Tissue & cell最新文献

Prostate cancer is the second leading cause of cancer-related among men globally, with a rising incidence rate, particularly in developing countries. This highlights the urgent need to identify novel therapeutic agents. Roemerine, a naturally abundant alkaloid, has demonstrated antibacterial and antitumor properties, suggesting its potential utility in prostate cancer treatment. This study evaluates the effects of roemerine on RM-1 prostate cancer cells using in vitro assays and an in vivo nude mouse subcutaneous xenograft tumor model. Through Cell Counting Kit-8(CCK8), MTT, Wound-Healing, and Transwell assays, we assessed roemerine's impact on RM-1 cell proliferation, migration, and invasion. Additionally, the antitumor efficacy of roemerine was evaluated in nude mice bearing subcutaneous RM-1 tumors. Our findings reveal that roemerine significantly inhibits RM-1 cell activity, migration, invasion, and tumor growth. These results highlight the potential of roemerine as a novel antitumor agent for prostate cancer, providing a foundation for further mechanistic and pharmacological investigations.

Background: PRMT7 is upregulated in breast cancer and promotes tumor metastasis. Here we aimed to explore the function and mechanism of PRMT7 in triple-negative breast cancer (TNBC).

Methods: The expression of PRMT7, METTL3 and IGF2BP1 was detected by immunohistochemistry (IHC), qRT-PCR and western blot. Cell viability and proliferation were measured using MTT and EdU assay. Flow cytometry and TUNEL assays were used to evaluate apoptosis. Invasion and migration were assessed by transwell and wound healing assays, respectively. Glucose consumption and lactate production were measured to assess glycolysis. In addition, the interaction between METTL3 and PRMT was verified by methylated RNA immunoprecipitation. The roles of METTL3 and PRMT in vivo were investigated through a xenograft model.

Results: PRMT7 was upregulated in TNBC tissues and cells, and the knockdown of PRMT7 inhibited cell proliferation, invasion, migration and glycolysis, but induced apoptosis in TNBC cells. METTL3/IGF2BP1 enhanced PRMT7 expression by mediating the m6A methylation modification of PRMT7. Besides, METTL3 knockdown suppressed the progression of TNBC cells and regulated the WNT/β-catenin pathway via PRMT7. Moreover, silencing METTL3 restrained TNBC tumor growth in vivo through regulating PRMT7.

Conclusion: METTL3/IGF2BP1 facilitates the progression of TNBC by mediating m6A methylation modification of PRMT7.

Objective: Mitochondria transfer from human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs-mt) and human endometrium-derived mesenchymal stem cells (hE-MSCs-mt), along with curcumin, were explored as potential treatments for age-related macular degeneration (AMD) caused by mitochondrial inefficiency, using a retinal model to assess impacts of curcumin and hWJ-MSCs-mt or hE-MSCs-mt on AMD.

Methods: ARPE-19 cells established an in vitro AMD model. Cells were exposed to 0-50 μM curcumin for 24 hours to determine optimal concentration by assessing their viability. Immunofluorescence examined SOD1, TNF-α, and TGF-β levels at optimal hydrogen peroxide (H₂O₂) concentration. β-galactosidase staining and DCFH analysis evaluated H₂O₂-induced cellular senescence. Immunofluorescence assessed REP65, CRALBP1 (RLBP1), Pink1, and Parkin expression, whereas qRT-PCR analyzed Nrf2, Ire1a, ARMS2, HTRA1, RPE65, RLBP1, NOX4, and TOMM20 expression following co-treatment with curcumin and hWJ-MSCs-mt or hE-MSCs-mt.

Results: Curcumin improved ARPE-19 cell survival under H₂O₂-induced oxidative stress by regulating SOD1, TNF-α, TGF-β, DCFH, and MDA levels. hWJ-MSCs-mt transfer increased RLBP1 and Parkin expression, whereas curcumin reduced Parkin expression. hE-MSCs-mt transfer upregulated Parkin, RPE65, Pink1, and RLBP1 expressions, with curcumin enhancing RPE65 expression. hWJ-MSCs-mt and curcumin combined more effectively downregulated expressions of stress-related genes (Nrf2, Ire1α, NOX4) and improved expression of mitochondrial function gene (TOMM20). hE-MSCs-mt transfer with curcumin synergistically enhanced expression of retinal health markers (RPE65, RLBP1) and downregulated expression of damage-associated genes (HTRA1, ARMS2) in AMD models.

Conclusion: Curcumin combined with hWJ-MSCs-mt or hE-MSCs-mt is a potential AMD therapy owing to its anti-inflammatory properties; however, further in vivo and human studies are needed to confirm its efficacy and safety.

Background and objective: Organ transplantation is a vital treatment for patients with end-stage organ diseases, and macrophages play a key role in the rejection process. This study seeks to pinpoint key genes responsible for the dynamic changes in macrophages during rejection and to evaluate their impact on macrophage polarization through bioinformatics analysis.

