The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in the literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than approximately 3.0, but the opposite is true when their LogP values are more than approximately 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Purpose: Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with a suboptimal 5-year overall survival of approximately 50% with surgery and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited. Immunotherapy with checkpoint blockade has emerged as a promising option for patients with recurrent/metastatic SCCHN; however, it has not been investigated in the curative-intent setting yet. The purpose of this study was to investigate the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease. Experimental Design: We performed T-cell receptor sequencing of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy and correlated the T-cell clonality and the mRNA expression levels of immune-related genes with clinicopathologic parameters. Results: Clonal expansion of T cells was significantly higher in human papilloma virus (HPV)–negative compared with HPV-positive tumors, signifying more robust antigen presentation in HPV-negative tumors. The latter was supported by the higher percentage of HPV-negative tumors expressing HLA-A protein compared with HPV-positive tumors (P = 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P = 0.003) independent of tumor size, nodal stage, and HPV status. Conclusions: Our findings support clonal expansion of T cells in SCCHN patients with locoregionally advanced disease and imply differences in the antigen presentation capacity between HPV-negative and HPV-positive tumors. Elevated GRZB mRNA levels may also serve as a favorable and independent predictor of outcome in SCCHN patients treated with chemoradiotherapy. These data provide rationale for the introduction of immunotherapeutic approaches in the curative-intent setting. Clin Cancer Res; 23(16); 4897–907. ©2017 AACR.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Background/Objectives: Antimicrobial resistance (AMR) poses a significant threat to human health, and combination therapy has proven effective in combating it. It has been reported that some plant flavonoids can enhance the antibacterial effects of antibiotics and even reverse AMR. This study systematically evaluated the synergistic effects of plant flavonoids and clinical antibiotics. Methods: The antibacterial activities of thirty-seven plant flavonoids and nine clinical antibiotics with various antimicrobial mechanisms were determined using the microbroth dilution method. Subsequently, the combined effects of twelve plant flavonoids presenting definite MICs against Staphylococcus aureus with these nine antibiotics were determined using the checkerboard test, together with those of thirty-two plant flavonoids presenting definite MICs against Escherichia coli with these nine antibiotics. Results: Plant flavonoids in combination with antibiotics present extensive synergistic effects, and 25% of combinations exhibited synergy against S. aureus and 50% against E. coli, particularly with antibiotics affecting cell membranes or ribosomes. Conclusions: The findings align with the drug selection principle of synergistic combinations and suggest that plant flavonoids could extensively enhance antibiotic efficacy. Considering that various metabolites from microorganisms, plants, and animals on the Earth would definitely impact the evolution of AMR, together with the rules, key factors, and important principles of drug combination for preventing AMR, we further propose the “One Earth-One Health (OE-OH)” concept, emphasizing ecosystem interactions in AMR prevention.

Introduction: Teratomas are rare neoplasms made up of mature embryonic germ cell layers. Extra-gonadal teratomas are rare and primarily in the mediastinum. Mature cystic teratomas (MCT) are slow-growing benign tumors accounting for a small number of mediastinal germ cell tumors. Patients with MCT are often asymptomatic, and even most symptomatic intrapulmonary teratomas present with vague and non-specific symptoms such as cough, hemoptysis, and chest pain. Case presentation and discussion: A Yemeni patient presented for two years with dry cough, shortness of breath, and stitching right-sided chest pain. Plain X-ray showed pleural thickening associated with two opacities in the right lung- one located centrally in the upper lobe and another peripherally- which were confirmed with a CT scan. During right-sided decortication with resection of the two masses, extensive adhesions were found between the right pleura and the chest wall. The adhesions were released, and right-sided decortication led to the removal of the peripheral cystic mass attached to the pleura. Histopathology reported the presence of squamous epithelium lining with ectodermal components such as hair follicles, sebaceous glands, keratin debris, fatty, and fibromuscular tissue. Conclusion: Intrapulmonary teratomas are rare tumors, with less than 100 cases reported in the past few years. All the reported cases are in the left lung lobes, yet our case is on the right side. Although the right-sided mature cystic teratoma is even scarcer, physicians should have a high index of suspicion for teratoma when encountering abnormal lesion in the right side of the lung confirming it either by CT or MRI. Highlights:

Background/Objectives: Antimicrobial resistance (AMR) has been seriously threatening to human health, and combination therapy has been proved to be an effective strategy to fight the AMR. Many plant flavonoids can enhance the antibacterial effects of antibiotics, and even reverse the AMR. Our objective was to explore the combined effects of plant flavonoids with antibiotics. Methods: The antibacterial activities of 37 plant flavonoids and 9 clinical antibiotics with various antimicrobial mechanisms were determined using microbroth dilution method. Subsequently, the combined effects of 12 plant flavonoids presenting definite MICs against Staphylococcus aureus with these 9 antibiotics were determined using checkerboard test, together with those of 32 plant flavonoids presenting definite MICs against Escherichia coli with these 9 antibiotics. Results: Approximate 50% of combinations exhibited synergistic effects against E. coli among 288 combinations, while only 25% of combinations exhibited synergistic effects against S. aureus among 108 combinations. Conclusions: Plant flavonoids present extensive synergistic effects when combined with antibiotics especially in combination with ones against Gram-negative bacteria, and their combined effects are consistent with the selection rule of antibacterial agents for synergistic combinations. Considering that various metabolites from microorganisms, plants and animals on the earth would definitely impact on the evolution of AMR, together with the rules, key factor and important principle of drug combination for preventing AMR, and the ecosystem of the earth also have enough buffering capacity and self-regulation ability to the fight between human and pathogenic microorganisms, the concept of One Earth-One Health (OE-OH) was proposed for preventing AMR.