Tissue Expression Research Articles

Uncoupling protein 1-driven Cre (Ucp1-Cre) is expressed in the epithelial cells of mammary glands and various non-adipose tissues

ObjectiveUncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. Ucp1-Cre mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported. MethodsWe employed Ucp1-Cre mice crossed with Cre-inducible transgenic reporter Nuclear tagging and Translating Ribosome Affinity Purification (NuTRAP) mice to investigate Ucp1-Cre expression in various tissues of adult female mice and developing embryos. Tamoxifen-inducible Ucp1-CreERT2 mice crossed with NuTRAP mice were used to assess active Ucp1 expression in adult mice. Immunostaining, RNA analysis, and single-cell/nucleus RNA-seq (sc/snRNA-seq) data analysis were performed to determine the expression of endogenous UCP1 and Ucp1-Cre-driven reporter expression. We also investigated the impact of UCP1 deficiency on mammary gland development and function using Ucp1-knockout (KO) mice. ResultsUcp1-Cre expression was observed in the mammary glands within the inguinal white adipose tissue of female Ucp1-Cre; NuTRAP mice. Ucp1-Cre was activated during embryonic development in various tissues, including mammary glands, as well as in the brain, kidneys, eyes, and ears, specifically in epithelial cells in these organs. However, Ucp1-CreERT2 showed no or only partial activation in these tissues of adult mice, indicating the potential for low or transient expression of endogenous Ucp1. While sc/snRNA-seq data suggest potential expression of UCP1 in mammary epithelial cells in adult mice and humans, Ucp1-KO female mice displayed normal mammary gland development and function. ConclusionsOur findings reveal widespread Ucp1-Cre expression in various non-adipose tissue types, starting during early development. These results highlight the importance of exercising caution when interpreting data and devising experiments involving Ucp1-Cre mice.

Detection of miR-203 expression using a nanofluorescent probe to study the neuroprotective effect of sevoflurane in a neuroinflammatory injury rat model

Ischemic cerebrovascular disease has high disability and mortality rates that can result in related sequelae if not treated promptly and properly. Nanofluorescent probes are useful in the early diagnosis of the disease due to their high sensitivity and specificity, thus facilitating early therapeutic measures and observation of disease progression. Here, a novel nanostructure probe was designed to detect the expression of miR-203 in a cerebral ischemia-reperfusion injury (CIRI) model after sevoflurane treatment, and the effects of sevoflurane and neuroinflammatory injury were discussed. A CIRI rat model was established to study miR-203 expression, nerve injury, oxidative stress, and inflammatory factors in the brain tissue of rats treated with sevoflurane. The nanofluorescent probe showed high specificity and sensitivity for miR-203 detection. miR-203 was over-expressed in CIRI rats, which was decreased by sevoflurane treatment. In addition, sevoflurane treatment significantly improved neurological function, learning, and memory in CIRI rats; decreased malondialdehyde, lactate dehydrogenase, and superoxide dismutase levels; and inhibited the expression of tumor necrosis factor α and interleukins 1 and 6. Moreover, an inverse correlation was determined between miR-203 expression and the degree of neuroinflammation. This study demonstrated that miR-203 may be a useful diagnostic and prognostic index for neuroinflammatory injury.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1–3), along with nine known ones (4–12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3–5, and 7 showed a potent neuroprotective effect at 25 or 50 μM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

GGTLC1 knockdown inhibits the progression of endometrial cancer by regulating the TGF-β/Smad signaling pathway

