American journal of translational research最新文献

Objective: In South Asia, Curcuma longa and Allium sativum are extensively used as household remedies for wound care for veterinary and human infectious diseases. However, little pharmacologic data is present to support this folklore. A series of in vitro and in vivo experiments were conducted to validate the folkloric practice of these herbs.

Methods: In vitro experiments, phytochemistry, polyphenolic content, acute dose dermal toxicity, antimicrobial activity, and antioxidant assays were conducted. For in vivo experiments, the decoction was prepared and tested for a wound cure against an experimentally induced excision wound on the dorsal region of rats under ketamine anesthesia. Rats were divided into five groups (5 rats in each). Group 1 was treated with standard Povidone-Iodine, Group 2 was treated with distilled water, group 3 received topical application of the decoction, Group 4 received topical as well as 1 mL oral decoction, and Group 5 received topical as well as oral 1 mL water. Histopathology, leukocyte count and acute oral dose toxicity were estimated.

Result: After the ninth post-wounding day, the wound contractions recorded in each group were group-1 (83.11%), group-2 (19.21%), group-3 (91.01%), group-4 (100%), and group-5 (16.55%) similarly less cytoarchitectural damage and more promising cellular repair were observed in both decoctions treated groups as compared to standard and control. A less exaggerated WBC profile was recorded in decoction-treated groups compared to standard and control, while decoction showed significant antibacterial potential even against the resistance strains of standard antibiotics. Decoction showed no dermal and oral toxicity in the animals tested.

Conclusion: Decoction of A. sativum and C. longa possesses excellent wound healing potential because of the variety of phytoconstituents linked to the antibacterial, antioxidant, and immunomodulator spectrum and can be used as an effective household remedy for wound healing with no notable toxicity.

Objective: To investigate the biological role of miR-132 in a murine model of chronic obstructive pulmonary disease (COPD) via activation of the SIRT1/FoxO1 axis.

Methods: COPD was induced in C57BL/6J male mice by exposing them to cigarette smoke (CS) for 8 weeks. A miR-132 knockout mouse model was used to assess the role of miR-132 in CS-induced COPD. Lung tissue apoptosis was evaluated using TUNEL assays and histopathology, along with lung functional tests which were performed to assess CS-induced lung injury.

Results: Elevated miR-132 expression was observed in lung tissues and bronchoalveolar lavage fluid in COPD mice. miR-132 depletion improved lung function, restored lung tissue morphology, and reduced apoptosis. Target prediction software identified miR-132 as a potential repressor of SIRT1. In COPD mice, SIRT1 and FoxO1 expression were reduced, but miR-132 knockout restored their levels.

Conclusion: Inhibition of miR-132 may serve as a therapeutic strategy for CS-induced COPD.

T-cell large granular lymphocyte leukemia (T-LGLL), which is associated with autoimmune diseases, has been described. However, T-LGLL with B-cell dyscrasias presenting as autoimmune hemolytic anemia has been less frequently reported. Here, we report a rare case of combined papillary thyroid cancer (PTC), discuss the possible relationship between autoimmune hemolytic anemia (AIHA) and TLGLL, and review the literature. The patient presented with pancytopenia and systemic jaundice. Fortunately, the patient responded well to hormone and immunosuppressive (methotrexate) therapy. However, this insight is based on one rare case, and the pathogenesis of this disease requires further clinical research for clarification.

Objective: To evaluate the efficacy of FOLFOX regimen combined with cetuximab in the treatment of advanced colon cancer.

Methods: This retrospective study involved 60 patients with primary colon cancer who were treated in the PLA Navy Anqing Hospital from January 2022 to February 2023. According to their treatment regimen, the patients were divided into a treatment group that received FOLFOX4 combined with cetuximab (n=30), and a control group treated with cetuximab alone (n=30). The general data of the two groups were compared, and the short-term response rate was assessed by comparing the proportions of complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) between the two groups. In addition, the progression free survival (PFS) and overall survival (OS) were compared between the two groups, along with the adverse reactions and changes in serum tumor marker (CEA and CA19-9) levels.

Result: The observation group showed a significantly higher short-term effective rate (CR+PR) compared to the control group (56.67% vs. 23.33%). The PFS and OS of the observation group were markedly longer compared to the control group. In terms of adverse reactions, the incidence of neutropenia, thrombocytopenia, nausea, vomiting, and diarrhea was similar between the two groups; however, the incidence of rash in the observation group was higher. After the treatment, the serum CEA and CA19-9 levels decreased markedly in both groups, and the observation group demonstrated obviously lower levels than the control group (P<0.001). Similarly, the decreases in VEGF-A and VEGFR2 levels in the observation group were more significant than those in the control group (all P<0.001).

Conclusion: Despite inducing rash, which is controllable, the combined therapy of FOLFOX and cetuximab significantly improves short-term efficacy, reduces the levels of CEA, CA19-9, VEGF-A and VEGFR2, and extends the PFS and OS of patients, which can be served as an effective treatment strategy for advanced colon cancer.

