Tissue & cell最新文献

Non-muscle-invasive bladder cancer (NMIBC) is a malignancy with a high recurrence and progression rate, particularly in patients who fail to respond to standard Bacillus Calmette-Guérin (BCG) therapy. OncoTherad (MRB-CFI-1) nanoimmunotherapy has emerged as a promising therapeutic option, with potential to modulate immune responses and inhibit tumor progression. This study evaluated the clinical efficacy of OncoTherad (MRB-CFI-1) nanoimmunotherapy in patients with BCG-unresponsive NMIBC and investigated correlations between therapeutic outcomes and histopathological and molecular findings. In this retrospective cross-sectional study, 20 patients with BCG-unresponsive NMIBC were treated with OncoTherad (MRB-CFI-1) across two clinical centers. Bladder tissue samples were collected before and after treatment, and immunohistochemical analyses were performed to assess the expression of SERBP1, HABP4, CD44, and Ki-67. Primary endpoints included pathological complete response (pCR), recurrence-free survival (RFS), and duration of response (DoR), which were analyzed in relation to immunohistochemical biomarker findings. Our results demonstrated that high Ki-67 proliferative index and elevated immunoreactivity for CD44 and SERBP1 were associated with shorter RFS. Treatment with OncoTherad (MRB-CFI-1) significantly reduced (p < 0.05) the immunoreactivity of SERBP1 and CD44, which was accompanied by a marked decrease in Ki-67 proliferative index, indicating effective suppression of tumor activity. Conversely, a significant increase (p < 0.05) in HABP4 immunoreactivity was observed, suggesting a protective role against NMIBC recurrence and progression. A pCR was achieved in 65 % of patients, with a median RFS of 21.1 months and a median DoR of 15.7 months, underscoring the clinical efficacy of OncoTherad (MRB-CFI-1). These findings suggest that OncoTherad (MRB-CFI-1) nanoimmunotherapy offers a novel and effective treatment strategy for patients with BCG-unresponsive NMIBC, providing a promising alternative to radical cystectomy and significantly improving patient outcomes.

Introduction: This study endeavors to draw a comparative analysis between a traditional herbal ointment, specifically Swalin, and silver sulfadiazine ointment in the context of repairing deep second-degree burns.

Methods: A randomized clinical trial was conducted at the Iran University of Medical Sciences. In this investigation, a cohort comprising eighty-two patients was stratified into two groups, namely Swalin (n = 41) and Silver sulfadiazine (SSD) (n = 41). Over 28 days, ointment applications were administered twice daily. The quantification of ointment compounds was conducted employing Gas Chromatography-Mass Spectrometry (GC-MS). The study encompassed a comprehensive assessment involving clinical examination, quantitative and qualitative histopathological evaluations, pain level determination, and scrutiny of wound closure. Statistical analyses, encompassing chi-square and Mann-Whitney U tests, were performed using SPSS software.

Results: Our investigation revealed that the predominant compounds in the ointment were linoleic acid (41.37 %) and elaidic acid (37.45 %). On the 28th day, the Swalin group demonstrated a significantly higher rate of wound closure (81.52 ± 7.76) compared to the SSD group (69.91 ± 2.48) (p < 0.001). Furthermore, a statistically significant distinction was observed between the two groups concerning the degree of epithelialization (P = 0.048). Fibroblast density exhibited a notable discrepancy between the groups (P = 0.02). In terms of angiogenesis and collagen deposition, the Swalin group displayed a significant contrast with the SSD group (P = 0.008 and P = 0.007, respectively), while no statistical distinction was discerned in the number of immune cells (P > 0.05). Histological examination of SSD illustrated a pronounced infiltration of inflammatory cells in the dermis, predominantly lymphocytes. Conversely, the Swalin group exhibited well-formed dermal layers, minimal infiltration, and a profusion of vessels.

Conclusion: In conclusion, the findings of this study highlight the potential therapeutic benefits of Swalin ointment, attributed to its rich composition of fatty acids, particularly linoleic acid, and the presence of vitamins C and E.

Background: The issue of using many food additives in food is becoming increasingly relevant. The effect of these substances on the nervous system, namely the cerebellum, is not unrelated. There are studies on the impact of food additives individually, but their combined effect has not been studied sufficiently. Therefore, the aim of our study was to determine structural changes in rats' ganglionic layer of the cerebellar cortex under the influence of monosodium glutamate and sodium nitrite in combination.

Methods: The experiment involved 84 white Wistar laboratory rats, which were divided into a control group and five experimental groups. The obtained cerebellar samples were paraffin-embedded and histological sections (3-4) μm thick were made. These sections were stained with hematoxylin, eosin, and silver impregnated by Grimmelius.

Results: After calculating the average thickness of the cerebellar cortex ganglionic layer at different administration periods of monosodium glutamate and sodium nitrite in combination, significant changes were observed after week 1, where this indicator was 1.18 times less than in the control. Also, a decrease in the average thickness was observed after the 4th and 12th and a significant decrease in the 16th week of the study, namely by 1.61 times, 1.43 times and 1.77 times, respectively. It indicates substantial structural changes in the ganglionic layer.

Conclusions: The study found that the ganglionic layer is formed of a single row of Purkinje cells, and they, in turn, are the main functional link in the entire grey matter of the cerebellum, which suggests that the use of a complex of food additives causes functional disorders of the cerebellum as a whole.