PurposeEndometrial cancer (EC) poses a serious risk to females worldwide; thus, a deep understanding of EC is urgently required. The role and mechanisms of gamma-glutamyltransferase light chain 1 (GGTLC1) in EC remain obscure. This study aims to elucidate the function and mechanisms underlying GGTLC1's involvement in EC. MethodsBioinformatic tools and databases were used to analyze GGTLC1 and its associated gene expression in EC tissues. Functional enrichment explorations and immune infiltration analyses were conducted, together with investigation into the methylation status of GGTLC1. Western blotting and Quantitative real-time PCR quantified expression levels. Additional experimental methodologies elucidated the role of GGTLC1 in EC progression. Transcriptome sequencing identified potential regulatory pathways for GGTLC1, and tumor growth was evaluated in vivo using HEC-1A cells in nude mice. ResultsGGTLC1 was upregulated and negatively correlated with immune cell infiltration and DNA methylation in EC. Cell migration and proliferation were reduced following GGTLC1 knockdown, together with arrest at the G0/G1 phase and an upsurge in apoptosis. Compared to the knockdown group, TGF-β/Smad signaling pathway was up-regulated in the negative control group of EC cells by transcriptome analysis. The levels of TGF-β, pSmad2, and pSmad3 followed the same decreasing trend, whereas Smad3 and Smad2 protein levels remained unchanged. ConclusionKnockdown of GGTLC1 attenuates EC development through the TGF-β/Smad pathway, positioning GGTLC1 as a promising target for EC treatment.

Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

Background and Objective:: Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-γ (PPAR-γ) coactivator-1α (PGC-1α), and PPAR-γ expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats. Methods:: Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases (endothelial (eNOS), inducible (iNOS), neuronal (nNOS)), and mRNA and protein levels of UCP-1, PGC-1α, and PPAR-γ. Result:: OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1α (65% and 39%), and PPAR-γ (66% and 34.5%) in GAT. Chronic inorganic nitrate administration in OVXrats increased mRNA and protein levels of UCP-1 (128% and 34%), PGC-1α (115% and 43%), and PPAR-γ (236% and 38%), respectively. Conclusion:: In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1α, and PPAR-γ in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT.

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-β1

PurposeRenal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. MethodsUsing db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. ResultsDOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. ConclusionDOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Expression of fibroblast activation protein in intrathoracic solitary fibrous tumor

PurposeFibroblast activation protein (FAP) is a serine integral membrane protease, the expression of which has been confirmed in various cancer types. Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal fibroblastic neoplasms. We present a case of 18F-labeled FAP inhibitor ([18F]FAPI-74) PET imaging and its correlation with histological FAP expression and review an SFTP series at our institution in relation to the extent of FAP expression. MethodsThis retrospective study included 13 patients who underwent surgery between March 2011 and December 2022 at our institute. One of the patients also underwent [18F]FAPI-74 PET imaging. We semi-quantitatively evaluated FAP expression in SFTPs using immunohistochemical staining and H-scores. ResultsNine of the 13 patients were male, with a median age of 64 years (range, 28–79 years). The median tumor size was 6.6 cm (1.1, 16 cm). In the pathological findings, expression levels of Ki67 were 1–5% in 12 of 13 cases. Furthermore, FAP expression was observed in all patients, and the median H-score was 160 (range, 10–280). The H-score of FAP expression in two of the 13 patients was low (10 in both), and that in two of the 13 patients was high (240 and 280). The SUVmax value of [18F]FAPI-74 PET was 3.57 in a patient in whom the H-score of FAP expression was 180. ConclusionsSFTPs expressed FAP to varying degrees in different patients and the [18F]FAPI-74 PET results in one patient reflected FAP expression in the tumor tissue.

Placental Transcriptome Analysis in Connection with Low Litter Birth Weight Phenotype (LBWP) Sows

It is possible to identify sub-populations of sows in every pig herd that consistently give birth to low birth weight (BW) piglets, irrespective of the litter size. A previous study from our group demonstrated that placental development is a main factor affecting the litter birth weight phenotype (LBWP) in sows, thereby impacting the BW of entire litters, but the biological and molecular pathways behind this phenomenon are largely unknown. The aim of this study was to investigate the differential gene expression in placental tissues at day 30 of gestation between low LBWP (LLBWP) vs. high LBWP (HLBWP) sows from a purebred Large White maternal line. Using mRNA sequencing, we found 45 differentially expressed genes (DEGs) in placental tissues of LLBWP and HLBWP sows. Furthermore, (GO) enrichment of upregulated DEGs predicted that there were two biological processes significantly related to cornification and regulation of cell population proliferation. To better understand the molecular interaction between cell proliferation and cornification, we conducted transcriptional factor binding site (TFBS) prediction analysis. The results indicated that a highly significant TFBS was located at the 5′ upstream of all four upregulated genes (CDSN, DSG3, KLK14, KRT17), recognized by transcription factors EGR4 and FOSL1. Our findings provide novel insight into how transcriptional regulation of two different biological processes interact in placental tissues of LLBWP sows.

Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer

DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial–mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/β-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.

Human mesenchymal stromal cells ameliorate cisplatin induced acute and chronic kidney injury via TSG-6.

Cisplatin is widely employed in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rhTSG-6), or PBS through tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. hBM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen (BUN), tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, knockdown of TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviate cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.

Role of LRP5/6/GSK-3β/β-catenin in the differences in exenatide- and insulin-promoted T2D osteogenesis and osteomodulation.

Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D. In vivo, micro-CT was used to detect differences in the peri-implant bone microstructure in vivo. Histology, dual-fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT-PCR and western blotting were used to measure the expression of osteogenesis- and Wnt signalling-related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT-PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation. Micro-CT and section staining showed exenatide extensively promoted peri-implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis-related and activated the LRP5/6/GSK-3β/β-catenin-related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation. Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK-3β/β-catenin signalling for osteogenic differentiation, exenatide-mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β-TrCP, respectively.

Expression of HER2 in urothelial carcinoma and its significance

Abstract Objectives We explored the expression levels and clinical significance of human epidermal growth factor receptor 2 (HER2) in urothelial carcinoma (UC) tissues. Materials and methods Patient data were reviewed, and 111 paraffin specimens of UC obtained from the Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, from 2020 to 2021 were collected. Immunohistochemistry was used to detect HER2 protein expression in all UC tumor tissues. χ 2 and Fisher exact tests were used to analyze the relationship between HER2 protein expression and clinicopathological data (sex, age, histopathological diagnosis, invasiveness, histopathological grade, maximum tumor diameter, muscle invasion, regional lymph node metastasis, and clinical stage). Results In this study, 92 cases (82.88%) showed HER2 protein expression, and there was a statistically significant difference in the distribution of HER2 positivity (immunohistochemistry 2+ and 3+) according to the pathological grades of UC (p = .021). Human epidermal growth factor receptor 2 positivity was not associated with sex, age, histopathological diagnosis, invasiveness, maximum tumor diameter, muscle invasion, regional lymph node metastasis, or clinical stage (all p < .05). Conclusions HER2 protein is highly expressed in UC, and its expression may be closely related to the high pathological grade of UC.

EDA2R-NIK signaling in cancer cachexia.

Cachexia is a debilitating condition causing weight loss and skeletal muscle wasting that negatively influences treatment and survival of cancer patients. The objective of this review is to describe recent discoveries on the role of a novel signaling pathway involving ectodysplasin A2 receptor (EDA2R) and nuclear factor κB (NFκB)-inducing kinase (NIK) in muscle atrophy. Studies identified tumor-induced upregulation of EDA2R expression in muscle tissues in pre-clinical cachexia models and patients with various cancers. Activation of EDA2R by its ligand promoted atrophy in cultured myotubes and muscle tissue, which depended on NIK activity. The non-canonical NFκB pathway via NIK also stimulated muscle atrophy. Mice lacking EDA2R or NIK were protected from muscle loss due to tumors. Tumor-induced cytokine oncostatin M (OSM) upregulated EDA2R expression in muscles whereas OSM receptor-deficient mice were resistant to muscle wasting. Recent discoveries revealed a mechanism involving EDA2R-NIK signaling and OSM that drives cancer-associated muscle loss, opening up new directions for designing anti-cachexia treatments. The therapeutic potential of targeting this mechanism to prevent muscle loss should be further investigated. Future research should also explore broader implications of the EDA2R-NIK pathway in other muscle wasting diseases and overall muscle health.