Objective: To investigate the pro-apoptotic effects of Indirubin, a traditional Chinese medicine, on ovarian cancer SKOV3 cell line and to explore its underlying mechanisms.

Methods: Ovarian cancer SKOV3 cells were divided into a control group (cells cultured normally) and an experimental group (cells cultured in medium containing Indirubin). SKOV3 cells at the logarithmic phase were treated with Indirubin at various concentrations. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, while apoptosis was detected by flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunofluorescence. Transcriptome sequencing was conducted to screen for apoptosis-related factors. qPCR and western blot were used to detect the mRNA and protein expression on added of molecules related to mitochondrial permeability transition pores.

Results: MTT assay showed that Indirubin inhibited the growth of SKOV3 cells in both plate and sphere cultures, with IC₅₀ values of 3.003 μM (plate culture) and 4.253 μM (sphere culture), respectively. Indirubin showed a lower inhibitory concentration than cisplatin (IC₅₀ 3.687 μM in plate culture and 7.023 μM in sphere culture), and its effect was comparable to adriamycin. Flow cytometry revealed an increase in apoptosis rates in SKOV3 cells treated with Indirubin. Transcriptome sequencing indicated significant changes in the transcription of various apoptosis-related genes, particularly those involved in the mitochondrial apoptosis pathway, such as Bcl-2-associated X protein (Bax) and Bcl2 associated agonist of cell death (Bad). After Indirubin treatment, the mRNA and protein expression levels of mitochondrial channel-related genes Cyclophilin D (CyPD), adenine nucleotide translocator 1 (ANT1), and voltage-dependent anion channel (VADC) were significantly elevated (all P < 0.05). By regulating the mitochondrial membrane permeability through the Bcl-2 family members, Indirubin promoted apoptosis in SKOV3 cells.

Conclusion: Indirubin inhibits the proliferation and promotes the apoptosis of ovarian cancer cells, exerting an anti-tumor effect. Its pro-apoptotic action is closely related to the mitochondrial apoptosis pathway.

Objective: To determine the diagnostic value of multimodal ultrasound combined with tumor markers in breast cancer (BC).

Methods: A retrospective analysis was conducted on 198 patients with breast lesions treated at the Affiliated Wuxi People's Hospital of Nanjing Medical University between May 2020 and May 2023. All patients underwent multimodal ultrasound and tumor marker testing. Among the 198 patients, 88 patients were pathologically diagnosed with benign disease (benign group) and 110 patients were pathologically diagnosed with malignant disease (malignant group). With the pathological results as the gold standard, the benign and malignant results from different diagnostic methods were compared, focusing on specificity, sensitivity and accuracy.

Results: The areas under the curves (AUCs) of carbohydrate antigen 153 (CA153), CA125, and carcinoembryonic antigen (CEA) for diagnosing BC were 0.810, 0.812, and 0.790, respectively. When these tumor markers were used in combination for diagnosing BC, the AUC increased to 0.928. The AUC of multimodal ultrasound alone in diagnosing BC was 0.845. Additionally, the AUC of multimodal ultrasound combined with tumor markers in diagnosing BC reached 0.971, with the corresponding specificity, sensitivity and accuracy of 90.00%, 94.43% and 91.92%, respectively.

Conclusion: In patients with early BC, the combination of multimodal ultrasound and tumor marker detection significantly improves the accuracy of diagnosing benign and malignant breast lesions compared to using either modality alone.

Objectives: This study aimed to develop a robust Reverse Phase-High-Performance Liquid Chromatography (RP-HPLC) method for simultaneous determination of Aspirin (ASP) and Apixaban (API) in bulk and in-house capsule formulations.

Methods: The separation was conducted on a Phenomenex Luna C₁₈ column using a Shimadzu LC20AT High-performance liquid chromatography (HPLC) system. The mobile phase consisted of 40:60 Acetonitrile (ACN): phosphate buffer (pH 4) modified by O-Phosphoric Acid (OPA). The parameters included a flow rate of 1 ml/min, a column temperature of 30°C, and Ultra-Violet (UV) detection at 227 nm. Method validation encompassed linearity, precision (Intraday and Interday), accuracy (% Recovery), and sensitivity (Limit of Detection (LOD) and Limit of Quantification (LOQ)). Stability testing followed The International Council for Harmonization (ICH) guidelines.

Results: The developed method demonstrated reliable separation of Aspirin and Apixaban with retention times of 5.37 min and 7.10 min, respectively. It exhibited linearity over the concentration ranges of 50-300 μg/mL for Aspirin and 5-15 μg/mL for Apixaban. The recovery percentage ranged from 90.02% to 101% for Aspirin and 98.18% to 101.18% for Apixaban. LOD and LOQ were determined as 0.84 μg/mL and 2.55 μg/mL for Aspirin, and 0.41 μg/mL and 1.24 μg/mL for Apixaban, respectively. Stability testing confirmed the method's robustness under various stress conditions.

Conclusions: The validated RP-HPLC method offers a reliable tool for routine analysis of Aspirin and Apixaban in pharmaceutical formulations, highlighting its potential for combined dosage applications and routine quality control.

