Article
Immunology
Bryna L. Fitzgerald, Barbara Graham, Mark J. Delorey, Adoracion Pegalajar-Jurado, M. Nurul Islam, Gary P. Wormser, John N. Aucott, Alison W. Rebman, Mark J. Soloski, John T. Belisle, Claudia R. Molins
Summary: This study used metabolomics to analyze metabolic responses in patients with Post-treatment Lyme disease symptoms/syndrome (PTLDS) compared to clinically cured non-PTLDS patients. The findings revealed observable metabolic differences between PTLDS and non-PTLDS patients at multiple time points, with distinct patterns of metabolite abundance. A small number of metabolites could be used to define PTLDS versus non-PTLDS patients at specific time points, and these findings were validated in a second patient cohort. These results suggest that metabolite-based measurement can help distinguish patients with PTLDS and provide insights into the underlying biochemistry of PTLDS.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Matthew K. Muramatsu, Jianli Zhou, Bryna L. Fitzgerald, Ranjit K. Deka, John T. Belisle, Michael Norgard
Summary: This research highlights the importance of riboflavin and Flavin pools for the growth of Borrelia burgdorferi and suggests that flavin utilization and its downstream products may play a more significant role in the pathogenesis of this spirochete than previously thought. Mutation in specific genes related to riboflavin import and synthesis can lead to resistance to certain antimicrobial agents and attenuation of disease in a murine model.
INFECTION AND IMMUNITY
(2021)
Article
Biology
Elsio A. Wunder, Haritha Adhikarla, Camila Hamond, Katharine A. Owers Bonner, Li Liang, Camila B. Rodrigues, Vimla Bisht, Jarlath E. Nally, David P. Alt, Mitermayer G. Reis, Peter J. Diggle, Philip L. Felgner, Albert Ko
Summary: Leptospirosis, a leading zoonotic disease worldwide, requires urgent prevention measures. Research has shown that a motility-deficient mutant vaccine can induce an immune response and enhance resistance against Leptospira infection in animals.
Article
Biology
Xiaotian Tang, Yongguo Cao, Gunjan Arora, Jesse Hwang, Andaleeb Sajid, Courtney L. Brown, Sameet Mehta, Alejandro Marin-Lopez, Yu-Min Chuang, Ming-Jie Wu, Hongwei Ma, Utpal Pal, Sukanya Narasimhan, Erol Fikrig
Summary: This study identified that ticks carry an adiponectin receptor-like protein (ISARL) but lack adiponectin, suggesting activation by alternative pathways. The ISARL signaling may be co-opted by the Lyme disease agent, as its expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection.
Article
Biochemistry & Molecular Biology
Christina Thompson, Sierra George, Maria L. White, Prahathees J. Eswara, Zhiming Ouyang
Summary: This study found that BB0761, a putative M23 family homolog, plays a role in cell division and virulence of the bacterial pathogen causing Lyme disease.
MOLECULAR MICROBIOLOGY
(2022)
Article
Infectious Diseases
Derick Thompson, John A. Watt, Catherine A. Brissette
Summary: The text discusses the host immune and inflammatory response induced by Lyme borreliosis bacterium and how these responses influence the pathology of Lyme disease.
TICKS AND TICK-BORNE DISEASES
(2021)
Article
Immunology
Christina Thompson, Connor Waldron, Sierra George, Zhiming Ouyang
Summary: The alternative sigma factor RpoS in Borrelia burgdorferi, the etiological agent of Lyme disease, has been found to regulate the bb0563 gene, which contributes to the optimal infectivity of B. burgdorferi. bb0563 showed similar expression patterns as other virulence-associated genes when B. burgdorferi was exposed to environmental stimuli. bb0563 expression was downregulated when rpoS was inactivated and restored in the complemented strain.
INFECTION AND IMMUNITY
(2023)
Article
Microbiology
Dawei Yang, Yongwu Yang, Pengfei Qiao, Fengwei Jiang, Xinyang Zhang, Zihui Zhao, Tao Cai, Ganwu Li, Wentong Cai
Summary: This study identified a two-component signaling system in EHEC that promotes adaptability and virulence expression in response to mannose, a sugar found in the intestinal mucus.
Article
Immunology
Michael A. Crowley, Troy Bankhead
Summary: This study focuses on a putative regulatory factor encoded by a transcriptionally active intergenic region of the bacterial agent Borrelia burgdorferi. The functional product of this region is not a protein as previously predicted. Transcription of this region is highly induced during murine infection and its targeted deletion results in significant changes to the transcriptome.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Anna J. Henningsson, Sandra Hellberg, Maria Lerm, Shumaila Sayyab
Summary: In this study, we conducted the first genome-wide analysis of DNA methylation in peripheral blood cells from patients with and without Lyme neuroborreliosis (LNB). The findings suggest that LNB is associated with immune-related DNA methylation changes.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Microbiology
Chang Liu, Hua Zhang, Xian Peng, Meghan S. Blackledge, Robert E. Furlani, Haoting Li, Zhaoming Su, Roberta J. Melander, Christian Melander, Suzanne Michalek, Hui Wu
Summary: Antibiotic resistance is a major concern in public health, and new alternatives to combat biofilm-driven infections are needed. A 2-aminoimidazole derivative has been identified to inhibit biofilm formation in Streptococcus mutans and Staphylococcus aureus by targeting a key transcriptional regulator. This compound shows promise as a new anti-infective agent that can attenuate virulence in bacterial infections.