Organic acids mitigate Streptococcus agalactiae virulence in Tilapia fish gut primary cells and in a gut infection model

BackgroundStreptococcus agalactiae, a Gram-positive bacterium, has emerged as an important pathogen for the aquaculture industry worldwide, due to its increased induced mortality rates in cultured fish. Developing interventions to cure or prevent infections based on natural alternatives to antibiotics has become a priority, however, given the absence of scientific evidence regarding their mode of action progress has been slow.MethodsIn this study we aimed to investigate the effect of a mixture of organic acids (natural antimicrobials), AuraAqua (Aq), on the virulence of S. agalactiae using Tilapia gut primary epithelial cells and an in vitro Tilapia gut culture model. Our results show that Aq was able to reduce significantly, in vitro, the S. agalactiae levels of infection in Tilapia gut primary epithelial cells (TGP) when the MIC concentration of 0.125% was tested.Results and discussionAt bacterial level, Aq was able to downregulate bacterial capsule polysaccharide (CPS) gene expression, capC, resulting in a significant decrease in bacterial surface capsule production. The decrease in CPS production was also associated with a reduction in the pro-inflammatory IFNγ, IL1β, TNFα, SOD and CAT gene expression and H2O2 production in the presence of 0.125% Aq (P < 0.0001). The antimicrobial mixture also reduced the levels of S. agalactiae infection in an in vitro gut culture model and significantly reduced the IFNγ, IL1β, TNFα, SOD, CAT gene expression and H2O2 production in infected tissue. Moreover, genes involved in Tilapia resistance to S. agalactiae induced disease, MCP-8 and Duo-1, were also downregulated by Aq, as a consequence of reduced bacterial levels of infection.ConclusionConclusively, our study shows that mixtures of organic acids can be considered as potential alternative treatments to antibiotics and prevent S. agalactiae infection and inflammation in the Tilapia fish digestive tract.

Ferredoxin 1: a gatekeeper in halting lung adenocarcinoma progression through activation of the GPRIN2 signaling pathway.

Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression. FDX1, a crucial protein in cellular redox reactions and energy metabolism, has been linked to several cancers. However, its exact role in the development of LUAD is not yet fully understood. We investigated the role of ferredoxin 1 (FDX1) in LUAD progression through analysis of its expression in LUAD tissues and its impact on patient survival. Functional assays were performed to assess the effects of FDX1 overexpression on LUAD cell proliferation, migration, and invasion. A xenograft model was employed to evaluate the tumorigenesis potential of LUAD cells with FDX1 overexpression. Mechanistic insights into FDX1 regulation were gained through depletion experiments targeting the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2)/PI3K signaling pathway. FDX1 expression was down-regulated in LUAD tissues, correlating with shorter patient survival. Overexpression of FDX1 suppressed LUAD cell proliferation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Mechanistically, the GPRIN2/PI3K signaling pathway was implicated in FDX1 regulation, as depletion of GPRIN2 reversed the effects of FDX1 overexpression on cellular functions. Our findings highlight FDX1 as a potential tumor suppressor in LUAD, acting through modulation of the GPRIN2/PI3K signaling pathway. These results suggest FDX1 as a promising therapeutic target for LUAD treatment, warranting further investigation into its clinical relevance.

RGC32 promotes the progression of ccRCC by activating the NF-κB/SHP2/EGFR signaling pathway.

The role and clinical significance of the response gene to complement 32 (RGC32) in various cancers have been documented, yet its implications in clear cell Renal Cell Carcinoma (ccRCC) remain underexplored. This study investigated RGC32's diagnostic and prognostic relevance in ccRCC using bioinformatics methods with data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The impact of RGC32 on ccRCC progression was assessed through nude mouse tumor assays. Immunohistochemistry evaluated RGC32 levels in ccRCC and adjacent normal tissues, while cell proliferation, migration, and invasion capabilities were analyzed using CCK-8, monoclonal proliferation assays, Transwell, and wound healing assays, respectively. Western blotting measured relevant protein expressions. Bioinformatics analysis highlighted RGC32's significant role in ccRCC pathogenesis. Elevated RGC32 expression in ccRCC tissues was linked to disease progression. Functionally, RGC32 was found to enhance the expression of proteins such as p-PI3K, CyclinA1, CyclinD1, p-STAT3, MMP2, MMP3, MMP9, p-SMAD2/3, Snail, Slug, and N-Cadherin via the NF-κB/SHP2/EGFR pathway, while decreasing E-cadherin levels. Moreover, RGC32 facilitated ccRCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). RGC32 is a pivotal factor in ccRCC development, primarily through the activation of the NF-κB/SHP2/EGFR signaling pathway.