Objective: To identify the influencing factors of dry eyes after cataract surgery and construct a prediction model to provide a reference for ophthalmologists in assessing the risk of postoperative dry eyes.

Methods: A retrospective study was conducted from January 2023 to April 2024, involving 219 patients (219 eyes) who underwent phacoemulsification with intraocular lens implantation at the Department of Ophthalmology, Ninth People's Hospital of Suzhou. Patients were divided into two groups based on the presence or absence of dry eyes at 2 weeks postoperatively. Data from both groups were analyzed to determine the influencing factors of dry eyes after cataract surgery. A nomogram prediction model was constructed using R software. The model's discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), and model calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and the Bootstrap method (self-sampling technique). Decision curve analysis was employed to evaluate the clinical utility of the model.

Results: Among the 219 cataract patients, 53 (24.20%) developed dry eyes during the 2-week follow-up period. Multivariate logistic regression analysis identified smoking (OR = 1.809, P = 0.037), diabetes mellitus (OR = 3.248, P = 0.002), elevated IL-6 (OR = 3.019, P = 0.016), a high Hospital Anxiety and Depression Scale (HADS) score (OR = 2.147, P = 0.029), and longer surgical incision length (OR = 2.995, P = 0.014) as significant risk factors for postoperative dry eye. The AUC of the nomogram model was 0.857 (95% CI: 0.803-0.913), and the H-L goodness-of-fit test showed no statistical significance (χ² = 4.472, P = 0.812), indicating good discrimination and calibration of the model. The average absolute error between predicted and actual probabilities after 1000 Bootstrap iterations was 0.021. Decision curve analysis demonstrated that the net benefit of the model was higher than the two extreme scenarios.

Conclusion: Postoperative dry eyes in cataract patients is associated with smoking, diabetes, elevated IL-6, high HADS scores, and longer incision lengths. The nomogram model demonstrates good predictive capability for assessing the risk of dry eyes after cataract surgery.

Objective: To evaluate the clinical efficacy of recombinant human interferon α-2b (rHuINF α-2b) gel combined with loop electrosurgical excision procedure (LEEP) conization in treating cervical intraepithelial neoplasia (CIN) with comorbid high-risk human papillomavirus (HR-HPV) infection.

Methods: A retrospective analysis was conducted on the clinical data of 202 CIN patients with HR-HPV infection who were treated at Wuhan Yaxin General Hospital between July 2021 and February 2024. Among these patients, 106 received treatment with rHuINF α-2b gel combined with LEEP conization (study group), and the other 96 were treated with LEEP conization alone (control group). The two groups were compared in terms of efficacy on CIN, HPV clearance, vaginal bleeding duration, hospital stay and occurrence of adverse reactions. Patient prognosis within six months post-treatment was analyzed, and the risk factors affecting prognosis were analyzed through logistic regression.

Results: The control group experienced notably longer vaginal bleeding duration and hospital stay than the study group (all P<0.0001). The study group showed a notably higher cure rate of CIN than the control group and presented a notably lower rate of persistent or residual CIN than the control group (P=0.0026). Six months after treatment, the total effective HPV clearance rate in the study group was greatly higher than that in the control group (P=0.0010). However, there was no insignificant difference between the two groups in the incidence of adverse reactions (P=0.4807). According to logistic regression analysis, age, grade of CIN, course of disease and treatment regimen were independent risk factors for patient prognosis.

Conclusion: For CIN patients with comorbid high HPV risk infection, rHuINF α-2b gel combined with LEEP conization can effectively treat CIN, clear HPV, and shorten the duration of vaginal bleeding and hospitalization, without increasing adverse reactions. In addition, age, grade of CIN, course of disease and treatment regimen were independent risk factors for the prognosis of patients.

Objective: Thymidylate synthase (TYMS) constitutes a pivotal and potent target in the context of chemoresistance. However, the oncogenic role of TYMS has received insufficient attention.

Methods: Leveraging data from the Cancer Genome Atlas (TCGA) and various public databases, we conducted an extensive investigation into the oncogenic role of TYMS across 33 cancer types. Subsequently, TYMS was inhibited using small interfering RNA (siRNA) in four different cell lines, and cell proliferation and migration were assessed using CellTiter-Glo and Transwell assays.

Results: TYMS exhibited pronounced expression across a spectrum of cancers and demonstrated associations with clinical outcome in diverse cancer patient cohorts. Furthermore, genetic alterations were identified as potential influencers of overall survival in specific tumor types. Notably, the expression of thymidylate synthase correlated with tumor-infiltrating CD4+ cells in select cancers. Additionally, the functional mechanism of TYMS encompassed nucleotidase activity, chromosome segregation, and DNA replication progress. In vitro experiments further substantiated these findings, demonstrating that the suppression of TYMS impeded the cell growth and invasive capabilities of HeLa, A549, 786-O, and U87_MG cells.

Conclusions: This study furnishes a comprehensive understanding of the oncogenic role played by TYMS in human tumors.