Background: Isoliquiritin belongs to flavanol glycosides and has a strong antiinflammatory activity. This study sought to investigate the anti-inflammatory effect of isoliquiritin and its underlying mechanism. Methods: The inflammatory (trinitro-benzene-sulfonic acid-TNBS-induced ulcerative colitis (UC)) model was established to ascertain the effect of isoliquiritin on the caspase-3/HMGB1/TLR4 pathway in rats. We also explored its protective effect on intestinal inflammation and its underlying mechanism using the LPS-induced inflammation model of Caco-2 cells. Besides, Deseq2 was used to analyze UCassociated protein levels. Results: Isoliquiritin treatment significantly attenuated shortened colon length (induced by TNBS), disease activity index (DAI) score, and body weight loss in rats. A decrease in the levels of inflammatory mediators (IL-1β, I IL-4, L-6, IL-10, PGE2, and TNF-α), coupled with malondialdehyde (MDA) and superoxide dismutase (SOD), was observed in colon tissue and serum of rats after they have received isoliquiritin. Results of techniques (like western blotting, real-time PCR, immunohistochemistry, and immunofluorescence-IF) demonstrated the potential of isoliquiritin to decrease expressions of key genes in the TLR4 downstream pathways, viz., MyD88, IRAK1, TRAF6, NF-κB, p38, and JNK at mRNA and protein levels as well as inhibit HMGB1 expression, which is the upstream ligand of TLR4. Bioinformational analysis showed enteritis to be associated with a high expression of HMGB1, TLR4, and caspase-3. Conclusion: Isoliquiritin could reduce intestinal inflammation and mucosal damage of TNBS-induced colitis in rats with a certain anti-UC effect. Meanwhile, isoliquiritin treatment also inhibited the expression of HMGB1, TLR4, and MyD88 in LPS-induced Caco-2 cells. These results indicated that isoliquiritin could ameliorate UC through the caspase-3/HMGB1/TLR4-dependent signaling pathway.
Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. It presents a significant challenge in terms of accurate diagnosis, disease progression monitoring, and the development of effective treatments. This article addresses the role of neuroimaging as an advancing tool for diagnosis, monitoring progression, and treatment of AD. A comprehensive review of existing literature on the use of neuroimaging in AD was conducted using various databases. The different imaging techniques, such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), were examined in terms of their ability to detect amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), the hallmark pathological features of AD. Neuroimaging enables the visualization of Alzheimer-related biomarkers, such as Aβ plaques, tau protein tangles, neuro-inflammation, and synaptic dysfunction, providing valuable insights into disease pathophysiology and progression. These imaging techniques assist in the early detection of AD, distinguishing it from other conditions and evaluating the effectiveness of treatments. This has the potential to significantly transform the way AD is managed clinically. By providing insights into the molecular changes that occur in the brain during the course of the disease, neuroimaging can facilitate early diagnosis, monitor disease progression, and inform treatment decisions. Furthermore, neuroimaging holds great potential for accelerating drug development by allowing researchers to assess the efficacy of novel therapies in real time. Overall, the integration of neuroimaging into the clinical management of AD has the potential to revolutionize the way we approach diagnosis, treatment, and research in AD.