MiR-625-5p Modulates the Metastasis and Proliferation of Gastric Cancer Cells by Governing the M6A Demethylase ALKBH5

Background: Gastric cancer is a prevalent malignant tumor globally, with metastasis and recurrence serving as primary contributors to the diminished survival rates observed in patients with advanced stages of the disease. Despite numerous investigations into the pathogenesis of gastric cancer, the significance of m6A demethylase ALKBH5 in the initiation and progression of the disease has been established, yet its precise mechanism remains incompletely understood. Methods: Immunohistochemistry was utilized for the evaluation of ALKBH5 expression in gastric cancer tissues, while RT-qPCR and WB were employed for the analysis of ALKBH5 expression in cells. Additionally, the levels of m6A methylation in RNA were assessed using the EpiQuikTM m6A methylation quantitative assay kit. The proliferative and metastatic potentials of gastric cancer cells were assessed using the CCK-8 and Transwell cell assays, respectively. The binding site between miR-625-5p and ALKBH5 was predicted through the TargetScan website, and the interaction was confirmed using a dual luciferase reporter assay. Results: The research findings indicated a significant increase in m6A methylation levels in gastric cancer cells, concomitant with a substantial decrease in ALKBH5 expression. ALKBH5 can inhibit the proliferation and metastasis of gastric cancer cells. Additionally, the interaction between miR- 625-5p and the 3'-UTR of ALKBH5 mRNA, resulting in the suppression of ALKBH5 expression, was validated. Conclusions: Through its specific interaction with ALKBH5, miR-625-5p modulates the proliferation and metastatic potential of gastric cancer cells, bridging a previously unexplored link in the pathogenesis of gastric cancer between miR-625-5p and ALKBH5. This finding suggests that miR- 625-5p could be a potential target for treating gastric cancer, with the goal of enhancing patient outcomes and quality of life.

Bovine papillomavirus vertical transmission: BPV diversity and expression in maternal and fetal tissues.

Bovine Papillomaviruses (BPVs) constitute a diverse group within the Papillomaviridae family, playing a crucial role in bovine health and economic considerations. This study investigates the dynamics of vertical transmission of BPV in cattle, focusing on five cows and their reproductive tissues, as well as three gravid cows and their fetuses. DNA and RNA samples were extracted from the warts, fetal skin, placenta, uterus, ovary, and blood of cows, as well as the skin and blood of fetuses. Polymerase Chain Reaction (PCR) targeted BPV types 1-6 and 8-14, was assessed in both cows and fetuses. Additionally, Reverse Transcription PCR (RT-PCR) examined BPV-2 E5 oncogene expression in the skin and reproductive sites of mother cows and fetuses. Our findings unveil a rich diversity of BPV types, including BPV-2, 3, 9, 10, 12, and 14, present in both maternal and fetal tissues. Intriguingly, certain types, namely BPV-4, 6, 8, and 11, were exclusively identified in maternal tissues A higher diversity of BPVs was observed in cow warts, followed by cow blood, fetal blood, and fetal skin. Strikingly similar BPV types in gravid cow blood and fetuses suggest primary dissemination through the bloodstream and transmission via the placenta, though detected in lower numbers in cow uterus and ovary. Histopathological analysis revealed no abnormalities in the reproductive tissues despite the presence of BPV. However, in one bladder sample from a cow that did not consume bracken fern, urothelial neoplasia in situ was observed. The study extends beyond detection, exploring the expression of the BPV-2 E5 oncogene in fetal tissues, providing insights into potential cell implications. Comparative analyses with previous studies highlight the uniqueness of our investigation, encompassing a broader array of BPV types in the gravid cows and their fetuses. The findings not only establish a foundation for further investigations into the mechanisms of vertical transmission but also highlight the need for targeted interventions and surveillance strategies to mitigate potential health risks associated with specific BPV types.

Transcriptomic characteristics analysis of bone from chronic osteomyelitis

To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKβ), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKβ, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.