Genistein exerts anti-colorectal cancer actions: clinical reports, computational and validated findings.

Colorectal cancer (CRC) is presently a health challenge in China. Although clinical chemotherapy is prescribed availably, the negative effects and poor prognoses still occur. Genistein has antitumor properties in our previous studies. However, the molecular mechanisms underlying the anti-CRC effects of genistein remain unclear. Increasing evidences have indicated that the induction of autophagy, one of cell death models, is closely associated with the formation and development of human cancer. In the current study, a systematic bioinformatics approach using network pharmacology and molecular docking imitation was aimed at identifying the pharmacological targets and anti-CRC mechanisms of genistein, characterized by autophagy-related processes and pathways. Moreover, experimental validation was conducted by using clinical and cell culture samples. All 48 potential targets of genistein-anti-CRC-associated autophagy were screened accordingly. Further bioinformatics analyses identified 10 core genistein-anti-CRC targets related to autophagy, and enrichment-assayed results revealed that the biological processes of these core targets might regulate multiple molecular pathways, including the estrogen signaling pathway. Additionally, molecular docking data demonstrated that genistein has a high affinity for epidermal growth factor receptor (EGFR) and estrogen receptor 1 (ESR1). Both EGFR and ESR1 proteins were highly expressed in clinical CRC samples. Preliminary in vitro data showed that genistein effectively reduced cellular proliferation, activated apoptosis, and suppressed EGFR and ESR1 protein expressions in CRC cells. Our research findings uncovered the molecular mechanisms of genistein against CRC, and the potential drug targets associated with autophagy in genistein treatment of CRC were identified and validated experimentally, including EGFR and ESR1.

Efficacy and safety of optional parenteral antimicrobial therapy for complicated skin and soft tissue infections: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus. This study aims to investigate the efficacy and safety of optional antimicrobial therapy for the treatment of complicated SSTIs (cSSTIs). METHODS: We searched PubMed, Medline (Via Ovid SP), Embase (Via Ovid SP), and the Cochrane Central Register of Controlled Trials from their inception to March 22, 2021 for randomized controlled trials (RCTs) that studied the use of optional antimicrobial therapy for cSSTIs. Citations' screening, study selection, data extraction, and risk of bias assessment were independently performed by 2 authors. The primary outcomes were clinical and microbiological treatment success, and adverse events (AEs) were also assessed. RESULTS: A total of 48 trials covering 24,381 patients assessing 20 types of antimicrobial treatment modalities were included. Overall, omadacycline was associated with the highest beneficial effect on clinical and microbiological treatment success and with the largest rank probability based on surface under the cumulative ranking curve values, avarofloxacin was closely followed. Both had, however, omadacycline was related to moderately safety profiles. Lefamulin ranked as the best option was associated with the lowest risk of severe AEs. Subgroup analysis showed similar results. The quality of primary outcomes was moderate to low. CONCLUSIONS: The use of omadacycline was associated with higher rates of clinical and microbiological treatment success for the treatment of cSSTIs, with a relative low risk of AEs. Due to the limitations of the included RCTs, high-quality and well-designed RCTs are needed to further confirm the results.

Aidi injection as adjunctive treatment to gemcitabine-based chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

CONTEXT: Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. OBJECTIVE: To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. RESULTS: In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29-1.48), DCR (RR = 1.15, 95% CI 1.12-1.19), QOL (RR = 1.71, 95% CI 1.54-1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. CONCLUSIONS: Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.