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Chronic renal failure is one of the leading causes of death in African lions, cheetahs, and tigers. Conventional methods to measure renal dysfunction include measuring serum creatinine and blood urea nitrogen (BUN). Symmetric dimethylarginine (SDMA) measurement is a reliable predictor of renal dysfunction in the domestic cat because SDMA serum levels increase early when the kidneys are damaged. Serum SDMA levels were assessed and correlated with creatinine as well as BUN from healthy captive Bengal tigers and lions at the Everland Zoo in Korea. Serum SDMA concentrations were increasingly associated with increased age in lions. However, SDMA concentrations were higher in some young Bengal tigers than in older ones, which may allow for earlier renal dysfunction detection in these young cats than would be BUN and creatinine alone. In Bengal tigers, the correlation between the SDMA and BUN was slightly higher than that between SDMA and creatinine. In lions, SDMA correlated better with creatinine than with BUN concentration. These results show that serum SDMA concentration can be used as a biomarker for age-associated renal dysfunction. SDMA measurement may be an essential preventive management method in zoos.

Autophagy is an essential lysosome-mediated degradation pathway that maintains cellular homeostasis and viability in response to various intra- and extracellular stresses. Mitophagy is a type of autophagy that is involved in the intricate removal of dysfunctional mitochondria during conditions of metabolic stress. In this review, we describe the multifaceted roles of autophagy and mitophagy in normal physiology and the field of cancer biology. Autophagy and mitophagy exhibit dual context-dependent roles in cancer development, acting as tumor suppressors and promoters. We also discuss the important role of autophagy and mitophagy within the cancer microenvironment and how autophagy and mitophagy influence tumor host–cell interactions to overcome metabolic deficiencies and sustain the activity of cancer-associated fibroblasts (CAFs) in a stromal environment. Finally, we explore the dynamic interplay between autophagy and the immune response in tumors, indicating their potential as immunomodulatory targets in cancer therapy. As the field of autophagy and mitophagy continues to evolve, this comprehensive review provides insights into their important roles in cancer and cancer microenvironment. [ABSTRACT FROM AUTHOR]

The complex process of bone regeneration is influenced by factors such as inflammatory responses, tissue interactions, and progenitor cells. Currently, multiple traumas can interfere with fracture healing, causing the prolonging or failure of healing. In these cases, bone grafting is the most effective treatment. However, there are several drawbacks, such as morbidity at the donor site and availability of suitable materials. Advantages have been provided in this field by a variety of stem cell types. Adipose-derived stem cells (ASCs) show promise. In the radiological examination of this study, it was confirmed that the C/S group showed faster regeneration than the other groups, and Micro-CT also showed that the degree of bone formation in the defect area was highest in the C/S group. Compared to the control group, the change in cortical bone area in the defect area decreased in the sham group (0.874), while it slightly increased in the C/S group (1.027). An increase in relative vascularity indicates a decrease in overall bone density, but a weak depression filled with fibrous tissue was observed outside the compact bone. It was confirmed that newly formed cortical bone showed a slight difference in bone density compared to surrounding normal bone tissue due to increased distribution of cortical bone. In this study, we investigated the effect of bone regeneration by ADMSCs measured by radiation and pathological effects. These data can ultimately be applied to humans with important clinical applications in various bone diseases, regenerative, and early stages of formative differentiation. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Because TNBC lacks the expression of commonly targeted receptors, it is challenging to develop a new imaging agent for this cancer subtype. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA–protein complexes that have been linked to tumor development and progression. Considering the high expression of hnRNPA2B1, an hnRNP subtype, in TNBC MDA-MB-231 cells, this study aimed to develop a novel hnRNPA2B1 antibody-based nuclear imaging agent. The hnRNPA2B1-specific antibody was radiolabeled with 64Cu and evaluated in vitro and in vivo. The trans-cyclooctene (TCO) was functionalized on the antibody to obtain hnRNP-PEG4-TCO and reactive tetrazine (Tz) on the ultrastable bifunctional chelator PCB-TE2A-alkyne to yield PCB-TE2A-Tz for the inverse electron demand Diels–Alder reaction. The 64Cu-radiolabeled antibody was administered and imaged at 1–18 h time points for conventional imaging. Alternatively, the unlabeled antibody conjugate was administered, and 48 h later radiolabeled 64Cu-PCB-TE2A-Tz was administered to the same mice for the pretargeting strategy and imaged at the same time intervals for direct comparison. The tumor was successfully visualized in both strategies, and comparatively, pretargeting showed superior results. The 64Cu-PCB-TE2A-Tz was successfully clicked at the tumor site with hnRNP-PEG4-TCO and the non-clicked were concurrently eliminated. This led to increase the tumor uptake with extremely high tumor-to-background ratio manifested by positron emission tomography (PET) imaging and biodistribution studies. [ABSTRACT FROM AUTHOR]

