BioMed Research International最新文献

[This retracts the article DOI: 10.1155/2014/725921.].

[This corrects the article DOI: 10.1155/2020/3189217.].

Background: Survival analyses often violate the proportional hazards (PH) assumption, compromising the validity of widely used statistical tests such as the log-rank test and Cox regression. To address this limitation, we introduce the event-adjusted rank sum (EARS) test, a nonparametric method designed to provide robust time-to-event data analysis without relying on PH.

Materials and methods: The EARS test adjusts survival times by dividing each event time by the proportion of events within its respective group. These adjusted survival times are then compared using the Kruskal-Wallis test. To account for censoring, the resulting p value is adjusted based on the overall proportion of censored observations. We validated the EARS test through simulations involving 1000 cohorts with group sizes ranging from 50 to 1000 patients and censoring rates between 5% and 75%. Additionally, we compared the performance of EARS to the log-rank test and restricted mean survival time (RMST) under both PH and non-PH conditions using both simulated and clinical datasets.

Results: In simulation studies, the EARS and log-rank tests agreed in 96.6% of cases. Under the null hypothesis, the EARS test demonstrated a Type I error rate of 2% across two to five groups, slightly higher than the log-rank test's 1%. Power analyses revealed that EARS detected true differences in 63% of cases compared to 68% for the log-rank test. In 1000 datasets violating the PH assumption, EARS identified significant differences in 94.4% of cases versus 98.0% for RMST, with both methods agreeing 96.4% of the time on null hypothesis rejection. Analyses of clinical cohorts further confirmed the reliability of the EARS test, showing consistent alignment with established tests in most scenarios.

Conclusion: The EARS test offers a simple, nonparametric alternative for survival analysis that remains reliable across diverse conditions and varying censoring distributions. Its accessibility and robust performance make it a valuable tool for researchers and clinicians, especially in settings where the PH assumption is violated or advanced statistical software is unavailable. An R package implementing the EARS test is openly available.

Objective: Despite the remarkable advances in approved therapeutic approaches, the recurrence rate of hepatocellular carcinoma (HCC) is very high after treatment. Therefore, introducing innovative therapeutic modalities such as targeted molecular therapies is inevitable. Lysine demethylase 6A (KDM6A) is a member of the KDM6 family with histone demethylase activity. This gene frequently mutates in different cancers, and its mutations are associated with the increased likelihood of carcinogenesis. This study is aimed at evaluating if inducing KDM6A expression could attenuate cancerous features of HCC cells.

Method: A lentiviral-based vector was used to induce KDM6A expression in Huh-7 cells. The impact of KDM6A overexpression on the cancerous phenotype of HCC cells was assessed by measuring proliferation rate, migration and colony formation capacity, and differentiation induction toward hepatocytes.

Results: KDM6A overexpression significantly altered cellular morphology, proliferation rate, cell cycle pattern, colony formation, and migration capacity of HCC cells. In addition, induction of differentiation toward hepatocytic fate resulted in down/upregulation of epithelial-mesenchymal transition (EMT) markers associated with the cadherin switch. Furthermore, the expressions of ALB and HNF4α, key hepatocytic hallmarks, were increased.

Conclusion: Overexpression of KDM6A could be used as a potential noninvasive molecular therapeutic strategy to prevent metastasis and recurrence rate in HCC.

Background: Rondeletia leucophylla has traditionally been used to treat various ailments, though scientific evidence is limited. This study is aimed at exploring its phytochemical profile through in vitro, in vivo, and in silico investigations.

Materials and methods: The dried coarse powder of R. leucophylla stem and leaves was extracted with methanol, then concentrated and dried using a rotary evaporator. The extract was subsequently evaluated through in vitro and in vivo pharmacological assays, preliminary phytochemical screening with standard reagents, gas chromatography-mass spectrometry (GC-MS) analysis, and various in silico approaches.

Results: Phytochemical screening of the methanolic extract of R. leucophylla (MERL) revealed the presence of steroids, carbohydrates, and glycosides, while GC-MS identified 70 bioactive compounds. MERL showed a total phenolic content of 34.075 mg GAE/μg. Its DPPH assay indicated strong antioxidant activity (IC₅₀: 28.87 μg/mL) compared to the standard butylated hydroxytoluene (BHT, IC₅₀: 26.82 μg/mL). The extract also exhibited moderate thrombolytic activity (39.42%) and antimicrobial effects against various bacterial and fungal strains. The anti-inflammatory results showed that the 400 mg/kg dose stopped paw edema by 49.01%, which is close to aceclofenac's 65.19% reduction. MERL showed strong antidiarrheal action, lowering the number of feces by 87.84% at 600 mg/kg, which was about the same as the standard drug (90.54%). The hypoglycemic effect depended on the dose; the 400 mg/kg dose lowered blood sugar levels significantly close to the control dose (p < 0.001). Molecular docking revealed strong binding affinities of selected compounds to key oxidative stress-related targets, exceeding standard benchmarks, while ADMET profiling indicated favorable drug-like properties and low toxicity.