Article
Fisheries
Liqing Chen, Yu Wang, Lixia Fan, Nuo Yang, Jifeng Zeng, Guiying Guo, Qian Li, Peng Wang, Weixin Zeng, Jiping Zheng
Summary: This study reveals the role of the two-component signal transduction system KdpDE in regulating the virulence of Aeromonas dhakensis. A Delta kdpE mutant was found to have attenuated growth, biofilm formation, mobility, ECPase activity, and resistance to H2O2 and antimicrobial peptides under conditions of potassium depletion. The mutant also showed reduced virulence in zebrafish and a higher survival rate after double immunization, making it a promising attenuated vaccine candidate.
Review
Immunology
Deyi Sun, Jiqian Xu, Wanying Zhang, Chaoying Song, Chenggang Gao, Yajun He, You Shang
Summary: NLRC3 is a pattern recognition receptor that plays a crucial regulatory role in immune cell activation. It inhibits the activation of multiple signaling pathways in macrophages and influences the function of T cells. NLRC3 is closely associated with regulatory activity and is involved in the development of various diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Martin Strnad, Natalie Rudenko, Ryan O. M. Rego
Summary: This review discusses the various well-defined and possible novel strategies and virulence mechanisms used by B. burgdorferi to evade obstacles during colonization and infection by tick vectors and mammalian hosts.
Article
Microbiology
Thays de Oliveira Pereira, Marie-Christine Groleau, Eric Deziel
Summary: The bacterium Pseudomonas aeruginosa relies on a communication system called quorum sensing (QS) to regulate its phenotype. A study found that, during surface growth, P. aeruginosa produces a signal molecule called 3-oxo-C-12-HSL, which can upregulate the expression of virulence determinants in neighboring cells, even in the absence of the regulator LasR. This suggests a possible role for 3-oxo-C-12-HSL in shaping community responses.
Article
Pharmacology & Pharmacy
Hannah Petrek, Pui Yan Ho, Neelu Batra, Mei-Juan Tu, Qianyu Zhang, Jing-Xin Qiu, Ai-Ming Yu
Summary: This study introduces a novel technology for dual-targeting of two miRNAs in NSCLC cells, showing greater efficacy in inhibiting cell growth and colony formation compared to using individual miRNAs alone. Additionally, a specific miRNA-loaded nanomedicine demonstrated the best effectiveness in controlling tumor growth in NSCLC patient-derived xenograft mouse models.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Young Hee Choi, Young-Won Chin
Summary: Studies have shown that metabolic enzyme and/or transporter-mediated pharmacokinetic changes in a drug caused by concomitant herbal products may affect efficacy and toxicity, but discrepancies between predictive data and clinical significance still exist, adding to confusion regarding the use of herbal products and drug combinations.
Article
Plant Sciences
Piseth Nhoek, Hee-Sung Chae, Young-Mi Kim, Pisey Pel, Jungmoo Huh, Hyun Woo Kim, Young Hee Choi, Kyeong Lee, Young-Won Chin
Summary: A phytochemical investigation of the methanol extract of Salvia plebeia led to the identification of 19 compounds, including new norsesquiterpene and eudesmane sesquiterpenoids. While most compounds did not inhibit the PCSK9-LDLR interactions, compounds 1, 9, and 10 were found to downregulate PCSK9 mRNA expression.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Pharmacology & Pharmacy
Young Hee Choi, Chao Zhang, Zhenzhen Liu, Mei-Juan Tu, Ai-Xi Yu, Ai-Ming Yu
Summary: This study developed a novel pharmacokinetic (PK)-pharmacodynamic (PD) model for assessing combination treatment by considering contributions from individual drugs, and incorporated the combination index method to define in vivo synergism accurately. The research found that sorafenib contributed more to tumor growth inhibition compared to coadministered doxorubicin, explaining previously inexplicable clinical observations. This model and strategy will have broad applications in translational research for identifying optimal dosage combinations with stronger synergy to improve therapeutic outcomes.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Oncology
Anastasia L. Berg, Ashley Rowson-Hodel, Michelle Hu, Michael Keeling, Hao Wu, Kacey VanderVorst, Jenny J. Chen, Jason Hatakeyama, Joseph Jilek, Courtney A. Dreyer, Madelyn R. Wheeler, Ai-Ming Yu, Yuanpei Li, Kermit L. Carraway
Summary: Preventing drug resistance in cancer stem cells is crucial for improving treatment outcomes in cancer patients. This study found that cationic amphiphilic drugs can effectively target therapy-resistant cancer stem cell populations by inducing cell death through a different mechanism. This discovery has the potential to improve treatment outcomes for breast cancer patients and reduce the risk of tumor recurrence and metastasis.
