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Cureus May 2024Cysticercosis is a rare condition associated with the development of cysticercus (larval form) of Taenia solium (pork tapeworm), within an intermediate host. Accidental...
Cysticercosis is a rare condition associated with the development of cysticercus (larval form) of Taenia solium (pork tapeworm), within an intermediate host. Accidental ingestion of infectious eggs is most likely the cause of humans becoming intermediate hosts. The most common site for larval cysts is the central nervous system followed by vitreous humor of the eye, striated muscle, and, in rare cases, subcutaneous and other tissues. Isolated muscular involvement with nonspecific symptoms makes this condition challenging to diagnose. We present an unusual case of cysticercus in the sternocleidomastoid muscle diagnosed with ultrasonography and contrast-enhanced scans, which was subsequently treated with surgical excision and a short course of anthelmintics.
PubMed: 38947570
DOI: 10.7759/cureus.61275 -
Frontiers in Immunology 2024Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from...
Severe thermal and major traumatic injury results in elevated plasma concentrations of total heme that are associated with poor clinical outcomes and systemic immune suppression.
BACKGROUND
Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression.
METHODS
Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following heme treatment was also examined.
RESULTS
Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response.
CONCLUSIONS
Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.
Topics: Humans; Heme; Burns; Male; Adult; Female; Middle Aged; Cytokines; Wounds and Injuries; Young Adult; Aged; THP-1 Cells; Leukocytes, Mononuclear; Biomarkers; Lipopolysaccharides; Heme Oxygenase-1
PubMed: 38947312
DOI: 10.3389/fimmu.2024.1416820 -
Journal of Pain Research 2024Chronic musculoskeletal pain (CMP), defined as persistent discomfort in musculoskeletal tissues persisting for over 3 months, afflicts an estimated 1.71 billion people... (Review)
Review
Chronic musculoskeletal pain (CMP), defined as persistent discomfort in musculoskeletal tissues persisting for over 3 months, afflicts an estimated 1.71 billion people globally, leading to significant functional impairments and psychological distress, thereby detrimentally affecting individuals' quality of life. The objective of this narrative review is to elucidate the complex relationship among dietary habits, sarcopenia, and gut microbiota composition, with an eye toward enhancing patient management and outcomes. Given the burgeoning interest in the influence of diet on CMP, a detailed examination of the current literature is warranted. Nutritional intake is a critical determinant of the gut microbiota profile, which, in turn, is linked to musculature integrity and performance, potentially leading to sarcopenia. The development of sarcopenia can aggravate CMP owing to diminished muscular strength and functionality. Additionally, disruptions in the gut microbiota may directly modulate nociception, intensifying CMP manifestations. Thus, nutritional optimization emerges as a viable approach to CMP management. Emphasizing a diet conducive to a healthy gut microbiome could forestall or mitigate sarcopenia, thereby attenuating CMP intensity. Nevertheless, the domain calls for further empirical exploration to unravel the nuances of these interactions and to forge efficacious dietary strategies for individuals with CMP. Beyond mere analgesia, comprehensive patient care for CMP requires acknowledgment of the complex and multifactorial nature of pain and its foundational elements. Embracing an integrative treatment model allows healthcare practitioners to promise better patient prognoses, enriched life quality, and a decrease in the sustained healthcare costs associated with CMP.
PubMed: 38947129
DOI: 10.2147/JPR.S456202 -
Journal of Hepatocellular Carcinoma 2024The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral...
PURPOSE
The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.
PATIENTS AND METHODS
Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.
RESULTS
A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS ( = 0.001). The protections of VATI ( = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared ( = 0.146), but the effect of SMD on OS did not ( = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.
CONCLUSION
This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.
PubMed: 38946842
DOI: 10.2147/JHC.S453262 -
Journal of Experimental Zoology. Part... Jul 2024Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most...
Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.
PubMed: 38946691
DOI: 10.1002/jez.b.23268 -
Endocrinology Jul 2024Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA...
Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA-seq data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by UHPLC MS/MS identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic sub-type. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.
PubMed: 38946397
DOI: 10.1210/endocr/bqae074 -
International Journal of Older People... Jul 2024To develop and validate an evidence-based home pursed lip breathing (PLB) intervention protocol for improving related health outcomes (e.g., dyspnea and exercise...
AIM
To develop and validate an evidence-based home pursed lip breathing (PLB) intervention protocol for improving related health outcomes (e.g., dyspnea and exercise capability) in patients with chronic obstructive pulmonary disease (COPD) and to present a detailed intervention development process.
