferente Pequeno/metabolismo , Caspases , Vesículas Extracelulares/patologia , Cartilagem Articular/metabolismo
19.
J Clin Med ; 12(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36835925

RESUMO

This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.

20.
Sci Rep ; 13(1): 638, 2023 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635323

RESUMO

Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.


Assuntos
Ligamento Amarelo , Ossificação do Ligamento Longitudinal Posterior , Ossificação Heterotópica , Humanos , Osteogênese , Ligamento Amarelo/diagnóstico por imagem , Coluna Vertebral , Ligamentos , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/complicações , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/complicações
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