Methods: We selected single-cell sequencing data of mouse heart transplant models from Genome Sequence Archive to construct a dynamic landscape of immune cells during acute rejection. Key genes involved in macrophage changes were screened using pseudotime analysis and hdWGCNA. The mouse heart transplant models also were established to validate changes of the key genes during rejection.

Results: Bioinformatics analysis identified Gbp2 as the key gene driving macrophage dynamics during rejection, which was also confirmed in another dataset showed Gbp2 levels increased in macrophages during acute rejection. Further experiments validated the upregulation of Gbp2 in both tissues and macrophages during acute rejection, and in vitro experiments confirmed Gbp2 increasing in M1 macrophages.

Conclusion: Gbp2 is a key gene that regulates macrophage polarization during acute rejection, making it a potential therapeutic target for the acute rejection.

Objective: Cholangiocarcinoma (CCA) presents a therapeutic challenge due to its aggressiveness and poor survival rates. This study introduces an approach using tissue inhibitor of metalloproteinase 2 (TIMP2)-enriched bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) encapsulated in chitosan hydrogels (CS), intending to provide novel insight into the CCA treatment.

Methods: BMSC-Exo was characterized by using TEM, nanoparticle tracking analysis, and western blotting. Role of TIMP2 in CCA was explored using bioinformatics analysis. Therapeutic efficacy and mechanisms of BMSC-Exo/CS in CCA were assessed through cell viability tests and colony formation assays. Angiogenic and Wnt/β-catenin signaling pathways-related key factors were detected through RT-qPCR or western blotting.

Results: BMSC-Exo displayed typical cup-shaped morphology and was positive for exosomal markers CD9 and TSG101, but negative for endoplasmic reticulum marker Calnexin, with a diameter of 124.6 nm. BMSC-Exo combined with CS showed synergistic anti-proliferative effects in CCA cells. High-expression TIMP2 samples indicated a better prognosis of CCA patients, and BMSC-Exo/CS increased the TIMP2 expression in CCA cells. Mechanistically, BMSC-Exo/CS TIMP2 overexpression inhibited key factors related to angiogenesis (VEGFA and VEGFR2) and Wnt/β-catenin pathway (β-catenin and c-Myc), thereby reducing CCA cell viability. Notably, these inhibitory effects were reversed by a Wnt signaling agonist (BML-284).

Conclusion: The study validates the therapeutic potential of BMSC-Exo/CS TIMP2 in CCA treatment. This innovative approach targets angiogenesis and Wnt/β-catenin signaling, providing a new avenue for more effective and comprehensive CCA therapies.

Malaria is endemic in poverty-stricken regions of the world, and most diagnosis reveal comorbidity with other infectious diseases some of which manifest as a deformity of the structural arrangement of the Red Blood Cells (RBCs) during thin blood smear microscopy. This common occurring deformity is termed rouleaux formation, and it is the stacking together of RBCs like chains of coins. The presence of rouleaux formation indicates either a bacterial infection, connective tissue disease, chronic liver disease, multiple myeloma or diabetes among others, it is a highly common occurrence in malaria infected patients and according to the international council for standardization of hematology (ICSH), microscopists are mandated to report its presence. Hence to develop unbiased automated malaria diagnostic systems capable of being deployed in malaria endemic regions, these systems need to be capable of identifying rouleaux formation and detecting malaria parasite within such type of RBC. Thus, this study developed a thin blood smear dataset with rouleaux formation RBCs infected with two species of malaria parasite: plasmodium falciparum and plasmodium malariae. YOLOv9s architecture was used to benchmark the dataset for the detection of plasmodium parasites and white blood cells in the developed dataset. Comparing the effect of using pretrained weights, YOLOv9s trained from scratch achieved a Precision, Recall and mAP50 of 75.4 %, 76.6 % and 80.3 % while YOLOv9s pretrained on the MS COCO dataset recorded an improvement in performance metrics with an increase in Precision by 0.4 %, an increase in Recall by 5.4 % and an increase in mAP50 by 2.5 .

Traumatic spinal cord injury (TSCI) is a serious medical issue where there is a loss of sensorimotor function. Current interventions continue to lack the ability to successfully enhance these conditions, therefore, it is crucial to consider alternative effective strategies. Currently, we investigated the effects of fibrin scaffold encapsulated with epigallocatechin gallate (EGCG) microspheres in the recovery of SCI in rats. A total of sixty mature male Sprague-Dawley rats were separated into four groups of the same size: TSCI, fibrin, EGCG, and Fibrin+EGCG. Samples of tissue were gathered at the location of the injury for additional examination. The treatment groups showed significantly higher levels of neurons, antioxidative biomarkers (T-AOC: total antioxidant capacity, GSH: glutathione, and SOD: superoxide dismutase), neurofilament light polypeptide (NEFL) and interleukin 10 (IL-10) genes, and neurological function scores compared to the TSCI group, with the Fibrin+EGCG group displaying the most noticeable improvements. Throughout the treatment process, there was a notable reduction in the amounts of apoptotic and glial cells, as well as levels of malondialdehyde (MDA) and proinflammatory genes (TNF-α: tumor necrosis factor alpha and IL-1β: interleukin-1 beta), especially in the Fibrin+EGCG group compared to the TSCI group. Our findings suggest that EGCG enclosed in microspheres could enhance the prevention of injury spreading and the enhancement of pathological and behavioral symptoms when delivered to the location of spinal cord injury using a fibrin scaffold.

