Escalating antimicrobial resistance is a global threat, emphasizing the need to explore alternative treatment options. Hence, we aimed to explore the in-vitro activity of ceftazidime-avibactam (CAZ-AVI) in clinical isolates of carbapenem-resistant gram-negative bacteria.

This was an observational, cross-sectional study conducted at the Microbiology Department of Indus Hospital, Karachi, Pakistan, from January 2023 to October 2024. Carbapenem-resistant gram-negative rods isolated from clinical specimens received from the outpatient, emergency, and inpatient departments were included. Consecutive, non-probability sampling was employed for the collection of isolates. Identification of the organisms was confirmed using API® ID strips, and antimicrobial susceptibility for carbapenems and CAZ-AVI was determined via the Kirby-Bauer disc diffusion method.

A total of 158 bacterial isolates were characterized as carbapenem-resistant. Of these, 92 (58%) were Enterobacterales, and 66 (42%) were Pseudomonas aeruginosa. CAZ-AVI was susceptible in 17 (11%) of the isolates, of which four (24%) were Klebsiella spp. and Escherichia coli each, and nine (52%) were P. aeruginosa. CAZ-AVI-susceptible strains were predominant among patients aged 26–50 years (n = 6; 35%), most of whom were females (n = 10; 59%) and inpatients (n = 8; 47%). Clinical samples from patients with urinary tract infections grew the most CAZ-AVI-susceptible strains (n = 9; 53%).

Our study demonstrated low CAZ-AVI susceptibility in our carbapenem-resistant gram-negative bacterial strains. Understanding regional antimicrobial patterns in multidrug-resistant bacteria is crucial for the effective use of CAZ-AVI, along with the strict implementation of strategies for controlling antimicrobial resistance.

Epileptogenesis involves complex mechanisms, including inflammation and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, possesses anti-inflammatory and neuroprotective properties. This study investigated whether rosiglitazone can prevent pentylenetetrazole (PTZ)-induced kindling in mice by modulating inflammatory cytokines and apoptosis pathways.

Male C57BL/6 mice (n = 8 per group) were assigned to sham, control, or rosiglitazone-treated groups. Kindling was induced with intraperitoneal PTZ (40 mg/kg) every 48 h for 17 days. Rosiglitazone (0.1 mg/kg) was administered 30 m before each PTZ injection. Seizure progression was monitored, and hippocampal tissues were analyzed via immunohistochemistry and Western blotting to assess cytokine levels (interleukin (IL)-10, IL-17A, tumor necrosis factor-alpha, interferon-gamma), caspase-3 activity, and glial fibrillary acidic protein expression.

Rosiglitazone significantly delayed seizure progression, reduced seizure scores, and lowered pro-inflammatory cytokine levels (IL-17A, tumor necrosis factor-alpha, interferon-gamma) while increasing IL-10. Immunohistochemical analysis revealed fewer caspase-3-positive cells and reduced glial fibrillary acidic protein expression in the treatment group compared to controls.

Rosiglitazone exerts neuroprotective effects in PTZ-induced kindling, likely through its anti-inflammatory and anti-apoptotic actions. These findings underscore its potential as a therapeutic agent for mitigating epileptogenesis, warranting further investigation in combination therapies and clinical trials.

This study investigates the potential of methyl eugenol (ME), a compound found in the essential oils of various plants, to inhibit oxidative stress and its impact on diseases associated with this process. ME has been shown to possess antioxidant properties and antiproliferative activity in several cancers. It also demonstrates neuroprotective potential in conditions such as Alzheimer’s disease and ischemic brain injury. The mechanism of action involves the activation of the nuclear factor erythroid 2-related factor 2, which facilitates the transcription of antioxidant genes and modulation of pathways such as AMP-activated protein kinase/glycogen synthase kinase 3 beta, thereby reducing the production of reactive oxygen species and pro-inflammatory cytokines. However, research has identified potential toxicological risks associated with ME, including hepatotoxicity and changes in the gut microbiota. These findings highlight the need for caution when considering prolonged exposure to this compound.

The diagnosis of hepatic precancerous lesions (HPC) and early hepatocellular carcinoma (HCC) has significant public health implications and holds the potential to reduce the global burden of HCC. This study aimed to identify molecular features and biomarkers associated with HPC progression and early HCC development.

RNA sequencing was used to identify differentially expressed genes in mouse HPC tissues and normal liver tissues. Cyclin E1 (CCNE1) expression in HPC tissues and HCC cells was assessed using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. The effects of CCNE1 on HCC cell proliferation, migration, invasion, and apoptosis were evaluated using colony formation, wound healing, Transwell assays, and flow cytometry. The mechanism of CCNE1 was explored through Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis and further validated through in vitro experiments. The interaction between CCNE1 and tumor-associated macrophages (TAMs) was investigated by co-culturing HCC cells with macrophages.

RNA sequencing and TCGA database analysis showed that CCNE1 expression was significantly elevated in mouse HPC tissues and human HCC samples and was associated with reduced survival rates. In vitro assays demonstrated that CCNE1 promoted HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Additionally, CCNE1 induced TAM polarization toward the M2 phenotype by promoting the expression of CCL2 and CCL5 in HCC cells.

