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BioRxiv : the Preprint Server For... Jun 2024Platelet Derived Growth Factor Receptor Beta (Pdgfrβ) suppresses the formation of cold temperature-induced beige adipocytes in aged mammals. We aimed to determine if...
OBJECTIVE
Platelet Derived Growth Factor Receptor Beta (Pdgfrβ) suppresses the formation of cold temperature-induced beige adipocytes in aged mammals. We aimed to determine if deleting Pdgfrβ in aged mice could rejuvenate metabolically active beige adipocytes by activating group 2 innate lymphoid cells (ILC2), and whether this effect could counteract diet-induced obesity-associated beige fat decline.
METHODS
We employed Pdgfrβ gain-of-function and loss-of-function mouse models targeting beige adipocyte progenitor cells (APCs). Our approach included cold exposure, metabolic cage analysis, and age and diet-induced obesity models to examine beige fat development and metabolic function under varied Pdgfrβ activity.
RESULTS
Acute cold exposure alone enhanced metabolic benefits in aged mice, irrespective of beige fat generation. However, Pdgfrβ deletion in aged mice reestablished the formation of metabolically functional beige adipocytes, enhancing metabolism. Conversely, constitutive Pdgfrβ activation in young mice stymied beige fat development. Mechanistically, Pdgfrβ deletion upregulated IL-33, promoting ILC2 recruitment and activation, whereas Pdgfrβ activation reduced IL-33 levels and suppressed ILC2 activity. Notably, diet-induced obesity markedly increased Pdgfrβ expression and Stat1 signaling, which inhibited IL-33 induction and ILC2 activation. Genetic deletion of Pdgfrβ restored beige fat formation in obese mice, improving whole-body metabolism.
CONCLUSION
This study reveals that cold temperature exposure alone can trigger metabolic activation in aged mammals. However, reversing Pdgfrβ signaling in aged and obese mice not only restores beige fat formation but also renews metabolic function and enhances the immunological environment of white adipose tissue (WAT). These findings highlight Pdgfrβ as a crucial target for therapeutic strategies aimed at combating age- and obesity-related metabolic decline.
PubMed: 38948810
DOI: 10.1101/2024.06.17.599436 -
Indian Journal of Orthopaedics Jul 2024Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years.... (Review)
Review
INTRODUCTION
Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA.
MATERIALS AND METHODS
The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were "osteoarthritis" OR "hip osteoarthritis" OR "orthobiologics" OR "efficacy or use of orthobiologic treatment" OR "bone-marrow concentrate" OR "bone-marrow aspirate concentrate", AND "BMAC". The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA.
RESULTS
A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL).
CONCLUSION
The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.
PubMed: 38948376
DOI: 10.1007/s43465-024-01183-7 -
Indian Journal of Orthopaedics Jul 2024In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous...
BACKGROUND
In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration.
PURPOSE OF THE STUDY
This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft.
METHODS
A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs.
RESULTS AND CONCLUSION
According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix.
PubMed: 38948364
DOI: 10.1007/s43465-024-01182-8 -
Journal of Inflammation Research 2024Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a...
BACKGROUND
Inflammation triggers atherosclerotic plaque rupture, leading to acute myocardial infarction (AMI). Following AMI, peri-coronary adipose tissue (PCAT) undergoes a transition from lipid-rich to hydrophilic characteristics due to vascular inflammation. This study investigates PCAT changes and neutrophil-to-lymphocyte ratio levels during AMI.
PATIENTS AND METHODS
60 AMI patients undergoing coronary computed tomography angiography and angiography (Jan 2020-Jun 2022) were studied 60 age, gender, BMI-matched stable angina, and 60 non-coronary artery disease patients were included. Siemens VB20.0 measured PCAT-volume and fat attenuation index (FAI). Neutrophil-to-lymphocyte ratio levels were calculated by peripheral blood tests.