METHODS
This home PLB intervention protocol employed phase one of the Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions to guide the development process of the PLB intervention. We searched for research evidence on 5 July 2023 from several databases, including PubMed, Embase (via Ovid), Cochrane Library, Google Scholar and China Biology Medicine Disk (CBM). Using the content validity index, a panel of experts assessed the appropriateness of the PLB protocol.
RESULTS
We developed the preliminary home PLB intervention protocol on the basis of several underlying rationales, which encompass the extension of expiration time, enhancement of respiratory muscle strength, augmentation of tidal volume and integration of the most reliable research evidence obtained from four systematic reviews, five RCTs, five clinical trials, and 10 recommendations. We structured the PLB intervention with a designated time ratio of inspiration to expiration, set at 1:2. Additionally, this study recommends that the training parameters of the PLB intervention were as follows: three sessions per day, each lasting for 10 min, over 8 weeks. Individualised PLB training intensity adjusted the inhalation component according to each participant's tolerance level while emphasising the exhalation phase to ensure the complete expulsion of air from the lungs. The home PLB intervention protocol established strong content validity through consensus, which was reached among all panel experts. The item-level and scale-level content validity indices (CVIs) reached a maximum score of 1.0, indicating a high level of agreement and credibility in the protocol's content as evaluated by the expert panel.
CONCLUSION
An optimal evidence-based home PLB protocol has been adapted and developed to manage health-related outcomes of patients with COPD. The protocol is transparent and fully supported by relevant mechanisms, concrete evidence, recommendations and experts' consensus.
IMPLICATIONS FOR PRACTICE
In this study, we consulted patients with COPD about the 'Prepared Conditions Before PLB Practice', to ensure appropriate measures to prevent patients with COPD from potential risks. In addition, patients with COPD also contributed to the PLB exercise frequency distribution.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Breathing Exercises; Aged; Home Care Services; Dyspnea
PubMed: 38946215
DOI: 10.1111/opn.12627 -
Journal of Cellular Physiology Jun 2024Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the...
Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the nicotinamide phosphoribosyltransferase (Nampt) activator P7C3 improves muscle repair following injury. In the present study, we tested the effect of P7C3 (1-anilino-3-(3,6-dibromocarbazol-9-yl) propan-2-ol) on chemically induced muscle injury. Muscle injury was induced by injecting 50 µL 1.2% barium chloride (BaCl) into the tibialis anterior (TA) muscle in C57Bl/6J wild-type male mice. Mice were then treated with either 10 mg/kg body weight of P7C3 or Vehicle intraperitoneally for 7 days and assessed for histological, biochemical, and molecular changes. In the present study, we show that the acute BaCl-induced TA muscle injury was robust and the P7C3-treated mice displayed a significant increase in the total number of myonuclei and blood vessels, and decreased serum CK activity compared with vehicle-treated mice. The specificity of P7C3 was evaluated using Nampt mice, which did not display any significant difference in muscle repair capacity among treated groups. RNA-sequencing analysis of the injured TA muscles displayed 368 and 212 genes to be exclusively expressed in P7C3 and Veh-treated mice, respectively. There was an increase in the expression of genes involved in cellular processes, inflammatory response, angiogenesis, and muscle development in P7C3 versus Veh-treated mice. Conversely, there is a decrease in muscle structure and function, myeloid cell differentiation, glutathione, and oxidation-reduction, drug metabolism, and circadian rhythm signaling pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) and reverse transcription-qPCR analyses identified increased Pax7, Myf5, MyoD, and Myogenin expression in P7C3-treated mice. Increased histone lysine (H3K) methylation and acetylation were observed in P7C3-treated mice, with significant upregulation in inflammatory markers. Moreover, P7C3 treatment significantly increased the myotube fusion index in the BaCl-injured human skeletal muscle in vitro. P7C3 also inhibited the lipopolysaccharide-induced inflammatory response and mitochondrial membrane potential of RAW 264.7 macrophage cells. Overall, we demonstrate that P7C3 activates muscle stem cells and enhances muscle injury repair with increased angiogenesis.
PubMed: 38946152
DOI: 10.1002/jcp.31346 -
Journal of Cellular Physiology Jun 2024Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number...
Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin-like growth factor 2 (IGF2), a well-known growth-promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3-mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.
PubMed: 38946060
DOI: 10.1002/jcp.31351 -
Experimental & Molecular Medicine Jul 2024Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors,... (Review)
Review
Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.
PubMed: 38945957
DOI: 10.1038/s12276-024-01270-7