Conclusion: This study supports the traditional use of R. leucophylla, highlighting its antioxidant, thrombolytic, antimicrobial, antidiarrheal, anti-inflammatory, and hypoglycemic potentials, warranting further pharmacological exploration.

[This corrects the article DOI: 10.1155/2019/4876078.].

Background and objective: Radioresistance is a significant factor affecting the therapeutic efficacy of radiotherapy. This study is aimed at investigating the molecular mechanism by which LBX2-AS1 regulates pyruvate kinase M2 (PKM2) to influence radioresistance and its potential as a biomarker for radioresistance in esophageal cancer.

Methods and key findings: Radioresistant sub-cell lines, KYSE150R, were established in KYSE150 cells, and PKM2, cyclin D1, HIF-1α, and LBX2-AS1 levels were elevated in KYSE150R. Upregulated and downregulated PKM2 sub-cell lines were established. Upregulating PKM2 increased the PKM2 level in the nucleus and increased levels of HIF-1α, cyclin D1, and LBX2-AS1. The knockdown of PKM2 showed the opposite result. Downregulated LBX2-AS1 sub-cell lines were established. Downregulation of LBX2-AS1 decreased cell proliferation, glycolysis, cell cycle progression, and radioresistance, along with a reduction in cyclin D1, HIF-1α, and PKM2 levels. The dual-luciferase reporter system was used to verify that LBX2-AS1 directly binds to miR-491-5p, and miR-491-5p directly binds to the 3 ^'UTR of PKM2 mRNA. Downregulation of miR-491-5p in sh-LBX2-AS1 cells could increase cell proliferation, cell cycle, glycolysis, and radiation resistance. The LBX2-AS1 level in serum of patients with esophageal cancer was detected, and its clinical relevance was analyzed. Results showed that high LBX2-AS1 levels correlated with worse disease control, increased lymphatic metastasis, and poorer overall and progression-free survival.

Conclusion and clinical implications: LBX2-AS1-miR-491-5p-PKM2 positive feedback loop enhances the radioresistance of esophageal cancer cells by altering the cell cycle and enhancing glycolysis. High level of LBX2-AS1 in serum was correlated with worse DCR, lymphatic metastasis, worse overall survival, and progression-free survival.

Colorectal cancer (CRC) is the third most common cancer worldwide. Around 1.8 million people were diagnosed with CRC in 2018, and 881,000 died. The limitations of chemotherapy and radiotherapy, as well as the uncertainty of CRC-specific therapies, encourage the development of alternative CRC prevention, treatment, and control measures. Probiotics are being studied as a strategy for preventing and treating CRC due to their potential health benefits. Lactobacillus casei (L. casei) shows promise in reducing tumor growth and cancer cell survival in CRC, according to recent studies. Due to the varying efficiency of probiotics depending on the specific strain, substantial research has been conducted on the L. casei strains to explore their potential anticancer effects in CRC. In this study, we aimed to conduct a systematic review of exploring the various mechanisms of L. casei strains to facilitate the development of effective probiotic supplements to complement standard CRC therapy. We conducted a meticulous search on Scopus, PubMed, Embase, and Web of Science. Initial research resulted in 433 records, from which 412 papers were excluded by reason. The remaining 21 papers were categorized into four topics. These papers discuss several mechanisms involved in anticancer properties against CRC, including apoptosis induction and antiproliferation activity, immunomodulation, gut microbiome, intestinal barrier function modulation, and detoxifying carcinogens. Our findings suggest that using the potential strains of L. casei in combination therapy and targeted therapy, along with conventional drugs, could be a promising approach against CRC.

Globally, wounds have become a growing health concern due to the increasing prevalence of vascular diseases. In Ethiopian traditional medicine, plants belonging to the genus Arisaema have long been used to treat wounds and infections. This study aimed at evaluating the wound healing and antimicrobial activities of 80% methanol extract and its solvent fractions from the tubers of Arisaema schimperianum Schott (Araceae). Wound healing activity was assessed in mice using excision and incision wound models, while skin irritation tests were conducted in rats. The evaluation included measurements of wound contraction rate, epithelialization period, tensile strength, hydroxyproline content, and histological analysis. Antibacterial and antifungal activities were assessed in vitro using the broth dilution method. Ointments formulated at 5% and 10% (w/w) concentrations were tested for wound healing efficacy. Both concentrations of the methanol extract and its fractions significantly enhanced wound contraction, accelerated epithelialization, and improved tensile strength compared to controls (p < 0.001), with the aqueous fraction demonstrating the most potent wound healing effect. These findings were corroborated by histopathological analysis. The aqueous fraction also inhibited the growth of all tested bacterial strains, exhibiting stronger activity against Gram-positive than Gram-negative bacteria. The study provides scientific validation for the traditional use of A. schimperianum tubers as a natural therapeutic agent for wound management.

[This corrects the article DOI: 10.1155/2020/6708061.].