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Frontiers in Bioscience (Landmark... Jun 2024Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration... (Review)
Review
Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use.
Topics: Humans; Mesenchymal Stem Cells; Tissue Scaffolds; Mesenchymal Stem Cell Transplantation; Animals; Polymers; Tissue Engineering
PubMed: 38940050
DOI: 10.31083/j.fbl2906228 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024Abdominal aortic aneurysm (AAA) is a life-threatening disease that remains undetected until it acutely ruptures. Due to lack of effective pharmaceutic therapies, it is... (Review)
Review
Abdominal aortic aneurysm (AAA) is a life-threatening disease that remains undetected until it acutely ruptures. Due to lack of effective pharmaceutic therapies, it is urgent to explore new prevention and treatment strategies. Metabolic reprogramming is a cellular process through which cells change their metabolic patterns to meet material and energy requirements, including glucose metabolism, lipid metabolism and amino acid metabolism. Recently, the regulatory role of metabolic reprogramming in cardiovascular diseases, especially AAA, has attracted significant attention. This review article focuses on the research progress regarding the effects of metabolic reprogramming of vascular smooth muscle cells (VSMCs) and macrophages on the occurrence and development of AAA, especially their roles in major pathological processes such as VSMCs apoptosis and phenotype transformation, extracellular matrix remodeling, oxidative stress, and inflammatory response. The aim is to provide new clues for the mechanism research and clinical treatment of AAA from the perspective of metabolism.
Topics: Aortic Aneurysm, Abdominal; Humans; Muscle, Smooth, Vascular; Animals; Myocytes, Smooth Muscle; Macrophages; Oxidative Stress; Apoptosis; Lipid Metabolism; Cellular Reprogramming; Metabolic Reprogramming
PubMed: 38939940
DOI: No ID Found -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging...
The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.
Topics: Animals; Male; Aging; Rats; Rats, Sprague-Dawley; Muscle, Skeletal; Physical Conditioning, Animal; Neuromuscular Junction; Muscle Proteins; Resistance Training; Forkhead Box Protein O1
PubMed: 38939932
DOI: No ID Found -
Experimental and Therapeutic Medicine Aug 2024Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms, primarily affecting middle-aged women. These tumors are characterized by a mix of...
Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms, primarily affecting middle-aged women. These tumors are characterized by a mix of epithelial and stromal components. While generally benign, MESTs require accurate diagnosis and appropriate management due to the potential for malignant transformation. The present study reports the case of a 75-year-old male patient who underwent a partial nephrectomy following the incidental discovery of a kidney tumor. Histopathological examination revealed a partially cystic tumor with solid areas, measuring 26 mm in diameter. The tumor had cysts lined with cuboidal cells and an ovarian-like stroma. The solid component consisted of elongated cells with eosinophilic cytoplasm and oval nuclei, showing angiocentric growth around small blood vessels without nuclear atypia or mitoses. Since the morphology of the solid component could not reveal the differentiation of those cells, immunohistochemical staining was performed and a myopericytoma/myofibroma component was established, mostly based on the positivity of smooth muscle actin, muscle-specific actin, h-caldesmon, estrogen receptor, progesterone receptor, solute carrier family 2 facilitated glucose transporter member 1 and collagen IV, along with a lack of staining for desmin, CD34, CD31 and CD99. Thus, to the best of our knowledge, for the first time in the literature, MEST with myopericytoma/myofibroma stromal component in a male patient was reported.
PubMed: 38939172
DOI: 10.3892/etm.2024.12610 -
Cureus Jun 2024Autoimmune hepatitis (AIH) is a condition resulting in chronic, inflammatory changes to the liver. Primary biliary cholangitis (PBC) is an autoimmune condition that...
Autoimmune hepatitis (AIH) is a condition resulting in chronic, inflammatory changes to the liver. Primary biliary cholangitis (PBC) is an autoimmune condition that destroys intrahepatic bile ducts. Overlap syndrome with concomitant AIH and PBC comprises a rare subgroup of patients with immune-mediated liver disease, with incidence rates of male patients being exceedingly uncommon in a predominantly female patient population. Our case report investigates a rare case of a 41-year-old male patient diagnosed with overlapping AIH and PBC. He initially presented with symptoms of fatigue, pruritus, and episodes of Raynaud's phenomenon, in addition to findings of persistently elevated liver enzymes despite lifestyle modifications. He had no past medical history, no history of alcohol use disorder, and no family medical history of chronic liver disease. Imaging did not reveal evidence of cirrhosis. Further diagnostic workup was significant for elevated immunologic markers for antinuclear antibodies (ANA) with positive centromere and cytoplasmic patterns, antimitochondrial antibodies (AMA) with F-actin antibodies, anti-smooth muscle antibodies (ASMA), and cytoplasmic antinuclear cytoplasmic antibodies (ANCA C). Liver biopsy showed prominent plasma cells and rare granulomas, consistent with the diagnosis of AIH with a component of PBC, respectively. He was started on ursodeoxycholic acid (UDCA), demonstrating a near-complete clinical response with resolution of symptoms and normalization of liver enzymes. Studies investigating the low incidence of male patients with overlap syndrome are limited, as current research is overwhelmingly based on studies with predominantly female subjects. However, most studies generally recommend treatment with both UDCA and corticosteroids to reduce symptoms and biochemical markers. Our case report highlights a rare case of a male patient documenting excellent biochemical and clinical responses to monotherapy with UDCA. A possible theory is that our patient's early treatment (prior to advanced disease progression) is associated with his near-complete biochemical response and symptomatic resolution on UDCA alone. Further research is needed to fully understand the clinical course and long-term prognosis of male patients with overlap syndrome. Our patient remains in life-long follow-up to monitor if or when he requires treatment with corticosteroids in addition to current monotherapy with UDCA..