In previous work, we established an equine induced pluripotent stem cell line (E-iPSCs) from equine adipose-derived stem cells (ASCs) using a lentiviral vector encoding four transcription factors: Oct4, Sox2, Klf4, and c-Myc. In the current study, we attempted to differentiate these established E-iPSCs into mesenchymal stem cells (MSCs) by serial passaging using MSC-defined media for stem cell expansion. Differentiation of the MSCs was confirmed by analyzing expression levels of the MSC surface markers CD44 and CD29, and the pluripotency markers Nanog and Oct4. Results indicated that the E-iPSC-derived MSCs (E-iPSC-MSCs) retained the characteristics of MSCs, including the ability to differentiate into chondrogenic, osteogenic, or myogenic lineages. E-iPSC-MSCs were rendered suitable for therapeutic use by inhibiting immune rejection through exposure to transforming growth factor beta 2 (TGF-β2) in culture, which down-regulated the expression of major histocompatibility complex class I (MHC class I) proteins that cause immune rejection if they are incompatible with the MHC antigen of the recipient. We reported 16 cases of E-iPSC-MSC transplantations into injured horses with generally positive effects, such as reduced lameness and fraction lines. Our findings indicate that E-iPSC-MSCs can demonstrate MSC characteristics and be safely and practically used in the treatment of musculoskeletal injuries in horses. [ABSTRACT FROM AUTHOR]

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases. [ABSTRACT FROM AUTHOR]

Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase involved in various biological functions via deacetylation of proteins, including histone protein. Hepatic fat accumulation from aging and excess caloric intake contribute to development of non-alcoholic fatty liver disease. The study aim was to elucidate the role of SIRT2 in lipid metabolism homeostasis. SIRT2+/+ (C57BL/6) and SIRT2−/− were randomly assigned to normal diet or high-fat diet (HFD) groups and fed for 6 weeks. Histological features of the livers were evaluated by hematoxylin and eosin and Masson's trichrome staining, and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction and western blot analysis. Although the SIRT2−/− mice were viable, their livers exhibited higher glycogen accumulation, and skeletal muscle showed features of increased metabolic demand. The SIRT2−/− mice attenuated HFD-induced weight gain, visceral adipose tissue formation, and fat accumulation in the liver in which the expressions of genes involved in metabolic substrate transport were modified. Additionally, the hepatocellular senescence and upregulated cell-cycle factors upon HFD intake in SIRT2−/− livers suggested a role of SIRT2 in gene expression during abnormal metabolism. Moreover, the fibrotic phenotype of liver tissue without fat accumulation and the increased expression of genes involved in liver fibrosis in the HFD-fed SIRT2−/− mice indicated that SIRT2 had a role in hepatocyte and hepatic stellate cell activation. Our results indicated that SIRT2 has a critical role in regulating lipid metabolic homeostasis and in sustaining liver integrity by modulating related gene expression. [Display omitted] [ABSTRACT FROM AUTHOR]

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

α-Lactalbumin and β-lactoglobulin are two major whey proteins that specifically bind immunoglobulin E and are suspected as major allergens causing cow's milk allergy (CMA). Recent studies have shown that thymic stromal lymphopoietin is a critical factor linking at the interface of the body and environment to the T-helper 2 response. However, it is not known whether thymic stromal lymphopoietin expression is changed by α-lactalbumin and β-lactoglobulin in immune cells. Using RT-PCR and ELISA, the present study was conducted to examine if intravenous injection of α-lactalbumin and β-lactoglobulin increased pro-inflammatory cytokines, T-helper 2 cytokines, and thymic stromal lymphopoietin expression in several immune cells, including macrophages, mast cells, and keratinocytes. Results showed that α-lactalbumin and β-lactoglobulin induced thymic stromal lymphopoietin, interleukin-6, and tumor necrosis factor-α expression. It was concluded that the allergenicity of α-lactalbumin and β-lactoglobulin may be attributed to thymic stromal lymphopoietin induction, T-helper 2 cytokines, and pro-inflammatory cytokines.