CCNE1 promotes HPC progression and HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Furthermore, CCNE1 enhances the secretion of CCL2 and CCL5 by HCC cells, promoting TAM infiltration and M2 polarization, thereby contributing to tumor progression.

Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer, characterized by insidious onset and high malignancy. Many patients are diagnosed at an inoperable stage, and the effectiveness of chemotherapy and radiotherapy remains limited. This study aimed to provide a comprehensive review of the histological classification, genetic alterations, molecular subtypes, and corresponding imaging signatures of iCCA, highlighting its heterogeneity and offering insights into targeted therapy and personalized treatment. The heterogeneity of iCCA poses significant challenges to both targeted therapy and immunotherapy, necessitating in-depth exploration at the molecular and subtyping levels. Investigating genetic variations, signaling pathway alterations, and molecular subtypes can aid in patient stratification. Stratifying iCCA patients allows for more precise treatment selection, ultimately improving survival outcomes. Imaging, as a non-invasive tool, holds substantial potential for predicting subtypes and molecular profiles. It is possible to infer histological and molecular features from imaging, or to interpret imaging signatures in light of known histological and molecular data. This integrative approach, combining external imaging with internal molecular insights, fosters a comprehensive understanding of iCCA’s characteristics and enhances clinical management.

Shenqi Fuzheng (SQ) is a widely used Chinese medicine formula known for its immune-enhancing and Qi-supplementing properties. However, the blood-absorbed components of SQ and their pharmacokinetics remain underexplored. This study aimed to comprehensively analyze the chemical constituents of SQ and investigate their absorption and pharmacokinetic behavior in rat plasma.

Ultra-performance liquid chromatography-triple quadrupole time-of-flight mass spectrometry (hereinafter referred to as UPLC-Triple-TOF/MS) is employed to identify the chemical components in SQ extract and quantify the components absorbed into the blood after oral administration in rats. This method provides fragmentation patterns of compounds and key pharmacokinetic profiles of blood-absorbed compounds.

A total of 105 compounds are identified from the SQ extract, and 40 are detected in the blood following oral administration. Organic acids and amino acids are found at higher concentrations in the bloodstream. Compounds such as Astragalosides promptly enter the bloodstream within 5 m after administration, with levels declining after 15 m. Flavonoids are absorbed within 15–30 m, and the peak of alkaloids occurs approximately 1 h after administration.

This study provides new insights into the chemical composition and pharmacokinetics of SQ, highlighting the dynamic changes in the content of absorbed compounds in the blood. It further promotes the comprehensive characterization of traditional Chinese medicine formulations through UPLC-Triple-TOF/MS. Future research should focus on elucidating the pharmacological activities of the identified compounds and investigating their potential synergistic effects within the formulation.

Prostate cancer is the second most diagnosed cancer in men worldwide and a significant cause of cancer-related death. Proteogenomic analysis offers insights into how genomic mutations influence protein expression and can identify novel biomarkers. This study aimed to investigate the impact of missense mutations on protein abundance in prostate cancer versus healthy tissues using SILAC-based quantitative proteomics.

Mass spectrometry data from prostate tumors and adjacent healthy tissues were analyzed using stable isotope labeling. Peptides were classified based on their abundance into RefSeq and Variant Abundant groups. Missense mutations were mapped via RefSeq and dbPepVar databases. Protein intensity metrics were compared, and Spearman’s correlation was used to evaluate the relationship between mutation presence and protein abundance.

Functional enrichment revealed that RefSeq Abundant proteins are involved in normal metabolic and structural functions, while Variant Abundant proteins are enriched in tumor-related pathways such as immune evasion and apoptosis suppression. A significant negative correlation was found between protein intensity difference and ratio (p < 0.05), indicating that missense mutations contribute to altered protein expression. Mutation hotspot analysis identified recurrent alterations in genes such as PPIF and ACTB. PROVEAN was used to evaluate the functional impact of variants, identifying several as deleterious to protein stability and function.

Missense mutations are associated with altered protein abundance and may promote oncogenic processes in prostate cancer. These findings enhance the understanding of genome-proteome interactions and could support the development of targeted biomarkers and therapies.

Chronic liver disease (CLD) is a major global health challenge, characterized by chronic inflammation that can progress to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Early identification of biomarkers is crucial for effective intervention. Traditional Chinese medicine (TCM) has shown potential in improving CLD symptoms and protecting the liver, although its mechanisms remain unclear. Metabolomics, the comprehensive study of metabolites, offers a promising approach to understanding CLD pathogenesis and identifying biomarkers. Notably, metabolomics aligns with TCM’s holistic approach and may help reveal its therapeutic mechanisms. This review summarizes key metabolites associated with CLD diagnosis and progression and discusses how TCM may modulate metabolic pathways to alleviate CLD symptoms. These insights could lead to improved diagnostic and therapeutic strategies for CLD.