PubMed: 38938909
DOI: 10.7759/cureus.63312 -
Frontiers in Cellular and Infection... 2024The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The...
The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of Las within ACP are critical to understanding how the transmission, spread and infection of Las occurs within its host vector in nature. In this study, the distribution and titer changes of Las in various tissues of ACP 5 instar nymphs and adults were examined by (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5 instar nymphs and adults were infected with Las following feeding on infected plants, and that Las had widespread distribution in most of the tissues of ACP. The titers of Las within the midgut, salivary glands and hemolymph tissues were the highest in both 5 instar nymphs and adults. When compared with adults, the titers of Las in these three tissues of 5 instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of Las demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of Las with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of Las, which is of much importance for developing novel strategies to halt the spread of Las, and therefore contribute to the efficient prevention and control of HLB.
Topics: Animals; Hemiptera; Insect Vectors; Plant Diseases; Nymph; Citrus; In Situ Hybridization, Fluorescence; Rhizobiaceae; Real-Time Polymerase Chain Reaction; Salivary Glands; Hemolymph
PubMed: 38938879
DOI: 10.3389/fcimb.2024.1408362 -
Frontiers in Neurology 2024Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two... (Review)
Review
Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.
PubMed: 38938781
DOI: 10.3389/fneur.2024.1421772 -
APL Bioengineering Jun 2024Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease...
Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human model systems complement animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms. This work established approaches for assessing the temporal dynamics of these responses using genetically encoded fluorescent reporters of alpha smooth muscle actin expression, an indicator of fibroblast activation. Specifically, we created a toolset of human lung fibroblast reporter cell lines from different origins (male, female; healthy, idiopathic pulmonary fibrosis) and used three different versions of the reporter with the fluorescent protein modified to exhibit different temporal stabilities, providing temporal resolution of protein expression processes over a range of timescales. Using this toolset, we demonstrated that reporters provide insight into population shifts in response to both mechanical and biochemical cues that are not detectable by traditional end point assessments with differential responses based on cell origin. Furthermore, individual cells can also be tracked over time, with opportunities for comparison to complementary end point measurements. The establishment of this reporter toolset enables dynamic cell investigations that can be translated into more complex synthetic culture environments for elucidating disease mechanisms and evaluating therapeutics for lung fibrosis and other complex biological processes more broadly.
PubMed: 38938687
DOI: 10.1063/5.0166152 -
Turk Patoloji Dergisi Jun 2024Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation,...
OBJECTIVE
Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation, express α-smooth muscle actin (α-SMA), and play a crucial role in injury and inflammation sites. This study aims to evaluate the relationship between α-SMA expression and histopathological parameters of pancreatic ductal adenocarcinoma (PDAC), and investigate their association with prognosis.
MATERIAL AND METHODS
Eighty-one consecutive pancreatectomies diagnosed as usual pancreatic ductal adenocarcinoma were included. The stromal density was scored as loose, moderate, or dense, and α-SMA expression was evaluated immunohistochemically.
RESULTS AND CONCLUSION
Mean survival was 19.6 months. Male gender, larger tumor diameter ( > 3.7 cm), and older age ( > 64 years) were identified as independent poor prognostic factors. Perineural invasion significantly effected survival. A statistically significant correlation was found between high α-SMA expression and the presence of angioinvasion (p=0.01). Stromal α-SMA expression in PDAC may help determine the risk of angioinvasion.
PubMed: 38938104
DOI: 10.5146/tjpath.2024.13521 -
Cell Reports Jun 2024GGGGCC (GC) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic...
GGGGCC (GC) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst function is partially maintained. Several disease-relevant cellular phenotypes in C9ORF72 iPSC-derived motor neurons are rescued due to, surprisingly, the decreased levels of dipeptide repeat (DPR) proteins and expanded GC repeats-containing RNA. The treatment of fully differentiated C9ORF72 neurons with EXOC2 antisense oligonucleotides also decreases expanded GC repeats-containing RNA and partially rescued disease phenotypes. These results indicate that EXOC2 directly or indirectly regulates the level of GC repeats-containing RNA, making it a potential therapeutic target in C9ORF72-ALS/FTD.
PubMed: 38935506
DOI: 10.1016/j.celrep.2024.114375