The diverse pharmacological role of dihydropyrimidinone scaffold has made it to be an interesting drug target. Because of the high incidence and mortality rate of breast cancer, there is a dire need of discovering new pharmacotherapeutic agents in managing this disease. A series of twenty-two derivatives of 6-(chloromethyl)-4-(4-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3a-3k) and ethyl 6-(chloromethyl)-4-(2-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a-4k) synthesized in a previous study were evaluated for their anticancer potential against breast cancer cell line. Molecular docking studies were performed to analyze the binding mode and interaction pattern of these compounds against nine breast cancer target proteins. The in vitro cell proliferation assay was performed against the breast cancer cell line MCF-7. The structure activity relationship of these compounds was further studied using QSARINS. Among nine proteins, the docking analysis revealed efficient binding of compounds 4f, 4e, 3e, 4g, and 4h against all target proteins. The in vitro cytotoxic assay revealed significant anticancer activity of compound 4f having of 2.15 μM. The compounds 4e, 3e, 4g, and 4h also showed anticancer activities with of 2.401, 2.41, 2.47 and 2.33 μM, respectively. The standard tamoxifen showed 1.88 μM. The 2D qualitative structure-activity relationship (QSAR) analysis was also carried out to identify potential breast cancer targets through QSARINS. The final QSAR equation revealed good predictivity and statistical validation and values for the model obtained from QSARINS was 0.98 and 0.97, respectively. The active compounds showed very good anticancer activities, and the binding analysis has revealed stable hydrogen bonding of these compounds with the target proteins. Moreover, the QSAR analysis has predicted useful information on the structural requirement of these compounds as anticancer agents with the importance of topological and autocorrelated descriptors in effecting the cancer activities.
Herein, capsaicin nanoparticles (NPs) were prepared by two different methods, namely, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP). The nanoparticles of the necessary sizes were obtained after optimizing experimental parameters such as the solvent-to-anti-solvent ratio and stirring speed. They had spherical shapes and an average diameter of 171.29 ± 1.94 and 78.91 ± 0.54 nm when prepared using the EPN and APSP methods, respectively. Differential scanning calorimetry and an X-ray diffractometer showed that the capsaicin crystallinity decreased. FTIR results showed that the NPs were produced with their original configuration and did not result in the synthesis of any additional structures. The NP formulation had a desirable drug content. They surpassed the unprocessed drug in solubility and displayed the desired stability. Capsaicin NP cream showed many folds of enhanced analgesic, anti-inflammatory, and antimicrobial effects compared to unprocessed capsaicin.
25 September 2024 in Journal of Pharmacy and Pharmacology
Objectives: This study investigates the dual role of ALKBH5, an eraser enzyme, in colorectal cancer (CRC), focusing on how N6-methyladenosine (m6A) mutations influence CRC development and progression. Methods: We reviewed various studies that highlighted the role of ALKBH5 in colorectal cancer (CRC). This includes the impact of ALKBH5 on tumor cell behavior including immune system interactions, invasion, and proliferation in CRC. We also looked into how ALKBH5 acts as a tumor suppressor under different conditions analyzed clinical data to assess the impact of ALKBH5 expression on outcomes in colorectal cancer patients. Key findings: In CRC, ALKBH5 plays a dual role. In certain situations, it inhibits the progression of the tumor, but in other circumstances, it promotes tumor growth and immunosuppression. The interaction with RABA5 plays a role in the development of CRC. Having elevated levels of ALKBH5 has been associated with unfavorable patient outcomes, such as reduced survival rates and more advanced cancer stages. Various factors, including tumor differentiation, TNM stages, and carcinoembryonic antigen (CEA) levels, be linked to ALKBH5 expression. Conclusions: ALKBH5 plays a complicated and situation-specific role in colorectal cancer (CRC). Targeting ALKBH5 could result in novel therapy options that balance its tumor-promoting and tumor-fighting properties in CRC. Further research into m6A alterations and ALKBH5 could enhance CRC treatment approaches and patient outcomes.
About Me
I am a pharmacist and PhD researcher in molecular pharmacology and tumor biology at China Pharmaceutical University, Nanjing, China. My research focuses on hepatocellular carcinoma, oxidative stress, DNA damage response, apoptosis, autophagy, and cancer-related signaling pathways. I use molecular, cellular, omics-based, and in vivo approaches to study mechanisms of cancer progression and therapy resistance.
I am a pharmacist and PhD researcher in molecular pharmacology and tumor biology at China Pharmaceutical University, Nanjing, China. My research focuses on hepatocellular carcinoma, oxidative stress, DNA damage response, apoptosis, autophagy, and cancer-related signaling pathways. I use molecular, cellular, omics-based, and in vivo approaches to study mechanisms of cancer progression and therapy resistance.