In this study, we investigated the efficacy of oxymatrine, a phytochemical alkaloid, in reducing inflammation and fibrosis in a rat model of IgA nephropathy (IgAN) through modulation of the TGF-β/SMAD signaling pathway. Thirty Sprague Dawley rats were randomized into control, IgAN, and treatment groups, the latter receiving oxymatrine postinduction of IgAN. Induced by bovine serum albumin, carbon tetrachloride, and lipopolysaccharides, the disease model was validated by immunofluorescence and histopathological analyses, confirming significant renal deposition of IgA and increased fibrosis markers (IL-6, TGF-β, SMAD 3, and α-SMA). Oxymatrine treatment led to a notable decrease in urine protein levels and red blood cells at 10 weeks, suggesting reduced kidney damage. There was no significant impact on the SGOT or SGPT levels, while it reduced the BUN, serum ALB and creatinine levels, indicating minimal hepatotoxicity and renoprotective effects. Histopathology demonstrated preservation of the glomerular diameter in the treatment group. Immunofluorescence and ELISA revealed a reduction in the levels of proinflammatory (IL-6,TNF-α) and profibrotic (TGF-β, SMAD 3, and α-SMA) markers in treated rats, suggesting that oxymatrine has renoprotective effects on the inhibition of pathological EMT processes and fibrosis in IgAN. Our results suggest that oxymatrine is a potential therapeutic agent for IgAN that attenuates disease progression by targeting the TGF-β/SMAD pathways involved in EMT and fibrosis. Further research is warranted to establish long-term efficacy and safety profiles.

Exocrine glands are important mediators of communication in eusocial insects and the description of novel glands reflects the complex context in which these animals live. Here we revisit the head-associated glands in workers of the Neotropical termite Cornitermes cumulans through histological analysis and describe a novel gland for this caste, the intramandibular glands. This structure is located underneath the cuticle of the dorsodistal part of each mandible. The glands showed an epithelial arrangement, but the cytological morphology is complex, comprising classes I and III of secretory cells. The present data highlight the importance of the intramandibular glands in the worker caste and demonstrate different morphology of these glands in Isoptera, probably related to the specialized function of the castes. Features of active glandular activity were also observed in the mandibular, labral, and salivary glands of these workers. Despite the intramandibular glands being also found in workers of other social insects, their occurrence in termites was restricted to the soldier caste of Machadotermes. Even so, their cytological structure differs from those of C. cumulans workers. The likely function of the worker intramandibular glands is discussed considering the separate-nest life type present by C. cumulans and tasks performed by workers. The chemical nature of the secretion and the occurrence of the glands in other termite taxa still require further investigation.

Endocrine multisystem defect polycystic ovary syndrome (PCOS) causes hyperandrogenism and infertility. Half of PCOS women have (non-alcoholic fatty liver disease) NAFLD, which increases metabolic disease risk. We tested decorin's effect on NAFLD and related processes in PCOS. NAFLD+PCOS, PCOS+decorin, and control rats were studied. Decorin was evaluated on NAFLD/PCOS rats. Test group rats received HF for eight weeks to generate NAFLD. The rats got 1 mg/kg letrozole orally daily for 21 days to diagnosis PCOS. Afterward, rats got injectable decorin for 14 days. Body weight, liver weight, liver coefficient Abdominal Circumference (AC) and body mass index (BMI) were determined. Blood triglycerides (TG), total cholesterol, LDL-c, AST, and glucose were measured. The insulin, testosterone, estrogen, LH, and FSH were measured by ELISA. GPx, SOD, MDA, TNF-, and Caspase-3 liver immunohistochemistry were evaluated. NAFLD liver tissues in PCOS models showed biochemical and histological alterations. NAFLD+PCOS raised BMI, AC, liver weight, and coefficient. Blood glucose, insulin resistance, TG, ALT, and AST increased. Lipid abnormalities (TG, cholesterol, LDL-c, and HDL-c), oxidative stress markers (MDA, SOD, and GPx), and liver dysfunction were found. Low serum E2 and high T supported PCO. Decorin reduced model rat BMI, liver weight, coefficient, insulin resistance, TG, ALT, and AST. It reduced liver inflammation, improved liver extract lipids, and normalized MDA, SOD, and GPx. In the model group, decorin lowered serum T, E2, LH, caspase 3, and TNF-alpha. Decorating improved NAFLD/PCOS group liver histology and function. Decorin reduces hepatosteatosis by reducing liver inflammation, oxidative stress, and dyslipidemia.