VGF peptides, such as NERPs (neuroendocrine regulatory peptides 1 and 2), are derived from amino acids 282-306 and 313-350, respectively, of the human proVGF, which is produced in spinal cord motor neurons. Although certain VGF-derived peptides are changed in ALS, less is known about NERPs. Possible modulations of NERPs and additional VGF peptides (NAPP and TPGH) were investigated using specific antibodies through competitive ELISA in the plasma of ALS patients (at both the initial and advanced phases; n = 46 each vs. 46 controls). As additional controls, naïve PD patients were also enrolled (n = 19 vs. 18 controls) while the potential VGF peptide role in oxidative stress was investigated using a motoneuron-like cell line (NSC34) stressed with sodium arsenate (SA). Western blot (WB) and sephadex chromatography (SC) were used to identify the molecular weight (MW) forms recognized by the VGF antibodies. Exclusively NERP-1 immunoreactivity was changed (elevated) in all plasma samples of ALS patients (compared to controls). Therefore, the NERP-1 antibody was the sole antibody used in ELISA with PD samples and NSC-34 cells. No alterations were seen in PD samples (vs. controls) while NERP-1 immunoreactivity decreased within SA-treated cells but increased in their culture medium. The viability test performed by adding NERP-1 to the stressed cells showed no protective effect. Using WB and SC, we revealed NERP-1 antibody reactivity against various MW forms, including those compatible with the NERP-1 peptide and/or proVGF. NERP-1 is suggested as a possible ALS blood biomarker.

Ischemia/reperfusion injury (IRI) is caused by the reduced blood flow and oxygen level due to the renal artery blockage. The effect of Schisandrae Sphenantherae Fructusandra fruit anwulignan (AN) on the renal IRI injury in rats was investigated. Four rat (Male SD) groups were set, including sham, IRI, sham+AN and IRI+AN groups. This experiment confirmed that AN could reduce renal IRI injury by detecting some biomarkers such as Cre, BUN, LDH, HIF-1α, KIM-1, NGAL, and AIM, which showed decreased levels. AN could increase GSH, CAT, T-AOC, and SOD levels, and decrease MDA and ROS levels in rat kidney tissue, demonstrating that AN can improve oxidative stress damage. In addition, AN diminished the total quantity of TNF-α, IL-1β, IL-6, IL-8, and IL-18 in the renal tissue of rats. In rats with renal IRI, the contents of p-Nrf2 and HO-1 proteins engaged in the Nrf2/HO-1 antioxidant controlled system were increased, and the expression level of Keap1 was diminished. NLRP3, ASC, Caspase-1, GSDMD, GSDMD-N, IL-18, and IL-1β protein levels in kidney tissues decreased significantly in AN group. The results indicate that AN can alleviate renal IRI by reducing the oxidative stress damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NLRP3-Caspase-1-GSDMD-mediated pyroptosis in rats.

Metastatic diseases are the major causes of cancer related deaths. Circulating tumor cells are important mediators for distant metastases. However, knowledge about circulating tumor cells is still limited due to their small quantity, lack of explicit markers, interferences from blood cells and immune cells, and so on. In this study, we discovered the concomitant tumor suspension cells in a human epidermal growth factor receptor 2 enriched type breast cancer cell line, SKBR-3. In vitro cultured SKBR-3 shed suspension cells in a spontaneous and continuous manner, which can survive and proliferate infinitely under suspension state. We therefore established the "progeny" suspension cell line of its adherent counterpart, or so-called the concomitant tumor suspension cell line. The concomitant tumor suspension cells were in an intermediate partial-epithelial-mesenchymal transition state and were highly adapted to survival in the blood circulation system. The tendency to form microtumors suggests that they are closely related to the metastases of cancers. This study provides a new direction for investigating metastases. By screening more cancer cell lines and establishing more concomitant tumor suspension cell lines, we can acquire much more knowledge implying the evolution of circulating tumor cells, and achieve a better understanding of cancer metastases.

Cisplatin (CIS) is effective against various cancers but causes significant side effects, including testicular damage. This study investigated the effects of taxifolin (TX), a potent flavonoid with well-known benefits, against CIS-induced testicular injury. Mice received TX (25 and 50 mg/kg) orally for 14 days, with a single injection of CIS (7 mg/kg) on day 8. CIS significantly impaired sperm parameters (motility, viability, and count) and caused notable histopathological alterations in testicular tissue. CIS-treated testicular tissue exhibited elevated MDA and protein carbonyl levels, alongside decreased antioxidant defenses, including GSH, SOD, and catalase activities. TX significantly mitigated the deterioration of sperm parameters and prevented testicular tissue damage. It also restored antioxidant levels and reduced MDA and protein carbonyl contents. Furthermore, CIS elevated pro-inflammatory markers (NF-κB p65, TNF-α, and IL-1β) and apoptosis markers (Bax and caspase-3), while reducing anti-apoptotic Bcl-2 levels. TX effectively suppressed NF-κB activation, reduced pro-inflammatory cytokine production, and inhibited apoptosis in CIS-treated mice. Overall, TX alleviated CIS-induced oxidative stress, inflammation, apoptosis, and testicular damage, thereby improving sperm quality. These findings emphasize TX's potential as a protective agent against CIS-induced testicular damage and warrant further research in human applications.