RESULTS
The PCAT volume and PCAT-FAI gradually increased across the control, stable angina, and AMI groups, with a corresponding gradual rise in NLR. NLR exhibited weak positive correlation with PCAT-FAI (r=0.35) and PCAT-volume (r=0.24). Multivariable logistic regression identified increased PCAT-volume, PCAT-FAI and neutrophil-to-lymphocyte ratio as possible independent AMI risk factors. No significant PCAT-volume difference was observed between infarct-related artery (IRA) and non-IRA for all three coronary arteries. Only PCAT-FAI around IRA-LAD was higher than non-IRA-LAD (-74.84±6.93 HU vs -79.04±8.68 HU). PCAT-FAI around culprit vessels in AMI was higher than corresponding lesion related vessel in SA. PCAT-volume around narrowed non-IRA in AMI was higher than that of corresponding LRV in SA. PCAT-FAI of narrowed non-IRA-LADs and non-IRA-LCXs in AMI were elevated compared to LADs (-78.46±8.56HU vs -83.13±8.34 HU) and LCXs (-73.83±10.63 HU vs -81.38±7.88 HU) of lesion related vessel in stable angina.
CONCLUSION
We found an association between AMI and inflammation in the coronary perivascular adipose tissue and systemic inflammatory response.
PubMed: 38948196
DOI: 10.2147/JIR.S465605 -
Avicenna Journal of Phytomedicine 2024Disruption of lipid droplets (LDs) is associated with many metabolic diseases. Spirulina, as a natural bioactive dietary supplement, along with exercise training, may...
OBJECTIVE
Disruption of lipid droplets (LDs) is associated with many metabolic diseases. Spirulina, as a natural bioactive dietary supplement, along with exercise training, may improve lipid metabolism; however, their effects on LDs-regulated genes in visceral adipose tissue are still unclear. This study aimed to investigate the effects of six-week Spirulina supplementation along with exercise training on LDs regulating gene expression.
MATERIALS AND METHODS
Fifty-six male Wistar rats were divided into six groups: saline (control), control+Spirulina (Spirulina), aerobic interval training (AIT), AIT+ Spirulina (AIT+Spirulina), resistance training and resistance+ Spirulina. The supplement groups consumed 500 mg/kg Spirulina five days per week. The training groups performed AIT (5 times per week) and resistance training (3 times per week) for 6 weeks. LDs regulating genes expression in visceral adipose tissue (, , , , , , and ) was analyzed by real-time PCR.
RESULTS
Spirulina and exercise training had no significant effects on the gene expression of Syntaxin18 (p=0.69) and (p=0. 84), (p=0.98), or (p=0.58). In addition, Spirulina was found to significantly attenuate the expression of (p=0.01) and (p=0.01) genes compared to the control, AIT, and resistance training groups. However, gene expression was higher in the resistance training than the AIT. Furthermore, Spirulina decreased (p=0.03) gene expression in visceral adipose tissue compared to the control, AIT, and resistance training groups. Unexpectedly, Spirulina supplementation decreased the expression of these genes even more when taken without exercise training.
CONCLUSION
Spirulina supplementation and exercise training have significant effects on LDs-regulated genes in visceral adipose tissue.
PubMed: 38948175
DOI: 10.22038/AJP.2023.22915 -
Plastic and Reconstructive Surgery.... Mar 2024Incorporation of new technologies to assist the liposuction procedure is becoming increasingly common. These technologies allow for a softer technique, balanced shaping,...
Incorporation of new technologies to assist the liposuction procedure is becoming increasingly common. These technologies allow for a softer technique, balanced shaping, elimination of excess adipose tissue, and skin tightening. Some of these technologies include ultrasound (US; US-assisted liposculpture, VASER-assisted liposuction), power suction (power-assisted liposuction), radiofrequency (RF; RF-assisted lipolysis), and laser (laser-assisted liposuction). In addition, some of these devices have been shown to reduce the incidence of hematomas/inflammation and shorten recovery time. We report our experience in high-definition liposculpture of the arms in addition to new technologies to improve skin retraction, comparing their results in terms of complications, satisfaction score, and aesthetic outcomes. We included patients with mild-to-moderate arm dermatochalasis (Duncan classification) fat deposits in the upper extremities who were considered candidates for third-generation US-assisted liposculpture, power-assisted liposuction, RF-assisted lipolysis/skin tightening, and laser-assisted liposuction. A total of 683 consecutive patients met the inclusion criteria for the study. Most of them were women (n = 605, 88%). Fat grafting was performed in 80 patients (11.7%). A significant portion of the patients were secondary cases (n = 223, 33%). Age ranged from 18 to 70 years (median = 38 years). BMI ranged from 17.8 to 34.8 kg/m (mean = 24.3 kg/m). RF-assisted and laser-assisted high-definition liposculpture of the arms are both effective and reproducible techniques for patients who seek an athletic and slim arm contour. A low rate of complications and high satisfaction index support our findings.