Article
Biochemistry & Molecular Biology
ZiJie Lim, Nur Khairiah Binte Mohd-Ismail, Evelyn Png, Ching Wooen Sze, Qifeng Lin, Wanjin Hong, Seng Gee Lim, Yee-Joo Tan, Jayantha Gunaratne
Summary: This study investigated the molecular signaling events during early phases of HBV infection by profiling the phosphoproteome of infected cells. The results showed that HBV infection significantly altered the host phosphoproteome and its associated proteins, including kinases. Computational analysis revealed dysregulation of immune response, cell cycle, and RNA processing pathways during HBV infection. Inhibition of CLKs was found to reduce HBV infection. These findings provide potential targets for developing novel therapeutic strategies for HBV treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Gavin M. Traber, Ai-Ming Yu
Summary: RNA interference (RNAi) is a versatile method for regulating gene expression. Endogenous microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs) form RNA-induced silencing complexes to achieve gene regulation. RNAi-based drugs have been approved for clinical use and advancements in technology aim to improve their efficacy and safety. Chemical modifications and delivery platforms are being explored to enhance the structure, stability, and activity of RNA molecules. Novel biologic RNAi agents are also being developed for research purposes.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Oncology
Shu Ning, Chengfei Liu, Wei Lou, Joy C. Yang, Alan P. Lombard, Leandro S. D'Abronzo, Neelu Batra, Ai-Ming Yu, Amy R. Leslie, Masuda Sharifi, Christopher P. Evans, Allen C. Gao
Summary: Next-generation antiandrogen drugs improve survival and quality of life in advanced prostate cancer patients, but resistance to these drugs is not well understood. This study found that the Wnt5a/FZD2 signaling pathway plays a critical role in promoting enzalutamide resistance, and targeting this pathway could be a potential therapy for advanced prostate cancer.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Phuong Linh Nguyen, Ahmed Elkamhawy, Young Hee Choi, Chang Hoon Lee, Kyeong Lee, Jungsook Cho
Summary: The study evaluated the antitumor effects of a series of CA inhibitors on various cancer cell lines, identifying two compounds with potent anticancer activity against breast cancer cells MCF-7 and SK-BR-3, especially in combination with DOX, demonstrating synergistic cytotoxic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Joseph M. Cronin, Ai -Ming Yu
Summary: The development of medications requires a thorough understanding of their pharmacokinetic and pharmacodynamic properties. The study of ADME gene products and their functions has been revolutionized by recombinant DNA technologies. These technologies enable the investigation of drug metabolism and disposition, as well as the study of posttranscriptional regulation of ADME genes.
DRUG METABOLISM AND DISPOSITION
(2023)
Article
Pharmacology & Pharmacy
Byoung Hoon You, Mingoo Bae, Seung Yon Han, Jieun Jung, Kiwon Jung, Young Hee Choi
Summary: The pharmacokinetic feasibility of the stability-enhanced SESS-TD crystal was evaluated and found to be comparable to TDF, with no changes observed even after 12 months of storage. This suggests that the SESS-TD crystal may have enough pharmacokinetic feasibility to replace TDF.
Article
Pharmacology & Pharmacy
Yixin Chen, Mei-Juan Tu, Fangwei Han, Zhenzhen Liu, Neelu Batra, Primo N. Lara, Hong -Wu Chen, Huichang Bi, Ai -Ming Yu
Summary: The research found that miR-22-3p, miR-9-5p, and miR-218-5p are antiproliferative miRNAs targeting non-small cell lung cancer (NSCLC) cells, and they inhibit folate metabolism and alter amino acid metabolism in NSCLC cells. In addition, the inhibition of glucose uptake by miR-22-3p and the reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p were also confirmed. Recombinant miR-22-3p was more effective than miR-9-5p and -218-5p in inhibiting NSCLC cell respiration, glycolysis, and colony formation, without causing any toxicity.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Pharmacology & Pharmacy
Seo-Yeon Kim, Byung Hoon You, Mingoo Bae, Seung Yon Han, Kiwon Jung, Young Hee Choi
Summary: This study aimed to characterize the pharmacokinetic profiles of co-amorphous dispersions of Mirabegron (MBR) in rats and mice. The results showed that these co-amorphous dispersions can improve the relative bioavailability and area under the curve of MBR.
Article
Biochemistry & Molecular Biology
Seung Yon Han, Jeong-Eun Yu, Byoung Hoon You, Seo-Yeon Kim, Mingoo Bae, Hee-Sung Chae, Young-Won Chin, Soo-Hwa Hong, Ju-Hee Lee, Seung Hyun Jung, Young Hee Choi
Summary: In a mouse model, the combination of trastuzumab and H9 extract for breast cancer treatment showed no changes in trastuzumab pharmacokinetics, indicating that H9 does not affect the exposure of trastuzumab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)