PubMed: 38948160
DOI: 10.1097/GOX.0000000000005649 -
Plastic and Reconstructive Surgery.... Mar 2024Breast reduction is one of the most required plastic surgery procedures worldwide, improving significantly the quality of life for patients with macromastia and...
Breast reduction is one of the most required plastic surgery procedures worldwide, improving significantly the quality of life for patients with macromastia and gigantomachia. Despite various proposed approaches aiming to yield more stable results postreduction, no single technique has demonstrated unequivocal superiority. Recurrence ptosis at 6-12 months postoperative remains a challenging concern. To improve this issue, the authors propose a novel application of the poly-4-hydroxybutyrate (P4HB) scaffold on the anterior surface of the Ribeiro dermo-adipose flap. The primary aim was to establish a durable and resilient biological connection between the mammary gland and the flap, thereby promoting long-lasting outcomes in breast reduction procedures. The P4HB scaffold is a monofilament, single-layer, biologically derived, fully resorbable, rapidly integrating within breast tissue; this biological process stimulates the formation of freshly vascularized connective tissue up to a thickness of 2-3 mm. Within 18-24 months, the scaffold undergoes gradual resorption through hydrolysis-based mechanism, providing enhanced strength and resistance to the native tissue, as shown in animal model. A key innovation proposed by the authors involves the division of a 15 × 20 cm rectangular sheet of the P4HB scaffold along its diagonal, resulting in two right triangles. This modification ensures increased height of the device if compared with the traditional splitting technique of the scaffold. The strategic establishment of a biological bridge between the mammary gland and flap through the implementation of the P4HB scaffold could potentially enhance the longevity and aesthetics of breast reduction outcomes.
PubMed: 38948158
DOI: 10.1097/GOX.0000000000005676 -
Current Developments in Nutrition Jun 2024Excessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA...
BACKGROUND
Excessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist.
OBJECTIVES
This study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex.
METHODS
Infants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines.
RESULTS
For total FM, there was a significant main effect for the DHA dose ( = 0.03); however, the dose by GWG status was nonsignificant ( = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose ( = 0.01) was detected for central FM. However, no interaction was detected ( = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose.
CONCLUSIONS
Greater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.
PubMed: 38948108
DOI: 10.1016/j.cdnut.2024.103771 -
World Journal of Stem Cells Jun 2024The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.
BACKGROUND
The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.
AIM
To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX) and exogenous mitochondria (mito) protect the lung from ARDS complicated by SS.
METHODS
study, including L2 cells treated with lipopolysaccharide (LPS) and study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX), 4 (ARDS-SS + mito), and 5 (ARDS-SS + EX + mito), were included in the present study.
RESULTS
study showed an abundance of mito found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels ( < 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX treatment than without EX treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all < 0.0001), whereas arterial oxygen-saturation (SaO%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO% among the groups (all < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all < 0.0001).
CONCLUSION
Combined EX-mito therapy was better than merely one for protecting the lung against ARDS-SS induced injury.
PubMed: 38948095
DOI: 10.4252/wjsc.v16.i6.690 -
Cureus May 2024Lipomas are common benign soft tissue tumors, typically presenting as painless, slow-growing masses of mature adipose tissue. However, their occurrence as pedunculated...
Lipomas are common benign soft tissue tumors, typically presenting as painless, slow-growing masses of mature adipose tissue. However, their occurrence as pedunculated lesions in the perianal region is rare. We present a case of a 70-year-old male with a 20-year history of a painless, cosmetically concerning mass in the perianal region. Clinical examination and ultrasonographic findings were consistent with a pedunculated lipoma. Surgical excision was performed successfully, and histopathological examination confirmed the diagnosis of lipofibroma. This case highlights the importance of considering unusual presentations of lipomas in the differential diagnosis of perianal masses. It emphasizes the role of surgical excision for symptomatic or cosmetically concerning lesions. Long-term follow-up is essential to monitor for recurrence and ensure optimal patient outcomes.
PubMed: 38947595
DOI: 10.7759/cureus.61304